2024 |
Idrees S, Paudel KR, Sadaf T, Hansbro PM, 'Uncovering domain motif interactions using high-throughput protein-protein interaction detection methods.', FEBS letters, (2024)
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2024 |
Kokkinis S, Singh M, Paudel KR, De Rubis G, Bani Saeid A, Jessamine V, et al., 'Plant-based therapeutics for chronic obstructive pulmonary diseases: Nanoformulation strategies to overcome delivery challenges', Food Bioscience, 58 (2024)
Chronic obstructive pulmonary disease (COPD) is a widespread global health problem marked by increasing airflow limitation and chronic airway inflammation. Conventional treatments... [more]
Chronic obstructive pulmonary disease (COPD) is a widespread global health problem marked by increasing airflow limitation and chronic airway inflammation. Conventional treatments for COPD offer limited efficacy and have potentially undesirable effects, requiring the investigation of other therapeutic options. Because of their anti-inflammatory, antioxidant, and bronchodilatory effects, plant-based chemicals have emerged as viable candidates for COPD therapy. The successful delivery of these compounds to the respiratory system, on the other hand, remains an enormous challenge. This extensive review article explores the promising potential of plant-based therapies for COPD and investigates leading-edge nanoformulation technologies targeted at addressing the complex delivery challenges that accompany these natural compounds. We discuss multiple plant-derived compounds (polyphenols, flavonoids, and alkaloids) and their modes of action in reducing COPD-related indications and complications. Additionally, the function of nanotechnology in improving the bioavailability, stability, and targeted delivery of plant-based pharmaceuticals in COPD treatment is explored. Nanoformulation techniques, such as nanoparticles, liposomes, and micelles, are described, with an emphasis on their potential to precisely encapsulate and transport plant-derived bioactive to the afflicted parts of the lung. Furthermore, constraints in the development of plant-based nanoformulations for COPD are also highlighted, including safety, scalability, and regulatory issues. The current review aims to provide a thorough understanding of the promising future of COPD treatment by combining knowledge of plant-based therapies and novel nanoformulation technologies. The intersection of nature-inspired medicines and nanotechnology may hold the key to more effective, safer, and patient-centred therapeutic choices for people suffering from this chronic respiratory illness.
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2024 |
Budden KF, Shukla SD, Bowerman KL, Vaughan A, Gellatly SL, Wood DLA, et al., 'Faecal microbial transfer and complex carbohydrates mediate protection against COPD.', Gut, (2024) [C1]
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2024 |
Jessamine V, Mehndiratta S, De Rubis G, Paudel KR, Shetty S, Suares D, et al., 'The application of nanoparticles as advanced drug delivery systems in Attenuating COPD', Heliyon, 10 (2024) [C1]
Chronic Obstructive Pulmonary Disease (COPD) is a dilapidating condition which is characterized by inflammation, an excess in free radical generation and airway obstruction. Curre... [more]
Chronic Obstructive Pulmonary Disease (COPD) is a dilapidating condition which is characterized by inflammation, an excess in free radical generation and airway obstruction. Currently, the drugs commercially available for the management of COPD pose several limitations such as systemic adverse effects, including bone density loss and an increased risk of developing pneumonia. Moreover, another limitation includes the need for regular and frequent dosing regimens; which can affect the adherence to the therapy. Furthermore, these current treatments provide symptomatic relief; however, they cannot stop the progression of COPD. Comparatively, nanoparticles (NPs) provide great therapeutic potential to treat COPD due to their high specificity, biocompatibility, and higher bioavailability. Furthermore, the NP-based drug delivery systems involve less frequent dosing requirements and in smaller doses which assist in minimizing side effects. In this review, the benefits and limitations of conventional therapies are explored, while providing an in-depth insight on advanced applications of NP-based systems in the treatment of COPD.
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2024 |
Idrees S, Paudel KR, Hansbro PM, 'Prediction of motif-mediated viral mimicry through the integration of host pathogen interactions', Archives of Microbiology, 206 (2024) [C1]
One of the mechanisms viruses use in hijacking host cellular machinery is mimicking Short Linear Motifs (SLiMs) in host proteins to maintain their life cycle inside host cells. In... [more]
One of the mechanisms viruses use in hijacking host cellular machinery is mimicking Short Linear Motifs (SLiMs) in host proteins to maintain their life cycle inside host cells. In the face of the escalating volume of virus-host protein¿protein interactions (vhPPIs) documented in databases; the accurate prediction of molecular mimicry remains a formidable challenge due to the inherent degeneracy of SLiMs. Consequently, there is a pressing need for computational methodologies to predict new instances of viral mimicry. Our present study introduces a DMI-de-novo pipeline, revealing that vhPPIs catalogued in the VirHostNet3.0 database effectively capture domain-motif interactions (DMIs). Notably, both affinity purification coupled mass spectrometry and yeast two-hybrid assays emerged as good approaches for delineating DMIs. Furthermore, we have identified new vhPPIs mediated by SLiMs across different viruses. Importantly, the de-novo prediction strategy facilitated the recognition of several potential mimicry candidates implicated in the subversion of host cellular proteins. The insights gleaned from this research not only enhance our comprehension of the mechanisms by which viruses co-opt host cellular machinery but also pave the way for the development of novel therapeutic interventions.
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2024 |
Solanki N, Gupta G, Chellappan DK, Singh SK, Gulati M, Paudel KR, et al., 'Boswellic Acids: A Critical Appraisal of Their Therapeutic and Nutritional Benefits in Chronic Inflammatory Diseases.', Endocr Metab Immune Disord Drug Targets, 24 116-129 (2024) [C1]
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2024 |
De Rubis G, Paudel KR, Allam VSRR, Malyla V, Subramaniyan V, Singh SK, et al., 'Involvement of osteopontin, EpCAM, estrogen receptor-alpha, and carbonic anhydrase IX protein in managing lung cancer via Berberine-loaded liquid crystalline nanoparticles', Pathology Research and Practice, 253 (2024) [C1]
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2024 |
De Rubis G, Paudel KR, Yeung S, Agarwal V, Hansbro PM, Oliver BGG, Dua K, 'Ribavirin attenuates carcinogenesis by downregulating IL-6 and IL-8 in vitro in human lung adenocarcinoma', Pathology Research and Practice, 253 (2024) [C1]
Lung cancer is one of the leading causes of death worldwide, whereby the major contributing factors are cigarette smoking and exposure to environmental pollutants. Despite the ava... [more]
Lung cancer is one of the leading causes of death worldwide, whereby the major contributing factors are cigarette smoking and exposure to environmental pollutants. Despite the availability of numerous treatment options, including chemotherapy, the five-year survival rate is still extremely low, highlighting the urgent need to develop novel, more effective therapeutic strategies. In this context, the repurposing of previously approved drugs is an advantage in terms of time and resources invested. Ribavirin is an antiviral drug approved for the treatment of hepatitis C, which shows potential for repurposing as an anticancer agent. Among the many signaling molecules promoting carcinogenesis, the interleukins (ILs) IL-6 and IL-8 are interesting therapeutic targets as they promote a variety of cancer hallmarks such as cell proliferation, migration, metastasis, and angiogenesis. In the present study, we show that ribavirin significantly downregulates the expression of IL-6 and IL-8 in vitro in A549 human lung adenocarcinoma cells. The results of this study shed light on the anticancer mechanisms of ribavirin, providing further proof of its potential as a repurposed drug for the treatment of lung cancer.
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2024 |
Mayall JR, Horvat JC, Mangan NE, Chevalier A, McCarthy H, Hampsey D, et al., 'Interferon-epsilon is a novel regulator of NK cell responses in the uterus', EMBO Molecular Medicine, 16 267-293 [C1]
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2024 |
Manandhar B, Paudel KR, Clarence DD, De Rubis G, Madheswaran T, Panneerselvam J, et al., 'Zerumbone-incorporated liquid crystalline nanoparticles inhibit proliferation and migration of non-small-cell lung cancer in vitro', Naunyn-Schmiedeberg's Archives of Pharmacology, 397 343-356 (2024) [C1]
Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up t... [more]
Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Zerumbone (ZER) is natural compound commonly found in the roots of Zingiber zerumbet which has recently demonstrated anti-cancer activity in both in vitro and in vivo studies. Despite their medical benefits, ZER has low aqueous solubility, poor GI absorption and oral bioavailability that hinders its effectiveness. Liquid crystalline nanoparticles (LCNs) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. This study aimed to formulate ZER-loaded LCNs and investigate their effectiveness against NSCLC in vitro using A549 lung cancer cells. ZER-LCNs, prepared in the study, inhibited the proliferation and migration of A549 cells. These inhibitory effects were superior to the effects of ZER alone at a concentration 10 times lower than that of free ZER, demonstrating a potent anti-cancer activity of ZER-LCNs. The underlying mechanisms of the anti-cancer effects by ZER-LCNs were associated with the transcriptional regulation of tumor suppressor genes P53 and PTEN, and metastasis-associated gene KRT18. The protein array data showed downregulation of several proliferation associated proteins such as AXL, HER1, PGRN, and BIRC5 and metastasis-associated proteins such as DKK1, CAPG, CTSS, CTSB, CTSD, and PLAU. This study provides evidence of potential for increasing the potency and effectiveness of ZER with LCN formulation and developing ZER-LCNs as a treatment strategy for mitigation and treatment of NSCLC.
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2024 |
Yin M, Wadhwa R, Marshall JE, Gillis CM, Kim RY, Dua K, et al., '4-Octyl Itaconate Alleviates Airway Eosinophilic Inflammation by Suppressing Chemokines and Eosinophil Development.', J Immunol, 212 13-23 (2024) [C1]
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Nova |
2023 |
'TSANZ Abstracts', Respirology, 28 110-246 (2023)
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2023 |
Tu X, Gomez HM, Kim RY, Brown AC, de Jong E, Galvao I, et al., 'Airway and parenchyma transcriptomics in a house dust mite model of experimental asthma', Respiratory Research, 24 (2023) [C1]
Lung transcriptomics studies in asthma have provided valuable information in the whole lung context, however, deciphering the individual contributions of the airway and parenchyma... [more]
Lung transcriptomics studies in asthma have provided valuable information in the whole lung context, however, deciphering the individual contributions of the airway and parenchyma in disease pathogenesis may expedite the development of novel targeted treatment strategies. In this study, we performed transcriptomics on the airway and parenchyma using a house dust mite (HDM)-induced model of experimental asthma that replicates key features of the human disease. HDM exposure increased the expression of 3,255 genes, of which 212 were uniquely increased in the airways, 856 uniquely increased in the parenchyma, and 2187 commonly increased in both compartments. Further interrogation of these genes using a combination of network and transcription factor enrichment analyses identified several transcription factors that regulate airway and/or parenchymal gene expression, including transcription factor EC (TFEC), transcription factor PU.1 (SPI1), H2.0-like homeobox (HLX), metal response element binding transcription factor-1 (MTF1) and E74-like factor 4 (ets domain transcription factor, ELF4) involved in controlling innate immune responses. We next assessed the effects of inhibiting lung SPI1 responses using commercially available DB1976 and DB2313 on key disease outcomes. We found that both compounds had no protective effects on airway inflammation, however DB2313 (8¿mg/kg) decreased mucus secreting cell number, and both DB2313 (1¿mg/kg) and DB1976 (2.5¿mg/kg and 1¿mg/kg) reduced small airway collagen deposition. Significantly, both compounds decreased airway hyperresponsiveness. This study demonstrates that SPI1 is important in HDM-induced experimental asthma and that its pharmacological inhibition reduces HDM-induced airway collagen deposition and hyperresponsiveness.
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Nova |
2023 |
Vanders RL, Gomez HM, Hsu AC, Daly K, Wark PAB, Horvat JC, Hansbro PM, 'Inflammatory and antiviral responses to influenza A virus infection are dysregulated in pregnant mice with allergic airway disease.', Am J Physiol Lung Cell Mol Physiol, 325 L385-L398 (2023) [C1]
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Nova |
2023 |
Alamil JMR, Xenaki D, Manandhar B, Paudel KR, Hansbro PM, Oliver BG, et al., 'AGARWOOD OIL NANOEMULSION ATTENUATES PRODUCTION OF LIPOPOLYSACCHARIDE (LPS)-INDUCED PROINFLAMMATORY CYTOKINES, IL-6 AND IL-8 IN HUMAN BRONCHIAL EPITHELIAL CELLS', EXCLI JOURNAL, 22 681-685 (2023)
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2023 |
Hansbro P, 'Omics technologies to study virus infection and chronic lung diseases', RESPIROLOGY, 28 403-403 (2023)
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2023 |
Paudel KR, Manandhar B, Singh SK, Gupta G, Hansbro PM, Chellappan DK, Dua K, 'CYTOTOXIC MECHANISMS OF BERBERINE-PHYTANTRIOL LIQUID CRYSTALLINE NANOPARTICLES AGAINST NON-SMALL-CELL LUNG CANCER', EXCLI JOURNAL, 22 516-519 (2023)
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2023 |
Ryan TAJ, Hooftman A, Rehill AM, Johansen MD, Brien ECO, Toller-Kawahisa JE, et al., 'Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon.', Nat Commun, 14 3513 (2023) [C1]
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2023 |
Mendes de Almeida V, Engel DF, Ricci MF, Cruz CS, Lopes ÍS, Alves DA, et al., 'Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms', Gut Microbes, 15 (2023) [C1]
Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut... [more]
Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.
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2023 |
Ullah TR, Johansen MD, Balka KR, Ambrose RL, Gearing LJ, Roest J, et al., 'Pharmacological inhibition of TBK1/IKKe blunts immunopathology in a murine model of SARS-CoV-2 infection.', Nat Commun, 14 5666 (2023) [C1]
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2023 |
Afrose D, Nikolic V, Orlic N, Mikovic Z, Stefanovic M, Cakic Z, et al., 'URIC ACID IS A PROMISING BIOMARKER AND TARGET OF PREECLAMPSIA', PLACENTA, 140 E50-E50 (2023) |
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2023 |
Martino DJ, Bui DS, Li S, Idrose S, Perret J, Lowe AJ, et al., 'Genetic and Epigenetic Associations with Pre-Chronic Obstructive Pulmonary Disease Lung Function Trajectories', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 208 1135-1137 (2023)
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2023 |
Chakraborty A, Paudel KR, Wang C, De Rubis G, Chellappan DK, Hansbro PM, et al., 'ANTI-INFLAMMATORY AND ANTI-FIBROTIC EFFECTS OF BERBERINE-LOADED LIQUID CRYSTALLINE NANOPARTICLES', EXCLI JOURNAL, 22 1104-1108 (2023)
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2023 |
Attia J, Horvat JC, Hunter T, Hansbro PM, Hure A, Peel R, et al., 'Persistence of Detectable Anti-Pneumococcal Antibodies 4 Years After Pneumococcal Polysaccharide Vaccination in a Randomised Controlled Trial: The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE)', Heart, Lung and Circulation, 32 1378-1385 (2023) [C1]
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Nova |
2023 |
Van Eeckhoutte HP, Donovan C, Kim RY, Conlon TM, Ansari M, Khan H, et al., 'RIPK1 kinase-dependent inflammation and cell death contribute to the pathogenesis of COPD.', Eur Respir J, 61 (2023) [C1]
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Nova |
2023 |
Imran M, Insaf A, Hasan N, Sugandhi VV, Shrestha D, Paudel KR, et al., 'Exploring the Remarkable Chemotherapeutic Potential of Polyphenolic Antioxidants in Battling Various Forms of Cancer', Molecules, 28 3475-3475 [C1]
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2023 |
Panthi VK, Dua K, Singh SK, Gupta G, Hansbro PM, Paudel KR, 'Nanoformulations-Based Metronomic Chemotherapy: Mechanism, Challenges, Recent Advances, and Future Perspectives', Pharmaceutics, 15 1192-1192 [C1]
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2023 |
Girkin JLN, Sokulsky LA, Starkey MR, Hansbro PM, Foster PS, Collison AM, Mattes J, 'A unique role for IL-13 in inducing esophageal eosinophilia through MID-1 and STAT6', Frontiers in Allergy, 4 [C1]
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Nova |
2023 |
Paudel KR, Rajput R, De Rubis G, Raju Allam VSR, Williams KA, Singh SK, et al., 'In vitro anti-cancer activity of a polyherbal preparation, VEDICINALS®9, against A549 human lung adenocarcinoma cells', Pathology Research and Practice, 250 (2023) [C1]
Purpose: Non-small cell lung cancer (NSCLC) is among the leading causes of morbidity and mortality worldwide. Despite the availability of several treatment options, the five-year ... [more]
Purpose: Non-small cell lung cancer (NSCLC) is among the leading causes of morbidity and mortality worldwide. Despite the availability of several treatment options, the five-year survival rate of NSCLC is extremely low (<20%). This underlines the necessity of more effective therapeutic alternatives. In this context, plant-derived extracts and bioactive molecules extracted from plants, known collectively as phytoceuticals, represent an extremely variegated source of bioactive compounds with potent anticancer potential. In the present study, we tested the in vitro anticancer activity of a polyherbal preparation, VEDICINALS®9, containing nine different bioactive principles extracted by medicinal plants. Methods: The anticancer activity of VEDICINALS®9 was investigated by measuring its impact on A549 human NSCLC cell proliferation (MTT assay and trypan blue staining), migration (wound healing assay and transwell chamber assay) and by measuring the impact on the expression of cancer-related proteins (Human XL Oncology Protein Array). Results: We show that VEDICINALS®9 at a concentration of 0.2% v/v has potent anticancer effect, significantly inhibiting A549 cell proliferation and migration. Mechanistically, this was achieved by downregulating the expression of proteins involved in cancer cell proliferation (Axl, FGF basic, enolase 2, progranulin, survivin) and migration (Dkk-1, cathepsins B and D, BCL-x, amphiregulin, CapG, u-plasminogen activator). Furthermore, treatment with VEDICINALS®9 resulted in increased expression of the oncosuppressor protein p53 and of the angiogenesis inhibitor endostatin. Conclusions: Taken together, our results provide proof of principle of the potent anticancer activity of the polyherbal preparation VEDICINALS®9, highlighting its enormous potential as an alternative or adjuvant therapy for lung cancer.
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2023 |
Datsyuk JK, Paudel KR, Rajput R, Kokkinis S, El Sherkawi T, Singh SK, et al., 'Emerging applications and prospects of NF B decoy oligodeoxynucleotides in managing respiratory diseases.', Chem Biol Interact, 385 110737 (2023) [C1]
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2023 |
Mishra N, Bhatt S, Paudel KR, Hansbro PM, Dua K, 'Preface', Synbiotics for the Management of Cancer, v-vi (2023) |
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2023 |
Fairley LH, Das S, Dharwal V, Amorim N, Hegarty KJ, Wadhwa R, et al., 'Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease.', Antioxidants (Basel), 12 (2023) [C1]
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2023 |
Shrestha J, Paudel KR, Nazari H, Dharwal V, Bazaz SR, Johansen MD, et al., 'Advanced models for respiratory disease and drug studies.', Med Res Rev, 43 1470-1503 (2023) [C1]
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2023 |
Bani Saeid A, Patel VK, Mehndiratta S, Rajput R, Kundu RK, Singh SK, et al., 'Dissecting the in vitro fate of plant-derived bioactive encapsulated nanoparticles in lung diseases', Food Bioscience, 56 (2023) [C1]
Lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are prevalent worldwide, with high mortality rates. There are many pathways involved in... [more]
Lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are prevalent worldwide, with high mortality rates. There are many pathways involved in the development of these diseases; if targeted, the conditions may be prevented and/or improved. Although current pharmacotherapies are available to treat various lung diseases, none act on all stages of disease progression. In recent years, plant-derived medicines have gained increasing attention as potential therapeutic agents for a variety of diseases. The in vitro effects of plant-derived bioactive agents such as resveratrol, quercetin, and liquorice for the treatment of asthma, COPD, and lung cancer, as well as their potential for translation into in vitro and clinical settings, are included in this review. Furthermore, the challenges associated with phytoconstituents delivery using conventional drug delivery systems is a significant challenge owing to their poor solubility, gastrointestinal degradation, poor bioavailability, poor drug loading as well as poor targeting. To overcome such challenges, various novel drug delivery systems (NDDS) have been developed by the researchers and in this review some of them including liposomes, polymeric nanoparticles, and solid-liquid nanoparticles, are discussed. The literature reviewed in this manuscript suggests that plant-derived bioactive nanoparticles may have a promising potential as targeted therapeutic agents for lung diseases. Hence, understanding their in vitro fate is essential for their successful development and translation into clinical use.
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2023 |
Ashique S, Gupta K, Gupta G, Mishra N, Singh S, Wadhwa S, et al., 'Vitamin D A prominent immunomodulator to prevent COVID-19 infection', International Journal of Rheumatic Diseases, 26 13-30 (2023) [C1]
COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, non... [more]
COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID-19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID-19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID-19 infection.
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2023 |
Rathnayake SNH, Ditz B, van Nijnatten J, Sadaf T, Hansbro PM, Brandsma CA, et al., 'Smoking induces shifts in cellular composition and transcriptome within the bronchial mucus barrier.', Respirology, 28 132-142 (2023) [C1]
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2023 |
Malyla V, Paudel KR, De Rubis G, Hansbro NG, Hansbro PM, Dua K, 'Cigarette smoking induces lung cancer tumorigenesis via upregulation of the WNT/ß-catenin signaling pathway', Life Sciences, 326 (2023) [C1]
Lung cancer has the highest mortality rate compared to any other cancer worldwide, and cigarette smoking is one of the major etiological factors. How cigarette smoke (CS) induces ... [more]
Lung cancer has the highest mortality rate compared to any other cancer worldwide, and cigarette smoking is one of the major etiological factors. How cigarette smoke (CS) induces tumorigenesis in healthy cells is still not completely understood. In this study, we treated healthy human bronchial epithelial cells (16HBE14o) with 1 % cigarette smoke extract (CSE) for one week. The CSE exposed cells showed upregulation of WNT/ß-catenin pathway genes like WNT3, DLV3, AXIN and ß-catenin, 30 oncology proteins were found to be upregulated after CSE treatment. Further, we explored whether the role of extracellular vesicles (EVs) obtained from CSE exposed cells can induce tumorigenesis. We observed that CSE EVs induced migration of healthy 16HBE14o cells by upregulation of various oncology proteins in recipient cells like AXL, EGFR, DKK1, ENG, FGF2, ICAM1, HMOX1, HIF1a, SERPINE1, SNAIL, HGFR, PLAU which are related to WNT signaling, epithelial mesenchymal transition (EMT) and Inflammation, whereas inflammatory marker, GAL-3 and EMT marker, VIM were downregulated. Moreover, ß-catenin RNA was found in CSE EVs, upon treatment of these EVs to healthy cells, the ß-catenin gene level was decreased in recipient cells compared to healthy 16HBE14o cells, indicating the utilisation of ß-catenin RNA in healthy cells. Overall, our study suggests that CS treatment can induce tumorigenesis of healthy cells by upregulating WNT/ß-catenin signaling in vitro and human lung cancer patients. Therefore targeting the WNT/ß-catenin signaling pathway is involved in tumorigenesis inhibition of this pathway could be a potential therapeutic approach for cigarette smoke induced lung cancer.
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2023 |
De Rubis G, Paudel KR, Corrie L, Mehndiratta S, Patel VK, Kumbhar PS, et al., 'Applications and advancements of nanoparticle-based drug delivery in alleviating lung cancer and chronic obstructive pulmonary disease', Naunyn-Schmiedeberg's Archives of Pharmacology, (2023) [C1]
Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are among the leading causes of mortality worldwide. Cigarette smoking is among the main aetiologic factors for b... [more]
Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are among the leading causes of mortality worldwide. Cigarette smoking is among the main aetiologic factors for both ailments. These diseases share common pathogenetic mechanisms including inflammation, oxidative stress, and tissue remodelling. Current therapeutic approaches are limited by low efficacy and adverse effects. Consequentially, LC has a 5-year survival of < 20%, while COPD is incurable, underlining the necessity for innovative treatment strategies. Two promising emerging classes of therapy against these diseases include plant-derived molecules (phytoceuticals) and nucleic acid-based therapies. The clinical application of both is limited by issues including poor solubility, poor permeability, and, in the case of nucleic acids, susceptibility to enzymatic degradation, large size, and electrostatic charge density. Nanoparticle-based advanced drug delivery systems are currently being explored as flexible systems allowing to overcome these limitations. In this review, an updated summary of the most recent studies using nanoparticle-based advanced drug delivery systems to improve the delivery of nucleic acids and phytoceuticals for the treatment of LC and COPD is provided. This review highlights the enormous relevance of these delivery systems as tools that are set to facilitate the clinical application of novel categories of therapeutics with poor pharmacokinetic properties. Graphical abstract: This picture was generated with BioRender [Figure not available: see fulltext.]
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2023 |
Sulaiman I, Wu BG, Chung M, Isaacs B, Tsay JCJ, Holub M, et al., 'Lower Airway Dysbiosis Augments Lung Inflammatory Injury in Mild-to-Moderate Chronic Obstructive Pulmonary Disease', American journal of respiratory and critical care medicine, 208 1101-1114 (2023) [C1]
Rationale: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and healthcare costs. Cigarette smoke is a causative factor; however, not all... [more]
Rationale: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and healthcare costs. Cigarette smoke is a causative factor; however, not all heavy smokers develop COPD. Microbial colonization and infections are contributing factors to disease progression in advanced stages. Objectives: We investigated whether lower airway dysbiosis occurs in mild-to-moderate COPD and analyzed possible mechanistic contributions to COPD pathogenesis. Methods: We recruited 57 patients with a >10 pack-year smoking history: 26 had physiological evidence of COPD, and 31 had normal lung function (smoker control subjects). Bronchoscopy sampled the upper airways, lower airways, and environmental background. Samples were analyzed by 16S rRNA gene sequencing, whole genome, RNA metatranscriptome, and host RNA transcriptome. A preclinical mouse model was used to evaluate the contributions of cigarette smoke and dysbiosis on lower airway inflammatory injury. Measurements and Main Results: Compared with smoker control subjects, microbiome analyses showed that the lower airways of subjects with COPD were enriched with common oral commensals. The lower airway host transcriptomics demonstrated differences in markers of inflammation and tumorigenesis, such as upregulation of IL-17, IL-6, ERK/MAPK, PI3K, MUC1, and MUC4 in mild-to-moderate COPD. Finally, in a preclinical murine model exposed to cigarette smoke, lower airway dysbiosis with common oral commensals augments the inflammatory injury, revealing transcriptomic signatures similar to those observed in human subjects with COPD. Conclusions: Lower airway dysbiosis in the setting of smoke exposure contributes to inflammatory injury early in COPD. Targeting the lower airway microbiome in combination with smoking cessation may be of potential therapeutic relevance.
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2023 |
Awatade NT, Reid AT, Nichol KS, Budden KF, Veerati PC, Pathinayake PS, et al., 'Comparison of commercially available differentiation media on cell morphology, function, and anti-viral responses in conditionally reprogrammed human bronchial epithelial cells.', Scientific reports, 13 11200 (2023) [C1]
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Nova |
2023 |
Allam VSRR, Pavlidis S, Liu G, Kermani NZ, Simpson J, To J, et al., 'Macrophage migration inhibitory factor promotes glucocorticoid resistance of neutrophilic inflammation in a murine model of severe asthma', THORAX, 78 661-673 (2023) [C1]
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2023 |
Chan Y, Raju Allam VSR, Paudel KR, Singh SK, Gulati M, Dhanasekaran M, et al., 'Nutraceuticals: unlocking newer paradigms in the mitigation of inflammatory lung diseases', CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, 63 3302-3332 (2023)
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2023 |
Liu G, Haw TJ, Starkey MR, Philp AM, Pavlidis S, Nalkurthi C, et al., 'TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.', Nat Commun, 14 7349 (2023) [C1]
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2023 |
Colarusso C, Terlizzi M, Falanga A, Stathopoulos G, De Lucia L, Hansbro PM, et al., 'Absent in melanoma 2 (AIM2) positive profile identifies a poor prognosis of lung adenocarcinoma patients', INTERNATIONAL IMMUNOPHARMACOLOGY, 124 (2023) [C1]
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2023 |
Imran M, Jin X, Ali M, Tapfumaneyi P, Lelasseur P, Carlo L, et al., 'The Pandemic and Your Skin Direct and Indirect Impact of COVID-19', Cosmetics, 10 34-34 [C1]
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2023 |
Mohamad MSB, Reyes RJ, De Rubis G, Paudel KR, Hansbro PM, Dua K, Chellappan DK, 'THE VERSATILITY OF 18 -GLYCYRRHETINIC ACID IN ATTENUATING PULMONARY INFLAMMATORY DISORDERS', EXCLI Journal, 22 188-190 (2023)
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2023 |
Malyla V, Paudel KR, Rubis GD, Hansbro NG, Hansbro PM, Dua K, 'Extracellular Vesicles Released from Cancer Cells Promote Tumorigenesis by Inducing Epithelial to Mesenchymal Transition via ß-Catenin Signaling', International Journal of Molecular Sciences, 24 3500-3500 [C1]
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2023 |
Horvat JC, Kim RY, Weaver N, Augood C, Brown AC, Donovan C, et al., 'Characterization and inhibition of inflammasome responses in severe and non-severe asthma.', Respir Res, 24 303 (2023) [C1]
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2023 |
Rouet R, Henry JY, Johansen MD, Sobti M, Balachandran H, Langley DB, et al., 'Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients', Nature Communications, 14 (2023) [C1]
Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutra... [more]
Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells of convalescent patients using SARS-CoV-2 receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (S309) by orders of magnitude. They also provide prophylactic and therapeutic in vivo protection of female hACE2 mice against viral challenge. Our results indicate that exposure to SARS-CoV-2 induces antibodies that maintain broad neutralization against emerging VOCs using two unique strategies: either by targeting the divergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14); or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design.
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2023 |
De Rubis G, Paudel KR, Manandhar B, Singh SK, Gupta G, Malik R, et al., 'Agarwood Oil Nanoemulsion Attenuates Cigarette Smoke-Induced Inflammation and Oxidative Stress Markers in BCi-NS1.1 Airway Epithelial Cells', Nutrients, 15 1019-1019 [C1]
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2023 |
Scaramuzzo G, Nucera F, Asmundo A, Messina R, Mari M, Montanaro F, et al., 'Cellular and molecular features of COVID-19 associated ARDS: therapeutic relevance.', J Inflamm (Lond), 20 11 (2023) [C1]
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2023 |
McDonald VM, Archbold G, Beyene T, Brew BK, Franklin P, Gibson PG, et al., 'Asthma and landscape fire smoke: A Thoracic Society of Australia and New Zealand position statement', Respirology, 28 1023-1035 (2023) [C1]
Landscape fires are increasing in frequency and severity globally. In Australia, extreme bushfires cause a large and increasing health and socioeconomic burden for communities and... [more]
Landscape fires are increasing in frequency and severity globally. In Australia, extreme bushfires cause a large and increasing health and socioeconomic burden for communities and governments. People with asthma are particularly vulnerable to the effects of landscape fire smoke (LFS) exposure. Here, we present a position statement from the Thoracic Society of Australia and New Zealand. Within this statement we provide a review of the impact of LFS on adults and children with asthma, highlighting the greater impact of LFS on vulnerable groups, particularly older people, pregnant women and Aboriginal and Torres Strait Islander peoples. We also highlight the development of asthma on the background of risk factors (smoking, occupation and atopy). Within this document we present advice for asthma management, smoke mitigation strategies and access to air quality information, that should be implemented during periods of LFS. We promote clinician awareness, and the implementation of public health messaging and preparation, especially for people with asthma.
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2023 |
Faiz A, Mahbub RM, Boedijono FS, Tomassen MI, Kooistra W, Timens W, et al., 'IL-33 Expression Is Lower in Current Smokers at both Transcriptomic and Protein Levels.', Am J Respir Crit Care Med, 208 1075-1087 (2023) [C1]
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2023 |
Tu J, Li W, Hansbro PM, Yan Q, Bai X, Donovan C, et al., 'Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m6 modification.', Mol Ther, 31 2524-2542 (2023) [C1]
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2023 |
Paudel KR, Clarence DD, Panth N, Manandhar B, De Rubis G, Devkota HP, et al., 'Zerumbone liquid crystalline nanoparticles protect against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro', Naunyn-Schmiedeberg's Archives of Pharmacology, (2023) [C1]
The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar ... [more]
The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1ß and Tnf-a, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.
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2023 |
De Rubis G, Paudel KR, Liu G, Agarwal V, MacLoughlin R, de Jesus Andreoli Pinto T, et al., 'Berberine-loaded engineered nanoparticles attenuate TGF-ß-induced remodelling in human bronchial epithelial cells', Toxicology in Vitro, 92 (2023) [C1]
Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epi... [more]
Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-ß (TGF-ß), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-ß is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-ß-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-ß-induced migration, reducing the levels of proteins upregulated by TGF-ß including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-ß. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-ß. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-ß-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.
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2023 |
Hardy SA, Liesinger L, Patrick R, Poettler M, Rech L, Gindlhuber J, et al., 'Extracellular Matrix Protein-1 as a Mediator of Inflammation-Induced Fibrosis After Myocardial Infarction', JACC: Basic to Translational Science, 8 1539-1554 (2023) [C1]
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2023 |
Malyla V, De Rubis G, Paudel KR, Chellappan DK, Hansbro NG, Hansbro PM, Dua K, 'Berberine nanostructures attenuate ß-catenin, a key component of epithelial mesenchymal transition in lung adenocarcinoma', Naunyn-Schmiedeberg's Archives of Pharmacology, 396 3595-3603 (2023) [C1]
Lung cancer (LC) is the leading cause of cancer-related deaths globally. It accounts for more than 1.9 million cases each year due to its complex and poorly understood molecular m... [more]
Lung cancer (LC) is the leading cause of cancer-related deaths globally. It accounts for more than 1.9 million cases each year due to its complex and poorly understood molecular mechanisms that result in unregulated cell proliferation and metastasis. ß-Catenin is a developmentally active protein that controls cell proliferation, metastasis, polarity and cell fate during homeostasis and aids in cancer progression via epithelial¿mesenchymal transition. Therefore, inhibition of the ß-catenin pathway could attenuate the progression of LC. Berberine, an isoquinoline alkaloid which is known for its anti-cancer and anti-inflammatory properties, demonstrates poor solubility and bioavailability. In our study, we have encapsulated berberine into liquid crystalline nanoparticles to improve its physiochemical functions and studied if these nanoparticles target the ß-catenin pathway to inhibit the human lung adenocarcinoma cell line (A549) at both gene and protein levels. We observed for the first time that berberine liquid crystalline nanoparticles at 5¿µM significantly attenuate the expression of the ß-catenin gene and protein. The interaction between berberine and ß-catenin was further validated by molecular simulation studies. Targeting ß-catenin with berberine nanoparticles represents a promising strategy for the management of lung cancer progression.
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2023 |
Shrestha J, Paudel KR, Nazari H, Dharwal V, Bazaz SR, Johansen MD, et al., 'Front Cover Image, Volume 43, Issue 5', Medicinal Research Reviews, 43 (2023)
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2023 |
Salvato I, Ricciardi L, Dal Col J, Nigro A, Giurato G, Memoli D, et al., 'Expression of targets of the RNA-binding protein AUF-1 in human airway epithelium indicates its role in cellular senescence and inflammation', Frontiers in Immunology, 14 (2023) [C1]
Introduction: The RNA-binding protein AU-rich-element factor-1 (AUF-1) participates to posttranscriptional regulation of genes involved in inflammation and cellular senescence, tw... [more]
Introduction: The RNA-binding protein AU-rich-element factor-1 (AUF-1) participates to posttranscriptional regulation of genes involved in inflammation and cellular senescence, two pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). Decreased AUF-1 expression was described in bronchiolar epithelium of COPD patients versus controls and in vitro cytokine- and cigarette smoke-challenged human airway epithelial cells, prompting the identification of epithelial AUF-1-targeted transcripts and function, and investigation on the mechanism of its loss. Results: RNA immunoprecipitation-sequencing (RIP-Seq) identified, in the human airway epithelial cell line BEAS-2B, 494 AUF-1-bound mRNAs enriched in their 3¿-untranslated regions for a Guanine-Cytosine (GC)-rich binding motif. AUF-1 association with selected transcripts and with a synthetic GC-rich motif were validated by biotin pulldown. AUF-1-targets¿ steady-state levels were equally affected by partial or near-total AUF-1 loss induced by cytomix (TNFa/IL1ß/IFN¿/10 nM each) and siRNA, respectively, with differential transcript decay rates. Cytomix-mediated decrease in AUF-1 levels in BEAS-2B and primary human small-airways epithelium (HSAEC) was replicated by treatment with the senescence- inducer compound etoposide and associated with readouts of cell-cycle arrest, increase in lysosomal damage and senescence-associated secretory phenotype (SASP) factors, and with AUF-1 transfer in extracellular vesicles, detected by transmission electron microscopy and immunoblotting. Extensive in-silico and genome ontology analysis found, consistent with AUF-1 functions, enriched RIP-Seq-derived AUF-1-targets in COPD-related pathways involved in inflammation, senescence, gene regulation and also in the public SASP proteome atlas; AUF-1 target signature was also significantly represented in multiple transcriptomic COPD databases generated from primary HSAEC, from lung tissue and from single-cell RNA-sequencing, displaying a predominant downregulation of expression. Discussion: Loss of intracellular AUF-1 may alter posttranscriptional regulation of targets particularly relevant for protection of genomic integrity and gene regulation, thus concurring to airway epithelial inflammatory responses related to oxidative stress and accelerated aging. Exosomal-associated AUF-1 may in turn preserve bound RNA targets and sustain their function, participating to spreading of inflammation and senescence to neighbouring cells.
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2023 |
Cooper GE, Mayall J, Donovan C, Haw TJ, Budden KF, Hansbro NG, et al., 'Antiviral Responses of Tissue-resident CD49a+ Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease.', Am J Respir Crit Care Med, 207 553-565 (2023) [C1]
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Nova |
2023 |
Awatade NT, Wark PAB, Chan ASL, Mamun SMAA, Mohd Esa NY, Matsunaga K, et al., 'The Complex Association between COPD and COVID-19.', J Clin Med, 12 (2023) [C1]
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Nova |
2023 |
Sahu P, Donovan C, Paudel KR, Pickles S, Chimankar V, Kim RY, et al., 'Pre-clinical lung squamous cell carcinoma mouse models to identify novel biomarkers and therapeutic interventions', FRONTIERS IN ONCOLOGY, 13 (2023) [C1]
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2023 |
Kapellos TS, Baßler K, Fujii W, Nalkurthi C, Schaar AC, Bonaguro L, et al., 'Systemic alterations in neutrophils and their precursors in early-stage chronic obstructive pulmonary disease', Cell Reports, 42 (2023) [C1]
Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stage... [more]
Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.
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2023 |
Patel VK, Vishwas S, Kumar R, De Rubis G, Shukla SD, Paudel KR, et al., 'Tackling the cytokine storm using advanced drug delivery in allergic airway disease', Journal of Drug Delivery Science and Technology, 82 (2023) [C1]
Asthma is one of the leading causes of mortality worldwide presenting a huge socio-economic burden with rising morbidity and mortality rates. It is a chronic inflammatory airway d... [more]
Asthma is one of the leading causes of mortality worldwide presenting a huge socio-economic burden with rising morbidity and mortality rates. It is a chronic inflammatory airway disease that is eminent with multiple epidemiological and pathophysiological features such as over production of pro-inflammatory cytokines that triggers an uncontrolled aberrant inflammatory response known as ¿cytokine storm¿. This phenomenon interferes with the signalling and production of cytokines over time leading to the progression of disease and the development of complications that lead to fatal consequences in many individuals. Targeting this overproduction and signalling of cytokines may prove a promising approach to develop novel cytokine specific therapies in the treatment of asthma. This review discusses on the various pharmacological strategies, recent advancements in drug delivery systems and significant findings from clinical trials that may have a potential to outweigh the limitations of the current therapies in the treatment of asthma.
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2023 |
Kannaujiya VK, De Rubis G, Paudel KR, Manandhar B, Chellappan DK, Singh SK, et al., 'Anticancer activity of NF B decoy oligonucleotide-loaded nanoparticles against human lung cancer', Journal of Drug Delivery Science and Technology, 82 (2023) [C1]
Non-small cell lung cancer (NSCLC) is among the leading global causes of cancer-related mortality. Current treatment options have limited efficacy and severe adverse effects, unde... [more]
Non-small cell lung cancer (NSCLC) is among the leading global causes of cancer-related mortality. Current treatment options have limited efficacy and severe adverse effects, underlining the necessity for innovative therapeutic strategies. Among emerging strategies, NF¿B inhibition is particularly promising, as NF¿B is considered a master regulator of NSCLC pathogenesis. NF¿B activity can be efficiently inhibited by double-stranded decoy oligodeoxynucleotides (ODNs). However, therapeutic use of ODNs is strongly limited by enzymatic degradation and poor transport across cell membranes. In this study, we report the encapsulation of a small hydrophilic NF¿B decoy ODN into a biodegradable, biocompatible, and acid-responsive dextran-based nanoparticle (NP) system. This formulation has shown excellent encapsulation efficiency (up to 99.5%) with 185 nm average particle size and pH-dependent ODN release at acidic pH. NF¿B decoy ODN NPs showed promising anticancer activity, with significant anti-proliferative, anti-migratory, and anti-colony formation activity. These were measured by MTT assay, Boyden chamber and scratch wound healing assays, and crystal violet staining, respectively. Mechanistically, the anti-proliferative effect was exerted through the activation of the expression of key genes regulating apoptosis and necroptosis such as TNF-a, RIPK1, RIPK3, and MLKL. The findings of this study provide the foundations for further investigation of the molecular mechanisms by which NF¿B inhibition results in anticancer activity, simultaneously providing proof-of-concept of the therapeutic potential of dextran-based nanoparticles carrying NF¿B decoy ODNs against NSCLC.
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2023 |
Ryan T, Hooftman A, Rehill A, Johansen M, O Brien E, Toller-Kawahisa J, et al., 'OC 55.2 Dimethyl Fumarate and 4-Octyl Itaconate are Anticoagulants that Suppress Tissue Factor in Macrophages Via Inhibition of Type I Interferon', Research and Practice in Thrombosis and Haemostasis, 7 100502-100502 (2023)
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2023 |
Malik R, Paudel KR, Manandhar B, De Rubis G, Shen J, Mujwar S, et al., 'Agarwood oil nanoemulsion counteracts LPS-induced inflammation and oxidative stress in RAW264.7 mouse macrophages', Pathology Research and Practice, 251 (2023) [C1]
Purpose: Oxidative stress and inflammation are key pathophysiological features of chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). ... [more]
Purpose: Oxidative stress and inflammation are key pathophysiological features of chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Agarwood oil obtained from Aquilaria trees has promising antioxidant and anti-inflammatory activities. However, its clinical application is hampered by poor solubility. A viable approach to overcome this involves formulation of oily constituents into emulsions. Here, we have investigated the antioxidant and anti-inflammatory potential of an agarwood oil-based nanoemulsion (DE'RAAQSIN) against lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages in vitro. Methods: The antioxidant and anti-inflammatory activity of DE'RAAQSIN was assessed by measuring the levels of ROS and nitric oxide (NO) produced, using the DCF-DA assay and the Griess reagent assay, respectively. The molecular pathways activated by DE'RAAQSIN were investigated via qPCR. Results: LPS stimulation of RAW264.7 cells increased the production of nitric oxide (NO) and ROS and resulted in the overexpression of the inducible nitric oxide synthase (iNOS) gene. Furthermore, LPS induced the upregulation of the expression of key proinflammatory genes (IL-6, TNF-a, IL-1ß, and CXCL1) and of the antioxidant gene heme oxygenase-1 (HO-1). DE'RAAQSIN demonstrated potent antioxidant and anti-inflammatory activity by significantly reducing the levels of ROS and of secreted NO, simultaneously counteracting the LPS-induced overexpression of iNOS, IL-6, TNF-a, IL-1ß, and HO-1. These findings were corroborated by in silico activity prediction and physicochemical analysis of the main agarwood oil components. Conclusions: We propose DE'RAAQSIN as a promising alternative managing inflammatory disorders, opening the platform for further studies aimed at understanding the effectiveness of DE'RAAQSIN.
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2023 |
Idrees S, Paudel KR, Sadaf T, Hansbro PM, 'HOW DIFFERENT VIRUSES PERTURB HOST CELLULAR MACHINERY VIA SHORT LINEAR MOTIFS', EXCLI Journal, 22 1113-1128 (2023) [C1]
The virus interacts with its hosts by developing protein-protein interactions. Most viruses employ protein interactions to imitate the host protein: A viral protein with the same ... [more]
The virus interacts with its hosts by developing protein-protein interactions. Most viruses employ protein interactions to imitate the host protein: A viral protein with the same amino acid sequence or structure as the host protein attaches to the host protein's binding partner and interferes with the host protein's pathways. Being opportunistic, viruses have evolved to manipulate host cellular mechanisms by mimicking short linear motifs. In this review, we shed light on the current understanding of mimicry via short linear motifs and focus on viral mimicry by genetically different viral subtypes by providing recent examples of mimicry evidence and how high-throughput methods can be a reliable source to study SLiM-mediated viral mimicry.
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2023 |
Ryan TAJ, Hooftman A, Rehill AM, Johansen MD, O' Brien EC, Toller-Kawahisa JE, et al., 'Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon (vol 14, 3513, 2023)', NATURE COMMUNICATIONS, 14 (2023)
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2022 |
Manandhar B, Paudel KR, Panth N, Hansbro P, Oliver BG, Dua K, 'Applications of extracellular vesicles as a drug-delivery system for chronic respiratory diseases', NANOMEDICINE, 17 817-820 (2022)
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2022 |
Dhanjal DS, Sharma P, Mehta M, Tambuwala MM, Prasher P, Paudel KR, et al., 'Concepts of advanced therapeutic delivery systems for the management of remodeling and inflammation in airway diseases', FUTURE MEDICINAL CHEMISTRY, 14 271-288 (2022) [C1]
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2022 |
Paudel KR, Mehta M, Yin GHS, Yen LL, Malyla V, Patel VK, et al., 'Berberine-loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro', Environmental Science and Pollution Research, 29 46830-46847 (2022) [C1]
Non-small cell lung cancer (NSCLC) is reported to have a high incidence rate and is one of the most prevalent types of cancer contributing towards 85% of all incidences of lung ca... [more]
Non-small cell lung cancer (NSCLC) is reported to have a high incidence rate and is one of the most prevalent types of cancer contributing towards 85% of all incidences of lung cancer. Berberine is an isoquinoline alkaloid which offers a broad range of therapeutical and pharmacological actions against cancer. However, extremely low water solubility and poor oral bioavailability have largely restricted its therapeutic applications. To overcome these limitations, we formulated berberine-loaded liquid crystalline nanoparticles (LCNs) and investigated their in vitro antiproliferative and antimigratory activity in human lung epithelial cancer cell line (A549). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), trypan blue staining, and colony forming assays were used to evaluate the anti-proliferative activity, while scratch wound healing assay and a modified Boyden chamber assay were carried out to determine the anti-migratory activity. We also investigated major proteins associated with lung cancer progression. The developed nanoparticles were found to have an average particle size of 181.3¿nm with spherical shape, high entrapment efficiency (75.35%) and have shown sustained release behaviour. The most remarkable findings reported with berberine-loaded LCNs were significant suppression of proliferation, inhibition of colony formation, inhibition of invasion or migration via epithelial mesenchymal transition, and proliferation related proteins associated with cancer progression. Our findings suggest that anti-cancer compounds with the problem of poor solubility and bioavailability can be overcome by formulating them into nanotechnology-based delivery systems for better efficacy. Further in-depth investigations into anti-cancer mechanistic research will expand and strengthen the current findings of berberine-LCNs as a potential NSCLC treatment option.
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2022 |
Runtsch MC, Angiari S, Hooftman A, Wadhwa R, Zhang Y, Zheng Y, et al., 'Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages', Cell Metabolism, 34 487-501.e8 (2022) [C1]
The Krebs cycle-derived metabolite itaconate and its derivatives suppress the inflammatory response in pro-inflammatory ¿M1¿ macrophages. However, alternatively activated ¿M2¿ mac... [more]
The Krebs cycle-derived metabolite itaconate and its derivatives suppress the inflammatory response in pro-inflammatory ¿M1¿ macrophages. However, alternatively activated ¿M2¿ macrophages can take up itaconate. We therefore examined the effect of itaconate and 4-octyl itaconate (OI) on M2 macrophage activation. We demonstrate that itaconate and OI inhibit M2 polarization and metabolic remodeling. Examination of IL-4 signaling revealed inhibition of JAK1 and STAT6 phosphorylation by both itaconate and OI. JAK1 activation was also inhibited by OI in response to IL-13, interferon-ß, and interferon-¿ in macrophages and in T helper 2 (Th2) cells. Importantly, JAK1 was directly modified by itaconate derivatives at multiple residues, including cysteines 715, 816, 943, and 1130. Itaconate and OI also inhibited JAK1 kinase activity. Finally, OI treatment suppressed M2 macrophage polarization and JAK1 phosphorylation in vivo. We therefore identify itaconate and OI as JAK1 inhibitors, suggesting a new strategy to inhibit JAK1 in M2 macrophage-driven diseases.
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2022 |
Zhang Y, Almazi JG, Ong HX, Johansen MD, Ledger S, Traini D, et al., 'Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract', International Journal of Molecular Sciences, 23 (2022) [C1]
Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, t... [more]
Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.
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2022 |
Ramanunny AK, Wadhwa S, Kumar Singh S, Kumar B, Gulati M, Kumar A, et al., 'Topical non-aqueous nanoemulsion of Alpinia galanga extract for effective treatment in psoriasis: In vitro and in vivo evaluation', International Journal of Pharmaceutics, 624 (2022) [C1]
Non-aqueous nanoemulsion (NANE) of Alpinia galanga extract (AGE) was prepared using Palmester 3595 (MCT oil) as oil phase, Cremophor RH 40-Transcutol P® as surfactant-co-surfactan... [more]
Non-aqueous nanoemulsion (NANE) of Alpinia galanga extract (AGE) was prepared using Palmester 3595 (MCT oil) as oil phase, Cremophor RH 40-Transcutol P® as surfactant-co-surfactant (Smix), and glycerin as non-aqueous polar continuous phase. The composition was optimized by applying three-level, four factor Box-Behnken design (BBD). The mean droplet size and zeta potential of the optimized AGE NANE was found to be 60.81 ± 18.88 nm and -7.99 ± 4.14 mV, respectively. The ex vivo permeation studies of AGE NANE and AGE per se on porcine skin reported flux of 125.58 ± 8.36 µg/cm2 h-1 and 12.02 ± 1.64 µg/cm2 h-1, respectively. Therefore, the enhancement ratio has shown 10-folds increase in the flux for AGE NANE when compared to extract per se. Later, confocal laser scanning microcopy confirmed that AGE NANE were able to penetrate into skin's stratum by trans-follicular transport mechanism. The stability studies of AGE NANE confirmed its stability at 30 ± 2 °C/75 ± 5 % RH and 5 ± 3 °C. The efficacy of AGE NANE was evaluated in vivo on imiquimod (IMQ) induced mouse model. The mice treated with low and high doses of AGE NANE (groups VI and VII) showed significant (p < 0.05) amelioration of psoriasis. Results of histopathology indicated reduction in psoriasis area severity index in AGE NANE treated mice (group VI and group VII).
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2022 |
Pinkerton JW, Kim RY, Brown AC, Rae BE, Donovan C, Mayall JR, et al., 'Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 149 1270-1280 (2022) [C1]
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2022 |
Donovan C, Kim RY, Galvao I, Jarnicki AG, Brown AC, Jones-Freeman B, et al., 'Aim2 suppresses cigarette smoke-induced neutrophil recruitment, neutrophil caspase-1 activation and anti-Ly6G-mediated neutrophil depletion', IMMUNOLOGY AND CELL BIOLOGY, 100 235-249 (2022) [C1]
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Nova |
2022 |
Tiotiu A, Badi Y, Kermani NZ, Sanak M, Kolmert J, Wheelock CE, et al., 'Association of Differential Mast Cell Activation with Granulocytic Inflammation in Severe Asthma.', Am J Respir Crit Care Med, 205 397-411 (2022) [C1]
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2022 |
Imran M, Paudel KR, Jha SK, Hansbro PM, Dua K, Mohammed Y, 'Dressing of multifunctional nanoparticles with natural cell-derived membranes for the superior chemotherapy', NANOMEDICINE, 17 665-670 (2022)
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2022 |
Francis I, Shrestha J, Paudel KR, Hansbro PM, Warkiani ME, Saha SC, 'Recent advances in lung-on-a-chip models', Drug Discovery Today, 27 2593-2602 (2022) [C1]
With the global burden of respiratory diseases, rapid identification of the best therapeutic measures to combat these diseases is essential. Animal models and 2D cell culture mode... [more]
With the global burden of respiratory diseases, rapid identification of the best therapeutic measures to combat these diseases is essential. Animal models and 2D cell culture models do not replicate the findings observed in vivo. To gain deeper insight into lung pathology and physiology, 3D and advanced lung-on-a-chip models have been developed recently. Lung-on-a-chip models more accurately simulate the lung's microenvironment and functions in vivo, resulting in more-accurate assessments of drug safety and effectiveness. This review discusses the transition from 2D to 3D models and the recent advances in lung-on-a-chip platforms, their implementation and the numerous challenges faced. Finally, a general overview of this platform and its potential applications in respiratory disease research and drug discovery is highlighted.
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2022 |
Chotirmall SH, Bogaert D, Chalmers JD, Cox MJ, Hansbro PM, Huang YJ, et al., 'Therapeutic Targeting of the Respiratory Microbiome', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 206 535-544 (2022) [C1]
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Nova |
2022 |
Clarence DD, Paudel KR, Manandhar B, Singh SK, Devkota HP, Panneerselvam J, et al., 'Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases', Nutrients, 14 3828-3828 [C1]
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2022 |
O Rourke MB, Roediger BR, Jolly CJ, Crossett B, Padula MP, Hansbro PM, 'Viral Biomarker Detection and Validation Using MALDI Mass Spectrometry Imaging (MSI)', Proteomes, 10 33-33 [C1]
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2022 |
Vanka KS, Shukla S, Gomez HM, James C, Palanisami T, Williams K, et al., 'Understanding the pathogenesis of occupational coal and silica dust-associated lung disease', EUROPEAN RESPIRATORY REVIEW, 31 (2022) [C1]
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Nova |
2022 |
Tan CL, Chan Y, Candasamy M, Chellian J, Madheswaran T, Sakthivel LP, et al., 'Unravelling the molecular mechanisms underlying chronic respiratory diseases for the development of novel therapeutics via in vitro experimental models', European Journal of Pharmacology, 919 (2022) [C1]
Chronic respiratory diseases have collectively become a major public health concern and have now taken form as one of the leading causes of mortality worldwide. Most chronic respi... [more]
Chronic respiratory diseases have collectively become a major public health concern and have now taken form as one of the leading causes of mortality worldwide. Most chronic respiratory diseases primarily occur due to prolonged airway inflammation. In addition, critical environmental factors such as cigarette smoke, industrial pollutants, farm dust, and pollens may also exacerbate such diseases. Moreover, alterations in the genetic sequence of an individual, abnormalities in the chromosomes or immunosuppression resulting from bacterial, fungal, and viral infections may also play a key role in the pathogenesis of respiratory diseases. Over the years, multiple in vitro models have been employed as the basis of existing as well as emerging advancements in chronic respiratory disease research. These include cell lines, gene expression techniques, single cell RNA sequencing, cytometry, culture techniques, as well as serum/sputum biomarkers that can be used to elucidate the molecular mechanisms underlying these diseases, and to identify novel diagnostic and management options for these diseases. This review summarizes the current understanding of the pathogenesis of various chronic respiratory diseases derived through in vitro experimental models, where the knowledge obtained from these studies can greatly benefit researchers in the discovery and development of novel screening techniques and advanced therapeutic strategies that could be translated into clinical use in the future.
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2022 |
Verma N, Arora V, Awasthi R, Chan Y, Jha NK, Thapa K, et al., 'Recent developments, challenges and future prospects in advanced drug delivery systems in the management of tuberculosis', Journal of Drug Delivery Science and Technology, 75 (2022) [C1]
Tuberculosis (TB) is reported as one of the most prevailing life-threatening health problems, affecting almost one third of the population globally. It is one of a major reason of... [more]
Tuberculosis (TB) is reported as one of the most prevailing life-threatening health problems, affecting almost one third of the population globally. It is one of a major reason of death with an imposing amplified socio-economic impact. Tuberculosis patients have infrequent endocrine and metabolic derangements, but they are important when they occur. Multiple drug regimen, poor patient compliance, and stiff administration schedule are factors that are answerable for the development of and extensive drug resistance (XDR) and multi drug resistance (MDR) instances in TB along with poor drug targeting effects. The emerging resistance strains and high transmittance rate of the disease have prompted the need for studies in advanced drug delivery, particularly nanotechnology for the management of TB. Nanocarriers offer unique physicochemical properties that provide beneficial outcomes such as targeted effects and better patient compliance as drug delivery, thereby presenting as a promising solution to the constraints linked with conventional treatment strategy for TB. Both in vitro and in vivo studies have been reported to access release behavior of antitubercular agents with a view to being interpreted in clinical practice in the future. The present review highlights contemporary trends and advancements in drug delivery systems employed for the effective management of TB. This communication will be useful to the researchers working in the field of drug delivery systems for effective management of TB.
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2022 |
Liu G, Jarnicki AG, Paudel KR, Lu W, Wadhwa R, Philp AM, et al., 'Adverse roles of mast cell chymase-1 in chronic obstructive pulmonary disease.', European Respiratory Journal, 60 2101431-2101431 (2022) [C1]
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Nova |
2022 |
Allam VSRR, Paudel KR, Gupta G, Singh SK, Vishwas S, Gulati M, et al., 'Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma', Environmental Science and Pollution Research, (2022) [C1]
Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mor... [more]
Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.
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2022 |
Shrestha J, Razavi Bazaz S, Ding L, Vasilescu S, Idrees S, Söderström B, et al., 'Rapid separation of bacteria from primary nasal samples using inertial microfluidics', Lab on a Chip, 23 146-156 (2022) [C1]
Microbial populations play a crucial role in human health and the development of many diseases. These diseases often arise from the explosive proliferation of opportunistic bacter... [more]
Microbial populations play a crucial role in human health and the development of many diseases. These diseases often arise from the explosive proliferation of opportunistic bacteria, such as those in the nasal cavity. Recently, there have been increases in the prevalence of these opportunistic pathogens displaying antibiotic resistance. Thus, the study of the nasal microbiota and its bacterial diversity is critical in understanding pathogenesis and developing microbial-based therapies for well-known and emerging diseases. However, the isolation and analysis of these populations for clinical study complicates the already challenging task of identifying and profiling potentially harmful bacteria. Existing methods are limited by low sample throughput, expensive labeling, and low recovery of bacteria with ineffective removal of cells and debris. In this study, we propose a novel microfluidic channel with a zigzag configuration for enhanced isolation and detection of bacteria from human clinical nasal swabs. This microfluidic zigzag channel separates the bacteria from epithelial cells and debris by size differential focusing. As such, pure bacterial cell fractions devoid of large contaminating debris or epithelial cells are obtained. DNA sequencing performed on the separated bacteria defines the diversity and species present. This novel method of bacterial separation is simple, robust, rapid, and cost-effective and has the potential to be used for the rapid identification of bacterial cell populations from clinical samples.
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2022 |
Pathinayake PS, Waters DW, Nichol KS, Brown AC, Reid AT, Hsu AC-Y, et al., 'Endoplasmic reticulum-unfolded protein response signalling is altered in severe eosinophilic and neutrophilic asthma', THORAX, 77 443-451 (2022) [C1]
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Nova |
2022 |
Quan DH, Kwong AJ, Hansbro PM, Britton WJ, 'No smoke without fire: the impact of cigarette smoking on the immune control of tuberculosis', European Respiratory Review, 31 (2022) [C1]
Cigarette smoke (CS) exposure is a key risk factor for both active and latent tuberculosis (TB). It is associated with delayed diagnosis, more severe disease progression, unfavour... [more]
Cigarette smoke (CS) exposure is a key risk factor for both active and latent tuberculosis (TB). It is associated with delayed diagnosis, more severe disease progression, unfavourable treatment outcomes and relapse after treatment. Critically, CS exposure is common in heavily populated areas with a high burden of TB, such as China, India and the Russian Federation. It is therefore prudent to evaluate interventions for TB while taking into account the immunological impacts of CS exposure. This review is a mechanistic examination of how CS exposure impairs innate barrier defences, as well as alveolar macrophage, neutrophil, dendritic cell and T-cell functions, in the context of TB infection and disease.
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2022 |
Johansen MD, Mahbub RM, Idrees S, Nguyen DH, Miemczyk S, Pathinayake P, et al., 'Increased SARS-CoV-2 Infection, Protease, and Inflammatory Responses in Chronic Obstructive Pulmonary Disease Primary Bronchial Epithelial Cells Defined with Single-Cell RNA Sequencing', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 206 712-729 (2022) [C1]
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Nova |
2022 |
Imran M, Jha SK, Hasan N, Insaf A, Shrestha J, Shrestha J, et al., 'Overcoming Multidrug Resistance of Antibiotics via Nanodelivery Systems', Pharmaceutics, 14 (2022) [C1]
Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to ov... [more]
Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such complications, novel drug delivery systems have gained pharmaceutical scientists¿ interest. Significant findings have validated the effectiveness of novel drug delivery systems such as polymeric nanoparticles, liposomes, metallic nanoparticles, dendrimers, and lipid-based nanoparticles against severe microbial infections and combating antimicrobial resistance. This review article comprises the specific mechanism of antibiotic resistance development in bacteria. In addition, the manuscript incorporated the advanced nanotechnological approaches with their mechanisms, including interaction with the bacterial cell wall, inhibition of biofilm formations, activation of innate and adaptive host immune response, generation of reactive oxygen species, and induction of intracellular effect to fight against antibiotic resistance. A section of this article demonstrated the findings related to the development of delivery systems. Lastly, the role of microfluidics in fighting antimicrobial resistance has been discussed. Overall, this review article is an amalgamation of various strategies to study the role of novel approaches and their mechanism to fight against the resistance developed to the antimicrobial therapies.
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2022 |
Prasher P, Sharma M, Singh SK, Gulati M, Jha NK, Gupta PK, et al., 'Targeting mucus barrier in respiratory diseases by chemically modified advanced delivery systems', CHEMICO-BIOLOGICAL INTERACTIONS, 365 (2022)
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2022 |
Paudel KR, Mehta M, Shukla SD, Panth N, Chellappan DK, Dua K, Hansbro P, 'Advancements in nanotherapeutics targeting senescence in chronic obstructive pulmonary disease', NANOMEDICINE, 17 1757-1760 (2022)
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2022 |
Jha SK, Imran M, Paudel KR, Mohammed Y, Hansbro P, Dua K, 'Treating primary lymphoma of the brain in AIDS patients via multifunctional oral nanoparticulate systems', NANOMEDICINE, 17 425-429 (2022)
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2022 |
Budden KF, Gellatly SL, Vaughan A, Amorim N, Horvat JC, Hansbro NG, et al., 'Probiotic Bifidobacterium longum subsp. longum Protects against Cigarette Smoke-Induced Inflammation in Mice.', Int J Mol Sci, 24 (2022) [C1]
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2022 |
Darmarajan T, Paudel KR, Candasamy M, Chellian J, Madheswaran T, Sakthivel LP, et al., 'Autoantibodies and autoimmune disorders in SARS-CoV-2 infection: pathogenicity and immune regulation', ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH, 29 54072-54087 (2022) [C1]
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2022 |
Afrose D, Chen H, Ranashinghe A, Liu C-C, Henessy A, Hansbro PM, McClements L, 'The diagnostic potential of oxidative stress biomarkers for preeclampsia: systematic review and meta-analysis', BIOLOGY OF SEX DIFFERENCES, 13 (2022) [C1]
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2022 |
Hardy S, Patrick R, Liesinger L, Pöttler M, Rech L, Gindlhuber J, et al., 'Extracellular Matrix Protein 1 as a Mediator of Inflammation-Induced Fibrosis After Myocardial Infarction', Heart, Lung and Circulation, 31 S311-S311 (2022)
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2022 |
Alnuqaydan AM, Almutary AG, Azam M, Manandhar B, Yin GHS, Yen LL, et al., 'Evaluation of the Cytotoxic Activity and Anti-Migratory Effect of Berberine-Phytantriol Liquid Crystalline Nanoparticle Formulation on Non-Small-Cell Lung Cancer In Vitro.', Pharmaceutics, 14 (2022) [C1]
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2022 |
Patel VK, Paudel KR, Shukla SD, Liu G, Oliver BG, Hansbro PM, Dua K, 'TOLL-LIKE RECEPTORS, INNATE IMMUNE SYSTEM, AND LUNG DISEASES: A VITAL TRILATERAL ASSOCIATION', EXCLI JOURNAL, 21 519-523 (2022)
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2022 |
Augustine R, Abhilash, Nayeem A, Salam SA, Augustine P, Dan P, et al., 'Increased complications of COVID-19 in people with cardiovascular disease: Role of the renin-angiotensin-aldosterone system (RAAS) dysregulation', CHEMICO-BIOLOGICAL INTERACTIONS, 351 (2022) [C1]
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2022 |
Asrani P, Tiwari K, Eapen MS, McAlinden KD, Haug G, Johansen MD, et al., 'Clinical features and mechanistic insights into drug repurposing for combating COVID-19', International Journal of Biochemistry and Cell Biology, 142 (2022) [C1]
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged from Wuhan in China before it spread to the entire globe. It causes coronavirus disease of 2019 (COVID-19) whe... [more]
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged from Wuhan in China before it spread to the entire globe. It causes coronavirus disease of 2019 (COVID-19) where mostly individuals present mild symptoms, some remain asymptomatic and some show severe lung inflammation and pneumonia in the host through the induction of a marked inflammatory ¿cytokine storm¿. New and efficacious vaccines have been developed and put into clinical practice in record time, however, there is a still a need for effective treatments for those who are not vaccinated or remain susceptible to emerging SARS-CoV-2 variant strains. Despite this, effective therapeutic interventions against COVID-19 remain elusive. Here, we have reviewed potential drugs for COVID-19 classified on the basis of their mode of action. The mechanisms of action of each are discussed in detail to highlight the therapeutic targets that may help in reducing the global pandemic. The review was done up to July 2021 and the data was assessed through the official websites of WHO and CDC for collecting the information on the clinical trials. Moreover, the recent research papers were also assessed for the relevant data. The search was mainly based on keywords like Coronavirus, SARS-CoV-2, drugs (specific name of the drugs), COVID-19, clinical efficiency, safety profile, side-effects etc.This review outlines potential areas for future research into COVID-19 treatment strategies.
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2022 |
Paudel KR, Panth N, Manandhar B, Singh SK, Gupta G, Wich PR, et al., 'Attenuation of Cigarette-Smoke-Induced Oxidative Stress, Senescence, and Inflammation by Berberine-Loaded Liquid Crystalline Nanoparticles: In Vitro Study in 16HBE and RAW264.7 Cells', Antioxidants, 11 (2022) [C1]
Cigarette smoke is considered a primary risk factor for chronic obstructive pulmonary dis-ease. Numerous toxicants present in cigarette smoke are known to induce oxidative stress ... [more]
Cigarette smoke is considered a primary risk factor for chronic obstructive pulmonary dis-ease. Numerous toxicants present in cigarette smoke are known to induce oxidative stress and airway inflammation that further exacerbate disease progression. Generally, the broncho-epithelial cells and alveolar macrophages exposed to cigarette smoke release massive amounts of oxidative stress and inflammation mediators. Chronic exposure of cigarette smoke leads to premature senescence of airway epithelial cells. This impairs cellular function and ultimately leads to the progression of chronic lung diseases. Therefore, an ideal therapeutic candidate should prevent disease progression by controlling oxidative stress, inflammation, and senescence during the initial stage of damage. In our study, we explored if berberine (an alkaloid)-loaded liquid crystalline nanoparticles (berberine-LCNs)-based treatment to human broncho-epithelial cells and macrophage inhibits oxidative stress, inflammation, and senescence induced by cigarette-smoke extract. The developed berberine-LCNs were found to have favourable physiochemical parameters, such as high entrapment efficiency and sustained in vitro release. The cellular-assay observations revealed that berberine-LCNs showed potent antioxi-dant activity by suppressing the generation of reactive oxygen species in both broncho-epithelial cells (16HBE) and macrophages (RAW264.7), and modulating the genes involved in inflammation and oxidative stress. Similarly, in 16HBE cells, berberine-LCNs inhibited the cigarette smoke-induced senescence as revealed by X-gal staining, gene expression of CDKN1A (p21), and immunofluorescent staining of p21. Further in-depth mechanistic investigations into antioxidative, anti-inflammatory, and antisenescence research will diversify the current findings of berberine as a promising therapeutic approach for inflammatory lung diseases caused by cigarette smoking.
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2022 |
Alamil JMR, Paudel KR, Chan Y, Xenaki D, Panneerselvam J, Singh SK, et al., 'Rediscovering the Therapeutic Potential of Agarwood in the Management of Chronic Inflammatory Diseases.', Molecules, 27 (2022) [C1]
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2022 |
Alnuqaydan AM, Almutary AG, Azam M, Manandhar B, De Rubis G, Madheswaran T, et al., 'Phytantriol-Based Berberine-Loaded Liquid Crystalline Nanoparticles Attenuate Inflammation and Oxidative Stress in Lipopolysaccharide-Induced RAW264.7 Macrophages.', Nanomaterials (Basel), 12 (2022) [C1]
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2022 |
Stewart EL, Counoupas C, Johansen MD, Nguyen DH, Miemczyk S, Hansbro NG, et al., 'Mucosal immunization with a delta-inulin adjuvanted recombinant spike vaccine elicits lung-resident immune memory and protects mice against SARS-CoV-2', Mucosal Immunology, 15 1405-1415 (2022) [C1]
Multiple SARS-CoV-2 vaccine candidates have been approved for use and have had a major impact on the COVID-19 pandemic. There remains, however, a significant need for vaccines tha... [more]
Multiple SARS-CoV-2 vaccine candidates have been approved for use and have had a major impact on the COVID-19 pandemic. There remains, however, a significant need for vaccines that are safe, easily transportable and protective against infection, as well as disease. Mucosal vaccination is favored for its ability to induce immune memory at the site of infection, making it appealing for SARS-CoV-2 vaccine strategies. In this study we performed in-depth analysis of the immune responses in mice to a subunit recombinant spike protein vaccine formulated with the delta-inulin adjuvant Advax when administered intratracheally (IT), versus intramuscular delivery (IM). Both routes produced robust neutralizing antibody titers (NAb) and generated sterilizing immunity against SARS-CoV-2. IT delivery, however, produced significantly higher systemic and lung-local NAb that resisted waning up to six months post vaccination, and only IT delivery generated inducible bronchus-associated lymphoid tissue (iBALT), a site of lymphocyte antigen presentation and proliferation. This was coupled with robust and long-lasting lung tissue-resident memory CD4+ and CD8+ T cells that were not observed in IM-vaccinated mice. This study provides a detailed view of the lung-resident cellular response to IT vaccination against SARS-CoV-2 and demonstrates the importance of delivery site selection in the development of vaccine candidates.
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2022 |
Ashhurst AS, Johansen MD, Maxwell JWC, Stockdale S, Ashley CL, Aggarwal A, et al., 'Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice', Nature Communications, 13 (2022) [C1]
Current vaccines against SARS-CoV-2 substantially reduce mortality, but protection against infection is less effective. Enhancing immunity in the respiratory tract, via mucosal va... [more]
Current vaccines against SARS-CoV-2 substantially reduce mortality, but protection against infection is less effective. Enhancing immunity in the respiratory tract, via mucosal vaccination, may provide protection against infection and minimise viral spread. Here, we report testing of a subunit vaccine in mice, consisting of SARS-CoV-2 Spike protein with a TLR2-stimulating adjuvant (Pam2Cys), delivered to mice parenterally or mucosally. Both routes of vaccination induce substantial neutralising antibody (nAb) titres, however, mucosal vaccination uniquely generates anti-Spike IgA, increases nAb in the serum and airways, and increases lung CD4+ T-cell responses. TLR2 is expressed by respiratory epithelia and immune cells. Using TLR2 deficient chimeric mice, we determine that TLR2 expression in either compartment facilitates early innate responses to mucosal vaccination. By contrast, TLR2 on hematopoietic cells is essential for optimal lung-localised, antigen-specific responses. In K18-hACE2 mice, vaccination provides complete protection against disease and sterilising lung immunity against SARS-CoV-2, with a short-term non-specific protective effect from mucosal Pam2Cys alone. These data support mucosal vaccination as a strategy to improve protection in the respiratory tract against SARS-CoV-2 and other respiratory viruses.
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2022 |
Ren S, Hansbro PM, Srikusalanukul W, Horvat JC, Hunter T, Brown AC, et al., 'Generation of cardio-protective antibodies after pneumococcal polysaccharide vaccine: Early results from a randomised controlled trial', Atherosclerosis, 346 68-74 (2022) [C1]
Background and aims: Observational studies have demonstrated that the pneumococcal polysaccharide vaccine (PPV) is associated with reduced risk of cardiovascular events. This may ... [more]
Background and aims: Observational studies have demonstrated that the pneumococcal polysaccharide vaccine (PPV) is associated with reduced risk of cardiovascular events. This may be mediated through IgM antibodies to OxLDL, which have previously been associated with cardioprotective effects. The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE) is a double-blind, randomised controlled trial (RCT) of PPV in preventing ischaemic events. Participants received PPV or placebo once at baseline and are being followed-up for incident fatal and non-fatal myocardial infarction or stroke over 6 years. Methods: A subgroup of participants at one centre (Canberra; n = 1,001) were evaluated at 1 month and 2 years post immunisation for changes in surrogate markers of atherosclerosis, as pre-specified secondary outcomes: high-sensitive C-reactive protein (CRP), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT). In addition, 100 participants were randomly selected in each of the intervention and control groups for measurement of anti-pneumococcal antibodies (IgG, IgG2, IgM) as well as anti-OxLDL antibodies (IgG and IgM to CuOxLDL, MDA-LDL, and PC-KLH). Results: Concentrations of anti-pneumococcal IgG and IgG2 increased and remained high at 2 years in the PPV group compared to the placebo group, while IgM increased and then declined, but remained detectable, at 2 years. There were statistically significant increases in all anti-OxLDL IgM antibodies at 1 month, which were no longer detectable at 2 years; there was no increase in anti-OxLDL IgG antibodies. There were no significant changes in CRP, PWV or CIMT between the treatment groups at the 2-year follow-up. Conclusions: PPV engenders a long-lasting increase in anti-pneumococcal IgG, and to a lesser extent, IgM titres, as well as a transient increase in anti-OxLDL IgM antibodies. However, there were no detectable changes in surrogate markers of atherosclerosis at the 2-year follow-up. Long-term, prospective follow-up of clinical outcomes is continuing to assess if PPV reduces CVD events.
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Nova |
2022 |
Paudel KR, Chellappan DK, MacLoughlin R, Andreoli Pinto TDJ, Dua K, Hansbro PM, 'Advanced therapeutic delivery for the management of chronic respiratory diseases', FRONTIERS IN MEDICINE, 9 (2022)
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2022 |
Colarusso C, Terlizzi M, Maglio A, Molino A, Candia C, Vitale C, et al., 'Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1a, IFN-a and TGF-ß', Frontiers in Immunology, 13 (2022) [C1]
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as ... [more]
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined. The goal of this study was to understand the involvement of the Absent in melanoma-2 (AIM2) inflammasome in PC-associated lung fibrosis-like changes revealed by chest CT scans. Peripheral blood mononuclear cells (PBMCs) obtained from PC patients who did not develop signs of lung fibrosis were not responsive to AIM2 activation by Poly dA:dT. In sharp contrast, PBMCs from PC patients with signs of lung fibrosis were highly responsive to AIM2 activation, which induced the release of IL-1a, IFN-a and TGF-ß. The recognition of Poly dA:dT was not due to the activation of cyclic GMP-AMP (cGAMP) synthase, a stimulator of interferon response (cGAS-STING) pathways, implying a role for AIM2 in PC conditions. The release of IFN-a was caspase-1- and caspase-4-dependent when AIM2 was triggered. Instead, the release of pro-inflammatory IL-1a and pro-fibrogenic TGF-ß were inflammasome independent because the inhibition of caspase-1 and caspase-4 did not alter the levels of the two cytokines. Moreover, the responsiveness of AIM2 correlated with higher expression of the receptor in circulating CD14+ cells in PBMCs from patients with signs of lung fibrosis.
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2022 |
Khursheed R, Dua K, Vishwas S, Gulati M, Jha NK, Aldhafeeri GM, et al., 'Biomedical applications of metallic nanoparticles in cancer: Current status and future perspectives', Biomedicine and Pharmacotherapy, 150 (2022) [C1]
The current advancements in nanotechnology are as an outcome of the development of engineered nanoparticles. Various metallic nanoparticles have been extensively explored for vari... [more]
The current advancements in nanotechnology are as an outcome of the development of engineered nanoparticles. Various metallic nanoparticles have been extensively explored for various biomedical applications. They attract lot of attention in biomedical field due to their significant inert nature, and nanoscale structures, with size similar to many biological molecules. Their intrinsic characteristics which include electronic, optical, physicochemical and, surface plasmon resonance, that can be changed by altering certain particle characteristics such as size, shape, environment, aspect ratio, ease of synthesis and functionalization properties have led to numerous applications in various fields of biomedicine. These include targeted drug delivery, sensing, photothermal and photodynamic therapy, imaging, as well as the modulation of two or three applications. The current article also discusses about the various properties of metallic nanoparticles and their applications in cancer imaging and therapeutics. The associated bottlenecks related to their clinical translation are also discussed.
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2022 |
Paudel KR, De Rubis G, Panth N, Singh SK, Chellappan DK, Hansbro PM, Dua K, 'NANOMEDICINE AND MEDICINAL PLANTS: EMERGING SYMBIOSIS IN MANAGING LUNG DISEASES AND ASSOCIATED INFECTIONS', EXCLI JOURNAL, 21 1299-1303 (2022)
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2022 |
Nucera F, Mumby S, Paudel KR, Dharwal V, DI Stefano A, Casolaro V, et al., 'Role of oxidative stress in the pathogenesis of COPD.', Minerva Med, 113 370-404 (2022) [C1]
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2022 |
Khursheed R, Paudel KR, Gulati M, Vishwas S, Jha NK, Hansbro PM, et al., 'Expanding the arsenal against pulmonary diseases using surface-functionalized polymeric micelles: breakthroughs and bottlenecks.', Nanomedicine (Lond), 17 881-911 (2022) [C1]
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2022 |
Flood RL, Danzenbaker M, Hansbro PM, Rogers C, Tanoi H, Tanoi S, 'More New Zealand Storm Petrels Fregetta maoriana off Gau Island, Fiji, in May 2022', Bulletin of the British Ornithologists' Club, 142 380-382 (2022) [C1]
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2022 |
Chellappan DK, Paudel KR, Tan NW, Cheong KS, Khoo SSQ, Seow SM, et al., 'Targeting the mitochondria in chronic respiratory diseases', Mitochondrion, 67 15-37 (2022) [C1]
Mitochondria are one of the basic essential components for eukaryotic life survival. It is also the source of respiratory ATP. Recently published studies have demonstrated that mi... [more]
Mitochondria are one of the basic essential components for eukaryotic life survival. It is also the source of respiratory ATP. Recently published studies have demonstrated that mitochondria may have more roles to play aside from energy production. There is an increasing body of evidence which suggest that mitochondrial activities involved in normal and pathological states contribute to significant impact to the lung airway morphology and epithelial function in respiratory diseases such as asthma, COPD, and lung cancer. This review summarizes the pathophysiological pathways involved in asthma, COPD, lung cancer and highlights potential treatment strategies that target the malfunctioning mitochondria in such ailments. Mitochondria are responsive to environmental stimuli such as infection, tobacco smoke, and inflammation, which are essential in the pathogenesis of respiratory diseases. They may affect mitochondrial shape, protein production and ultimately cause dysfunction. The impairment of mitochondrial function has downstream impact on the cytosolic components, calcium control, response towards oxidative stress, regulation of genes and proteins and metabolic activities. Several novel compounds and alternative medicines that target mitochondria in asthma and chronic lung diseases have been discussed here. Moreover, mitochondrial enzymes or proteins that may serve as excellent therapeutic targets in COPD are also covered. The role of mitochondria in respiratory diseases is gaining much attention and mitochondria-based treatment strategies and personalized medicine targeting the mitochondria may materialize in the near future. Nevertheless, more in-depth studies are urgently needed to validate the advantages and efficacy of drugs that affect mitochondria in pathological states.
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2022 |
Lao JC, Bui CB, Pang MA, Cho SX, Rudloff I, Elgass K, et al., 'Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants', Science Translational Medicine, 14 (2022) [C1]
Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-... [more]
Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3+CD4+ T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1ß and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.
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Nova |
2022 |
Sharma K, Zhang Y, Paudel KR, Kachelmeier A, Hansbro PM, Shi X, 'The Emerging Role of Pericyte-Derived Extracellular Vesicles in Vascular and Neurological Health.', Cells, 11 (2022) [C1]
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2022 |
Paudel KR, Patel V, Vishwas S, Gupta S, Sharma S, Chan Y, et al., 'Nutraceuticals and COVID-19: A mechanistic approach toward attenuating the disease complications.', J Food Biochem, 46 e14445 (2022) [C1]
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2022 |
Chopra N, Menounos S, Choi JP, Hansbro PM, Diwan AD, Das A, 'Blood-Spinal Cord Barrier: Its Role in Spinal Disorders and Emerging Therapeutic Strategies', NeuroSci, 3 1-27 (2022) [C1]
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2022 |
Wille M, Grillo V, de Gouvea Pedroso SB, Burgess GW, Crawley A, Dickason C, et al., 'Australia as a global sink for the genetic diversity of avian influenza A virus', PLoS Pathogens, 18 (2022) [C1]
Most of our understanding of the ecology and evolution of avian influenza A virus (AIV) in wild birds is derived from studies conducted in the northern hemisphere on waterfowl, wi... [more]
Most of our understanding of the ecology and evolution of avian influenza A virus (AIV) in wild birds is derived from studies conducted in the northern hemisphere on waterfowl, with a substantial bias towards dabbling ducks. However, relevant environmental conditions and patterns of avian migration and reproduction are substantially different in the southern hemisphere. Through the sequencing and analysis of 333 unique AIV genomes collected from wild birds collected over 15 years we show that Australia is a global sink for AIV diversity and not integrally linked with the Eurasian gene pool. Rather, AIV are infrequently introduced to Australia, followed by decades of isolated circulation and eventual extinction. The number of co-circulating viral lineages varies per subtype. AIV haemagglutinin (HA) subtypes that are rarely identified at duck-centric study sites (H8-12) had more detected introductions and contemporary co-circulating lineages in Australia. Combined with a lack of duck migration beyond the Australian-Papuan region, these findings suggest introductions by long-distance migratory shorebirds. In addition, on the available data we found no evidence of directional or consistent patterns in virus movement across the Australian continent. This feature corresponds to patterns of bird movement, whereby waterfowl have nomadic and erratic rainfall-dependant distributions rather than consistent intra-continental migratory routes. Finally, we detected high levels of virus gene segment reassortment, with a high diversity of AIV genome constellations across years and locations. These data, in addition to those from other studies in Africa and South America, clearly show that patterns of AIV dynamics in the Southern Hemisphere are distinct from those in the temperate north.
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2022 |
Hortle E, Tran VLT, Wright K, Fontaine ARM, Pinello N, O Rourke MB, et al., 'OXSR1 inhibits inflammasome activation by limiting potassium efflux during mycobacterial infection', Life Science Alliance, 5 (2022) [C1]
Pathogenic mycobacteria inhibit inflammasome activation to establish infection. Although it is known that potassium efflux is a trigger for inflammasome activation, the interactio... [more]
Pathogenic mycobacteria inhibit inflammasome activation to establish infection. Although it is known that potassium efflux is a trigger for inflammasome activation, the interaction between mycobacterial infection, potassium efflux, and inflammasome activation has not been investigated. Here, we use Mycobacterium marinum infection of zebrafish embryos and Mycobacterium tuberculosis infection of THP-1 cells to demonstrate that pathogenic mycobacteria up-regulate the host WNK signalling pathway kinases SPAK and OXSR1 which control intracellular potassium balance. We show that genetic depletion or inhibition of OXSR1 decreases bacterial burden and intracellular potassium levels. The protective effects of OXSR1 depletion are at least partially mediated by NLRP3 inflammasome activation, caspase-mediated release of IL-1ß, and downstream activation of protective TNF-a. The elucidation of this druggable pathway to potentiate inflammasome activation provides a new avenue for the development of host-directed therapies against intracellular infections.
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2022 |
Gupta M, Sharma V, Sharma K, Kumar A, Sharma A, Kazmi I, et al., 'A kNGR Peptide-Tethered Lipid Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment', Pharmaceutics, 14 (2022) [C1]
The present study aims to design, develop and characterize kNGR (Asn-Gly-Arg) peptide-conjugated lipid¿polymer-based nanoparticles for the target-specific delivery of anticancer b... [more]
The present study aims to design, develop and characterize kNGR (Asn-Gly-Arg) peptide-conjugated lipid¿polymer-based nanoparticles for the target-specific delivery of anticancer bioactive(s), i.e., Paclitaxel (PTX). The kNGR-PEG-DSPE conjugate was synthesized and characterized by using spectral analysis. The dual-targeted PLGA¿lecithin¿PEG core-shell nanoparticles (PLNs-kNGR-NPs) were synthesized using a modified nanoprecipitation process, and their physiological properties were determined. The results support that, compared to other NPs, PLNs-kNGR-NPs are highly cytotoxic, owing to higher apoptosis and intracellular uptake. The significance of rational nanoparticle design for synergistic treatment is shown by the higher tumor volume inhibition percentage rate (59.7%), compared to other designed formulations in Balb/c mice in the HT-1080 tumor-induced model. The overall results indicate that the PLNs-kNGR-NPs-based hybrid lipid¿polymer nanoparticles present the highest therapeutic efficacy against solid tumor overexpressing the CD13 receptors.
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2022 |
Majumder R, Alam MB, Paudel KR, Ahmed KA, Devkota HP, Lee S-H, et al., 'Anti-Influenza Virus Potential of Probiotic Strain Lactoplantibacillus plantarum YML015 Isolated from Korean Fermented Vegetable', Fermentation, 8 572-572
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2022 |
Kaur J, Gulati M, Famta P, Corrie L, Awasthi A, Saini S, et al., 'Polymeric micelles loaded with glyburide and vanillic acid: I. Formulation development, in-vitro characterization and bioavailability studies', International Journal of Pharmaceutics, 624 (2022) [C1]
The co-formulation of glyburide (Gly) and vanillic acid (VA) as such in the form of nanomedicine has never been explored to treat metabolic diseases including type 2 diabetes mell... [more]
The co-formulation of glyburide (Gly) and vanillic acid (VA) as such in the form of nanomedicine has never been explored to treat metabolic diseases including type 2 diabetes mellitus. Both the drugs possess dissolution rate-limited oral bioavailability leading to poor therapeutic efficacy. Hence, co-loading these drugs into a nanocarrier could overcome their poor oral bioavailability related challenges. Owing to this objective, both drugs were co-loaded in amphiphilic polymeric micelles (APMs) and evaluated for their biopharmaceutical outcomes. The APMs were prepared using mPEG-b-PCL/CTAB as a copolymer-surfactant system via the liquid antisolvent precipitation (LAP) method. The design of these APMs were optimized using Box Behnken Design by taking various process/formulation based variables to achieve the desired micellar traits. The release of both the drugs from the optimized co-loaded APMs was compared in different media and displayed a remarkable sustained release profile owing to their hydrophobic interactions with the PCL core. The in vitro cytotoxicity study of co-loaded APMs on Caco-2 cells revealed 70 % cell viability in a concentration-dependent manner. The preventive effects of Gly and VA co-loaded in APMs on glucose uptake was studied in insulin-responsive human HepG2 cells treated with high glucose. The co-loading of both the drugs in optimized APMs exhibited synergistic glucose-lowering activity (p < 0.001) than raw drugs with low cytotoxicity on HepG2 cells within the test concentration. This could be attributed to an increase in the relative oral bioavailability of both the drugs in APMs i.e., 868 % for Gly and 87 % for VA respectively.
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2022 |
Paudel KR, Dua K, Panth N, Hansbro PM, Chellappan DK, 'Advances in research with rutin-loaded nanoformulations in mitigating lung diseases', FUTURE MEDICINAL CHEMISTRY, 14 1293-1295 (2022)
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2022 |
Prasher P, Sharma M, Singh SK, Haghi M, MacLoughlin R, Chellappan DK, et al., 'Advances and applications of dextran-based nanomaterials targeting inflammatory respiratory diseases', Journal of Drug Delivery Science and Technology, 74 (2022) [C1]
Dextran, a hydrophilic polysaccharide consists essentially of a-1,6 linked glucopyranoside residues that form the parent chain, along with a-1,2/3/4 linked residues that constitut... [more]
Dextran, a hydrophilic polysaccharide consists essentially of a-1,6 linked glucopyranoside residues that form the parent chain, along with a-1,2/3/4 linked residues that constitute its side chain. A considerable biocompatibility, stability under mildly acidic and basic conditions, solubility in water, non-immunogenicity, and presence of chemically modifiable ¿OH groups make dextran an ideal candidate for development of drug delivery vehicles and excipients. The presence of a-1,6 linkages in the parent chain provides enhanced chain mobility that determines the aqueous solubility of dextran, while its metabolism by the digestive enzymes to generate physiologically harmless degradation products validates its biocompatibility. Native dextran can be tuned for the development of pH-sensitive delivery systems by chemical modification that ensure an optimal drug concentration at the target site, and lowered dosing frequency that may ensure an overall improved patient compliance. The physicochemical properties of dextran can be changed by performing a chemical modification predominantly at the ¿OH group to obtain ester, ether, acetal, and dialdehyde of dextran. The review presented by us is a comprehensive account of the chemical modification strategies for native dextran and their clinical applications in containing pulmonary diseases. Furthermore, the presented review highlights the importance of nanomaterials derived from chemically modified dextran for the management of an optimal respiratory health by containing the inflammatory respiratory diseases.
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2022 |
Ashique S, De Rubis G, Sirohi E, Mishra N, Rihan M, Garg A, et al., 'Short Chain Fatty Acids: Fundamental mediators of the gut-lung axis and their involvement in pulmonary diseases', Chemico-Biological Interactions, 368 (2022) [C1]
The human microbiota is fundamental to correct immune system development and balance. Dysbiosis, or microbial content alteration in the gut and respiratory tract, is associated wi... [more]
The human microbiota is fundamental to correct immune system development and balance. Dysbiosis, or microbial content alteration in the gut and respiratory tract, is associated with immune system dysfunction and lung disease development. The microbiota's influence on human health and disease is exerted through the abundance of metabolites produced by resident microorganisms, where short-chain fatty acids (SCFAs) represent the fundamental class. SCFAs are mainly produced by the gut microbiota through anaerobic fermentation of dietary fibers, and are known to influence the homeostasis, susceptibility to and outcome of many lung diseases. This article explores the microbial species found in healthy human gastrointestinal and respiratory tracts. We investigate factors contributing to dysbiosis in lung illness, and the gut-lung axis and its association with lung diseases, with a particular focus on the functions and mechanistic roles of SCFAs in these processes. The key focus of this review is a discussion of the main metabolites of the intestinal microbiota that contribute to host-pathogen interactions: SCFAs, which are formed by anaerobic fermentation. These metabolites include propionate, acetate, and butyrate, and are crucial for the preservation of immune homeostasis. Evidence suggests that SCFAs prevent infections by directly affecting host immune signaling. This review covers the various and intricate ways through which SCFAs affect the immune system's response to infections, with a focus on pulmonary diseases including chronic obstructive pulmonary diseases, asthma, lung cystic fibrosis, and tuberculosis. The findings reviewed suggest that the immunological state of the lung may be indirectly influenced by elements produced by the gut microbiota. SCFAs represent valuable potential therapeutic candidates in this context.
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2022 |
Moheimani F, Shahdab N, Cummings S, Hansbro PM, Ward C, 'Key role of dysregulated airway epithelium in response to respiratory viral infections in asthma', ERJ OPEN RESEARCH, 8 (2022)
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2022 |
Tu X, Kim RY, Brown AC, de Jong E, Jones-Freeman B, Ali MK, et al., 'Airway and parenchymal transcriptomics in a novel model of asthma and COPD overlap', Journal of Allergy and Clinical Immunology, 150 817-829.e6 (2022) [C1]
Background: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COP... [more]
Background: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COPD overlap (ACO). Patients characterized with ACO have increased disease severity; however, the mechanisms driving this have not been widely studied. Objectives: This study sought to characterize the phenotypic and transcriptomic features of experimental ACO in mice induced by chronic house dust mite antigen and cigarette smoke exposure. Methods: Female BALB/c mice were chronically exposed to house dust mite antigen for 11 weeks to induce experimental asthma, cigarette smoke for 8 weeks to induce experimental COPD, or both concurrently to induce experimental ACO. Lung inflammation, structural changes, and lung function were assessed. RNA-sequencing was performed on separated airway and parenchyma lung tissues to assess transcriptional changes. Validation of a novel upstream driver SPI1 in experimental ACO was assessed using the pharmacological SPI1 inhibitor, DB2313. Results: Experimental ACO recapitulated features of both asthma and COPD, with mixed pulmonary eosinophilic/neutrophilic inflammation, small airway collagen deposition, and increased airway hyperresponsiveness. Transcriptomic analysis identified common and distinct dysregulated gene clusters in airway and parenchyma samples in experimental asthma, COPD, and ACO. Upstream driver analysis revealed increased expression of the transcription factor Spi1. Pharmacological inhibition of SPI1 using DB2313, reduced airway remodeling and airway hyperresponsiveness in experimental ACO. Conclusions: A new experimental model of ACO featuring chronic dual exposures to house dust mite and cigarette smoke mimics key disease features observed in patients with ACO and revealed novel disease mechanisms, including upregulation of SPI1, that are amenable to therapy.
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Nova |
2022 |
Devkota HP, Paudel KR, Khanal S, Baral A, Panth N, Adhikari-Devkota A, et al., 'Stinging Nettle (Urtica dioica L.): Nutritional Composition, Bioactive Compounds, and Food Functional Properties', Molecules, 27 5219-5219 [C1]
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2021 |
Kuchibhotla VNS, Starkey MR, Reid AT, Heijink IH, Nawijn MC, Hansbro PM, Knight DA, 'Inhibition of beta-Catenin/CREB Binding Protein Signaling Attenuates House Dust Mite-Induced Goblet Cell Metaplasia in Mice', FRONTIERS IN PHYSIOLOGY, 12 (2021) [C1]
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Nova |
2021 |
Moecking J, Laohamonthonkul P, Chalker K, White MJ, Harapas CR, Yu CH, et al., 'NLRP1 variant M1184V decreases inflammasome activation in the context of DPP9 inhibition and asthma severity', Journal of Allergy and Clinical Immunology, 147 2134-2145.e20 (2021) [C1]
Background: NLRP1 is an innate immune sensor that can form cytoplasmic inflammasome complexes. Polymorphisms in NLRP1 are linked to asthma; however, there is currently no function... [more]
Background: NLRP1 is an innate immune sensor that can form cytoplasmic inflammasome complexes. Polymorphisms in NLRP1 are linked to asthma; however, there is currently no functional or mechanistic explanation for this. Objective: We sought to clarify the role of NLRP1 in asthma pathogenesis. Methods: Results from the GALA II cohort study were used to identify a link between NLRP1 and asthma in Mexican Americans. In vitro and in vivo models for NLRP1 activation were applied to investigate the role of this inflammasome in asthma at the molecular level. Results: We document the association of an NLRP1 haplotype with asthma for which the single nucleotide polymorphism rs11651270 (M1184V) individually is the most significant. Surprisingly, M1184V increases NLRP1 activation in the context of N-terminal destabilization, but decreases NLRP1 activation on dipeptidyl peptidase 9 inhibition. In vitro studies demonstrate that M1184V increases binding to dipeptidyl peptidase 9, which can account for its inhibitory role in this context. In addition, in vivo data from a mouse model of airway inflammation reveal a protective role for NLRP1 inflammasome activation reducing eosinophilia in this setting. Conclusions: Linking our in vitro and in vivo results, we found that the NLRP1 variant M1184V reduces inflammasome activation in the context of dipeptidyl peptidase 9 inhibition and could thereby increase asthma severity. Our studies may have implications for the treatment of asthma in patients carrying this variant of NLRP1.
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Nova |
2021 |
Liu G, Philp AM, Corte T, Travis MA, Schilter H, Hansbro NG, et al., 'Therapeutic targets in lung tissue remodelling and fibrosis', Pharmacology and Therapeutics, 225 (2021) [C1]
Structural changes involving tissue remodelling and fibrosis are major features of many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD) and idio... [more]
Structural changes involving tissue remodelling and fibrosis are major features of many pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Abnormal deposition of extracellular matrix (ECM) proteins is a key factor in the development of tissue remodelling that results in symptoms and impaired lung function in these diseases. Tissue remodelling in the lungs is complex and differs between compartments. Some pathways are common but tissue remodelling around the airways and in the parenchyma have different morphologies. Hence it is critical to evaluate both common fibrotic pathways and those that are specific to different compartments; thereby expanding the understanding of the pathogenesis of fibrosis and remodelling in the airways and parenchyma in asthma, COPD and IPF with a view to developing therapeutic strategies for each. Here we review the current understanding of remodelling features and underlying mechanisms in these major respiratory diseases. The differences and similarities of remodelling are used to highlight potential common therapeutic targets and strategies. One central pathway in remodelling processes involves transforming growth factor (TGF)-ß induced fibroblast activation and myofibroblast differentiation that increases ECM production. The current treatments and clinical trials targeting remodelling are described, as well as potential future directions. These endeavours are indicative of the renewed effort and optimism for drug discovery targeting tissue remodelling and fibrosis.
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2021 |
Huang Q, Jacquelot N, Preaudet A, Hediyeh-zadeh S, Souza-fonseca-guimaraes F, McKenzie ANJ, et al., 'Type 2 innate lymphoid cells protect against colorectal cancer progression and predict improved patient survival', Cancers, 13 1-16 (2021) [C1]
Chronic inflammation of the gastrointestinal (GI) tract contributes to colorectal cancer (CRC) progression. While the role of adaptive T cells in CRC is now well established, the ... [more]
Chronic inflammation of the gastrointestinal (GI) tract contributes to colorectal cancer (CRC) progression. While the role of adaptive T cells in CRC is now well established, the role of innate immune cells, specifically innate lymphoid cells (ILCs), is not well understood. To define the role of ILCs in CRC we employed complementary heterotopic and chemically-induced CRC mouse models. We discovered that ILCs were abundant in CRC tumours and contributed to anti-tumour immunity. We focused on ILC2 and showed that ILC2-deficient mice developed a higher tumour burden compared with littermate wild-type controls. We generated an ILC2 gene signature and using machine learning models revealed that CRC patients with a high intratumor ILC2 gene signature had a favourable clinical prognosis. Collectively, our results highlight a critical role for ILC2 in CRC, suggesting a potential new avenue to improve clinical outcomes through ILC2-agonist based therapeutic approaches.
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2021 |
Peneaux C, Hansbro PM, Griffin AS, 'The potential utility of carotenoid-based coloration as a biomonitor of environmental change', IBIS, 163 20-37 (2021) [C1]
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Nova |
2021 |
Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al., 'Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro.', Life Sci, 276 119436 (2021) [C1]
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2021 |
Christie MJ, Irving AT, Forster SC, Marsland BJ, Hansbro PM, Hertzog PJ, et al., 'Of bats and men: Immunomodulatory treatment options for COVID-19 guided by the immunopathology of SARS-CoV-2 infection.', Sci Immunol, 6 eabd0205 (2021) [C1]
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2021 |
Morris S, Wright K, Malyla V, Britton WJ, Hansbro PM, Manuneedhi Cholan P, Oehlers SH, 'Exposure to the gut microbiota from cigarette smoke-exposed mice exacerbates cigarette smoke extract-induced inflammation in zebrafish larvae.', Curr Res Immunol, 2 229-236 (2021) [C1]
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2021 |
Devkota HP, Paudel KR, Jha NK, Gupta PK, Singh SK, Chellappan DK, et al., 'Applications of drug-delivery systems targeting inflammasomes in pulmonary diseases', NANOMEDICINE, 16 2407-2410 (2021)
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2021 |
Tu X, Donovan C, Kim RY, Wark PAB, Horyat JC, Hansbro PM, 'Asthma-COPD overlap: current understanding and the utility of experimental models', EUROPEAN RESPIRATORY REVIEW, 30 (2021) [C1]
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Nova |
2021 |
Dirar AI, Adhikari-Devkota A, Kunwar RM, Paudel KR, Belwal T, Gupta G, et al., 'Genus Blepharis (Acanthaceae): A review of ethnomedicinally used species, and their phytochemistry and pharmacological activities', Journal of Ethnopharmacology, 265 1-12 (2021) [C1]
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Nova |
2021 |
Mehta M, Satija S, Paudel KR, Malyla V, Kannaujiya VK, Chellappan DK, et al., 'Targeting respiratory diseases using miRNA inhibitor based nanotherapeutics: Current status and future perspectives', Nanomedicine: Nanotechnology, Biology, and Medicine, 31 (2021) [C1]
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Nova |
2021 |
Jacquelot N, Seillet C, Wang M, Pizzolla A, Liao Y, Hediyeh-zadeh S, et al., 'Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma', NATURE IMMUNOLOGY, 22 851-+ (2021) [C1]
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Nova |
2021 |
Menounos S, Hansbro PM, Diwan AD, Das A, 'Pathophysiological Correlation between Cigarette Smoking and Amyotrophic Lateral Sclerosis', NEUROSCI, 2 120-134 (2021)
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2021 |
Martins Costa Gomes G, de Gouveia Belinelo P, Starkey MR, Murphy VE, Hansbro PM, Sly PD, et al., 'Cord blood group 2 innate lymphoid cells are associated with lung function at 6 weeks of age', CLINICAL & TRANSLATIONAL IMMUNOLOGY, 10 (2021) [C1]
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Nova |
2021 |
Gomes GMC, Karmaus W, Murphy VE, Gibson PG, Percival E, Hansbro PM, et al., 'Environmental Air Pollutants Inhaled during Pregnancy Are Associated with Altered Cord Blood Immune Cell Profiles', INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, 18 (2021) [C1]
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Nova |
2021 |
Skerrett-Byrne DA, Bromfield EG, Murray HC, Jamaluddin MFB, Jarnicki AG, Fricker M, et al., 'Time-resolved proteomic profiling of cigarette smoke-induced experimental chronic obstructive pulmonary disease', Respirology, 26 960-973 (2021) [C1]
Background and objective: Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness and death worldwide. Current treatments aim to control symptoms with n... [more]
Background and objective: Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness and death worldwide. Current treatments aim to control symptoms with none able to reverse disease or stop its progression. We explored the major molecular changes in COPD pathogenesis. Methods: We employed quantitative label-based proteomics to map the changes in the lung tissue proteome of cigarette smoke-induced experimental COPD that is induced over 8 weeks and progresses over 12 weeks. Results: Quantification of 7324 proteins enabled the tracking of changes to the proteome. Alterations in protein expression profiles occurred in the induction phase, with 18 and 16 protein changes at 4- and 6-week time points, compared to age-matched controls, respectively. Strikingly, 269 proteins had altered expression after 8 weeks when the hallmark pathological features of human COPD emerge, but this dropped to 27 changes at 12 weeks with disease progression. Differentially expressed proteins were validated using other mouse and human COPD bronchial biopsy samples. Major changes in RNA biosynthesis (heterogeneous nuclear ribonucleoproteins C1/C2 [HNRNPC] and RNA-binding protein Musashi homologue 2 [MSI2]) and modulators of inflammatory responses (S100A1) were notable. Mitochondrial dysfunction and changes in oxidative stress proteins also occurred. Conclusion: We provide a detailed proteomic profile, identifying proteins associated with the pathogenesis and disease progression of COPD establishing a platform to develop effective new treatment strategies.
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Nova |
2021 |
Johansen MD, Shalini, Kumar S, Raynaud C, Quan DH, Britton WJ, et al., 'Biological and biochemical evaluation of isatin-isoniazid hybrids as bactericidal candidates against mycobacterium tuberculosis', Antimicrobial Agents and Chemotherapy, 65 (2021) [C1]
Tuberculosis remains a leading cause of mortality among infectious diseases worldwide, prompting the need to discover new drugs to fight this disease. We report here the design, s... [more]
Tuberculosis remains a leading cause of mortality among infectious diseases worldwide, prompting the need to discover new drugs to fight this disease. We report here the design, synthesis, and antimycobacterial activity of isatin-mono/ bis-isoniazid hybrids. Most of the compounds exhibited very high activity against Mycobacterium tuberculosis, with MICs in the range of 0.195 to 0.39mg/ml, and exerted a more potent bactericidal effect than the standard antitubercular drug isoniazid (INH). Importantly, these compounds were found to be well tolerated at high doses (.200mg/ml) on Vero kidney cells, leading to high selectivity indices. Two of the most promising hybrids were evaluated for activity in THP-1 macrophages infected with M. tuberculosis, among which compound 11e was found to be slightly more effective than INH. Overexpression of InhA along with cross-resistance determination of the most potent compounds, selection of resistant mutants, and biochemical analysis, allowed us to decipher their mode of action. These compounds effectively inhibited mycolic acid biosynthesis and required KatG to exert their biological effects. Collectively, this suggests that the synthesized isatin-INH hybrids are promising antitubercular molecules for further evaluation in preclinical settings.
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2021 |
Counoupas C, Johansen MD, Stella AO, Nguyen DH, Ferguson AL, Aggarwal A, et al., 'A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection', npj Vaccines, 6 (2021) [C1]
Global control of COVID-19 requires broadly accessible vaccines that are effective against SARS-CoV-2 variants. In this report, we exploit the immunostimulatory properties of baci... [more]
Global control of COVID-19 requires broadly accessible vaccines that are effective against SARS-CoV-2 variants. In this report, we exploit the immunostimulatory properties of bacille Calmette-Guérin (BCG), the existing tuberculosis vaccine, to deliver a vaccination regimen with potent SARS-CoV-2-specific protective immunity. Combination of BCG with a stabilised, trimeric form of SARS-CoV-2 spike antigen promoted rapid development of virus-specific IgG antibodies in the blood of vaccinated mice, that was further augmented by the addition of alum. This vaccine formulation, BCG:CoVac, induced high-titre SARS-CoV-2 neutralising antibodies (NAbs) and Th1-biased cytokine release by vaccine-specific T cells, which correlated with the early emergence of T follicular helper cells in local lymph nodes and heightened levels of antigen-specific plasma B cells after vaccination. Vaccination of K18-hACE2 mice with a single dose of BCG:CoVac almost completely abrogated disease after SARS-CoV-2 challenge, with minimal inflammation and no detectable virus in the lungs of infected animals. Boosting BCG:CoVac-primed mice with a heterologous vaccine further increased SARS-CoV-2-specific antibody responses, which effectively neutralised B.1.1.7 and B.1.351 SARS-CoV-2 variants of concern. These findings demonstrate the potential for BCG-based vaccination to protect against major SARS-CoV-2 variants circulating globally.
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2021 |
Tiotiu A, Badi Y, Kermani N, Hansbro P, Wheelock C, Dahlen SE, et al., 'Rôle des mastocytes dans l asthme sévère : analyse de données transcriptomiques dans la cohorte U-BIOPRED', Revue des Maladies Respiratoires Actualités, 13 68-68 (2021)
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2021 |
Burnett DL, Jackson KJL, Langley DB, Aggrawal A, Stella AO, Johansen MD, et al., 'Immunizations with diverse sarbecovirus receptor-binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability', Immunity, 54 2908-2921.e6 (2021) [C1]
Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are ... [more]
Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse sarbecovirus receptor-binding domains (RBDs) to identify antibodies targeting conserved sites of vulnerability. Antibodies with broad reactivity against diverse clade B RBDs targeting the conserved class 4 epitope, with recurring IGHV/IGKV pairs, were readily elicited but were non-neutralizing. However, rare class 4 antibodies binding this conserved RBD supersite showed potent neutralization of SARS-CoV-2 and all variants of concern. Structural analysis revealed that the neutralizing ability of cross-reactive antibodies was reserved only for those with an elongated CDRH3 that extends the antiparallel beta-sheet RBD core and orients the antibody light chain to obstruct ACE2-RBD interactions. These results identify a structurally defined pathway for vaccine strategies eliciting escape-resistant SARS-CoV-2 neutralizing antibodies.
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2021 |
AlAjmi MF, Khan S, Choudhury A, Mohammad T, Noor S, Hussain A, et al., 'Impact of Deleterious Mutations on Structure, Function and Stability of Serum/Glucocorticoid Regulated Kinase 1: A Gene to Diseases Correlation', FRONTIERS IN MOLECULAR BIOSCIENCES, 8 (2021) [C1]
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Nova |
2021 |
Loering S, Cameron GJM, Bhatt NP, Belz GT, Foster PS, Hansbro PM, Starkey MR, 'Differences in pulmonary group 2 innate lymphoid cells are dependent on mouse age, sex and strain', IMMUNOLOGY AND CELL BIOLOGY, 99 542-551 (2021) [C1]
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2021 |
Munoz MA, Fletcher EK, Skinner OP, Jurczyluk J, Kristianto E, Hodson MP, et al., 'Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages', eLife, 10 (2021) [C1]
Bisphosphonates drugs target the skeleton and are used globally for the treatment of common bone disorders. Nitrogen-containing bisphosphonates act by inhibiting the mevalonate pa... [more]
Bisphosphonates drugs target the skeleton and are used globally for the treatment of common bone disorders. Nitrogen-containing bisphosphonates act by inhibiting the mevalonate pathway in bone-resorbing osteoclasts but, surprisingly, also appear to reduce the risk of death from pneumonia. We overturn the long-held belief that these drugs act only in the skeleton and show that a fluorescently labelled bisphosphonate is internalised by alveolar macrophages and large peritoneal macrophages in vivo. Furthermore, a single dose of a nitrogen-containing bisphosphonate (zole-dronic acid) in mice was sufficient to inhibit the mevalonate pathway in tissue-resident macrophages, causing the build-up of a mevalonate metabolite and preventing protein prenylation. Importantly, one dose of bisphosphonate enhanced the immune response to bacterial endotoxin in the lung and increased the level of cytokines and chemokines in bronchoalveolar fluid. These studies suggest that bisphosphonates, as well as preventing bone loss, may boost immune responses to infection in the lung and provide a mechanistic basis to fully examine the potential of bisphosphonates to help combat respiratory infections that cause pneumonia.
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2021 |
Kar R, Jha SK, Ojha S, Sharma A, Dholpuria S, Raju VSR, et al., 'The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues', Cancer Reports, 4 (2021) [C1]
Background: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing comple... [more]
Background: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable ¿super-enzymatic¿ process that might respond to targeted therapeutic modalities in cancer. Recent findings: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like ßTrcP1 and ßTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis. Conclusion: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.
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2021 |
Mehta M, Paudel KR, Shukla SD, Shastri MD, Satija S, Singh SK, et al., 'Rutin-loaded liquid crystalline nanoparticles attenuate oxidative stress in bronchial epithelial cells: a PCR validation.', Future Med Chem, 13 543-549 (2021) [C1]
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2021 |
Chan Y, Mehta M, Paudel KR, Madheswaran T, Panneerselvam J, Gupta G, et al., 'Versatility of liquid crystalline nanoparticles in inflammatory lung diseases', NANOMEDICINE, 16 1545-1548 (2021)
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2021 |
Tiotiu A, Zounemat Kermani N, Badi Y, Pavlidis S, Hansbro PM, Guo YK, et al., 'Sputum macrophage diversity and activation in asthma: Role of severity and inflammatory phenotype', Allergy: European Journal of Allergy and Clinical Immunology, 76 775-788 (2021) [C1]
Background: Macrophages control innate and acquired immunity, but their role in severe asthma remains ill-defined. We investigated gene signatures of macrophage subtypes in the sp... [more]
Background: Macrophages control innate and acquired immunity, but their role in severe asthma remains ill-defined. We investigated gene signatures of macrophage subtypes in the sputum of 104 asthmatics and 16 healthy volunteers from the U-BIOPRED cohort. Methods: Forty-nine gene signatures (modules) for differentially stimulated macrophages, one to assess lung tissue-resident cells (TR-Mf) and two for their polarization (classically and alternatively activated macrophages: M1 and M2, respectively) were studied using gene set variation analysis. We calculated enrichment scores (ES) across severity and previously identified asthma transcriptome-associated clusters (TACs). Results: Macrophage numbers were significantly decreased in severe asthma compared to mild-moderate asthma and healthy volunteers. The ES for most modules were also significantly reduced in severe asthma except for 3 associated with inflammatory responses driven by TNF and Toll-like receptors via NF-¿B, eicosanoid biosynthesis via the lipoxygenase pathway and IL-2 biosynthesis (all P¿<.01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll-like and TNF receptor activation and arachidonic acid metabolism (P¿<.001) and in TAC2 for the inflammasome and interferon signalling pathways (P¿<.001). Data were validated in the ADEPT cohort. Module analysis provides additional information compared to conventional M1 and M2 classification. TR-Mf were enriched in TAC3 and associated with mitochondrial function. Conclusions: Macrophage activation is attenuated in severe granulocytic asthma highlighting defective innate immunity except for specific subsets characterized by distinct inflammatory pathways.
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2021 |
Hardwick J, Taylor J, Mehta M, Satija S, Paudel KR, Hans-Bro PM, et al., 'Targeting cancer using curcumin encapsulated vesicular drug delivery systems', Current Pharmaceutical Design, 27 2-14 (2021) [C1]
Curcumin is a major curcuminoid present in turmeric. The compound is attributed to various therapeutic properties, which include anti-oxidant, anti-inflammatory, anti-bacterial, a... [more]
Curcumin is a major curcuminoid present in turmeric. The compound is attributed to various therapeutic properties, which include anti-oxidant, anti-inflammatory, anti-bacterial, anti-malarial, and neuroprotection. Due to its therapeutic potential, curcumin has been employed for centuries in treating different ailments. Curcu-min has been investigated lately as a novel therapeutic agent in the treatment of cancer. However, the mechanisms by which curcumin exerts its cytotoxic effects on malignant cells are still not fully understood. One of the main limiting factors in the clinical use of curcumin is its poor bioavailability and rapid elimination. Advancements in drug delivery systems such as nanoparticle-based vesicular drug delivery platforms have improved several parameters, namely, drug bioavailability, solubility, stability, and controlled release properties. The use of curcumin-encapsulated niosomes to improve the physical and pharmacokinetic properties of curcumin is one such approach. This review provides an up-to-date summary of nanoparticle-based vesicular drug carriers and their therapeutic applications. Specifically, we focus on niosomes as novel drug delivery formulations and their potential in improving the delivery of challenging small molecules, including curcumin. Overall, the applications of such carriers will provide a new direction for novel pharmaceutical drug delivery, as well as for biotechnology, nutraceutical, and functional food industries.
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2021 |
Deng K, Zhang X, Liu Y, Zhang L, Wang G, Feng M, et al., 'Heterogeneity of Paucigranulocytic Asthma: A Prospective Cohort Study with Hierarchical Cluster Analysis', Journal of Allergy and Clinical Immunology: In Practice, 9 2344-2355 (2021) [C1]
Background: Asthma, a heterogeneous disease, can be divided into 4 inflammatory phenotypes using induced sputum cell counts¿eosinophilic asthma (EA), neutrophilic asthma (NA), mix... [more]
Background: Asthma, a heterogeneous disease, can be divided into 4 inflammatory phenotypes using induced sputum cell counts¿eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma, and paucigranulocytic asthma (PGA). Although research has focused on EA and NA, there is little known about PGA. Objective: To study the heterogeneity of PGA and identify possible PGA clusters to guide clinical treatment. Methods: Patients with PGA were grouped by hierarchical cluster analysis and enrolled into a prospective cohort study to validate the clusters, relative to future risk of asthma exacerbations in a real-world setting. Clusters were validated by tree analysis in a separate population. Finally, we explored PGA stability. Results: Cluster analysis of 145 patients with PGA identified 3 clusters: cluster 1 (n = 110, 75.9%) was ¿mild PGA,¿ cluster 2 (n = 20, 13.8%) was ¿PGA with psychological dysfunction and rhinoconjunctivitis and other allergic diseases,¿ and cluster 3 (n = 15, 10.3%) was ¿smoking-associated PGA.¿ Cluster 3 had significantly increased risk of severe exacerbation (relative risk [RR] = 6.43, P =.01), emergency visit (RR = 8.61, P =.03), and hospitalization (RR = 12.94, P <.01). Results of the cluster analysis were successfully validated in an independent PGA population classified using decision tree analysis. Although PGA can transform into or develop from other phenotypes, 70% were stable over time. Conclusions: Among 3 identified PGA clusters, cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions.
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2021 |
Chong WC, Shastri MD, Peterson GM, Patel RP, Pathinayake PS, Dua K, et al., 'The complex interplay between endoplasmic reticulum stress and the NLRP3 inflammasome: a potential therapeutic target for inflammatory disorders', Clinical and Translational Immunology, 10 (2021) [C1]
Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, pa... [more]
Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome-induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress- and inflammasome-related inflammatory disorders.
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2021 |
Ashcroft SP, Fletcher G, Philp AM, Jenkinson C, Das S, Hansbro PM, et al., 'Diet-induced vitamin D deficiency reduces skeletal muscle mitochondrial respiration', JOURNAL OF ENDOCRINOLOGY, 249 113-124 (2021) [C1]
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2021 |
Mehta M, Paudel KR, Panth N, Xenaki D, Macloughlin R, Oliver BG, et al., 'Drug delivery advances in mitigating inflammation via matrix metalloproteinases in respiratory diseases', NANOMEDICINE, 16 437-439 (2021)
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2021 |
Shrestha J, Ryan ST, Mills O, Zhand S, Razavi Bazaz S, Hansbro PM, et al., 'A 3D-printed microfluidic platform for simulating the effects of CPAP on the nasal epithelium', BIOFABRICATION, 13 (2021) [C1]
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2021 |
Shastri MD, Allam VSRR, Shukla SD, Jha NK, Paudel KR, Peterson GM, et al., 'Interleukin-13: A pivotal target against influenza-induced exacerbation of chronic lung diseases', Life Sciences, 283 (2021) [C1]
Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic... [more]
Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.
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2021 |
Mehta M, Paudel KR, Shukla SD, Allam VSRR, Kannaujiya VK, Panth N, et al., 'Recent trends of NF B decoy oligodeoxynucleotide-based nanotherapeutics in lung diseases', Journal of Controlled Release, 337 629-644 (2021) [C1]
Nuclear factor ¿B (NF¿B) is a unique protein complex that plays a major role in lung inflammation and respiratory dysfunction. The NF¿B signaling pathway, therefore becomes an ave... [more]
Nuclear factor ¿B (NF¿B) is a unique protein complex that plays a major role in lung inflammation and respiratory dysfunction. The NF¿B signaling pathway, therefore becomes an avenue for the development of potential pharmacological interventions, especially in situations where chronic inflammation is often constitutively active and plays a key role in the pathogenesis and progression of the disease. NF¿B decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NF¿B binding sequences. They prevent the formation of NF¿B-mediated inflammatory cytokines and thus have been employed in the treatment of a variety of chronic inflammatory diseases. However, the systemic administration of naked decoy ODNs restricts their therapeutic effectiveness because of their poor pharmacokinetic profile, instability, degradation by cellular enzymes and their low cellular uptake. Both structural modification and nanotechnology have shown promising results in enhancing the pharmacokinetic profiles of potent therapeutic substances and have also shown great potential in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. In this review, we examine the contribution of NF¿B activation in respiratory diseases and recent advancements in the therapeutic use of decoy ODNs. In addition, we also highlight the limitations and challenges in use of decoy ODNs as therapeutic molecules, cellular uptake of decoy ODNs, and the current need for novel delivery systems to provide efficient delivery of decoy ODNs. Furthermore, this review provides a common platform for discussion on the existence of decoy ODNs, as well as outlining perspectives on the latest generation of delivery systems that encapsulate decoy ODNs and target NF¿B in respiratory diseases.
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2021 |
Nucera F, Lo Bello F, Shen SS, Ruggeri P, Coppolino I, Di Stefano A, et al., 'Role of Atypical Chemokines and Chemokine Receptors Pathways in the Pathogenesis of COPD', CURRENT MEDICINAL CHEMISTRY, 28 2577-2653 (2021) [C1]
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2021 |
Dhouib R, Nasreen M, Othman DSMP, Ellis D, Lee S, Essilfie A-T, et al., 'The DmsABC Sulfoxide Reductase Supports Virulence in Non-typeable Haemophilus influenzae.', Front Microbiol, 12 686833 (2021) [C1]
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2021 |
Wark PAB, Pathinayake PS, Kaiko G, Nichol K, Ali A, Chen L, et al., 'ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma', Respirology, 26 442-451 (2021) [C1]
Background and objective: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine protea... [more]
Background and objective: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. Methods: We obtained lower AEC from 145 people from two independent cohorts, aged 2¿89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.
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2021 |
Prasher P, Sharma M, Mehta M, Satija S, Aljabali AA, Tambuwala MM, et al., 'Current-status and applications of polysaccharides in drug delivery systems', Colloids and Interface Science Communications, 42 (2021) [C1]
The polysaccharide-based advanced drug delivery system owing to their biocompatibility, ability to encapsulate the drug molecules in their interspaces, and ability to achieve a co... [more]
The polysaccharide-based advanced drug delivery system owing to their biocompatibility, ability to encapsulate the drug molecules in their interspaces, and ability to achieve a controlled release of the cargo drug molecules result in improved drug pharmacokinetics. The drug-loaded polysaccharides possess ability to evade the multidrug-resistant microbial efflux pumps by aggregation effect, whereas the drug loaded polysaccharide-fabricated metal nanoparticles present an exceptional candidature for effectively transporting the drug molecules across the membrane barriers while enabling the theranostic applications at the same time. The biodegradability of polysaccharide based drug delivery systems ensure a sustained release of the encapsulated drug molecules, which minimizes the side effects caused by a burst release of the cargo therapeutics. These drug delivery systems proved highly beneficial for the NSAIDs that otherwise manifest ulcerogenic effect in the gastrointestinal tract. The large surface area of polysaccharides further provide a higher drug-loading capacity, which maintains the optimal concentration of the cargo drug at the target sites. The emerging applications of biodegradable polysaccharides in the designing of multicompartmental microspheres revolutionized tissue engineering, multi drug delivery, and cell culturing technologies. The present review deals with the current-status of polysaccharides as advanced drug delivery systems.
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2021 |
Blomme EE, Provoost S, De Smet EG, De Grove KC, Van Eeckhoutte HP, De Volder J, et al., 'Quantification and role of innate lymphoid cell subsets in Chronic Obstructive Pulmonary Disease.', Clin Transl Immunology, 10 e1287 (2021) [C1]
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2021 |
Alemao CA, Budden KF, Gomez HM, Rehman SF, Marshall JE, Shukla SD, et al., 'Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders', Allergy: European Journal of Allergy and Clinical Immunology, 76 714-734 (2021) [C1]
The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmo... [more]
The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a ¿poor¿ diet or protection against disease with a ¿healthy¿ diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.
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2021 |
Barnes JL, Plank MW, Asquith K, Maltby S, Sabino LR, Kaiko GE, et al., 'T-helper 22 cells develop as a distinct lineage from Th17 cells during bacterial infection and phenotypic stability is regulated by T-bet', MUCOSAL IMMUNOLOGY, 14 1077-1087 (2021) [C1]
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2021 |
Kim RY, Sunkara KP, Bracke KR, Jarnicki AG, Donovan C, Hsu AC, et al., 'microRNA-21-mediated SATB1/S100A9/NF-kappa B axis promotes chronic obstructive pulmonary disease pathogenesis', SCIENCE TRANSLATIONAL MEDICINE, 13 (2021) [C1]
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2021 |
Devkota HP, Gaire BP, Hori K, Subedi L, Adhikari-Devkota A, Belwal T, et al., 'The science of matcha: Bioactive compounds, analytical techniques and biological properties', Trends in Food Science and Technology, 118 735-743 (2021) [C1]
Background: The interest in the plant-derived healthy foods, nutraceuticals, functional foods and food supplements is increasing in recent times as potential agents in maintenance... [more]
Background: The interest in the plant-derived healthy foods, nutraceuticals, functional foods and food supplements is increasing in recent times as potential agents in maintenance of health and the prevention and treatment of diseases. Matcha tea powder is obtained from the leaves of tea plant (Camellia sinensis (L.) Kuntze) grown under specific condition using about 90% shade. As compared to green tea, a hot water extract of tea leaves, matcha is consumed as a powder of whole leaves. Matcha powder is reported to have higher content of some bioactive components such as catechins, theanine and caffeine. In recent years, there is an increased market demand and consumption of matcha as a drink and as a component in various beverages, snacks and other food products. Scope and approach: In this review, the available scientific information of the chemical constituents and their analysis and biological activities were critically analyzed. These results may help to understand current status of research on matcha and the gaps which help to guide future research related to evidence based product formulations. Key findings and conclusions: Various studies have reported the difference in bioactive compounds in matcha as compared to green tea and other tea formulations. The content and composition were mostly affected by the cultivation and processing techniques. Analysis of marketed samples in various countries have shown the variable content of the bioactive compounds. Thus, there is a need for proper standardization for maintaining the quality. Matcha as a whole, its extract and compounds have shown promising biological activities in in vitro and animal studies. However, comparatively only a few clinical studies are performed, which need future attention. There should also be more detailed studies regarding matcha-containing food products' formulation, quality control and biological activities.
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2021 |
Devkota HP, Paudel KR, Hassan MM, Dirar AI, Das N, Adhikari-Devkota A, et al., 'Bioactive compounds from zingiber montanum and their pharmacological activities with focus on zerumbone', Applied Sciences (Switzerland), 11 (2021) [C1]
The genus Zingiber consists of about 85 species and many of these species are used as food, spices, and medicines. One of the species, Zingiber montanum (J. Koenig) Link ex A. Die... [more]
The genus Zingiber consists of about 85 species and many of these species are used as food, spices, and medicines. One of the species, Zingiber montanum (J. Koenig) Link ex A. Dietr. is native to Southeast Asia and has been extensively used as traditional medicines and food. The aim of this review was to collect and critically analyze the scientific information about the bioactive compounds and pharmacological activities of Z. montanum with focus on one of the main components, zerumbone (ZER). Various studies have reported the analysis of volatile constituents of the essential oils from Z. montanum. Similarly, many phenylbutanoids, flavonoids and terpenes were also isolated from rhizomes. These essential oils, extracts and compounds showed potent antimicrobial, anti-inflammatory and antioxidant activities among others. Zerumbone has been studied widely for its anticancer, anti-inflammatory, and other pharmacological activities. Future studies should focus on the exploration of various pharmacological activities of other compounds including phenylbutanoids and flavonoids. Bioassay guided isolation may result in the separation of other active components from the extracts. Z. montanum could be a promising source for the development of pharmaceutical products and functional foods.
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2021 |
Mehta M, Malyla V, Paudel KR, Chellappan DK, Hansbro PM, Oliver BG, Dua K, 'Berberine loaded liquid crystalline nanostructure inhibits cancer progression in adenocarcinomic human alveolar basal epithelial cells in vitro.', J Food Biochem, 45 e13954 (2021) [C1]
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2021 |
Chellappan DK, Dharwal V, Paudel KR, Jha NK, MacLoughlin R, Oliver BG, et al., 'Mitochondrial dysfunctions associated with chronic respiratory diseases and their targeted therapies: an update', FUTURE MEDICINAL CHEMISTRY, 13 1249-1251 (2021)
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2021 |
Kim RY, Oliver BG, Wark PAB, Hansbro PM, Donovan C, 'COPD exacerbations: targeting IL-33 as a new therapy', LANCET RESPIRATORY MEDICINE, 9 1213-1214 (2021)
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2021 |
Wadhwa R, Paudel KR, Chin LH, Hon CM, Madheswaran T, Gupta G, et al., 'Anti-inflammatory and anticancer activities of Naringenin-loaded liquid crystalline nanoparticles in vitro', JOURNAL OF FOOD BIOCHEMISTRY, 45 (2021) [C1]
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2021 |
Shastri MD, Chong WC, Dua K, Peterson GM, Patel RP, Mahmood MQ, et al., 'Emerging concepts and directed therapeutics for the management of asthma: regulating the regulators', INFLAMMOPHARMACOLOGY, 29 15-33 (2021) [C1]
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2021 |
Schanin J, Gebremeskel S, Korver W, Falahati R, Butuci M, Haw TJ, et al., 'A monoclonal antibody to Siglec-8 suppresses non-allergic airway inflammation and inhibits IgE-independent mast cell activation', MUCOSAL IMMUNOLOGY, 14 366-376 (2021) [C1]
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2021 |
Lu Z, Van Eeckhoutte HP, Liu G, Nair PM, Jones B, Gillis CM, et al., 'Necroptosis Signaling Promotes Inflammation, Airway Remodeling, and Emphysema in Chronic Obstructive Pulmonary Disease', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 204 667-681 (2021) [C1]
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Nova |
2021 |
Gomez HM, Pillar AL, Brown AC, Kim RY, Ali MK, Essilfie A-T, et al., 'Investigating the Links between Lower Iron Status in Pregnancy and Respiratory Disease in Offspring Using Murine Models', NUTRIENTS, 13 (2021) [C1]
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Nova |
2021 |
Pacitti D, Scotton CJ, Kumar V, Khan H, Wark PAB, Torregrossa R, et al., 'Gasping for sulfide: A critical appraisal of hydrogen sulfide in lung disease and accelerated aging', Antioxidants and Redox Signaling, 35 551-579 (2021) [C1]
Hydrogen sulfide (H2S) is a gaseous signaling molecule involved in a plethora of physiological and pathological processes. It is primarily synthesized by cystathionine-b-synthase,... [more]
Hydrogen sulfide (H2S) is a gaseous signaling molecule involved in a plethora of physiological and pathological processes. It is primarily synthesized by cystathionine-b-synthase, cystathionine-c-lyase, and 3-mercaptopyruvate sulfurtransferase as a metabolite of the transsulfuration pathway. H2S has been shown to exert beneficial roles in lung disease acting as an anti-inflammatory and antiviral and to ameliorate cell metabolism and protect from oxidative stress. H2S interacts with transcription factors, ion channels, and a multitude of proteins via post-translational modifications through S-persulfidation (¿¿sulfhydration¿¿). Perturbation of endogenous H2S synthesis and/or levels have been implicated in the development of accelerated lung aging and diseases, including asthma, chronic obstructive pulmonary disease, and fibrosis. Furthermore, evidence indicates that persulfidation is decreased with aging. Here, we review the use of H2S as a biomarker of lung pathologies and discuss the potential of using H2S-generating molecules and synthesis inhibitors to treat respiratory diseases. Furthermore, we provide a critical appraisal of methods of detection used to quantify H2S concentration in biological samples and discuss the challenges of characterizing physiological and pathological levels. Considerations and caveats of using H2S delivery molecules, the choice of generating molecules, and concentrations are also reviewed. Antioxid. Redox Signal. 35, 551¿579.
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Nova |
2021 |
Wang Y, Xu X, Marshall JE, Gong M, Zhao Y, Dua K, et al., 'Loss of Hyaluronan and Proteoglycan Link Protein-1 Induces Tumorigenesis in Colorectal Cancer', Frontiers in Oncology, 11 (2021) [C1]
Colorectal cancer (CRC) is the third most common diagnosed cancer worldwide, but there are no effective cures for it. Hyaluronan and proteoglycan link protein-1 (HAPLN1) is a comp... [more]
Colorectal cancer (CRC) is the third most common diagnosed cancer worldwide, but there are no effective cures for it. Hyaluronan and proteoglycan link protein-1 (HAPLN1) is a component of the extracellular matrix (ECM) proteins and involved in the tumor environment in the colon. Transforming growth factor (TGF)-ß is a key cytokine that regulates the deposition of ECM proteins in CRC. However, the role of HAPLN1 in TGF-ß contributions to CRC remains unknown. We found that the mRNA expression of HAPLN1 was decreased in tumors from CRC patients compared with healthy controls and normal tissue adjacent to the tumor using two existing microarray datasets. This was validated at the protein level by tissue array from CRC patients (n¿=¿59). HAPLN1 protein levels were also reduced in human CRC epithelial cells after 24¿h of TGF-ß stimulation, and its protein expression correlated with type I collagen alpha-1 (COL1A1) in CRC. Transfection of HAPLN1 overexpression plasmids into these cells increased protein levels but reduced COL1A1 protein, tumor growth, and cancer cell migration. TGF-ß stimulation increased Smad2/3, p-Smad2/3, Smad4, and E-adhesion proteins; however, HAPLN1 overexpression restored these proteins to baseline levels in CRC epithelial cells after TGF-ß stimulation. These findings suggest that HAPLN1 regulates the TGF-ß signaling pathway to control collagen deposition via the TGF-ß signaling pathway and mediates E-adhesion to control tumor growth. Thus, treatments that increase HAPLN1 levels may be a novel therapeutic option for CRC.
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2021 |
Paudel KR, Jha SK, Allam VSRR, Prasher P, Gupta PK, Bhattacharjee R, et al., 'Recent advances in chronotherapy targeting respiratory diseases', Pharmaceutics, 13 (2021) [C1]
Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is a natural biological process where our bodily functions a... [more]
Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is a natural biological process where our bodily functions align with the 24 h oscillation (sleep¿wake cycle) process and are controlled by the circadian clock protein/gene. Disruption of the circadian rhythm could alter normal lung function. Chronotherapy is a type of therapy provided at specific time intervals based on an individual¿s circadian rhythm. This would allow the drug to show optimum action, and thereby modulate its pharmacokinetics to lessen unwanted or unintended effects. In this review, we deliberated on the recent advances employed in chrono-targeted therapeutics for chronic respiratory diseases.
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2020 |
Prihandoko R, Kaur D, Wiegman CH, Alvarez-Curto E, Donovan C, Chachi L, et al., 'Pathophysiological regulation of lung function by the free fatty acid receptor FFA4', SCIENCE TRANSLATIONAL MEDICINE, 12 (2020) [C1]
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Nova |
2020 |
Liu G, Baird AW, Parsons MJ, Fan K, Skerrett-Byrne DA, Nair PM, et al., 'Platelet activating factor receptor acts to limit colitis-induced liver inflammation', FASEB JOURNAL, 34 7718-7732 (2020) [C1]
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Nova |
2020 |
Griffin AS, Brown C, Woodworth BK, Ballard G-A, Blanch S, Campbell HA, et al., 'A large-scale automated radio telemetry network for monitoring movements of terrestrial wildlife in Australia', Australian Zoologist, 40 379-391 (2020) [C1]
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Nova |
2020 |
Mehta M, Dhanjal DS, Satija S, Wadhwa R, Paudel KR, Chellappan DK, et al., 'Advancing of Cellular Signaling Pathways in Respiratory Diseases Using Nanocarrier Based Drug Delivery Systems.', Curr Pharm Des, 26 5380-5392 (2020) [C1]
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2020 |
Aggarwal T, Wadhwa R, Gupta R, Paudel KR, Collet T, Chellappan DK, et al., 'MicroRNAs as Biomarker for Breast Cancer.', Endocr Metab Immune Disord Drug Targets, 20 1597-1610 (2020) [C1]
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Nova |
2020 |
Woods JJ, Skelding KA, Martin KL, Aryal R, Sontag E, Johnstone DM, et al., 'Assessment of evidence for or against contributions of Chlamydia pneumoniae infections to Alzheimer's disease etiology', Brain, Behavior, and Immunity, 83 22-32 (2020) [C1]
Alzheimer's disease, the most common form of dementia, was first formally described in 1907 yet its etiology has remained elusive. Recent proposals that Aß peptide may be par... [more]
Alzheimer's disease, the most common form of dementia, was first formally described in 1907 yet its etiology has remained elusive. Recent proposals that Aß peptide may be part of the brain immune response have revived longstanding contention about the possibility of causal relationships between brain pathogens and Alzheimer's disease. Research has focused on infectious pathogens that may colonize the brain such as herpes simplex type I. Some researchers have proposed the respiratory bacteria Chlamydia pneumoniae may also be implicated in Alzheimer's disease, however this remains controversial. This review aims to provide a balanced overview of the current evidence and its limitations and future approaches that may resolve controversies. We discuss the evidence from in vitro, animal and human studies proposed to implicate Chlamydia pneumoniae in Alzheimer's disease and other neurological conditions, the potential mechanisms by which the bacterium may contribute to pathogenesis and limitations of previous studies that may explain the inconsistencies in the literature.
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Nova |
2020 |
Schofield Z, Wu MCL, Hansbro PM, Cooper MA, Woodruff TM, 'Acetate protects against intestinal ischemia-reperfusion injury independent of its cognate free fatty acid 2 receptor', FASEB JOURNAL, 34 10418-10430 (2020)
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2020 |
Mehta M, Chellappan DK, Wich PR, Hansbro NG, Hansbro PM, Dua K, 'miRNA nanotherapeutics: potential and challenges in respiratory disorders', FUTURE MEDICINAL CHEMISTRY, 12 987-990 (2020)
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2020 |
Vidaillac C, Yong VFL, Aschtgen MS, Qu J, Yang S, Xu G, et al., 'Sex steroids induce membrane stress responses and virulence properties in pseudomonas aeruginosa', mBio, 11 1-19 (2020) [C1]
Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid Pseudomonas aeruginosa in the airways of patients with chronic respiratory diseases... [more]
Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid Pseudomonas aeruginosa in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study, we demonstrate that at physiological concentrations, sex steroids, including testosterone and estriol, induce membrane stress responses in P. aeruginosa. This is characterized by increased virulence and consequent inflammation and release of proinflammatory outer membrane vesicles promoting in vivo persistence of the bacteria. The steroid-induced P. aeruginosa response correlates with the molecular polarity of the hormones and membrane fluidic properties of the bacteria. This novel mechanism of interaction between sex steroids and P. aeruginosa explicates the reported increased disease severity observed in females with cystic fibrosis and provides evidence for the therapeutic potential of the modulation of sex steroids to achieve better clinical outcomes in patients with hormone-responsive strains. IMPORTANCE Molecular mechanisms by which sex steroids interact with P. aeruginosa to modulate its virulence have yet to be reported. Our work provides the first characterization of a steroid-induced membrane stress mechanism promoting P. aeruginosa virulence, which includes the release of proinflammatory outer membrane vesicles, resulting in inflammation, host tissue damage, and reduced bacterial clearance. We further demonstrate that at nanomolar (physiological) concentrations, male and female sex steroids promote virulence in clinical strains of P. aeruginosa based on their dynamic membrane fluidic properties. This work provides, for the first-time, mechanistic insight to better understand and predict the P. aeruginosa related response to sex steroids and explain the interindividual patient variability observed in respiratory diseases such as cystic fibrosis that are complicated by gender differences and chronic P. aeruginosa infection.
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Nova |
2020 |
Shinde T, Hansbro PM, Sohal SS, Dingle P, Eri R, Stanley R, 'Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives', MICROORGANISMS, 8 (2020)
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2020 |
Marshall RJ, Armart P, Hulme KD, Chew KY, Brown AC, Hansbro PM, et al., 'Glycemic Variability in Diabetes Increases the Severity of Influenza', MBIO, 11 (2020) [C1]
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Nova |
2020 |
Mehta M, Paudel KR, Shukla SD, Shastri MD, Singh SK, Gulati M, et al., 'Letter to the editor: INTERFERON THERAPY FOR PREVENTING COPD EXACERBATIONS', EXCLI JOURNAL, 19 1477-1480 (2020)
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2020 |
Bezerra-Santos CR, Bondarenko E, Essilfie AT, Nair PM, Horvat JC, Barbosa-Filho JM, et al., 'Cissampelos sympodialis and Warifteine Suppress Anxiety-Like Symptoms and Allergic Airway Inflammation in Acute Murine Asthma Model', REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, 30 224-232 (2020) [C1]
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Nova |
2020 |
Gosens R, Hiemstra PS, Adcock IM, Bracke KR, Dickson RP, Hansbro PM, et al., 'Host-microbe cross-talk in the lung microenvironment: Implications for understanding and treating chronic lung disease', European Respiratory Journal, 56 1-8 (2020) [C1]
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Nova |
2020 |
Shukla SD, Walters EH, Simpson JL, Keely S, Wark PAB, O'Toole RF, Hansbro PM, 'Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease', RESPIROLOGY, 25 53-63 (2020) [C1]
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Nova |
2020 |
Reid AT, Nichol KS, Veerati PC, Moheimani F, Kicic A, Stick SM, et al., 'Blocking notch3 signaling abolishes MUC5AC production in airway epithelial cells from individuals with asthma', American Journal of Respiratory Cell and Molecular Biology, 62 513-523 (2020) [C1]
In asthma, goblet cell numbers are increased within the airway epithelium, perpetuating the production of mucus that is more difficult to clear and results in airway mucus pluggin... [more]
In asthma, goblet cell numbers are increased within the airway epithelium, perpetuating the production of mucus that is more difficult to clear and results in airway mucus plugging. Notch1, Notch2, or Notch3, or a combination of these has been shown to influence the differentiation of airway epithelial cells. How the expression of specific Notch isoforms differs in fully differentiated adult asthmatic epithelium and whether Notch influences mucin production after differentiation is currently unknown. We aimed to quantify different Notch isoforms in the airway epithelium of individuals with severe asthma and to examine the impact of Notch signaling on mucin MUC5AC. Human lung sections and primary bronchial epithelial cells from individuals with and without asthma were used in this study. Primary bronchial epithelial cells were differentiated at the air-liquid interface for 28 days. Notch isoform expression was analyzed by Taqman quantitative PCR. Immunohistochemistry was used to localize and quantify Notch isoforms in human airway sections. Notch signaling was inhibited in vitro using dibenzazepine or Notch3-specific siRNA, followed by analysis of MUC5AC. NOTCH3 was highly expressed in asthmatic airway epithelium compared with nonasthmatic epithelium. Dibenzazepine significantly reduced MUC5AC production in air-liquid interface cultures of primary bronchial epithelial cells concomitantly with suppression of NOTCH3 intracellular domain protein. Specific knockdown using NOTCH3 siRNA recapitulated the dibenzazepine-induced reduction in MUC5AC. We demonstrate that NOTCH3 is a regulator of MUC5AC production. Increased NOTCH3 signaling in the asthmatic airway epithelium may therefore be an underlying driver of excess MUC5AC production.
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Nova |
2020 |
Lo Bello F, Hansbro PM, Donovan C, Coppolino I, Mumby S, Adcock IM, Caramori G, 'New drugs under development for COPD', Expert Opinion on Emerging Drugs, 25 419-431 (2020) [C1]
Introduction: Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by chronic bronchitis, emphysema, and remodeling. Its prevalence is increasing worldwide... [more]
Introduction: Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by chronic bronchitis, emphysema, and remodeling. Its prevalence is increasing worldwide; however, there are few effective therapies, and none of the treatments currently available prevent the progression of the disease or target all of the hallmark features. The development and progression of COPD are heterogeneous, which has hampered the development of new therapies. Areas covered: In this review, we cover the emergence of the improvement of existing classes of drugs including glucocorticoids, ß2-adrenoceptor agonists, phosphodiesterase inhibitors, PDE4 selective inhibitors, PDE3/PDE4 inhibitors, protease inhibitors, recombinant a1-antitrypsin and neutrophil elastase inhibitors. We also highlight new compounds that target recently identified mechanisms of COPD, new dual-action muscarinic antagonists, and ß2-agonists, kinase inhibitors, cytokine modifiers, chemokines modifiers, NF-¿B inhibitors, senolytics, antioxidants, inhaled antiviral agents, anti-fibrotic compounds, and compounds stimulating lung regeneration. Expert opinion: Given the myriad of potential therapeutic avenues that can be pursued, careful consideration of the phenotypes/endotypes of COPD patients will be important for personalized treatment options in the future, and a full understanding of disease mechanisms in patient subsets will ensure these emerging therapies are targeted appropriately.
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Nova |
2020 |
Idowu O, Semple KT, Ramadass K, O'Connor W, Hansbro P, Thavamani P, 'Analysis of polycyclic aromatic hydrocarbons (PAHs) and their polar derivatives in soils of an industrial heritage city of Australia', Science of the Total Environment, 699 (2020) [C1]
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Nova |
2020 |
Paudel KR, Dharwal V, Patel VK, Galvao I, Wadhwa R, Malyla V, et al., 'Role of Lung Microbiome in Innate Immune Response Associated With Chronic Lung Diseases', FRONTIERS IN MEDICINE, 7 (2020) [C1]
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Nova |
2020 |
Lo Bello F, Ieni A, Hansbro PM, Ruggeri P, Di Stefano A, Nucera F, et al., 'Role of the mucins in pathogenesis of COPD: implications for therapy', Expert Review of Respiratory Medicine, 14 465-483 (2020) [C1]
Introduction: Evidence accumulated in the last decade has started to reveal the enormous complexity in the expression, interactions and functions of the large number of different ... [more]
Introduction: Evidence accumulated in the last decade has started to reveal the enormous complexity in the expression, interactions and functions of the large number of different mucins present in the different compartments of the human lower airways. This occurs both in normal subjects and in COPD patients in different clinical phases and stages of severity. Areas covered: We review the known physiological mechanisms that regulate mucin production in human lower airways of normal subjects, the changes in mucin synthesis/secretion in COPD patients and the clinical efficacy of drugs that modulate mucin synthesis/secretion. Expert opinion: It is evident that the old simplistic concept that mucus hypersecretion in COPD patients is associated with negative clinical outcomes is not valid and that the therapeutic potential of ¿mucolytic drugs¿ is under-appreciated due to the complexity of the associated molecular network(s). Likewise, our current knowledge of the effects of the drugs already available on the market that target mucin synthesis/secretion/structure in the lower airways is extremely limited and often indirect and more well-controlled clinical trials are needed in this area.
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2020 |
Jin-Ying WYW, Yin Ng Z, Mehta M, Shukla SD, Panneerselvam J, Madheswaran T, et al., 'Curcumin-loaded niosomes downregulate mRNA expression of pro-inflammatory markers involved in asthma: An in vitro study', Nanomedicine, 15 2955-2970 (2020) [C1]
Aim: In this study, curcumin was encapsulated in niosomes (Nio-Curc) to increase its effectiveness for the treatment of asthma. Materials & methods: The formulation underwent ... [more]
Aim: In this study, curcumin was encapsulated in niosomes (Nio-Curc) to increase its effectiveness for the treatment of asthma. Materials & methods: The formulation underwent various physicochemical characterization experiments, an in vitro release study, molecular simulations and was evaluated for in vitro anti-inflammatory activity. Results: Results showed that Nio-Curc had a mean particle size of 284.93 ± 14.27 nm, zeta potential of -46.93 and encapsulation efficacy of 99.62%, which demonstrates optimized physicochemical characteristics. Curcumin release in vitro could be sustained for up to 24 h. Additionally, Nio-Curc effectively reduced mRNA transcript expression of pro-inflammatory markers; IL-6, IL-8, IL-1ß and TNF-a in immortalized human airway basal cell line (BCi-NS1.1). Conclusion: In this study, we have demonstrated that Nio-Curc mitigated the mRNA expression of pro-inflammatory markers in an in vitro study, which could be applied to treatment of asthma with further studies.
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Nova |
2020 |
Soon L, Ng PQ, Chellian J, Madheswaran T, Panneerselvam J, Hsu A, et al., 'Green synthesis and antibacterial potential of artemisia vulgaris extract in silver nanoparticles against wound bacteria', Jurnal Ilmiah Farmasi, 16 9-18 (2020) [C1]
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Nova |
2020 |
Mehta M, Satija S, Paudel KR, Liu G, Chellappan DK, Hansbro PM, Dua K, 'Incipient need of targeting airway remodeling using advanced drug delivery in chronic respiratory diseases', FUTURE MEDICINAL CHEMISTRY, 12 873-875 (2020)
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2020 |
Peneaux C, Hansbro PM, Jobling P, Holdsworth JL, Griffin AS, 'Tissue structure contributes to the production of a coloured skin display in the Common Myna', Avian Biology Research, 13 100-107 (2020) [C1]
Conspicuous coloured displays from ultraviolet to bright red have been documented in many species throughout the animal kingdom. These colours often occur as sexual signals and ca... [more]
Conspicuous coloured displays from ultraviolet to bright red have been documented in many species throughout the animal kingdom. These colours often occur as sexual signals and can be incorporated into different types of integuments (e.g. scales, feathers, skin). Two main mechanisms are known to produce coloured integuments: pigmentation and tissue structure. Although pigmental and structural coloration are separate mechanisms and can occur independently, some coloured displays might emerge from a combination of both. Here, we demonstrate, using biochemical, optical and morphological methodologies, that the yellow coloration of the skin located around the eye of Common (Indian) Mynas (Acridotheres tristis) is produced by both light-reflecting nanostructures and light-absorbing carotenoid pigments. Our analysis confirms that nanostructured collagen in the avian dermis work in combination with carotenoid pigments to produce vivid integumentary colours. Identifying the mechanisms behind the production of a coloured signal provides a basis for predicting how a signal¿s function might be influenced by environmental factors such as fledgling nutrition.
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Nova |
2020 |
Chellappan DK, Yee LW, Xuan KY, Kunalan K, Rou LC, Jean LS, et al., 'Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases', Drug Development Research, 81 419-436 (2020) [C1]
Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chron... [more]
Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.
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Nova |
2020 |
Lee JM, Mayall JR, Chevalier A, McCarthy H, Van Helden D, Hansbro PM, et al., 'Chlamydia muridarum infection differentially alters smooth muscle function in mouse uterine horn and cervix', American Journal of Physiology - Endocrinology and Metabolism, 318 E981-E994 (2020) [C1]
Lee JM, Mayall JR, Chevalier A, McCarthy H, Van Helden D, Hansbro PM, Horvat JC, Jobling P. Chlamydia muridarum infection differentially alters smooth muscle function in mouse ute... [more]
Lee JM, Mayall JR, Chevalier A, McCarthy H, Van Helden D, Hansbro PM, Horvat JC, Jobling P. Chlamydia muridarum infection differentially alters smooth muscle function in mouse uterine horn and cervix. Am J Physiol Endocrinol Metab 318: E981 E994, 2020. First published April 21, 2020; doi:10.1152/ajpendo.00513. 2019. Chlamydia trachomatis infection is a primary cause of reproductive tract diseases including infertility. Previous studies showed that this infection alters physiological activities in mouse oviducts. Whether this occurs in the uterus and cervix has never been investigated. This study characterized the physiological activities of the uterine horn and the cervix in a Chlamydia muridarum (Cmu)-infected mouse model at three infection time points of 7, 14, and 21 days postinfection (dpi). Cmu infection significantly decreased contractile force of spontaneous contraction in the cervix (7 and 14 dpi; P < 0.001 and P < 0.05, respectively), but this effect was not observed in the uterine horn. The responses of the uterine horn and cervix to oxytocin were significantly altered by Cmu infection at 7 dpi (P < 0.0001), but such responses were attenuated at 14 and 21 dpi. Cmu infection increased contractile force to prostaglandin (PGF2_) by 53 83% in the uterine horn. This corresponded with the increased messenger ribonucleic acid (mRNA) expression of Ptgfr that encodes for its receptor. However, Cmu infection did not affect contractions of the uterine horn and cervix to PGE2 and histamine. The mRNA expression of Otr and Ptger4 was inversely correlated with the mRNA expression of Il1b, Il6 in the uterine horn of Cmu-inoculated mice (P < 0.01 to P < 0.001), suggesting that the changes in the Otr and Ptger4 mRNA expression might be linked to the changes in inflammatory cytokines. Lastly, this study also showed a novel physiological finding of the differential response to PGE2 in mouse uterine horn and cervix.
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Nova |
2020 |
Yong DOC, Saker SR, Chellappan DK, Madheswaran T, Panneerselvam J, Choudhury H, et al., 'Molecular and immunological mechanisms underlying the various pharmacological properties of the potent bioflavonoid, rutin', Endocrine, Metabolic and Immune Disorders - Drug Targets, 20 1590-1596 (2020) [C1]
The application of medicinal plants has captured the interest of researchers in recent times due to their potent therapeutic properties and a better safety profile. The prominent ... [more]
The application of medicinal plants has captured the interest of researchers in recent times due to their potent therapeutic properties and a better safety profile. The prominent role of herbal products in treating and preventing multiple diseases dates back to ancient history and most of the modern drugs today originated from their significant sources owing to their ability to control multiple targets via different signalling pathways. Among them, flavonoids consist of a large group of polyphenols, which are well known for their various therapeutic benefits. Rutin is considered one of the attractive phytochemicals and important flavonoids in the pharmaceutical industry due to its diverse pharmacological activities via various underlying molecular mechanisms. It is usually prescribed for various disease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, we have discussed and highlighted the different molecular mechanisms attributed to the various pharmacological activities of rutin, such as antioxidant, anti-inflammatory, anticancer, anti-allergic and anti-diabetic. This review will be beneficial to herbal, biological and molecular scientists in understanding the pharmacological relevance of rutin at the molecular level.
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Nova |
2020 |
Zhang R, Wang P, Yu S, Hansbro P, Wang H, 'Computerized screening of G-protein coupled receptors to identify and characterize olfactory receptors', Journal of Toxicology and Environmental Health - Part A: Current Issues, 83 9-19 (2020) [C1]
Olfactory receptors (ORs) are a group of G protein coupled receptors (GPCRs) that initiate chemical odorant signals. Although ORs are predominantly located in nasal epithelia to d... [more]
Olfactory receptors (ORs) are a group of G protein coupled receptors (GPCRs) that initiate chemical odorant signals. Although ORs are predominantly located in nasal epithelia to detect smell, these receptors are also present in peripherally in non-nasal organs/tissues. Since the quality of life and cognitive and sensorial features of sense of smell are worsened in multiple chemical sensitivity due to the interaction of ORs with offending compounds, it is important to not only differentiate these receptors from other GPCRs but also characterize these organelles to understand the underlying mechanisms of smelling disorders. The aim of this study was develop computerized programs to differentiate ORs from GPCRs. The computer program was developed on the basis of widely accepted basic algorithms. It is noteworthy that an accuracy of 95.5% was attained, a level not achieved using other established techniques for screening of ORs from GPCRs. The high accuracy rate indicates that this method of differential identification appears reliable. Our findings indicate that this novel method may be considered as a tool for identification and characterization of receptors which might aid in therapeutic approaches to human chemical-mediated sensitization.
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Nova |
2020 |
Xu J, Xu X, Jiang L, Dua K, Hansbro PM, Liu G, 'SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis', RESPIRATORY RESEARCH, 21 (2020)
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2020 |
Kc R, Hyland IK, Smith JA, Shukla SD, Hansbro PM, Zosky GR, et al., 'Cow Dung Biomass Smoke Exposure Increases Adherence of Respiratory Pathogen Nontypeable Haemophilus influenzae to Human Bronchial Epithelial Cells', Exposure and Health, 12 883-895 (2020) [C1]
Biomass smoke exposure is associated with a heightened risk of development of respiratory diseases that include chronic obstructive pulmonary disease (COPD). The aim of this study... [more]
Biomass smoke exposure is associated with a heightened risk of development of respiratory diseases that include chronic obstructive pulmonary disease (COPD). The aim of this study was to increase our understanding of how biomass smoke could contribute to an increased susceptibility to respiratory infection. We investigated the effects of cow dung and wood smoke exposure on human bronchial epithelial cells with respect to adherence of a major respiratory bacterial pathogen in COPD, nontypeable Haemophilus influenzae (NTHi), using immunofluorescence microscopy. In addition, expression of a known receptor of NTHi, platelet-activating factor receptor (PAFR), and two pro-inflammatory cytokines, interleukin 6 (IL-6) and interleukin-8 (IL-8), were determined using quantitative polymerase chain reaction. We observed a dose-dependent increase in NTHi adhesion to human bronchial epithelial cells following exposure to cow dung but not wood smoke extracts. Pre-treatment with PAFR antagonists, WEB-2086 and its analogue, C17, decreased adherence by NTHi to airway epithelial cells exposed to cow dung smoke. Both cow dung and wood smoke-induced expression of PAFR, as well as of IL-6 and IL-8, which was inhibited by WEB-2086 and C17. In conclusion, biomass smoke from combustion of cow dung and wood-induced expression of PAFR and airway inflammatory markers in human bronchial epithelial cells. Cow dung exposure, but not wood smoke exposure, mediated a measurable increase in NTHi adhesion to airway epithelial cells that was inhibited by PAFR antagonists. This work highlights the potential of PAFR as a therapeutic target for reducing the impact of hazardous biomass smoke exposure on respiratory health.
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Nova |
2020 |
Solanki N, Mehta M, Chellappan DK, Gupta G, Hansbro NG, Tambuwala MM, et al., 'Antiproliferative effects of boswellic acids-loaded chitosan nanoparticles on human lung cancer cell line A549.', Future medicinal chemistry, 12 2019-2034 (2020) [C1]
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Nova |
2020 |
Malyla V, Paudel KR, Shukla SD, Donovan C, Wadhwa R, Pickles S, et al., 'Recent advances in experimental animal models of lung cancer', FUTURE MEDICINAL CHEMISTRY, 12 567-570 (2020)
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2020 |
Khatak S, Mehta M, Awasthi R, Paudel KR, Singh SK, Gulati M, et al., 'Solid lipid nanoparticles containing anti-tubercular drugs attenuate the Mycobacterium marinum infection', Tuberculosis, 125 1-10 (2020) [C1]
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Nova |
2020 |
Dharwal V, Paudel KR, Hansbro PM, 'Impact of bushfire smoke on respiratory health', MEDICAL JOURNAL OF AUSTRALIA, 213 (2020)
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2020 |
Chan Y, Ng SW, Chellappan DK, Madheswaran T, Zeeshan F, Kumar P, et al., 'Celastrol-loaded liquid crystalline nanoparticles as an anti-inflammatory intervention for the treatment of asthma', INTERNATIONAL JOURNAL OF POLYMERIC MATERIALS AND POLYMERIC BIOMATERIALS, 70 754-763 (2020) [C1]
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Nova |
2020 |
Galvao I, Kim RY, Shen S, Budden KF, Vieira AT, Hansbro PM, 'Emerging therapeutic targets and preclinical models for severe asthma', EXPERT OPINION ON THERAPEUTIC TARGETS, 24 845-857 (2020) [C1]
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Nova |
2020 |
Ali MK, Kim RY, Brown AC, Donovan C, Vanka KS, Mayall JR, et al., 'Critical role for iron accumulation in the pathogenesis of fibrotic lung disease', JOURNAL OF PATHOLOGY, 251 49-62 (2020) [C1]
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Nova |
2020 |
Ali MK, Kim RY, Brown AC, Mayall JR, Karim R, Pinkerton JW, et al., 'Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma', EUROPEAN RESPIRATORY JOURNAL, 55 (2020) [C1]
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Nova |
2020 |
Bowerman KL, Rehman SF, Vaughan A, Lachner N, Budden KF, Kim RY, et al., 'Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease', NATURE COMMUNICATIONS, 11 (2020) [C1]
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Nova |
2020 |
Ng PQ, Ling LSC, Chellian J, Madheswaran T, Panneersel-Vam J, Kunnath AP, et al., 'Applications of nanocarriers as drug delivery vehicles for active phytoconstituents', Current Pharmaceutical Design, 26 4580-4590 (2020) [C1]
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2020 |
Li J, Xu X, Jiang Y, Hansbro NG, Hansbro PM, Xu J, Liu G, 'Elastin is a key factor of tumor development in colorectal cancer', BMC CANCER, 20 (2020) [C1]
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Nova |
2020 |
Wadhwa R, Paudel KR, Mehta M, Shukla SD, Sunkara K, Prasher P, et al., 'Beyond the obvious: Smoking and respiratory infection implications on alzheimer's disease', CNS and Neurological Disorders - Drug Targets, 19 698-708 (2020) [C1]
Tobacco smoke is not only a leading cause for chronic obstructive pulmonary disease, cardiovascular disorders, and lung and oral cancers, but also causes neurological disorders su... [more]
Tobacco smoke is not only a leading cause for chronic obstructive pulmonary disease, cardiovascular disorders, and lung and oral cancers, but also causes neurological disorders such as Alzheimer ¿s disease. Tobacco smoke consists of more than 4500 toxic chemicals, which form free radicals and can cross blood-brain barrier resulting in oxidative stress, an extracellular amyloid plaque from the aggregation of amyloid ß (Aß) peptide deposition in the brain. Further, respiratory infections such as Chlamydia pneumoniae, respiratory syncytial virus have also been involved in the induction and development of the disease. The necessary information collated on this review has been gathered from various literature published from 1995 to 2019. The review article sheds light on the role of smoking and respiratory infections in causing oxidative stress and neuroinflammation, resulting in Alzheimer's disease (AD). This review will be of interest to scientists and researchers from biological and medical science disciplines, including microbiology, pharmaceutical sciences and the translational researchers, etc. The increasing understanding of the relationship between chronic lung disease and neurological disease is two-fold. First, this would help to identify the risk factors and possible therapeutic interventions to reduce the development and progression of both diseases. Second, this would help to reduce the probable risk of development of AD in the population prone to chronic lung diseases.
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Nova |
2020 |
Vidaillac C, Yong VFL, Aschtgen M-S, Qu J, Yang S, Xu G, et al., 'Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa (vol 11, e01774-20, 2020)', MBIO, 11 (2020)
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2020 |
Pinkerton JW, Kim RY, Koeninger L, Armbruster NS, Hansbro NG, Brown AC, et al., 'Human beta-defensin-2 suppresses key features of asthma in murine models of allergic airways disease', CLINICAL AND EXPERIMENTAL ALLERGY, 51 120-131 (2020) [C1]
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Nova |
2020 |
Johansen MD, Irving A, Montagutelli X, Tate MD, Rudloff I, Nold MF, et al., 'Animal and translational models of SARS-CoV-2 infection and COVID-19', Mucosal Immunology, 13 877-891 (2020) [C1]
COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The m... [more]
COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The major features of disease are described but clinical trials have been hampered by competing interests, small scale, lack of defined patient cohorts and defined readouts. What is needed now is head-to-head comparison of existing drugs, testing of safety including in the background of predisposing chronic diseases, and the development of new and targeted preventions and treatments. This is most efficiently achieved using representative animal models of primary infection including in the background of chronic disease with validation of findings in primary human cells and tissues. We explore and discuss the diverse animal, cell and tissue models that are being used and developed and collectively recapitulate many critical aspects of disease manifestation in humans to develop and test new preventions and treatments.
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Nova |
2020 |
Tew XN, Lau NJX, Chellappan DK, Madheswaran T, Zeeshan F, Tambuwala MM, et al., 'Immunological axis of berberine in managing inflammation underlying chronic respiratory inflammatory diseases', CHEMICO-BIOLOGICAL INTERACTIONS, 317 (2020) [C1]
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Nova |
2020 |
Prasher P, Sharma M, Mehta M, Paudel KR, Satija S, Chellappan DK, et al., 'Plants derived therapeutic strategies targeting chronic respiratory diseases: Chemical and immunological perspective', Chemico-Biological Interactions, 325 (2020) [C1]
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Nova |
2020 |
Chin LH, Hon CM, Chellappan DK, Chellian J, Madheswaran T, Zeeshan F, et al., 'Molecular mechanisms of action of naringenin in chronic airway diseases', European Journal of Pharmacology, 879 (2020) [C1]
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Nova |
2020 |
Donovan C, Liu G, Shen S, Marshall JE, Kim RY, Alemao CA, et al., 'The role of the microbiome and the NLRP3 inflammasome in the gut and lung', Journal of Leukocyte Biology, 108 925-935 (2020) [C1]
The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized infla... [more]
The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized inflammasomes, activated by pathogen-associated molecular patterns and damage-associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut¿lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut¿lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.
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Nova |
2020 |
Paudel KR, Wadhwa R, Mehta M, Chellappan DK, Hansbro PM, Dua K, 'Rutin loaded liquid crystalline nanoparticles inhibit lipopolysaccharide induced oxidative stress and apoptosis in bronchial epithelial cells in vitro', Toxicology in Vitro, 68 (2020) [C1]
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Nova |
2020 |
Donovan C, Hansbro PM, 'IL-33 in Chronic Respiratory Disease: From Preclinical to Clinical Studies', ACS Pharmacology and Translational Science, 3 56-62 (2020) [C1]
IL-33 has been deorphanized as a member of the IL-1 family and has key roles as an alarmin and cytokine with potent capacity to drive type 2 inflammation. This has led to a pletho... [more]
IL-33 has been deorphanized as a member of the IL-1 family and has key roles as an alarmin and cytokine with potent capacity to drive type 2 inflammation. This has led to a plethora of studies surrounding its role in chronic diseases with a type 2 inflammatory component. Here, we review the roles of IL-33 in two chronic respiratory diseases, asthma and chronic obstructive pulmonary disease (COPD). We discuss the hallmark and paradigm-shifting studies that have contributed to our understanding of IL-33 biology. We cover animal studies that have elucidated the mechanisms of IL-33 and assessed the role of anti-IL-33 treatment and immunization against IL-33. We highlight key clinical evidence for the potential of targeting increased IL-33 in respiratory diseases including exacerbations, and we outline current clinical trials using an anti-IL-33 monoclonal antibody in asthma patients. Finally, we discuss some of the challenges that have arisen in IL-33 biology and highlight potential future directions in targeting this cytokine in chronic respiratory diseases.
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Nova |
2020 |
Mehta M, Dhanjal DS, Paudel KR, Singh B, Gupta G, Rajeshkumar S, et al., 'Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update', INFLAMMOPHARMACOLOGY, 28 795-817 (2020) [C1]
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Nova |
2020 |
Hansbro NG, Pacitti D, Brown A, Torregrossa R, Balachandran L, Kumar V, et al., 'Mitochondria-targeted Sulfide Delivery Molecules New and Novel Players that can Suppress and Reverse Cigarette Smoke-induced Inflammasome Activity', The Journal of Immunology, 204 68.9-68.9 (2020)
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2020 |
Idowu O, Tran TKA, Webster G, Chapman I, Baker P, Farrel H, et al., 'Quantitative biomonitoring of polycyclic aromatic compounds (PACs) using the Sydney rock oyster (Saccostrea glomerata)', Science of the Total Environment, 742 (2020) [C1]
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Nova |
2020 |
Hadjigol S, Netto KG, Maltby S, Tay HL, Nguyen TH, Hansbro NG, et al., 'Lipopolysaccharide induces steroid-resistant exacerbations in a mouse model of allergic airway disease collectively through IL-13 and pulmonary macrophage activation', Clinical and Experimental Allergy, 50 82-94 (2020) [C1]
Background: Acute exacerbations of asthma represent a major burden of disease and are often caused by respiratory infections. Viral infections are recognized as significant trigge... [more]
Background: Acute exacerbations of asthma represent a major burden of disease and are often caused by respiratory infections. Viral infections are recognized as significant triggers of exacerbations; however, less is understood about the how microbial bioproducts such as the endotoxin (lipopolysaccharide (LPS)) trigger episodes. Indeed, increased levels of LPS have been linked to asthma onset, severity and steroid resistance. Objective: The goal of this study was to identify mechanisms underlying bacterial-induced exacerbations by employing LPS as a surrogate for infection. Methods: We developed a mouse model of LPS-induced exacerbation on the background of pre-existing type-2 allergic airway disease (AAD). Results: LPS-induced exacerbation was characterized by steroid-resistant airway hyperresponsiveness (AHR) and an exaggerated inflammatory response distinguished by increased numbers of infiltrating neutrophils/macrophages and elevated production of lung inflammatory cytokines, including TNFa, IFN¿, IL-27 and MCP-1. Expression of the type-2 associated inflammatory factors such as IL-5 and IL-13 were elevated in AAD but not altered by LPS exposure. Furthermore, AHR and airway inflammation were no longer suppressed by corticosteroid (dexamethasone) treatment after LPS exposure. Depletion of pulmonary macrophages by administration of 2-chloroadenosine into the lungs suppressed AHR and reduced IL-13, TNFa and IFN¿ expression. Blocking IL-13 function, through either IL-13-deficiency or administration of specific blocking antibodies, also suppressed AHR and airway inflammation. Conclusions & Clinical Relevance: We present evidence that IL-13 and innate immune pathways (in particular pulmonary macrophages) contribute to LPS-induced exacerbation of pre-existing AAD and provide insight into the complex molecular processes potentially underlying microbial-induced exacerbations.
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Nova |
2019 |
Keenan CR, Iannarella N, Garnham AL, Brown AC, Kim RY, Horvat JC, et al., 'Polycomb repressive complex 2 is a critics mediator of allergic inflammation', JCI INSIGHT, 4 (2019) [C1]
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Nova |
2019 |
Ramsahai JM, Hansbro PM, Wark PAB, 'Mechanisms and management of asthma exacerbations', American Journal of Respiratory and Critical Care Medicine, 199 423-432 (2019) [C1]
Acute asthma remains an important medical emergency, the most frequent cause of acute admissions in children and a major source of morbidity for adults with asthma. In all ages wi... [more]
Acute asthma remains an important medical emergency, the most frequent cause of acute admissions in children and a major source of morbidity for adults with asthma. In all ages with asthma, the presence of exacerbations is an important defining characteristic of asthma severity. In this review, we assess the epidemiology of acute asthma, the triggers of acute exacerbations, and the mechanisms that underlie these exacerbations. We also assess current treatments that prevent exacerbations, with an emphasis on the role of type 2 airway inflammation in the context of acute exacerbations and the novel treatments that effectively target this. Finally we review current mana ement strate ies of the exacerbations themselves
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Nova |
2019 |
Dua K, Wadhwa R, Singhvi G, Rapalli V, Shukla SD, Shastri MD, et al., 'The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress', Drug Development Research, 80 714-730 (2019) [C1]
Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-... [more]
Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.
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Nova |
2019 |
Hayman TJ, Hsu AC, Kolesnik TB, Dagley LF, Willemsen J, Tate MD, et al., 'RIPLET, and not TRIM25, is required for endogenous RIG-I-dependent antiviral responses', Immunology and Cell Biology, 97 840-852 (2019) [C1]
The innate immune system is our first line of defense against viral pathogens. Host cell pattern recognition receptors sense viral components and initiate immune signaling cascade... [more]
The innate immune system is our first line of defense against viral pathogens. Host cell pattern recognition receptors sense viral components and initiate immune signaling cascades that result in the production of an array of cytokines to combat infection. Retinoic acid¿inducible gene-I (RIG-I) is a pattern recognition receptor that recognizes viral RNA and, when activated, results in the production of type I and III interferons (IFNs) and the upregulation of IFN-stimulated genes. Ubiquitination of RIG-I by the E3 ligases tripartite motif-containing 25 (TRIM25) and Riplet is thought to be requisite for RIG-I activation; however, recent studies have questioned the relative importance of these two enzymes for RIG-I signaling. In this study, we show that deletion of Trim25 does not affect the IFN response to either influenza A virus (IAV), influenza B virus, Sendai virus or several RIG-I agonists. This is in contrast to deletion of either Rig-i or Riplet, which completely abrogated RIG-I-dependent IFN responses. This was consistent in both mouse and human cell lines, as well as in normal human bronchial cells. With most of the current TRIM25 literature based on exogenous expression, these findings provide critical evidence that Riplet, and not TRIM25, is required endogenously for the ubiquitination of RIG-I. Despite this, loss of TRIM25 results in greater susceptibility to IAV infection in¿vivo, suggesting that it may have an alternative role in host antiviral defense. This study refines our understanding of RIG-I signaling in viral infections and will inform future studies in the field.
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Nova |
2019 |
Rutting S, Xenaki D, Malouf M, Horvat JC, Wood LG, Hansbro PM, Oliver BG, 'Short-chain fatty acids increase tnfa-induced inflammation in primary human lung mesenchymal cells through the activation of p38 mapk', American Journal of Physiology - Lung Cellular and Molecular Physiology, 316 L157-L174 (2019) [C1]
Short-chain fatty acids (SCFAs), produced as by-products of dietary fiber metabolism by gut bacteria, have anti-inflammatory properties and could potentially be used for the treat... [more]
Short-chain fatty acids (SCFAs), produced as by-products of dietary fiber metabolism by gut bacteria, have anti-inflammatory properties and could potentially be used for the treatment of inflammatory diseases, including asthma. The direct effects of SCFAs on inflammatory responses in primary human lung mesenchymal cells have not been assessed. We investigated whether SCFAs can protect against tumor necrosis factor (TNF) a-induced inflammation in primary human lung fibroblasts (HLFs) and airway smooth muscle (ASM) cells in vitro. HLFs and ASM cells were exposed to SCFAs, acetate (C2:0), propionate (C3:0), and butyrate (C4:0) (0.01¿25 mM) with or without TNFa, and the release of proinflammatory cytokines, IL-6, and CXCL8 was measured using ELISA. We found that none of the SCFAs suppressed TNFa-induced cytokine release. On the contrary, challenge with supraphysiological concentrations (10 ¿25 mM), as might be used therapeutically, of propionate or butyrate in combination with TNFa resulted in substantially greater IL-6 and CXCL8 release from HLFs and ASM cells than challenge with TNFa alone, demonstrating synergistic effects. In ASM cells, challenge with acetate also enhanced TNFa-induced IL-6, but not CXCL8 release. Synergistic upregulation of IL-6 and CXCL8 was mediated through the activation of free fatty acid receptor (FFAR)3, but not FFAR2. The signaling pathways involved were further examined using specific inhibitors and immunoblotting, and responses were found to be mediated through p38 MAPK signaling. This study demonstrates that proinflammatory, rather than anti-inflammatory effects of SCFAs are evident in lung mesenchymal cells.
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Nova |
2019 |
Eapen MS, Sharma P, Gaikwad AV, Lu W, Myers S, Hansbro PM, Sohal SS, 'Epithelial mesenchymal transition is driven by transcriptional and post transcriptional modulations in copd: Implications for disease progression and new therapeutics', International Journal of COPD, 14 1603-1610 (2019) [C1]
COPD is a common and highly destructive disease with huge impacts on people and health services throughout the world. It is mainly caused by cigarette smoking though environmental... [more]
COPD is a common and highly destructive disease with huge impacts on people and health services throughout the world. It is mainly caused by cigarette smoking though environmental pollution is also significant. There are no current treatments that affect the overall course of COPD; current drugs focus on symptomatic relief and to some extent reducing exacerbation rates. There is an urgent need for in-depth studies of the fundamental pathogenic mechanisms that underpin COPD. This is vital, given the fact that nearly 40%¿ 60% of the small airway and alveolar damage occurs in COPD well before the first measurable changes in lung function are detected. These individuals are also at a high risk of lung cancer. Current COPD research is mostly centered around late disease and/or innate immune activation within the airway lumen, but the actual damage to the airway wall has early onset. COPD is the end result of complex mechanisms, possibly triggered through initial epithelial activation. To change the disease trajectory, it is crucial to understand the mechanisms in the epithelium that are switched on early in smokers. One such mechanism we believe is the process of epithelial to mesenchymal transition. This article highlights the importance of this profound epithelial cell plasticity in COPD and also its regulation. We consider that understanding early changes in COPD will open new windows for therapy.
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Nova |
2019 |
Wadhwa R, Dua K, Adcock IM, Horvat JC, Kim RY, Hansbro PM, 'Cellular mechanisms underlying steroid-resistant asthma (vol 28, 190021, 2019)', EUROPEAN RESPIRATORY REVIEW, 28 (2019)
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2019 |
Donovan C, Starkey MR, Kim RY, Rana BMJ, Barlow JL, Jones B, et al., 'Roles for T/B lymphocytes and ILC2s in experimental chronic obstructive pulmonary disease', Journal of Leukocyte Biology, 105 143-150 (2019) [C1]
Pulmonary inflammation in chronic obstructive pulmonary disease (COPD) is characterized by both innate and adaptive immune responses; however, their specific roles in the pathogen... [more]
Pulmonary inflammation in chronic obstructive pulmonary disease (COPD) is characterized by both innate and adaptive immune responses; however, their specific roles in the pathogenesis of COPD are unclear. Therefore, we investigated the roles of T and B lymphocytes and group 2 innate lymphoid cells (ILC2s) in airway inflammation and remodelling, and lung function in an experimental model of COPD using mice that specifically lack these cells (Rag1 -/- and Rora fl/fl Il7r Cre [ILC2-deficient] mice). Wild-type (WT) C57BL/6 mice, Rag1 -/- , and Rora fl/fl Il7r Cre mice were exposed to cigarette smoke (CS; 12 cigarettes twice a day, 5 days a week) for up to 12¿weeks, and airway inflammation, airway remodelling (collagen deposition and alveolar enlargement), and lung function were assessed. WT, Rag1 -/- , and ILC2-deficient mice exposed to CS had similar levels of airway inflammation and impaired lung function. CS exposure increased small airway collagen deposition in WT mice. Rag1 -/- normal air- and CS-exposed mice had significantly increased collagen deposition compared to similarly exposed WT mice, which was associated with increases in IL-33, IL-13, and ILC2 numbers. CS-exposed Rora fl/fl Il7r Cre mice were protected from emphysema, but had increased IL-33/IL-13 expression and collagen deposition compared to WT CS-exposed mice. T/B lymphocytes and ILC2s play roles in airway collagen deposition/fibrosis, but not inflammation, in experimental COPD.
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Nova |
2019 |
Dua K, Malyla V, Singhvi G, Wadhwa R, Krishna RV, Shukla SD, et al., 'Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems', Chemico-Biological Interactions, 299 168-178 (2019) [C1]
Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), inf... [more]
Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic.
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Nova |
2019 |
Wadhwa R, Aggarwal T, Malyla V, Kumar N, Gupta G, Chellappan DK, et al., 'Identification of biomarkers and genetic approaches toward chronic obstructive pulmonary disease.', Journal of cellular physiology, 234 16703-16723 (2019) [C1]
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Nova |
2019 |
Liu L, Zhang X, Liu Y, Zhang L, Zheng J, Wang J, et al., 'Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations', Respiratory Research, 20 1-12 (2019) [C1]
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Nova |
2019 |
Caramori G, Ruggeri P, Mumby S, Ieni A, Lo Bello F, Chaminka V, et al., 'Molecular links between COPD and lung cancer: new targets for drug discovery?', Expert Opinion on Therapeutic Targets, 23 539-553 (2019) [C1]
Introduction: COPD and lung cancer are leading causes of morbidity and mortality worldwide, and they share a common environmental risk factor in cigarette smoke exposure and a gen... [more]
Introduction: COPD and lung cancer are leading causes of morbidity and mortality worldwide, and they share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by their incidence in only a fraction of smokers. This reflects the ability of cigarette smoke to induce an inflammatory response in the airways of susceptible smokers. Moreover, COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage and repression of the DNA repair mechanisms, chronic exposure to pro-inflammatory cytokines, repression of innate immunity and increased cellular proliferation. Areas covered: We have focused our review on the potential pathogenic molecular links between tobacco smoking-related COPD and lung cancer and the potential molecular targets for new drug development by understanding the common signaling pathways involved in COPD and lung cancer. Expert commentary: Research in this field is mostly limited to animal models or small clinical trials. Large clinical trials are needed but mostly combined models of COPD and lung cancer are necessary to investigate the processes caused by chronic inflammation, including genetic and epigenetic alteration, and the expression of inflammatory mediators that link COPD and lung cancer, to identify new molecular therapeutic targets.
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Nova |
2019 |
Rutting S, Zakarya R, Bozier J, Xenaki D, Horvat JC, Wood LG, et al., 'Dietary Fatty Acids Amplify Inflammatory Responses to Infection through p38 MAPK Signaling.', American journal of respiratory cell and molecular biology, 60 554-568 (2019) [C1]
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Nova |
2019 |
Eapen MS, Sharma P, Thompson IE, Lu W, Myers S, Hansbro PM, Sohal SS, 'Heparin-binding epidermal growth factor (HB-EGF) drives EMT in patients with COPD: implications for disease pathogenesis and novel therapies', Laboratory Investigation, 99 150-157 (2019) [C1]
Chronic obstructive pulmonary disease (COPD) is a progressive and devastating chronic lung condition that has a significant global burden, both medically and financially. Currentl... [more]
Chronic obstructive pulmonary disease (COPD) is a progressive and devastating chronic lung condition that has a significant global burden, both medically and financially. Currently there are no medications that can alter the course of disease. At best, the drugs in clinical practice provide symptomatic relief to suffering patients by alleviating acute exacerbations. Most of current clinical research activities are in late severe disease with lesser attention given to early disease manifestations. There is as yet, a lack of understanding of the underlying mechanisms of disease progression and the molecular switches that are involved in their manifestation. Small airway fibrosis and obliteration are known to cause fixed airflow obstruction in COPD, and the consequential damage to the lung has an early onset. So far, there is little evidence of the mechanisms that underlie this aspect of pathology. However, emerging research confirms that airway epithelial reprogramming or epithelial to mesenchymal transition (EMT) is a key mechanism that drives fibrotic remodelling changes in smokers and patients with COPD. A recent study by Lai et al. further highlights the importance of EMT in smoking-related COPD pathology. The authors identify HB-EGF, an EGFR ligand, as a key driver of EMT and a potential new therapeutic target for the amelioration of EMT and airway remodelling. There are also wider implications in lung cancer prophylaxis, which is another major comorbidity associated with COPD. We consider that improved molecular understanding of the intricate pathways associated with epithelial cell plasticity in smokers and patients with COPD will have major therapeutic implications.
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Nova |
2019 |
Hu MJ, Schulze KE, Ghildyal R, Henstridge DC, Kolanowski JL, New EJ, et al., 'Respiratory syncytial virus co-opts host mitochondrial function to favour infectious virus production', eLife, 8 1-30 (2019) [C1]
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Nova |
2019 |
Mehta M, Deeksha, Sharma N, Vyas M, Khurana N, Maurya PK, et al., 'Interactions with the macrophages: An emerging targeted approach using novel drug delivery systems in respiratory diseases', Chemico-Biological Interactions, 304 10-19 (2019) [C1]
Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages a... [more]
Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase.
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Nova |
2019 |
Nixon B, Johnston SD, Skerrett-Byrne DA, Anderson AL, Stanger SJ, Bromfield EG, et al., 'Modification of Crocodile Spermatozoa Refutes the Tenet That Post-testicular Sperm Maturation Is Restricted To Mammals', MOLECULAR & CELLULAR PROTEOMICS, 18 S59-S76 (2019) [C1]
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Nova |
2019 |
Donovan C, Hansbro PM, 'TRPA1: A potential target for cold-induced airway disease?', RESPIROLOGY, 24 193-194 (2019)
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2019 |
Hardy S, Mabotuwana NS, Murtha LA, Coulter B, Bezenilla SS, Al-Omary MS, et al., 'P6296The role of extracellular matrix protein 1 (ECM1) - a novel link between inflammation and cardiac fibrosis', European Heart Journal, 40 (2019)
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2019 |
CAMERON G, Loering S, Deshpande A, Jiang S, Molofsky A, McKenzie A, et al., 'SAT-129 GROUP 2 INNATE LYMPHOID CELLS ARE REDUNDANT IN EXPERIMENTAL RENAL ISCHEMIA-REPERFUSION INJURY', Kidney International Reports, 4 S59-S59 (2019)
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2019 |
Idowu O, Semple KT, Ramadass K, O'Connor W, Hansbro P, Thavamani P, 'Beyond the obvious: Environmental health implications of polar polycyclic aromatic hydrocarbons', ENVIRONMENT INTERNATIONAL, 123 543-557 (2019) [C1]
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Nova |
2019 |
Peel R, Ren S, Hure A, Evans TJ, D'Este CA, Abhayaratna WP, et al., 'Evaluating recruitment strategies for AUSPICE, a large Australian community-based randomised controlled trial', Medical Journal of Australia, 210 409-415 (2019) [C1]
Objectives: To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the... [more]
Objectives: To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE). Design, setting, participants: Men and women aged 55¿60 years with at least two cardiovascular risk factors (hypertension, hypercholesterolaemia, overweight/obesity) were recruited for a multicentre placebo-controlled RCT assessing the effectiveness of 23-valent pneumococcal polysaccharide vaccine (23vPPV) for preventing cardiovascular events. Methods: Invitations were mailed by the Australian Department of Human Services to people in the Medicare database aged 55¿60 years; reminders were sent 2 weeks later. Invitees could respond in hard copy or electronically. Direct recruitment was supplemented by asking invitees to extend the invitation to friends and family (snowball sampling) and by Facebook advertising. Main outcome: Proportions of invitees completing screening questionnaire and recruited for participation in the RCT. Results: 21¿526 of 154¿992 invited people (14%) responded by completing the screening questionnaire, of whom 4725 people were eligible and recruited for the study. Despite the minimal study burden (one questionnaire, one clinic visit), the overall participation rate was 3%, or an estimated 10% of eligible persons. Only 16% of eventual participants had responded within 2 weeks of the initial invitation letter (early responders); early and late responders did not differ in their demographic or medical characteristics. Socio-economic disadvantage did not markedly influence response rates. Facebook advertising and snowball sampling did not increase recruitment. Conclusions: Trial participation rates are low, and multiple concurrent methods are needed to maximise recruitment. Social media strategies may not be successful in older age groups. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12615000536561.
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2019 |
Wadhwa R, Pandey P, Gupta G, Aggarwal T, Kumar N, Mehta M, et al., 'Emerging Complexity and the Need for Advanced Drug Delivery in Targeting Candida Species', CURRENT TOPICS IN MEDICINAL CHEMISTRY, 19 2593-2609 (2019)
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2019 |
Shukla SD, Shastri MD, Chong WC, Dua K, Budden KF, Mahmood MQ, et al., 'Microbiome-focused asthma management strategies', Current Opinion in Pharmacology, 46 143-149 (2019) [C1]
Asthma is a common, heterogeneous and serious disease with high prevalence globally. Poorly controlled, steroid-resistant asthma is particularly important as there are no effectiv... [more]
Asthma is a common, heterogeneous and serious disease with high prevalence globally. Poorly controlled, steroid-resistant asthma is particularly important as there are no effective therapies and it exerts substantial healthcare and societal burden. The role of microbiomes, particularly in chronic diseases has generated considerable interest in recent times. Existing evidence clearly demonstrates an association between asthma initiation and the microbiome, both respiratory and gastro-intestinal, although its¿ roles are poorly understood when assessing the asthma progression or heterogeneity (i.e. phenotypes/endotypes) across different geographical locations. Moreover, modulating microbiomes could be preventive and/or therapeutic in patients with asthma warrants urgent attention. Here, we review recent advances in assessing the role of microbiomes in asthma and present the challenges associated with the potential therapeutic utility of modifying microbiomes in management.
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2019 |
Hardy SA, Mabotuwana NS, Murtha LA, Coulter B, Sanchez-Bezanilla S, Al-Omary MS, et al., 'Novel role of extracellular matrix protein 1 (ECM1) in cardiac aging and myocardial infarction', PLoS ONE, 14 (2019) [C1]
Introduction The prevalence of heart failure increases in the aging population and following myocardial infarction (MI), yet the extracellular matrix (ECM) remodeling underpinning... [more]
Introduction The prevalence of heart failure increases in the aging population and following myocardial infarction (MI), yet the extracellular matrix (ECM) remodeling underpinning the development of aging- and MI-associated cardiac fibrosis remains poorly understood. A link between inflammation and fibrosis in the heart has long been appreciated, but has mechanistically remained undefined. We investigated the expression of a novel protein, extracellular matrix protein 1 (ECM1) in the aging and infarcted heart. Methods Young adult (3-month old) and aging (18-month old) C57BL/6 mice were assessed. Young mice were subjected to left anterior descending artery-ligation to induce MI, or transverse aortic constriction (TAC) surgery to induce pressure-overload cardiomyopathy. Left ventricle (LV) tissue was collected early and late post-MI/TAC. Bone marrow cells (BMCs) were isolated from young healthy mice, and subject to flow cytometry. Human cardiac fibroblast (CFb), myocyte, and coronary artery endothelial & smooth muscle cell lines were cultured; human CFbs were treated with recombinant ECM1. Primary mouse CFbs were cultured and treated with recombinant angiotensin-II or TGF-ß1. Immunoblotting, qPCR and mRNA fluorescent in-situ hybridization (mRNA-FISH) were conducted on LV tissue and cells. Results ECM1 expression was upregulated in the aging LV, and in the infarct zone of the LV early post-MI. No significant differences in ECM1 expression were found late post-MI or at any time-point post-TAC. ECM1 was not expressed in any resident cardiac cells, but ECM1 was highly expressed in BMCs, with high ECM1 expression in granulocytes. Flow cytometry of bone marrow revealed ECM1 expression in large granular leucocytes. mRNA-FISH revealed that ECM1 was indeed expressed by inflammatory cells in the infarct zone at day-3 post-MI. ECM1 stimulation of CFbs induced ERK1/2 and AKT activation and collagen-I expression, suggesting a pro-fibrotic role. Conclusions ECM1 expression is increased in ageing and infarcted hearts but is not expressed by resident cardiac cells. Instead it is expressed by bone marrow-derived granulocytes. ECM1 is sufficient to induce cardiac fibroblast stimulation in vitro. Our findings suggest ECM1 is released from infiltrating inflammatory cells, which leads to cardiac fibroblast stimulation and fibrosis in aging and MI. ECM1 may be a novel intermediary between inflammation and fibrosis.
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2019 |
Wood LG, Li Q, Scott HA, Rutting S, Berthon BS, Gibson PG, et al., 'Saturated fatty acids, obesity, and the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in asthmatic patients', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 143 305-315 (2019) [C1]
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2019 |
Usman B, Sharma N, Satija S, Mehta M, Vyas M, Khatik GL, et al., 'Recent Developments in Alpha-Glucosidase Inhibitors for Management of Type-2 Diabetes: An Update', CURRENT PHARMACEUTICAL DESIGN, 25 2510-2525 (2019)
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2019 |
Vaughan A, Frazer ZA, Hansbro PM, Yang IA, 'COPD and the gut-lung axis: the therapeutic potential of fibre', JOURNAL OF THORACIC DISEASE, 11 S2173-S2180 (2019) [C1]
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2019 |
Collison AM, Li J, de Siqueira AP, Lv X, Toop HD, Morris JC, et al., 'TRAIL signals through the ubiquitin ligase MID1 to promote pulmonary fibrosis', BMC PULMONARY MEDICINE, 19 (2019) [C1]
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2019 |
Eapen MS, Sharma P, Moodley YP, Hansbro PM, Sohal SS, 'Dysfunctional Immunity and Microbial Adhesion Molecules in Smoking-induced Pneumonia', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 199 250-251 (2019)
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2019 |
Budden KF, Shukla SD, Rehman SF, Bowerman KL, Keely S, Hugenholtz P, et al., 'Functional effects of the microbiota in chronic respiratory disease', The Lancet Respiratory Medicine, 7 907-920 (2019) [C1]
The composition of the lung microbiome is increasingly well characterised, with changes in microbial diversity or abundance observed in association with several chronic respirator... [more]
The composition of the lung microbiome is increasingly well characterised, with changes in microbial diversity or abundance observed in association with several chronic respiratory diseases such as asthma, cystic fibrosis, bronchiectasis, and chronic obstructive pulmonary disease. However, the precise effects of the microbiome on pulmonary health and the functional mechanisms by which it regulates host immunity are only now beginning to be elucidated. Bacteria, viruses, and fungi from both the upper and lower respiratory tract produce structural ligands and metabolites that interact with the host and alter the development and progression of chronic respiratory diseases. Here, we review recent advances in our understanding of the composition of the lung microbiome, including the virome and mycobiome, the mechanisms by which these microbes interact with host immunity, and their functional effects on the pathogenesis, exacerbations, and comorbidities of chronic respiratory diseases. We also describe the present understanding of how respiratory microbiota can influence the efficacy of common therapies for chronic respiratory disease, and the potential of manipulation of the microbiome as a therapeutic strategy. Finally, we highlight some of the limitations in the field and propose how these could be addressed in future research.
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2019 |
Findlay AD, Foot JS, Buson A, Deodhar M, Jarnicki AG, Hansbro PM, et al., 'Identification and Optimization of Mechanism-Based Fluoroallylamine Inhibitors of Lysyl Oxidase-like 2/3', Journal of Medicinal Chemistry, 62 9874-9889 (2019) [C1]
Lysyl oxidase-like 2 (LOXL2) is a secreted enzyme that catalyzes the formation of cross-links in extracellular matrix proteins, namely, collagen and elastin, and is indicated in f... [more]
Lysyl oxidase-like 2 (LOXL2) is a secreted enzyme that catalyzes the formation of cross-links in extracellular matrix proteins, namely, collagen and elastin, and is indicated in fibrotic diseases. Herein, we report the identification and subsequent optimization of a series of indole-based fluoroallylamine inhibitors of LOXL2. The result of this medicinal chemistry campaign is PXS-5120A (12k), a potent, irreversible inhibitor that is >300-fold selective for LOXL2 over LOX. PXS-5120A also shows potent inhibition of LOXL3, an emerging therapeutic target for lung fibrosis. Key to the development of this compound was the utilization of a compound oxidation assay. PXS-5120A was optimized to show negligible substrate activity in vitro for related amine oxidase family members, leading to metabolic stability. PXS-5120A, in a pro-drug form (PXS-5129A, 12o), displayed anti-fibrotic activity in models of liver and lung fibrosis, thus confirming LOXL2 as an important target in diseases where collagen cross-linking is implicated.
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2019 |
Wadhwa R, Dua K, Adcock IM, Horvat JC, Kim RY, Hansbro PM, 'Cellular mechanisms underlying steroid-resistant asthma.', European respiratory review : an official journal of the European Respiratory Society, 28 (2019) [C1]
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Nova |
2019 |
Yong DOC, Saker SR, Wadhwa R, Chellappan DK, Madheswaran T, Panneerselvam J, et al., 'Preparation, characterization and in-vitro efficacy of quercetin loaded liquid crystalline nanoparticles for the treatment of asthma', JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 54 (2019) [C1]
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2019 |
Xin GLL, Khee YP, Ying TY, Chellian J, Gupta G, Kunnath AP, et al., 'Current Status on Immunological Therapies for Type 1 Diabetes Mellitus', CURRENT DIABETES REPORTS, 19 (2019) [C1]
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2019 |
Liu G, Cooley MA, Jarnicki AG, Borghuis T, Nair PM, Tjin G, et al., 'Fibulin-1c regulates transforming growth factor-beta activation in pulmonary tissue fibrosis', JCI INSIGHT, 4 (2019) [C1]
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2019 |
Nair PM, Starkey MR, Haw TJ, Liu G, Collison AM, Mattes J, et al., 'Enhancing tristetraprolin activity reduces the severity of cigarette smoke-induced experimental chronic obstructive pulmonary disease', CLINICAL & TRANSLATIONAL IMMUNOLOGY, 8 (2019) [C1]
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2019 |
Dua K, Gupta G, Chellappan DK, Shukla S, Hansbro PM, 'Targeting bacterial biofilms in pulmonary diseases in pediatric population', MINERVA PEDIATRICA, 71 309-310 (2019)
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2019 |
Atto B, Eapen MS, Sharma P, Frey U, Ammit AJ, Markos J, et al., 'New therapeutic targets for the prevention of infectious acute exacerbations of COPD: Role of epithelial adhesion molecules and inflammatory pathways', Clinical Science, 133 1663-1703 (2019) [C1]
Chronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approxima... [more]
Chronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD) drive clinical and functional decline in COPD and are associated with accelerated loss of lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and consequently constitute a significant comorbidity in COPD. However, current pharmacological interventions are ineffective in preventing infectious exacerbations and their treatment is compromised by the rapid development of antibiotic resistance. Thus, alternative preventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infection of surrounding structures. Thus, disruption of bacterial-host cell interactions with receptor antagonists or modulation of the ensuing inflammatory profile present attractive avenues for therapeutic development. This review explores key mediators of pathogen-host interactions that may offer new therapeutic targets with the potential to prevent viral/bacterial-mediated AECOPD. There are several conceptual and methodological hurdles hampering the development of new therapies that require further research and resolution.
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2019 |
Ng SW, Chan Y, Chellappan DK, Madheswaran T, Zeeshan F, Chan YL, et al., 'Molecular modulators of celastrol as the keystones for its diverse pharmacological activities', Biomedicine and Pharmacotherapy, 109 1785-1792 (2019) [C1]
In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their ... [more]
In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.
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2019 |
Waters DW, Blokland KEC, Pathinayake PS, Wei L, Schuliga M, Jaffar J, et al., 'STAT3 Regulates the Onset of Oxidant-induced Senescence in Lung Fibroblasts.', Am J Respir Cell Mol Biol, 61 61-73 (2019) [C1]
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2019 |
Mehta M, Deeksha, Tewari D, Gupta G, Awasthi R, Singh H, et al., 'Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases', Chemico-Biological Interactions, 308 206-215 (2019) [C1]
Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (C... [more]
Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases.
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2019 |
Cameron GJM, Jiang SH, Loering S, Deshpande AV, Hansbro PM, Starkey MR, 'Emerging therapeutic potential of group 2 innate lymphoid cells in acute kidney injury', Journal of Pathology, 248 9-15 (2019) [C1]
Acute kidney injury (AKI) remains a global challenge and, despite the availability of dialysis and transplantation, can be fatal. Those that survive an AKI are at increased risk o... [more]
Acute kidney injury (AKI) remains a global challenge and, despite the availability of dialysis and transplantation, can be fatal. Those that survive an AKI are at increased risk of developing chronic kidney disease and end stage renal failure. Understanding the fundamental mechanisms underpinning the pathophysiology of AKI is critical for developing novel strategies for diagnosis and treatment. A growing body of evidence indicates that amplifying type 2 immunity may have therapeutic potential in kidney injury and disease. Of particular interest are the recently described subset of innate immune cells, termed group 2 innate lymphoid cells (ILCs). Group 2 ILCs are crucial tissue-resident immune cells that maintain homeostasis and regulate tissue repair at multiple organ sites, including the kidney. They are critical mediators of type 2 immune responses following infection and injury. The existing literature suggests that activation of group 2 ILCs and production of a local type 2 immune milieu is protective against renal injury and associated pathology. In this review, we describe the emerging role for group 2 ILCs in renal homeostasis and repair. We provide an in-depth discussion of the most recent literature that use preclinical models of AKI and assess the therapeutic effect of modulating group 2 ILC function. We debate the potential for targeting these cells as novel cellular therapies in AKI and discuss the implications for future studies and translation. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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2019 |
Starkey MR, Plank MW, Casolari P, Papi A, Pavlidis S, Guo Y, et al., 'IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis', EUROPEAN RESPIRATORY JOURNAL, 54 (2019) [C1]
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2019 |
Cameron GJM, Cautivo KM, Loering S, Jiang SH, Deshpande AV, Foster PS, et al., 'Group 2 Innate Lymphoid Cells Are Redundant in Experimental Renal Ischemia-Reperfusion Injury', Frontiers in Immunology, 10 (2019) [C1]
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2019 |
Soon L, Ng PQ, Chellian J, Madheswaran T, Panneerselvam J, Gupta G, et al., 'Therapeutic potential of artemisia vulgaris: An insight into underlying immunological mechanisms', Journal of Environmental Pathology, Toxicology and Oncology, 38 205-216 (2019) [C1]
Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is comm... [more]
Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup. The plant has garnered the attention of researchers in the past few decades, and several research studies have investigated its biological effects, including antioxidant, anti-inflammatory, anticancer, hypolipidemic, and antimicrobial properties. In this review, various studies on these biological effects are discussed along with the tests conducted, compounds involved, and proposed mechanisms of action. This review will be of interest to the researchers working in the field of herbal medicine, pharmacology, medical sciences, and immunology.
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2019 |
Starkey MR, McKenzie AN, Belz GT, Hansbro PM, 'Pulmonary group 2 innate lymphoid cells: surprises and challenges', Mucosal Immunology, 12 299-311 (2019) [C1]
Group 2 innate lymphoid cells (ILC2s) are a recently described subset of innate lymphocytes with important immune and homeostatic functions at multiple tissue sites, especially th... [more]
Group 2 innate lymphoid cells (ILC2s) are a recently described subset of innate lymphocytes with important immune and homeostatic functions at multiple tissue sites, especially the lung. These cells expand locally after birth and during postnatal lung maturation and are present in the lung and other peripheral organs. They are modified by a variety of processes and mediate inflammatory responses to respiratory pathogens, inhaled allergens and noxious particles. Here, we review the emerging roles of ILC2s in pulmonary homeostasis and discuss recent and surprising advances in our understanding of how hormones, age, neurotransmitters, environmental challenges, and infection influence ILC2s. We also review how these responses may underpin the development, progression and severity of pulmonary inflammation and chronic lung diseases and highlight some of the remaining challenges for ILC2 biology.
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2019 |
Loering S, Cameron GJM, Starkey MR, Hansbro PM, 'Lung development and emerging roles for type 2 immunity', Journal of Pathology, 247 686-696 (2019) [C1]
Lung development is a complex process mediated through the interaction of multiple cell types, factors and mediators. In mice, it starts as early as embryonic day 9 and continues ... [more]
Lung development is a complex process mediated through the interaction of multiple cell types, factors and mediators. In mice, it starts as early as embryonic day 9 and continues into early adulthood. The process can be separated into five different developmental stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar. Whilst lung bud formation and branching morphogenesis have been studied extensively, the mechanisms of alveolarisation are incompletely understood. Aberrant lung development can lead to deleterious consequences for respiratory health such as bronchopulmonary dysplasia (BPD), a disease primarily affecting preterm neonates, which is characterised by increased pulmonary inflammation and disturbed alveolarisation. While the deleterious effects of type 1-mediated inflammatory responses on lung development have been well established, the role of type 2 responses in postnatal lung development remains poorly understood. Recent studies indicate that type 2-associated immune cells, such as group 2 innate lymphoid cells and alveolar macrophages, are increased in number during postnatal alveolarisation. Here, we present the current state of understanding of the postnatal stages of lung development and the key cell types and mediators known to be involved. We also provide an overview of how stem cells are involved in lung development and regeneration, and the negative influences of respiratory infections. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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2019 |
Liu G, Mateer SW, Hsu A, Goggins BJ, Tay H, Mathe A, et al., 'Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome', Mucosal Immunology, 12 862-873 (2019) [C1]
Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patient... [more]
Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patients. In animal models of colitis, pulmonary inflammation is driven by neutrophilic infiltrations, primarily in response to the systemic bacteraemia and increased bacterial load in the lungs. Platelet activating factor receptor (PAFR) plays a critical role in regulating pulmonary responses to infection in conditions, such as chronic obstructive pulmonary disease and asthma. We investigated the role of PAFR in pulmonary EIMs of IBD, using dextran sulfate sodium (DSS) and anti-CD40 murine models of colitis. Both models induced neutrophilic inflammation, with increased TNF and IL-1ß levels, bacterial load and PAFR protein expression in mouse lungs. Antagonism of PAFR decreased lung neutrophilia, TNF, and IL-1ß in an NLRP3 inflammasome-dependent manner. Lipopolysaccharide from phosphorylcholine (ChoP)-positive bacteria induced NLRP3 and caspase-1 proteins in human alveolar epithelial cells, however antagonism of PAFR prevented NLRP3 activation by ChoP. Amoxicillin reduced bacterial populations in the lungs and reduced NLRP3 inflammasome protein levels, but did not reduce PAFR. These data suggest a role for PAFR in microbial pattern recognition and NLRP3 inflammasome signaling in the lung.
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2019 |
Chellappan DK, Sze Ning QL, Su Min SK, Bin SY, Chern PJ, Shi TP, et al., 'Interactions between microbiome and lungs: Paving new paths for microbiome based bio-engineered drug delivery systems in chronic respiratory diseases', Chemico-Biological Interactions, 310 (2019) [C1]
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2018 |
Stifter SA, Matthews AY, Mangan NE, Fung KY, Drew A, Tate MD, et al., 'Defining the distinct, intrinsic properties of the novel type I interferon, IFN .', The Journal of biological chemistry, 293 3168-3179 (2018) [C1]
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2018 |
Shastri MD, Shukla SD, Chong WC, Dua K, Peterson GM, Patel RP, et al., 'Role of Oxidative Stress in the Pathology and Management of Human Tuberculosis', OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2018 (2018) [C1]
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2018 |
Reid AT, Veerati PC, Gosens R, Bartlett NW, Wark PA, Grainge CL, et al., 'Persistent induction of goblet cell differentiation in the airways: Therapeutic approaches', Pharmacology and Therapeutics, 185 155-169 (2018) [C1]
Dysregulated induction of goblet cell differentiation results in excessive production and retention of mucus and is a common feature of several chronic airways diseases. To date, ... [more]
Dysregulated induction of goblet cell differentiation results in excessive production and retention of mucus and is a common feature of several chronic airways diseases. To date, therapeutic strategies to reduce mucus accumulation have focused primarily on altering the properties of the mucus itself, or have aimed to limit the production of mucus-stimulating cytokines. Here we review the current knowledge of key molecular pathways that are dysregulated during persistent goblet cell differentiation and highlights both pre-existing and novel therapeutic strategies to combat this pathology.
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2018 |
Eapen MS, Hansbro PM, Larsson-Callerfelt A-K, Jolly MK, Myers S, Sharma P, et al., 'Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities.', Drugs, 78 1717-1740 (2018) [C1]
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2018 |
Liu G, Mateer S, Mathe A, Goggins B, Hsu A, Minahan K, et al., 'Platelet Activating Factor Receptor (PAFR) Regulates Colitis-induced Pulmonary Inflammation', The FASEB Journal, 32 (2018)
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2018 |
Sunkara KP, Gupta G, Hansbro PM, Dua K, Bebawy M, 'Functional relevance of SATB1 in immune regulation and tumorigenesis', Biomedicine and Pharmacotherapy, 104 87-93 (2018) [C1]
The Special AT-rich Sequence Binding Protein 1 (SATB1) is a chromatin organiser and transcription factor which regulates numerous cellular processes such as differentiation, proli... [more]
The Special AT-rich Sequence Binding Protein 1 (SATB1) is a chromatin organiser and transcription factor which regulates numerous cellular processes such as differentiation, proliferation and apoptosis through effects on gene expression. SATB1 undergoes various post-translational modifications, which determine its interaction with co-activators and co-repressors to induce regulation of gene transcription. SATB1 is an identified oncogene, its increased expression is associated with poor prognosis in many cancers. This paper provides a review on SATB1-mediated immune responses and on its target genes in the context of tumorigenesis and tumour progression. Specifically, we discuss the role of SATB1 in tumour immunity, Epithelial to Mesenchymal Transition (EMT), metastasis and multidrug resistance. Therapeutic targeting of aberrant SATB1 may be an important strategy in the treatment of cancer.
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2018 |
Nair PM, Starkey MR, Haw TJ, Ruscher R, Liu G, Maradana MR, et al., 'RelB-deficient Dendritic Cells Promote the Development of Spontaneous Allergic Airway Inflammation.', American journal of respiratory cell and molecular biology, (2018) [C1]
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2018 |
Periyalil HA, Wood LG, Wright TA, Karihaloo C, Starkey MR, Miu AS, et al., 'Obese asthmatics are characterized by altered adipose tissue macrophage activation', CLINICAL AND EXPERIMENTAL ALLERGY, 48 641-649 (2018) [C1]
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2018 |
Knight DA, Hansbro PM, 'Restricted access or access all areas?: a new cadherin-like protein upregulated in the inflamed esophagus', MUCOSAL IMMUNOLOGY, 11 1-2 (2018)
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2018 |
Dua K, Rapalli VK, Shukla SD, Singhvi G, Shastri MD, Chellappan DK, et al., 'Multi-drug resistant Mycobacterium tuberculosis & oxidative stress complexity: Emerging need for novel drug delivery approaches', Biomedicine and Pharmacotherapy, 107 1218-1229 (2018) [C1]
Tuberculosis (caused by Mycobacterium tuberculosis, Mtb) treatment involves multiple drug regimens for a prolonged period. However, the therapeutic benefit is often limited by poo... [more]
Tuberculosis (caused by Mycobacterium tuberculosis, Mtb) treatment involves multiple drug regimens for a prolonged period. However, the therapeutic benefit is often limited by poor patient compliance, subsequently leading to treatment failure and development of antibiotic resistance. Notably, oxidative stress is a crucial underlying factor that adversely influences the various treatment regimens in tuberculosis. Little information is available with advanced drug delivery systems that could be effectively utilized, in particular, for targeting the oxidative stress in tuberculosis. Thus, this presents an opportunity to review the utility of various available, controlled-release drug delivery systems (e.g., microspheres, liposomes, niosomes, solid lipid nanoparticles, dendrimers) that could be beneficial in tuberculosis treatments. This will help the biological and formulation scientists to pave a new path in formulating a treatment regimen for multi-drug resistant Mtb.
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2018 |
Dua K, Hansbro NG, Foster PS, Hansbro PM, 'Targeting MicroRNAs: Promising Future Therapeutics in the Treatment of Allergic Airway Disease', CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION, 28 125-127 (2018)
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2018 |
Mateer SW, Mathe A, Bruce J, Liu G, Maltby S, Fricker M, et al., 'IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis', American Journal of Pathology, 188 1625-1639 (2018) [C1]
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathol... [more]
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathology, most commonly neutrophil-mediated diseases, such as bronchiectasis and chronic bronchitis. Using murine models of colitis, we aimed to identify the immune mechanisms driving pulmonary manifestations of IBD. We found increased neutrophil numbers in lung tissue associated with the pulmonary vasculature in both trinitrobenzenesulfonic acid¿ and dextran sulfate sodium¿induced models of colitis. Analysis of systemic inflammation identified that neutrophilia was associated with bacteremia and pyrexia in animal models of colitis. We further identified IL-6 as a systemic mediator of neutrophil recruitment from the bone marrow of dextran sulfate sodium animals. Functional inhibition of IL-6 led to reduced systemic and pulmonary neutrophilia, but it did not attenuate established colitis pathology. These data suggest that systemic bacteremia and pyrexia drive IL-6 secretion, which is a critical driver for pulmonary manifestation of IBD. Targeting IL-6 may reduce neutrophil-associated extraintestinal manifestations in IBD patients.
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Nova |
2018 |
Dua K, de Jesus Andreoli Pinto T, Chellappan DK, Gupta G, Bebawy M, Hansbro PM, 'Advancements in nano drug delivery systems: a challenge for biofilms in respiratory diseases', PANMINERVA MEDICA, 60 35-36 (2018)
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2018 |
Terlizzi M, Molino A, Colarusso C, Donovan C, Imitazione P, Somma P, et al., 'Activation of the Absent in Melanoma 2 Inflammasome in Peripheral Blood Mononuclear Cells From Idiopathic Pulmonary Fibrosis Patients Leads to the Release of Pro-Fibrotic Mediators', FRONTIERS IN IMMUNOLOGY, 9 (2018) [C1]
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2018 |
Gupta G, Chellappan DK, de Jesus Andreoli Pinto T, Hansbro PM, Bebawy M, Dua K, 'Tumor suppressor role of miR-503.', Panminerva Medica, 60 17-24 (2018) [C1]
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2018 |
Chellappan DK, Sivam NS, Teoh KX, Leong WP, Fui TZ, Chooi K, et al., 'Gene therapy and type 1 diabetes mellitus', Biomedicine and Pharmacotherapy, 108 1188-1200 (2018) [C1]
Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet ß cells. Management of T1DM is c... [more]
Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet ß cells. Management of T1DM is challenging and complicated especially with conventional medications. Gene therapy has emerged as one of the potential therapeutic alternatives to treat T1DM. This review primarily focuses on the current status and the future perspectives of gene therapy in the management of T1DM. A vast number of the studies which are reported on gene therapy for the management of T1DM are done in animal models and in preclinical studies. In addition, the safety of such therapies is yet to be established in humans. Currently, there are several gene level interventions that are being investigated, notably, overexpression of genes and proteins needed against T1DM, transplantation of cells that express the genes against T1DM, stem-cells mediated gene therapy, genetic vaccination, immunological precursor cell-mediated gene therapy and vectors. Methods: We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review. Findings: Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.
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2018 |
Rajendra KC, Shukla SD, Gautam SS, Hansbro PM, O'Toole RF, 'The role of environmental exposure to non-cigarette smoke in lung disease', CLINICAL AND TRANSLATIONAL MEDICINE, 7 (2018) [C1]
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2018 |
Ng ZY, Wong JY, Panneerselvam J, Madheswaran T, Kumar P, Pillay V, et al., 'Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma', Colloids and Surfaces B: Biointerfaces, 172 51-59 (2018) [C1]
Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the an... [more]
Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties. The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1ß (IL-1ß) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3 ± 3.06 nm and -61.0 mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%. Both curcumin-loaded liposomes formulation (1 µg/mL, 5 µg/mL) resulted in significant (p < 0.05) reduction in the level of pro-inflammatory marker expression such as IL-6, IL-8, IL-1ß and TNF-a compared to positive control group. Liposomal curcumin with the dose of 1 µg/mL reduced the inflammatory markers more effectively compared to that of 5 µg/mL. Liposomal curcumin could be a promising intervention for asthma therapy showing their efficacy in suppressing the important pro-inflammatory markers involved in the pathogenesis of asthma.
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2018 |
Dua K, Awasthi R, Madan JR, Chellappan DK, Nalluri BN, Gupta G, et al., 'Novel drug delivery approaches in treating pulmonary fibrosis', PANMINERVA MEDICA, 60 238-240 (2018)
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2018 |
Fricker M, Goggins BJ, Mateer S, Jones B, Kim RY, Gellatly SL, et al., 'Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction.', JCI insight, 3 1-19 (2018) [C1]
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2018 |
Awasthi R, Roseblade A, Hansbro PM, Rathbone MJ, Dua K, Bebawy M, 'Nanoparticles in Cancer Treatment: Opportunities and Obstacles', CURRENT DRUG TARGETS, 19 1696-1709 (2018)
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2018 |
Dua K, Awasthi R, Madan JR, Chellappan DK, Nalluri BN, Gupta G, et al., 'Novel drug delivery approaches in treating pulmonary fibrosis', PANMINERVA MEDICA, 60 238-240 (2018)
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2018 |
Baines KJ, Wright TK, Gibson PG, Powell H, Hansbro PM, Simpson JL, 'Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD.', ERJ open research, 4 (2018) [C1]
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2018 |
Haw TJ, Starkey MR, Pavlidis S, Fricker M, Arthurs AL, Nair PM, et al., 'Toll-like receptor 2 and 4 have opposing roles in the pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease.', American journal of physiology. Lung cellular and molecular physiology, 314 L298-L317 (2018) [C1]
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2018 |
Singhvi G, Girdhar V, Patil S, Gupta G, Hansbro PM, Dua K, 'Microbiome as therapeutics in vesicular delivery', Biomedicine and Pharmacotherapy, 104 738-741 (2018) [C1]
Microbiome refers to an ecological community of various symbiotic and pathogenic microorganisms, which plays a crucial role in human health and disease. The concept of novel drug ... [more]
Microbiome refers to an ecological community of various symbiotic and pathogenic microorganisms, which plays a crucial role in human health and disease. The concept of novel drug delivery systems particularly the vesicular drug delivery systems is gaining massive attention. This emerging technology has started expanding its horizons in the area of microbiome delivery. This mini-review highlights the role of vesicular systems such as nanoparticles, liposomes etc. as a host/carrier for the microbiome in targeting various diseases. This review will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of vesicular delivery system as carrier for microbiome delivery.
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2018 |
Rutting S, Xenaki D, Lau E, Horvat J, Wood LG, Hansbro PM, Oliver BG, 'Dietary omega-6, but not omega-3, polyunsaturated or saturated fatty acids increase inflammation in primary lung mesenchymal cells', American Journal of Physiology - Lung Cellular and Molecular Physiology, 314 L922-L935 (2018) [C1]
Obesity is an important risk factor for developing severe asthma. Dietary fatty acids, which are increased in sera of obese individuals and after high-fat meals, activate the inna... [more]
Obesity is an important risk factor for developing severe asthma. Dietary fatty acids, which are increased in sera of obese individuals and after high-fat meals, activate the innate immune system and induce inflammation. This study investigated whether dietary fatty acids directly cause inflammation and/or synergize with obesity-induced cytokines in primary human pulmonary fibroblasts in vitro. Fibroblasts were challenged with BSA-conjugated fatty acids [¿-6 polyunsaturated fatty acids (PUFAs) and ¿-3 PUFAs or saturated fatty acids (SFAs)], with or without TNF-a, and release of the proinflammatory cytokines, IL-6 and CXCL8, was measured. We found that the ¿-6 PUFA arachidonic acid (AA), but not ¿-3 PUFAs or SFAs, upregulates IL-6 and CXCL8 release. Combined AA and TNF-a challenge resulted in substantially greater cytokine release than either alone, demonstrating synergy. Synergistic upregulation of IL-6, but not CXCL8, was mainly mediated via cyclooxygenase (COX). Inhibition of p38 MAPK reduced CXCL8 release, induced by AA and TNF-a alone, but not in combination. Synergistic CXCL8 release, following AA and TNF-a challenge, was not medicated via a single signaling pathway (MEK1, JNK, phosphoinositide 3-kinase, and NF-¿B) nor by hyperactivation of NF-¿B or p38. To investigate if these findings occur in other airway cells, effects of AA in primary human airway smooth muscle (ASM) cells and human bronchial epithelial cells were also investigated. We found proinflammatory effects in ASM cells but not epithelial cells. This study suggests that diets rich in ¿-6 PUFAs might promote airway inflammation via multiple pathways, including COX-depen-dent and-independent pathways, and in an obese person, may lead to more severe airway inflammation.
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2018 |
Obeidat M, Dvorkin-Gheva A, Li X, Bosse Y, Brandsma C-A, Nickle DC, et al., 'The Overlap of Lung Tissue Transcriptome of Smoke Exposed Mice with Human Smoking and COPD', SCIENTIFIC REPORTS, 8 (2018) [C1]
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2018 |
Rutting S, Papanicolaou M, Xenaki D, Wood LG, Mullin AM, Hansbro PM, Oliver BG, 'Dietary -6 polyunsaturated fatty acid arachidonic acid increases inflammation, but inhibits ECM protein expression in COPD.', Respiratory research, 19 (2018) [C1]
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2018 |
Dua K, Chellappan DK, Singhvi G, de Jesus Andreoli Pinto T, Gupta G, Hansbro PM, 'Targeting microRNAs using nanotechnology in pulmonary diseases', PANMINERVA MEDICA, 60 230-232 (2018)
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2018 |
Pathinayake PS, Hsu AC-Y, Waters DW, Hansbro PM, Wood LG, Wark PAB, 'Understanding the Unfolded Protein Response in the Pathogenesis of Asthma', FRONTIERS IN IMMUNOLOGY, 9 (2018) [C1]
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2018 |
Moheimani F, Koops J, Williams T, Reid AT, Hansbro PM, Wark PA, Knight DA, 'Influenza A virus infection dysregulates the expression of microRNA-22 and its targets; CD147 and HDAC4, in epithelium of asthmatics', Respiratory Research, 19 (2018) [C1]
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2018 |
Awasthi R, Rathbone MJ, Hansbro PM, Bebawy M, Dua K, 'Therapeutic prospects of microRNAs in cancer treatment through nanotechnology', Drug Delivery and Translational Research, 8 97-110 (2018) [C1]
MicroRNAs (miRNAs) represent a new class of diagnostic and prognostic biomarker as well as new therapeutic targets in cancer therapy. miRNAs are gaining significant interest due t... [more]
MicroRNAs (miRNAs) represent a new class of diagnostic and prognostic biomarker as well as new therapeutic targets in cancer therapy. miRNAs are gaining significant interest due to extensive advancements in knowledge since their discovery and, more recently, their translational application as therapeutic moieties and targets in the management of disease. miRNAs used in the treatment of cancer would position them as a new class of emerging therapeutic agents. Indeed, numerous candidate miRNAs have been identified as having therapeutic application in the treatment of cancer, but there is still much to learn about how to transform these into effective, patient-compliant, and targeted drug delivery systems. In this mini review, we discuss the utility and potential of nanotechnology in miRNA formulation and delivery with particular emphasis on cancer, including their role in conferring multidrug resistance and metastatic capacity. This review benefits both the formulation and biological scientists in understanding and exploring the new vistas of miRNA delivery using nanotechnology in the cancer clinically.
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2018 |
Schofield ZV, Croker D, Robertson AAB, Massey NL, Donovan C, Tee E, et al., 'Characterisation of small molecule ligands 4CMTB and 2CTAP as modulators of human FFA2 receptor signalling', SCIENTIFIC REPORTS, 8 (2018) [C1]
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2018 |
Chellappan DK, Ng ZY, Wong JY, Hsu A, Wark P, Hansbro N, et al., 'Immunological axis of curcumin-loaded vesicular drug delivery systems', Future Medicinal Chemistry, 10 839-844 (2018) [C1]
Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immunological pathways. Suc... [more]
Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immunological pathways. Such systems use particles at a nanoscale range, bringing about their intended use through a range of complex mechanisms. Apart from delivering drug substances into target tissues, these vesicular systems also effectively overcome problems like insolubility and unequal drug distribution. Several mechanisms are explored lately by different workers, and interest over vesicular curcumin has been renewed in the past decade. This commentary discusses several immunological targets in which curcumin is employed in a vesicular form.
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2017 |
Chellappan DK, Hansbro PM, Dua K, Hsu A, Gupta G, Ng ZY, et al., 'Vesicular Systems Containing Curcumin and Their Applications in Respiratory Disorders A Mini Review', Pharmaceutical Nanotechnology, 5 250-254 (2017)
Background: Vesicular systems like nanotechnology and liposomes are gaining tremen-dous attention lately in the field of respiratory diseases. These formulations enhance bioavaila... [more]
Background: Vesicular systems like nanotechnology and liposomes are gaining tremen-dous attention lately in the field of respiratory diseases. These formulations enhance bioavailability of the drug candidate, which could be achieved through a novel drug delivery mechanism. Moreover, the therapeutic potential achieved through these systems is highly controllable over long durations of time providing better efficacy and patient compliance. Objective: The objective of this paper is to review the recent literature on vesicular drug delivery systems containing curcumin. Methods: We have collated and summarized various recent attempts made to develop different controlled release drug delivery systems containing curcumin which would be of great interest for herbal, formulation and biological scientists. There are several vesicular nanotechnological techniques involv-ing curcumin which have been studied recently, targeting pulmonary diseases. Results: Different vesicular systems containing curcumin are being studied for their therapeutic potential in different respiratory diseases. There has been a renewed interest in formulations containing cur-cumin recently, primarily owing to the broad spectrum therapeutic potential of this miracle substance. Various types of formulations, containing curcumin, targeting different bodily systems have recently emerged and, nevertheless, the search for newer frontiers with this drug goes on. Conclusion: This mini review, in this direction, tries to highlight the key research interventions em-ploying vesicular systems of drug delivery with curcumin.
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2017 |
Hansbro PM, Kim RY, Starkey MR, Donovan C, Dua K, Mayall JR, et al., 'Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma', Immunological Reviews, 278 41-62 (2017) [C1]
Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with... [more]
Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid-resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid-resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid-resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity-or pollution-associated asthma.
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2017 |
Conickx G, Mestdagh P, Cobos FA, Verhamme FM, Maes T, Vanaudenaerde BM, et al., 'MicroRNA profiling reveals a role for MicroRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease', American Journal of Respiratory and Critical Care Medicine, 195 43-56 (2017) [C1]
Rationale: Aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis. Objectives: To identify dysregulated miRNAs in lung tissue of patients wi... [more]
Rationale: Aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis. Objectives: To identify dysregulated miRNAs in lung tissue of patients with chronic obstructive pulmonary disease (COPD). Methods: We performed miRNA and mRNA profiling using high throughput stem-loop reverse-transcriptase quantitative polymerase chain reaction and mRNA microarray, respectively, on lung tissue of 30 patients (screening cohort) encompassing 8 never-smokers, 10 smokers without airflow limitation, and 12 smokers with COPD. Differential expression of miRNA-218-5p (miR-218-5p) was validated by reverse-transcriptase quantitative polymerase chain reaction in an independent cohort of 71 patients, an in vivo murine model of COPD, and primary human bronchial epithelial cells. Localization of miR-218-5p was assessed by in situ hybridization. In vitro and in vivo perturbation of miR-218-5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COPD pathogenesis. Measurements and Main Results: Several miRNAs were differentially expressed among the different patient groups. Interestingly, miR-218-5p was significantly down-regulated in smokers without airflow limitation and in patients with COPD compared with never-smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice, and in human bronchial epithelial cells. Importantly, expression of miR-218-5p strongly correlated with airway obstruction. Furthermore, cellular localization of miR-218-5p in human and murine lung revealed highest expression of miR-218-5p in the bronchial airway epithelium. Perturbation experiments with a miR-218-5p mimic or inhibitor demonstrated a protective role of miR-218-5p in cigarette smoke-induced inflammation and COPD. Conclusions: We highlight a role for miR-218-5p in the pathogenesis of COPD.
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2017 |
Maheshwari R, Sharma P, Tekade M, Atneriya U, Dua K, Hansbro PM, Tekade RK, 'Microsponge Embedded Tablets for Sustained Delivery of Nifedipine.', Pharmaceutical nanotechnology, 5 192-202 (2017) [C1]
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2017 |
Ng Kee Kwong F, Nicholson AG, Harrison CL, Hansbro PM, Adcock IM, Chung KF, 'Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?', European Respiratory Review, 26 (2017) [C1]
Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechani... [more]
Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechanisms behind this observation are not clear, established drivers of carcinogenesis in COPD include oxidative stress and sustained chronic inflammation. Mitochondria are critical in these two processes and recent evidence links increased oxidative stress in COPD patients to mitochondrial damage. We therefore postulate that mitochondrial damage in COPD patients leads to increased oxidative stress and chronic inflammation, thereby increasing the risk of carcinogenesis. The functional state of the mitochondrion is dependent on the balance between its biogenesis and degradation (mitophagy). Dysfunctional mitochondria are a source of oxidative stress and inflammasome activation. In COPD, there is impaired translocation of the ubiquitin-related degradation molecule Parkin following activation of the Pink1 mitophagy pathway, resulting in excessive dysfunctional mitochondria. We hypothesise that deranged pathways in mitochondrial biogenesis and mitophagy in COPD can account for the increased risk in carcinogenesis. To test this hypothesis, animal models exposed to cigarette smoke and developing emphysema and lung cancer should be developed. In the future, the use of mitochondria-based antioxidants should be studied as an adjunct with the aim of reducing the risk of COPD-associated cancer.
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2017 |
Dua K, Bebawy M, Awasthi R, Tekade RK, Tekade M, Gupta G, et al., 'Application of Chitosan and its Derivatives in Nanocarrier Based Pulmonary Drug Delivery Systems.', Pharmaceutical nanotechnology, 5 243-249 (2017) [C1]
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2017 |
Chotirmall SH, Gellatly SL, Budden KF, Mac Aogain M, Shukla SD, Wood DLA, et al., 'Microbiomes in respiratory health and disease: An Asia-Pacific perspective', Respirology, 22 240-250 (2017) [C1]
There is currently enormous interest in studying the role of the microbiome in health and disease. Microbiome's role is increasingly being applied to respiratory diseases, in... [more]
There is currently enormous interest in studying the role of the microbiome in health and disease. Microbiome's role is increasingly being applied to respiratory diseases, in particular COPD, asthma, cystic fibrosis and bronchiectasis. The changes in respiratory microbiomes that occur in these diseases and how they are modified by environmental challenges such as cigarette smoke, air pollution and infection are being elucidated. There is also emerging evidence that gut microbiomes play a role in lung diseases through the modulation of systemic immune responses and can be modified by diet and antibiotic treatment. There are issues that are particular to the Asia-Pacific region involving diet and prevalence of specific respiratory diseases. Each of these issues is further complicated by the effects of ageing. The challenges now are to elucidate the cause and effect relationships between changes in microbiomes and respiratory diseases and how to translate these into new treatments and clinical care. Here we review the current understanding and progression in these areas.
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2017 |
Camlin NJ, Jarnicki AG, Vanders RL, Walters KA, Hansbro PM, McLaughlin EA, Holt JE, 'Grandmaternal smoke exposure reduces female fertility in a murine model, with great-grandmaternal smoke exposure unlikely to have an effect', HUMAN REPRODUCTION, 32 1270-1281 (2017) [C1]
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2017 |
Leung JM, Tiew PY, Mac Aogáin M, Budden KF, Yong VFL, Thomas SS, et al., 'The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD', Respirology, 22 634-650 (2017) [C1]
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2017 |
Hansbro PM, Haw TJ, Starkey MR, Miyake K, 'Toll-like receptors in COPD', EUROPEAN RESPIRATORY JOURNAL, 49 (2017) [C1]
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2017 |
Budden KF, Gellatly SL, Wood DLA, Cooper MA, Morrison M, Hugenholtz P, Hansbro PM, 'Emerging pathogenic links between microbiota and the gut-lung axis', Nature Reviews Microbiology, 15 55-63 (2017) [C1]
The microbiota is vital for the development of the immune system and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the respiratory tract and the... [more]
The microbiota is vital for the development of the immune system and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the respiratory tract and the gut have recently been linked to alterations in immune responses and to disease development in the lungs. In this Opinion article, we review the microbial species that are usually found in healthy gastrointestinal and respiratory tracts, their dysbiosis in disease and interactions with the gut-lung axis. Although the gut-lung axis is only beginning to be understood, emerging evidence indicates that there is potential for manipulation of the gut microbiota in the treatment of lung diseases.
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2017 |
Nair PM, Starkey MR, Haw TJ, Liu G, Horvat JC, Morris JC, et al., 'Targeting PP2A and proteasome activity ameliorates features of allergic airway disease in mice', Allergy: European Journal of Allergy and Clinical Immunology, 72 1891-1903 (2017) [C1]
Background: Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase ... [more]
Background: Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed whether enhancing PP2A activity with fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL (S) ), or inhibiting proteasome activity with bortezomib (BORT), could suppress experimental AAD. Methods: Acute AAD was induced in C57BL/6 mice by intraperitoneal sensitization with ovalbumin (OVA) in combination with intranasal (i.n) exposure to OVA. Chronic AAD was induced in mice with prolonged i.n exposure to crude house dust mite (HDM) extract. Mice were treated with vehicle, FTY720, AAL (S) , BORT or AAL (S) +BORT and hallmark features of AAD assessed. Results: AAL (S) reduced the severity of acute AAD by suppressing tissue eosinophils and inflammation, mucus-secreting cell (MSC) numbers, type 2-associated cytokines (interleukin (IL)-33, thymic stromal lymphopoietin, IL-5 and IL-13), serum immunoglobulin (Ig)E and airway hyper-responsiveness (AHR). FTY720 only suppressed tissue inflammation and IgE. BORT reduced bronchoalveolar lavage fluid (BALF) and tissue eosinophils and inflammation, IL-5, IL-13 and AHR. Combined treatment with AAL (S) +BORT had complementary effects and suppressed BALF and tissue eosinophils and inflammation, MSC numbers, reduced the production of type 2 cytokines and AHR. AAL (S) , BORT and AAL (S) +BORT also reduced airway remodelling in chronic AAD. Conclusion: These findings highlight the potential of combination therapies that enhance PP2A and inhibit proteasome activity as novel therapeutic strategies for asthma.
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2017 |
Dua K, Hansbro NG, Hansbro PM, 'STEROID RESISTANCE AND CONCOMITANT RESPIRATORY INFECTIONS: A CHALLENGING BATTLE IN PULMONARY CLINIC', EXCLI JOURNAL, 16 981-985 (2017)
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2017 |
Sohal SS, Hansbro PM, Shukla SD, Eapen MS, Walters EH, 'Potential Mechanisms of Microbial Pathogens in Idiopathic Interstitial Lung Disease', CHEST, 152 899-900 (2017)
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2017 |
Pinkerton JW, Kim RY, Robertson AAB, Hirota JA, Wood LG, Knight DA, et al., 'Inflammasomes in the lung', Molecular Immunology, 86 44-55 (2017) [C1]
Innate immune responses act as first line defences upon exposure to potentially noxious stimuli. The innate immune system has evolved numerous intracellular and extracellular rece... [more]
Innate immune responses act as first line defences upon exposure to potentially noxious stimuli. The innate immune system has evolved numerous intracellular and extracellular receptors that undertake surveillance for potentially damaging particulates. Inflammasomes are intracellular innate immune multiprotein complexes that form and are activated following interaction with these stimuli. Inflammasome activation leads to the cleavage of pro-IL-1ß and release of the pro-inflammatory cytokine, IL-1ß, which initiates acute phase pro-inflammatory responses, and other responses are also involved (IL-18, pyroptosis). However, excessive activation of inflammasomes can result in chronic inflammation, which has been implicated in a range of chronic inflammatory diseases. The airways are constantly exposed to a wide variety of stimuli. Inflammasome activation and downstream responses clears these stimuli. However, excessive activation may drive the pathogenesis of chronic respiratory diseases such as severe asthma and chronic obstructive pulmonary disease. Thus, there is currently intense interest in the role of inflammasomes in chronic inflammatory lung diseases and in their potential for therapeutic targeting. Here we review the known associations between inflammasome-mediated responses and the development and exacerbation of chronic lung diseases.
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2017 |
Bazett M, Biala A, Huff RD, Zeglinksi MR, Hansbro PM, Bosiljcic M, et al., 'Attenuating immune pathology using a microbial-based intervention in a mouse model of cigarette smoke-induced lung inflammation', RESPIRATORY RESEARCH, 18 (2017) [C1]
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2017 |
Kim RY, Horvat JC, Pinkerton JW, Starkey MR, Essilfie AT, Mayall JR, et al., 'MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase mediated suppression of histone deacetylase 2', Journal of Allergy and Clinical Immunology, 139 519-532 (2017) [C1]
Background Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of und... [more]
Background Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The¿mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. Objective We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. Methods Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory¿tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Results Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21¿specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. Conclusion We identify a previously unrecognized role for an¿miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma.
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2017 |
Huff RD, Hsu ACY, Nichol KS, Jones B, Knight DA, Wark PAB, et al., 'Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells', PLoS ONE, 12 1-17 (2017) [C1]
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2017 |
Dua K, Shukla SD, Hansbro PM, 'Aspiration techniques for bronchoalveolar lavage in translational respiratory research: Paving the way to develop novel therapeutic moieties.', Journal of biological methods, 4 e73 (2017)
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2017 |
Jones B, Donovan C, Liu G, Gomez HM, Chimankar V, Harrison CL, et al., 'Animal models of COPD: What do they tell us?', Respirology, 22 21-32 (2017) [C1]
COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progr... [more]
COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanisms and identify biomarkers that may be therapeutic targets that would facilitate the development of improved standard of care. Here, we review the different established animal models of COPD and the various aspects of disease pathophysiology that have been successfully recapitulated in these models including chronic lung inflammation, airway remodelling, emphysema and impaired lung function. Furthermore, some of the mechanistic features, and thus biomarkers and therapeutic targets of COPD identified in animal models are outlined. Some of the existing therapies that suppress some disease symptoms that were identified in animal models and are progressing towards therapeutic development have been outlined. Further studies of representative animal models of human COPD have the strong potential to identify new and effective therapeutic approaches for COPD.
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2017 |
Girkin JL, Hatchwell LM, Collison AM, Starkey MR, Hansbro PM, Yagita H, et al., 'TRAIL signaling is proinflammatory and proviral in a murine model of rhinovirus 1B infection', American Journal of Physiology - Lung Cellular and Molecular Physiology, 312 L89-L99 (2017) [C1]
The aim of this study is to elucidate the role of TRAIL during rhinovirus (RV) infection in vivo. Naïve wild-type and tumor necrosis factor-related apoptosis-inducing ligand (TRAI... [more]
The aim of this study is to elucidate the role of TRAIL during rhinovirus (RV) infection in vivo. Naïve wild-type and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-deficient (Tnfsf10-/-) BALB/c mice were infected intranasally with RV1B. In separate experiments, Tnfsf10-/-mice were sensitized and challenged via the airway route with house dust mite (HDM) to induce allergic airways disease and then challenged with RVIB or UV-RVIB. Airway hyperreactivity (AHR) was invasively assessed as total airways resistance in response to increasing methacholine challenge and inflammation was assessed in bronchoalveolar lavage fluid at multiple time points postinfection. Chemokines were quantified by ELISA of whole lung lysates and viral load was determined by quantitative RT-PCR and tissue culture infective dose (TCID50). Human airway epithelial cells (BEAS2B) were infected with RV1B and stimulated with recombinant TRAIL or neutralizing anti-TRAIL antibodies and viral titer assessed by TCID50. HDM-challenged Tnfsf10-/-mice were protected against RV-induced AHR and had suppressed cellular infiltration in the airways upon RV infection. Chemokine C-X-C-motif ligand 2 (CXCL2) production was suppressed in naïve Tnfsf10-/-mice infected with RV1B, with less RV1B detected 24 h postinfection. This was associated with reduced apoptotic cell death and a reduction of interferon (IFN)-¿2/3 but not IFN-a or IFN-ß. TRAIL stimulation increased, whereas anti-TRAIL antibodies reduced viral replication in RV1B-infected BEAS2B cells in vitro. In conclusion, TRAIL promotes RV-induced AHR, inflammation and RV1B replication, implicating this molecule and its downstream signaling pathways as a possible target for the amelioration of RV1B-induced allergic and nonallergic lung inflammation and AHR.
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2017 |
Ali MK, Kim RY, Karim R, Mayall JR, Martin KL, Shahandeh A, et al., 'Role of iron in the pathogenesis of respiratory disease', INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 88 181-195 (2017) [C1]
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2017 |
Al-Kouba J, Wilkinson AN, Starkey MR, Rudraraju R, Werder RB, Liu X, et al., 'Allergen-encoding bone marrow transfer inactivates allergic T cell responses, alleviating airway inflammation', JCI INSIGHT, 2 (2017) [C1]
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Nova |
2017 |
Liu G, Cooley MA, Nair PM, Donovan C, Hsu AC, Jarnicki AG, et al., 'Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c', JOURNAL OF PATHOLOGY, 243 510-523 (2017) [C1]
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2017 |
Sohal SS, Hansbro PM, Walters EH, 'Epithelial Mesenchymal Transition in Chronic Obstructive Pulmonary Disease, a Precursor for Epithelial Cancers: Understanding and Translation to Early Therapy', ANNALS OF THE AMERICAN THORACIC SOCIETY, 14 1491-1492 (2017)
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2017 |
Dua K, Hansbro NG, Foster PS, Hansbro PM, 'MicroRNAs as therapeutics for future drug delivery systems in treatment of lung diseases', Drug Delivery and Translational Research, 7 168-178 (2017) [C1]
The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the ma... [more]
The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the management of disease pathology. The miRNAs can potentially be a new class of drugs in the near future for the treatment of various lung diseases, but it lacks the current knowledge how these identified therapeutic moieties can be designed into an effective, patient complaint and targeted drug delivery system. miRNAs have characteristic features like small size and low molecular weight which makes them easily translated into an effective drug delivery system. In this review, we have summarised the concept of miRNAs and different approaches which can be employed to deliver miRNAs effectively and safely to the target cells including the challenges associated with their development in particular emphasis on pulmonary diseases. Such approaches will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of miRNA delivery for pulmonary inflammatory diseases.
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2017 |
Dua K, Shukla SD, Tekade RK, Hansbro PM, 'Whether a novel drug delivery system can overcome the problem of biofilms in respiratory diseases?', Drug Delivery and Translational Research, 7 179-187 (2017) [C1]
Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases... [more]
Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease, etc. The treatment strategies for such infections are difficult due to the resistance of the microflora existing in the biofilms against various antimicrobial agents, thus posing threats to the patient population. The present era witnesses the beginning of research to understand the biofilm physiology and the associated microfloral diversity by applying -omics approaches. There is very limited information about how the deposition of biofilm on the respiratory devices and lung itself affects the drug delivered, the delivery system, and other implications. The present mini review summarizes the basic introduction to the biofilms and its avoidance using various drug delivery systems with special emphasis on the respiratory diseases. Understanding the approaches, principles, and modes of drug delivery involved in preventing biofilm deposition will be of interest to both biological and formulation scientists, thereby opening avenues to explore the new vistas in biofilm research for identifying better treatments for pulmonary infectious diseases.
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Nova |
2017 |
Eapen MS, Hansbro PM, McAlinden K, Kim RY, Ward C, Hackett T-L, et al., 'Abnormal M1/M2 macrophage phenotype profiles in the small airway wall and lumen in smokers and chronic obstructive pulmonary disease (COPD).', Scientific Reports, 7 (2017) [C1]
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Nova |
2017 |
Sohal SS, Hansbro PM, Walters EH, 'Epithelial Mesenchymal Transition in Chronic Obstructive Pulmonary Disease, a Precursor for Epithelial Cancers: Understanding and Translation to Early Therapy.', Annals of the American Thoracic Society, 14 1491-1492 (2017)
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2017 |
Stevens RL, McNeil HP, Wensing LA, Shin K, Wong GW, Hansbro PM, Krilis SA, 'Experimental arthritis is dependent on mouse mast cell protease-5', Journal of Biological Chemistry, 292 5392-5404 (2017) [C1]
The constitutive heparin+ (HP) mast cells (MCs) in mice express mouseMCprotease (mMCP)-5 and carboxypeptidaseA (mMC-CPA). The amino acid sequence ofmMCP-5is most similar to that o... [more]
The constitutive heparin+ (HP) mast cells (MCs) in mice express mouseMCprotease (mMCP)-5 and carboxypeptidaseA (mMC-CPA). The amino acid sequence ofmMCP-5is most similar to that of human chymase-1, as are the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP-2+ MCs in the jejunal mucosa of Trichinella spiralisinfected mice. In contrast, the constitutive HP+ MCs in the tongues of mMCP-5-null mice were poorly granulated and lacked mMC-CPA protein. Bone marrow-derived MCs were readily developed from the transgenic mice using IL-3. Although these MCs contained high levels of mMC-CPA mRNA, they also lacked the latter exopeptidase. mMCP-5 protein is therefore needed to target translated mMC-CPA to the secretory granule along with HP-containing serglycin proteoglycans. Alternately, mMCP-5 is needed to protect mMC-CPA from autolysis in the cell's granules. Fibronectin was identified as a target of mMCP-5, and the exocytosis ofmMCP-5from theMCs in the mouse's peritoneal cavity resulted in the expression of metalloproteinase protease-9, which has been implicated in arthritis. In support of the latter finding, experimental arthritis was markedly reduced in mMCP-5-null mice relative to wildtype mice in two disease models.
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2017 |
Kim RY, Pinkerton JW, Essilfie AT, Robertson AAB, Baines KJ, Brown AC, et al., 'Role for NLRP3 inflammasome-mediated, IL-1ß-dependent responses in severe, steroid-resistant asthma', American Journal of Respiratory and Critical Care Medicine, 196 283-297 (2017) [C1]
Rationale: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identifica... [more]
Rationale: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and concomitant IL-1ß responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma. Objectives: To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1ß in severe, steroid-resistant asthma. Methods: We developed mouse models of Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1ß responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1ß responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1ß antibody. Roles for IL-1ß-induced neutrophilic inflammation were examined using IL-1ß and anti-Ly6G. Measurements and Main Results: Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1ß responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1ß expression. Treatment with anti-IL-1ß, Ac- YVAD-cho, and MCC950 suppressed IL-1ß responses and the important steroid-resistant features of disease in mice, whereas IL-1ß administration recapitulated these features. Neutrophil depletion suppressed IL-1ß-induced steroid-resistant airway hyperresponsiveness. Conclusions: NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.
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Nova |
2017 |
Kedzierski L, Tate MD, Hsu AC, Kolesnik TB, Linossi EM, Dagley L, et al., 'Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling', eLife, 6 1-27 (2017) [C1]
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Nova |
2017 |
Soni N, Tekade M, Kesharwani P, Bhattacharya P, Maheshwari R, Dua K, et al., 'Recent advances in oncological submissions of dendrimer', Current Pharmaceutical Design, 23 3084-3098 (2017) [C1]
Background: Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently low... [more]
Background: Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently lower survival rate and hampered quality of life of patients. Methods: Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body. Results: Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation. Conclusion: Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.
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2017 |
Shukla SD, Budden KF, Neal R, Hansbro PM, 'Microbiome effects on immunity, health and disease in the lung', CLINICAL & TRANSLATIONAL IMMUNOLOGY, 6 (2017) [C1]
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Nova |
2017 |
Dua K, Shukla SD, Andreoli Pinto TDJ, Hansbro PM, 'Nanotechnology: Advancing the translational respiratory research', INTERVENTIONAL MEDICINE AND APPLIED SCIENCE, 9 39-41 (2017)
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2017 |
Shukla SD, Hansbro PM, Walters EH, 'Blocking rhinoviral adhesion molecule (ICAM-1): potential to prevent COPD exacerbations', INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, 12 1413-1414 (2017)
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2017 |
Foster PS, Maltby S, Rosenberg HF, Tay HL, Hogan SP, Collison AM, et al., 'Modeling T(H)2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma', IMMUNOLOGICAL REVIEWS, 278 20-40 (2017) [C1]
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Nova |
2017 |
Shukla SD, Hansbro PM, Walters EH, 'Upregulated pneumococcal adhesion molecule (platelet-activating factor receptor) may predispose COPD patients to community-acquired pneumonia', INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, 12 3111-3112 (2017)
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2017 |
Horvat JC, Mayall JR, Mangan NE, Brown AC, Chevalier A, Starkey MR, et al., 'IFN- regulated innate immune responses in the female reproductive tract during
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2017 |
Horvat JC, Ali MK, Johnstone D, Kim RY, Mayall JR, Karim R, et al., 'Role for dysregulated iron in the pathogenesis of murine models of lung disease', The Journal of Immunology, 198 53.8-53.8 (2017)
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2017 |
Hsu AC-Y, Dua K, Starkey MR, Haw T-J, Nair PM, Nichol K, et al., 'MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD', JCI INSIGHT, 2 (2017) [C1]
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Nova |
2016 |
Kim RY, Rae B, Neal R, Donovan C, Pinkerton J, Balachandran L, et al., 'Elucidating novel disease mechanisms in severe asthma', CLINICAL & TRANSLATIONAL IMMUNOLOGY, 5 (2016) [C1]
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Nova |
2016 |
Sokulsky LA, Collison AM, Nightingale S, Le Fevre A, Percival E, Starkey MR, et al., 'TRAIL deficiency and PP2A activation with salmeterol ameliorates egg allergen-driven eosinophilic esophagitis', American Journal of Physiology - Gastrointestinal and Liver Physiology, 311 G998-G1008 (2016) [C1]
Food antigens are common inflammatory triggers in pediatric eosinophilic esophagitis (EoE). TNFrelated apoptosis-inducing ligand (TRAIL) promotes eosinophilic inflammation through... [more]
Food antigens are common inflammatory triggers in pediatric eosinophilic esophagitis (EoE). TNFrelated apoptosis-inducing ligand (TRAIL) promotes eosinophilic inflammation through the upregulation of the E3 ubiquitin ligase Midline (MID)-1 and subsequent downregulation of protein phosphatase 2A (PP2A), but the role of this pathway in EoE that is experimentally induced by repeated food antigen challenges has not been investigated. Esophageal mucosal biopsies were collected from children with EoE and controls and assessed for TRAIL and MID-1 protein and mRNA transcript levels. Wild-type and TRAIL-deficient (Tnfsf10-/-) mice were administered subcutaneous ovalbumin (OVA) followed by oral OVA challenges. In separate experiments, OVA-challenged mice were intraperitoneally administered salmeterol or dexamethasone. Esophageal biopsies from children with EoE revealed increased levels of TRAIL and MID-1 and reduced PP2A activation compared with controls. Tnfsf10-/- mice were largely protected from esophageal fibrosis, eosinophilic inflammation, and the upregulation of TSLP, IL-5, IL-13, and CCL11 when compared with wild-type mice. Salmeterol administration to wild-type mice with experimental EoE restored PP2A activity and also prevented esophageal eosinophilia, inflammatory cytokine expression, and remodeling, which was comparable to the treatment effect of dexamethasone. TRAIL and PP2A regulate inflammation and fibrosis in experimental EoE, which can be therapeutically modulated by salmeterol.
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2016 |
Russell KE, Chung KF, Clarke CJ, Durham AL, Mallia P, Footitt J, et al., 'The MIF antagonist ISO-1 attenuates corticosteroid-insensitive inflammation and airways hyperresponsiveness in an ozone-induced model of COPD', PLoS ONE, 11 (2016) [C1]
Introduction. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. I... [more]
Introduction. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however. Methods. Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from nonsmokers, smokers and COPD patients. To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure. BAL fluid and lung tissue were collected after the final exposure. Airway hyperresponsiveness (AHR) and lung function were measured using whole body plethysmography. HIF-1a binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays. Results. MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels. MIF expression correlated with that of HIF-1a in all patients groups and in ozone-exposed mice. BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR. Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR. Conclusion MIF and HIF-1a levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR. Inhibition of MIF may provide a novel anti-inflammatory approach in COPD.
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2016 |
Simpson JL, Baines KJ, Horvat JC, Essilfie AT, Brown AC, Tooze M, et al., 'COPD is characterized by increased detection of Haemophilus influenzae, Streptococcus pneumoniae and a deficiency of Bacillus species', Respirology, 21 697-704 (2016) [C1]
Background and objective Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and inflammation. Airway bacterial colonization is increas... [more]
Background and objective Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and inflammation. Airway bacterial colonization is increased in COPD; however, the role of potentially pathogenic and non-pathogenic bacteria in the pathogenesis of disease is unclear. This study characterized the presence of bacteria in a well-characterized cohort of adults with COPD and healthy controls. Methods Adults with COPD (n = 70) and healthy controls (n = 51) underwent clinical assessment and sputum induction. Sputum was dispersed, and total and differential cell counts were performed. Bacteria were cultured, identified and enumerated. Supernatants were assessed for neutrophil elastase (NE) and IL-1ß. Common respiratory pathogens were also determined using real-time PCR. Results Participants with COPD had a typical neutrophilic inflammatory profile. The total load of bacteria was increased in COPD and was associated with poorer respiratory health status, as measured by the St George's Respiratory Questionnaire (Spearman's r = 0.336, P = 0.013). Significantly lower levels of culturable Bacillus species were identified compared with healthy controls. PCR analyses revealed increased rates of detection of potentially pathogenic bacteria with Haemophilus influenzae detection associated with higher sputum levels of NE and IL-1ß, while Streptococcus pneumoniae was more common in male ex-smokers with emphysema and a deficit in diffusion capacity. Conclusion Non-pathogenic and pathogenic bacteria were altered in the sputum of patients with COPD. These observations highlight the potential to identify treatment and management strategies that both target specific bacterial pathogens and restore the microbial balance, which may lead to reductions in inflammation and subsequent improvements in lung health.
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Nova |
2016 |
Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al., 'A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease', Mucosal Immunology, 9 859-872 (2016) [C1]
Chronic obstructive pulmonary disease (COPD) is a life-Threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective ... [more]
Chronic obstructive pulmonary disease (COPD) is a life-Threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-Type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL + CD11b + monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.
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Nova |
2016 |
Thorburn AN, Tseng H-Y, Donovan C, Hansbro NG, Jarnicki AG, Foster PS, et al., 'TLR2, TLR4 AND MyD88 Mediate Allergic Airway Disease (AAD) and Streptococcus pneumoniae-Induced Suppression of AAD.', PLoS One, 11 e0156402 (2016) [C1]
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Nova |
2016 |
Tang FSM, Hansbro PM, Burgess JK, Ammit AJ, Baines KJ, Oliver BG, 'A novel immunomodulatory function of neutrophils on rhinovirus-Activated monocytes in vitro', Thorax, 71 1039-1049 (2016) [C1]
Background Rhinovirus (RV) infections are the major precipitant of asthma exacerbations. While neutrophilic lung inflammation occurs during such infections, its role remains uncle... [more]
Background Rhinovirus (RV) infections are the major precipitant of asthma exacerbations. While neutrophilic lung inflammation occurs during such infections, its role remains unclear. Neutrophilic inflammation is associated with increased asthma severity and steroid refractory disease. Neutrophils are vital for controlling infections but also have immunomodulatory functions. Previously, we found that neutrophils respond to viral mimetics but not replication competent RV. We aimed to investigate if neutrophils are activated and/or modulate immune responses of monocytes during RV16 infection. Methods Primary human monocytes and autologous neutrophils were cocultured with or without RV16, in direct contact or separated by transwells. RV16-stimulated monocytes were also exposed to lysed neutrophils, neutrophil membrane components or soluble neutrophil intracellular components. Interleukin 6 (IL-6) and C-X-C motif (CXC)L8 mRNA and proteins were measured by quantitative PCR and ELISA at 24â ¿..hours. Results RV16 induced IL-6 and CXCL8 in monocytes, but not neutrophils. RV16-induced IL-6 and CXCL8 from monocytes was reduced in the presence of live neutrophils. Transwell separation abolished the inhibitory effects. Lysed neutrophils inhibited RV16-induced IL-6 and CXCL8 from monocytes. Neutrophil intracellular components alone effectively inhibited RV16-induced monocyte-derived IL-6 and CXCL8. Neutrophil intracellular components reduced RV16-induced IL-6 and CXCL8 mRNA in monocytes. Conclusions Cell contact between monocytes and neutrophils is required, and preformed neutrophil mediator(s) are likely to be involved in the suppression of cytokine mRNA and protein production. This study demonstrates a novel regulatory function of neutrophils on RV-Activated monocytes in vitro, challenging the paradigm that neutrophils are predominantly proinflammatory.
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Nova |
2016 |
Rahman MM, Rumzhum NN, Hansbro PM, Morris JC, Clark AR, Verrills NM, Ammit AJ, 'Activating protein phosphatase 2A (PP2A) enhances tristetraprolin (TTP) anti-inflammatory function in A549 lung epithelial cells', Cellular Signalling, 28 325-334 (2016) [C1]
Chronic respiratory diseases are driven by inflammation, but some clinical conditions (severe asthma, COPD) are refractory to conventional anti-inflammatory therapies. Thus, novel... [more]
Chronic respiratory diseases are driven by inflammation, but some clinical conditions (severe asthma, COPD) are refractory to conventional anti-inflammatory therapies. Thus, novel anti-inflammatory strategies are necessary. The mRNA destabilizing protein, tristetraprolin (TTP), is an anti-inflammatory molecule that functions to induce mRNA decay of cytokines that drive pathogenesis of respiratory disorders. TTP is regulated by phosphorylation and protein phosphatase 2A (PP2A) is responsible for dephosphorylating (and hence activating) TTP, amongst other targets. PP2A is activated by small molecules, FTY720 and AAL(S), and in this study we examine whether these compounds repress cytokine production in a cellular model of airway inflammation using A549 lung epithelial cells stimulated with tumor necrosis factor a (TNFa) in vitro. PP2A activators significantly increase TNFa-induced PP2A activity and inhibit mRNA expression and protein secretion of interleukin 8 (IL-8) and IL-6; two key pro-inflammatory cytokines implicated in respiratory disease and TTP targets. The effect of PP2A activators is not via an increase in TNFa-induced TTP mRNA expression; instead we demonstrate a link between PP2A activation and TTP anti-inflammatory function by showing that specific knockdown of TTP with siRNA reversed the repression of TNFa-induced IL-8 and IL-6 mRNA expression and protein secretion by FTY720. Therefore we propose that PP2A activators affect the dynamic equilibrium regulating TTP; shifting the equilibrium from phosphorylated (inactive) towards unphosphorylated (active) but unstable TTP. PP2A activators boost the anti-inflammatory function of TTP and have implications for future pharmacotherapeutic strategies to combat inflammation in respiratory disease.
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2016 |
Gold MJ, Hiebert PR, Park HY, Stefanowicz D, Le A, Starkey MR, et al., 'Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization', Mucosal Immunology, 9 809-820 (2016) [C1]
Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contrib... [more]
Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contributes to allergic sensitization, although the mechanisms governing this process remain unclear. Lung mucosal uric acid has also been linked to allergic sensitization. The links among PM exposure, uric acid, and allergic sensitization remain unexplored. We therefore investigated the mechanisms behind PM-induced allergic sensitization in the context of lung mucosal uric acid. PM 10 and house dust mite exposure selectively induced lung mucosal uric acid production and secretion in vivo, which did not occur with other challenges (lipopolysaccharide, virus, bacteria, or inflammatory/fibrotic stimuli). PM 10 -induced uric acid mediates allergic sensitization and augments antigen-specific T-cell proliferation, which is inhibited by uricase. We then demonstrate that human airway epithelial cells secrete uric acid basally and after stimulation through a previously unidentified mucosal secretion system. Our work discovers a previously unknown mechanism of air pollution-induced, uric acid-mediated, allergic sensitization that may be important in the pathogenesis of asthma.
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Nova |
2016 |
Jarnicki AG, Schilter H, Liu G, Wheeldon K, Essilfie AT, Foot JS, et al., 'The inhibitor of semicarbazide-sensitive amine oxidase, PXS-4728A, ameliorates key features of chronic obstructive pulmonary disease in a mouse model', British Journal of Pharmacology, 173 3161-3175 (2016) [C1]
Background and Purpose: Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death, often induced by cigarette smoking (CS). It is characterized by pulmona... [more]
Background and Purpose: Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death, often induced by cigarette smoking (CS). It is characterized by pulmonary inflammation and fibrosis that impairs lung function. Existing treatments aim to control symptoms but have low efficacy, and there are no broadly effective treatments. A new potential target is the ectoenzyme, semicarbazide-sensitive mono-amine oxidase (SSAO; also known as vascular adhesion protein-1). SSAO is elevated in smokers¿ serum and is a pro-inflammatory enzyme facilitating adhesion and transmigration of leukocytes from the vasculature to sites of inflammation. Experimental Approach: PXS-4728A was developed as a low MW inhibitor of SSAO. A model of COPD induced by CS in mice reproduces key aspects of human COPD, including chronic airway inflammation, fibrosis and impaired lung function. This model was used to assess suppression of SSAO activity and amelioration of inflammation and other characteristic features of COPD. Key Results: Treatment with PXS-4728A completely inhibited lung and systemic SSAO activity induced by acute and chronic CS-exposure. Daily oral treatment inhibited airway inflammation (immune cell influx and inflammatory factors) induced by acute CS-exposure. Therapeutic treatment during chronic CS-exposure, when the key features of experimental COPD develop and progress, substantially suppressed inflammatory cell influx and fibrosis in the airways and improved lung function. Conclusions and Implications: Treatment with a low MW inhibitor of SSAO, PXS-4728A, suppressed airway inflammation and fibrosis and improved lung function in experimental COPD, demonstrating the therapeutic potential of PXS-4728A for this debilitating disease.
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2016 |
Hsu ACY, Parsons K, Moheimani F, Knight DA, Hansbro PM, Fujita T, Wark PA, 'Impaired antiviral stress granule and IFN-ß enhanceosome formation enhances susceptibility to influenza infection in chronic obstructive pulmonary disease epithelium', American Journal of Respiratory Cell and Molecular Biology, 55 117-127 (2016) [C1]
Chronic obstructive pulmonary disease (COPD) is a serious lung disease that progressively worsens lung function. Those affected are highly susceptible to influenza virus infection... [more]
Chronic obstructive pulmonary disease (COPD) is a serious lung disease that progressively worsens lung function. Those affected are highly susceptible to influenza virus infections that result in exacerbations with exaggerated symptoms with increased mortality. The mechanisms underpinning this increased susceptibility to infection in COPD are unclear. In this study, we show that primary bronchial epithelial cells (pBECs) from subjects with COPD have impaired induction of type I IFN (IFN-ß) and lead to heightened viral replication after influenza viral infection. COPD pBECs have reduced protein levels of protein kinase (PK) R and decreased formation of PKR-mediated antiviral stress granules, which are critical in initiating type I IFNinductions. In addition, reduced protein expression of p300 resulted in decreased activation of IFN regulatory factor 3 and subsequent formation of IFN-ß enhanceosome in COPD pBECs. The decreased p300 induction was the result of enhanced levels of microRNA (miR)-132. Ectopic expression of PKR or miR-132 antagomiR alone failed to restore IFN-ß induction, whereas cotreatment increased antiviral stress granule formation, induction of p300, and IFN-ß in COPD pBECs. This study reveals that decreased induction of both PKR and p300 proteins contribute to impaired induction of IFN-ß in COPD pBECs upon influenza infection.
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Nova |
2016 |
Woods JJ, Martin KL, Freeman-Acquah E, Smith M, Hansbro P, Horvat J, Johnstone D, 'Cigarette Smoking: A Causal Factor for Alzheimers Disease?', Journal of Gerontology & Geriatric Research, 05 (2016)
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2016 |
Rahman MM, Prunte L, Lebender LF, Patel BS, Gelissen I, Hansbro PM, et al., 'The phosphorylated form of FTY720 activates PP2A, represses inflammation and is devoid of S1P agonism in A549 lung epithelial cells', SCIENTIFIC REPORTS, 6 (2016) [C1]
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Nova |
2016 |
Dhouib R, Othman DSMP, Lin V, Lai XJ, Wijesinghe HGS, Essilfie A-T, et al., 'A Novel, Molybdenum-Containing Methionine Sulfoxide Reductase Supports Survival of Haemophilus influenzae in an In vivo Model of Infection', FRONTIERS IN MICROBIOLOGY, 7 (2016) [C1]
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Nova |
2016 |
Ge L, Habiel DM, Hansbro PM, Kim RY, Gharib SA, Edelman JD, et al., 'miR-323a-3p regulates lung fibrosis by targeting multiple profibrotic pathways', JCI INSIGHT, 1 (2016) [C1]
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Nova |
2016 |
Starkey MR, Nguyen DH, Brown AC, Essilfie AT, Kim RY, Yagita H, et al., 'PD-L1 Promotes Early-life Chlamydia Respiratory Infection-induced Severe Allergic Airway Disease.', American journal of respiratory cell and molecular biology, (2016) [C1]
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Nova |
2016 |
Rahman MM, Prabhala P, Rumzhum NN, Patel BS, Wickop T, Hansbro PM, et al., 'TLR2 ligation induces corticosteroid insensitivity in A549 lung epithelial cells: Anti-inflammatory impact of PP2A activators', International Journal of Biochemistry and Cell Biology, 78 279-287 (2016) [C1]
Corticosteroids are effective anti-inflammatory therapies widely utilized in chronic respiratory diseases. But these medicines can lose their efficacy during respiratory infection... [more]
Corticosteroids are effective anti-inflammatory therapies widely utilized in chronic respiratory diseases. But these medicines can lose their efficacy during respiratory infection resulting in disease exacerbation. Further in vitro research is required to understand how infection worsens lung function control in order to advance therapeutic options to treat infectious exacerbation in the future. In this study, we utilize a cellular model of bacterial exacerbation where we pretreat A549 lung epithelial cells with the synthetic bacterial lipoprotein Pam3CSK4 (a TLR2 ligand) to mimic bacterial infection and tumor necrosis factor a (TNFa) to simulate inflammation. Under these conditions, Pam3CSK4 induces corticosteroid insensitivity; demonstrated by substantially reduced ability of the corticosteroid dexamethasone to repress TNFa-induced interleukin 6 secretion. We then explored the molecular mechanism responsible and found that corticosteroid insensitivity induced by bacterial mimics was not due to altered translocation of the glucocorticoid receptor into the nucleus, nor an impact on the NF-¿B pathway. Moreover, Pam3CSK4 did not affect corticosteroid-induced upregulation of anti-inflammatory MAPK deactivating phosphatase¿MKP-1. However, Pam3CSK4 can induce oxidative stress and we show that a proportion of the MKP-1 produced in response to corticosteroid in the context of TLR2 ligation was rendered inactive by oxidation. Thus to combat inflammation in the context of bacterial exacerbation we sought to discover effective strategies that bypassed this road-block. We show for the first time that known (FTY720) and novel (theophylline) activators of the phosphatase PP2A can serve as non-steroidal anti-inflammatory alternatives and/or corticosteroid-sparing approaches in respiratory inflammation where corticosteroid insensitivity exists.
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Nova |
2016 |
Ren S, Hure A, Peel R, D'Este C, Abhayaratna W, Tonkin A, et al., 'Rationale and design of a randomized controlled trial of pneumococcal polysaccharide vaccine for prevention of cardiovascular events: The Australian Study for the Prevention through Immunization of Cardiovascular Events (AUSPICE)', American Heart Journal, 177 58-65 (2016)
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2016 |
Gang L, Hsu A, Cooley MA, Jarnicki AG, Nair PM, Haw TJ, et al., 'Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases', Journal of Clinical Investigation Insight, 1 (2016) [C1]
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Nova |
2016 |
Camlin NJ, Sobinoff AP, Sutherland JM, Beckett EL, Jarnicki AG, Vanders RL, et al., 'Maternal Smoke Exposure Impairs the Long-Term Fertility of Female Offspring in a Murine Model.', Biol Reprod, 94 39 (2016) [C1]
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Nova |
2016 |
Moores N, Rogers DI, Rogers K, Hansbro PM, 'Reclamation of tidal flats and shorebird declines in Saemangeum and elsewhere in the Republic of Korea', Emu, 116 136-146 (2016) [C1]
Saemangeum, in the Republic of Korea (ROK, commonly called South Korea) was one of the most important shorebird staging sites in the Yellow Sea. It supported at least 330000 shore... [more]
Saemangeum, in the Republic of Korea (ROK, commonly called South Korea) was one of the most important shorebird staging sites in the Yellow Sea. It supported at least 330000 shorebirds annually between 1997 and 2001, including ~30% of the world population of Great Knots (Calidris tenuirostris) during both northward and southward migration. Construction of a 33-km long sea-wall was completed in April 2006. We show that shorebird numbers at Saemangeum and two adjacent wetlands decreased by 130000 during northward migration in the next two years and that all species have declined at Saemangeum since completion of the sea-wall. Great Knots were among the most rapidly affected species. Fewer than 5000 shorebirds were recorded at Saemangeum during northward migration in 2014. We found no evidence to suggest that most shorebirds of any species displaced from Saemangeum successfully relocated to other sites in the ROK. Instead, by 2011-13 nearly all species had declined substantially in the ROK since previous national surveys in 1998 and 2008, especially at more heavily reclaimed sites. It is likely that these declines were driven by increased mortality rather than movement to alternate staging sites given that other studies have shown concurrent declines in numbers and survival on the non-breeding grounds. This is the first study in the East Asian-Australasian Flyway to confirm declines of shorebirds at a range of geographical scales following a single reclamation project. The results indicate that if migratory shorebirds are displaced from major staging sites by reclamation they are probably unable to relocate successfully to alternate sites.
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Nova |
2016 |
Moheimani F, Hsu AC-Y, Reid AT, Williams T, Kicic A, Stick SM, et al., 'The genetic and epigenetic landscapes of the epithelium in asthma', RESPIRATORY RESEARCH, 17 (2016) [C1]
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Nova |
2016 |
Ormerod KL, Wood DLA, Lachner N, Gellatly SL, Daly JN, Parsons JD, et al., 'Genomic characterization of the uncultured Bacteroidales family S24-7 inhabiting the guts of homeothermic animals.', Microbiome, 4 36 (2016) [C1]
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Nova |
2015 |
Essilfie A, Horvat JC, Kim RY, Mayall JR, Pinkerton JW, Beckett EL, et al., 'Macrolide therapy suppresses key features of experimental steroid-sensitive and steroid-insensitive asthma', Thorax Journal, 70 458-467 (2015) [C1]
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Nova |
2015 |
Vanders RL, Murphy VE, Gibson PG, Hansbro PM, Wark PAB, 'CD8 T cells and dendritic cells: Key players in the attenuated maternal immune response to influenza infection', Journal of Reproductive Immunology, 107 1-9 (2015) [C1]
Pregnancy provides a unique challenge for maternal immunity, requiring the ability to tolerate the presence of a semi-allogeneic foetus, and yet still being capable of inducing an... [more]
Pregnancy provides a unique challenge for maternal immunity, requiring the ability to tolerate the presence of a semi-allogeneic foetus, and yet still being capable of inducing an immune response against invading pathogens. To achieve this, numerous changes must occur in the activity and function of maternal immune cells throughout the course of pregnancy. Respiratory viruses take advantage of these changes, altering the sensitive balance of maternal immunity, leaving the mother with increased susceptibility to viral infections and increased disease severity. Influenza virus is one of the most common respiratory virus infections during pregnancy, leading to an increased risk of ICU hospitalisations, pneumonia, acute respiratory distress syndrome and even death. Whilst much research has been performed to understand the changes that must take place in maternal immunity during pregnancy, considerable work is still needed to fully comprehend this tremendous feat. To date, few studies have focused on the alterations that occur in maternal immunity during respiratory virus infections. This review highlights the role of dendritic cells (DCs) and CD8 T cells during pregnancy, and the changes that occur in these antiviral cells following influenza virus infections.
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Nova |
2015 |
Griekspoor P, Hansbro PM, Waldenström J, Olsen B, 'Campylobacter jejuni sequence types show remarkable spatial and temporal stability in Blackbirds.', Infection ecology & epidemiology, 5 1-5 (2015) [C1]
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Nova |
2015 |
Zouikr I, Ahmed AF, Horvat JC, Beagley KW, Clifton VL, Ray A, et al., 'Programming of formalin-induced nociception by neonatal LPS exposure: Maintenance by peripheral and central neuroimmune activity', Brain, Behavior, and Immunity, 44 235-246 (2015) [C1]
The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of develop... [more]
The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of development are known to produce long-lasting effects on the immune and nociceptive responses. It is less clear, however, whether inflammatory pain responses are primed by neonatal exposure to mild immunological stimuli, such as with lipopolysaccharide (LPS). Here, we examine the impact of neonatal LPS exposure on inflammatory pain responses, peripheral and hippocampal interleukin-1ß (IL-1ß), as well as mast cell number and degranulation in preadolescent and adult rats. Wistar rats were injected with LPS (0.05 mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 22 and 80-97. At both time-points, and one-hour after formalin injection, blood and hippocampus were collected for measuring circulating and central IL-1ß levels using ELISA and Western blot, respectively. Paw tissue was also isolated to assess mast cell number and degree of degranulation using Toluidine Blue staining. Behavioural analyses indicate that at PND 22, LPS-challenged rats displayed enhanced flinching (p<.01) and licking (p<.01) in response to formalin injection. At PNDs 80-97, LPS-challenged rats exhibited increased flinching (p<.05), an effect observed in males only. Furthermore, neonatal LPS exposure enhanced circulating IL-1ß and mast cell degranulation in preadolescent but not adult rats following formalin injection. Hippocampal IL-1ß levels were increased in LPS-treated adult but not preadolescent rats in response to formalin injection. These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, peripheral and central IL-1ß levels, as well as mast cell degranulation following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping immune response and pain sensitivity later in life. This is of clinical relevance given the high prevalence of bacterial infection during the neonatal period, particularly in the vulnerable population of preterm infants admitted to neonatal intensive care units.
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Nova |
2015 |
Tay HL, Kaiko GE, Plank M, Li J, Maltby S, Essilfie A-T, et al., 'Correction: Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung.', PLoS pathogens, 11 e1004956 (2015) [O1]
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2015 |
King PT, Sharma R, O'Sullivan K, Selemidis S, Lim S, Radhakrishna N, et al., 'Nontypeable Haemophilus influenzae Induces Sustained Lung Oxidative Stress and Protease Expression', PLOS ONE, 10 (2015) [C1]
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Nova |
2015 |
Zouikr I, James MH, Campbell EJ, Ahmed AF, Horvat JC, Hansbro PM, et al., 'Early life programming of pain: Neuroimmune to endocrine symphony', Brain, Behavior, and Immunity, 49 e13-e13 (2015)
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2015 |
Moheimani F, Roth HM, Cross J, Reid AT, Shaheen F, Warner SM, et al., 'Disruption of ß-catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repair', International Journal of Biochemistry and Cell Biology, 68 59-69 (2015) [C1]
The epithelium of asthmatics is characterized by reduced expression of E-cadherin and increased expression of the basal cell markers ck-5 and p63 that is indicative of a relativel... [more]
The epithelium of asthmatics is characterized by reduced expression of E-cadherin and increased expression of the basal cell markers ck-5 and p63 that is indicative of a relatively undifferentiated repairing epithelium. This phenotype correlates with increased proliferation, compromised wound healing and an enhanced capacity to undergo epithelial-mesenchymal transition (EMT). The transcription factor ß-catenin plays a vital role in epithelial cell differentiation and regeneration, depending on the co-factor recruited. Transcriptional programs driven by the ß-catenin/CBP axis are critical for maintaining an undifferentiated and proliferative state, whereas the ß-catenin/p300 axis is associated with cell differentiation. We hypothesized that disrupting the ß-catenin/CBP signaling axis would promote epithelial differentiation and inhibit EMT. We treated monolayer cultures of human airway epithelial cells with TGFß1 in the presence or absence of the selective small molecule ICG-001 to inhibit ß-catenin/CBP signaling. We used western blots to assess expression of an EMT signature, CBP, p300, ß-catenin, fibronectin and ITGß1 and scratch wound assays to assess epithelial cell migration. Snai-1 and -2 expressions were determined using q-PCR. Exposure to TGFß1 induced EMT, characterized by reduced E-cadherin expression with increased expression of a-smooth muscle actin and EDA-fibronectin. Either co-treatment or therapeutic administration of ICG-001 completely inhibited TGFß1-induced EMT. ICG-001 also reduced the expression of ck-5 and -19 independent of TGFß1. Exposure to ICG-001 significantly inhibited epithelial cell proliferation and migration, coincident with a down regulation of ITGß1 and fibronectin expression. These data support our hypothesis that modulating the ß-catenin/CBP signaling axis plays a key role in epithelial plasticity and function.
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Nova |
2015 |
Baillet AC, Rehaume LM, Benham H, O'Meara CP, Armitage CW, Ruscher R, et al., 'High Chlamydia Burden Promotes Tumor Necrosis Factor-Dependent Reactive Arthritis in SKG Mice', ARTHRITIS & RHEUMATOLOGY, 67 1535-1547 (2015) [C1]
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Nova |
2015 |
Hsu ACY, Starkey MR, Hanish I, Parsons K, Haw TJ, Howland LJ, et al., 'Targeting PI3K-p110a suppresses influenza virus infection in chronic obstructive pulmonary disease', American Journal of Respiratory and Critical Care Medicine, 191 1012-1023 (2015) [C1]
Rationale: Chronic obstructive pulmonary disease (COPD) and influenza virus infections are major global health issues. Patients with COPD are more susceptible to infection, which ... [more]
Rationale: Chronic obstructive pulmonary disease (COPD) and influenza virus infections are major global health issues. Patients with COPD are more susceptible to infection, which exacerbates their condition and increases morbidity and mortality. The mechanisms of increased susceptibility remain poorly understood, and current preventions and treatments have substantial limitations. Objectives: To characterize the mechanisms of increased susceptibility to influenza virus infection in COPD and the potential for therapeutic targeting. Methods: We used a combination of primary bronchial epithelial cells (pBECs) from COPD and healthy control subjects, a mouse model of cigarette smoke-induced experimental COPD, and influenza infection. The role of the phosphoinositide-3-kinase (PI3K) pathway was characterized using molecular methods, and its potential for targeting assessed using inhibitors. Measurements and Main Results: COPDpBECs were susceptible to increased viral entry and replication. Infected mice with experimental COPD also had more severe infection (increased viral titer and pulmonary inflammation, and compromised lung function). These processes were associated with impaired antiviral immunity, reduced retinoic acid-inducible gene-I, and IFN/cytokine and chemokine responses. Increased PI3K-p110a levels and activity inCOPDpBECs and/or mice were responsible for increased infection and reduced antiviral responses. Global PI3K, specific therapeutic p110a inhibitors, or exogenous IFN-b restored protective antiviral responses, suppressed infection, and improved lung function. Conclusions: The increased susceptibility of individuals with COPD to influenza likely results from impaired antiviral responses, which are mediated by increased PI3K-p110a activity. This pathway may be targeted therapeutically in COPD, or in healthy individuals, during seasonal or pandemic outbreaks to prevent and/or treat influenza.
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Nova |
2015 |
Sozo F, Horvat JC, Essilfie A-T, O'Reilly M, Hansbro PM, Harding R, 'Altered lung function at mid-adulthood in mice following neonatal exposure to hyperoxia.', Respir Physiol Neurobiol, 218 21-27 (2015) [C1]
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Nova |
2015 |
Grillo VL, Arzey KE, Hansbro PM, Hurt AC, Warner S, Bergfeld J, et al., 'Avian influenza in Australia: A summary of 5 years of wild bird surveillance', Australian Veterinary Journal, 93 387-393 (2015) [C1]
Background: Avian influenza viruses (AIVs) are found worldwide in numerous bird species, causing significant disease in gallinaceous poultry and occasionally other species. Survei... [more]
Background: Avian influenza viruses (AIVs) are found worldwide in numerous bird species, causing significant disease in gallinaceous poultry and occasionally other species. Surveillance of wild bird reservoirs provides an opportunity to add to the understanding of the epidemiology of AIVs. Methods: This study examined key findings from the National Avian Influenza Wild Bird Surveillance Program over a 5-year period (July 2007-June 2012), the main source of information on AIVs circulating in Australia. Results: The overall proportion of birds that tested positive for influenza A via PCR was 1.9±0.1%, with evidence of widespread exposure of Australian wild birds to most low pathogenic avian influenza (LPAI) subtypes (H1-13, H16). LPAI H5 subtypes were found to be dominant and widespread during this 5-year period. Conclusion: Given Australia's isolation, both geographically and ecologically, it is important for Australia not to assume that the epidemiology of AIV from other geographic regions applies here. Despite all previous highly pathogenic avian influenza outbreaks in Australian poultry being attributed to H7 subtypes, widespread detection of H5 subtypes in wild birds may represent an ongoing risk to the Australian poultry industry.
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2015 |
Singanayagam A, Glanville N, Walton RP, Aniscenko J, Pearson RM, Pinkerton JW, et al., 'A short-term mouse model that reproduces the immunopathological features of rhinovirus-induced exacerbation of COPD.', Clin Sci (Lond), 129 245-258 (2015) [C1]
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Nova |
2015 |
Plank MW, Maltby S, Tay HL, Stewart J, Eyers F, Hansbro PM, Foster PS, 'MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity.', PloS one, 10 1-25 (2015) [C1]
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Nova |
2015 |
Tolosa JM, Parsons KS, Hansbro PM, Smith R, Wark PB, 'The placental protein syncytin-1 impairs antiviral responses and exaggerates inflammatory responses to influenza', PLoS ONE, 10 (2015) [C1]
Background Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1.We hypothesised that exposure of pe... [more]
Background Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1.We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm09 influenza. Methods and Findings Recombinant syncytin-1 was produced. PBMCs from non-pregnant women (n=10) were exposed to H1N1pdm09 in the presence and absence of syncytin-1 and compared to responses of PBMCs from pregnant women (n=12). PBMCs were characterised using flow cytometry, release of interferon (IFN)-a, IFN-¿, IFN-¿, IL-10, IL-2, IL-6 and IL-1ß were measured by cytometric bead array or ELISA. Exposure of PBMCs to H1N1pdm09 resulted in the release of IFN-a, (14,787 pg/mL, 95% CI 7311-22,264 pg/mL) IFN-¿ (1486 pg/mL, 95% CI 756-2216 pg/mL) and IFN-¿ (852 pg/mL, 95% CI 193-1511 pg/mL) after 48 hours. This was significantly impaired in pregnant women (IFN-a; p<0.0001 and IFN-¿; p<0.001). Furthermore, in the presence of syncytin-1, PBMCs demonstrated marked reductions in IFN-a and IFN-¿, while enhanced release of IL-10 as well as IL-6 and IL-1ß. Conclusions Our data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza.
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Nova |
2015 |
Hirota JA, Gold MJ, Hiebert PR, Parkinson LG, Wee T, Smith D, et al., 'The Nucleotide-Binding Domain, Leucine-Rich Repeat Protein 3 Inflammasome/IL-1 Receptor I Axis Mediates Innate, but Not Adaptive, Immune Responses after Exposure to Particulate Matter under 10 mu m', AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 52 96-105 (2015) [C1]
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Nova |
2015 |
Ge Q, Chen L, Jaffar J, Argraves WS, Twal WO, Hansbro P, et al., 'Fibulin1C peptide induces cell attachment and extracellular matrix deposition in lung fibroblasts', SCIENTIFIC REPORTS, 5 (2015) [C1]
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Nova |
2015 |
Kim RY, Pinkerton JW, Gibson PG, Cooper MA, Horvat JC, Hansbro PM, 'Inflammasomes in COPD and neutrophilic asthma', THORAX, 70 1199-1201 (2015) [C1]
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Nova |
2015 |
Tay HL, Kaiko GE, Plank M, Li JJ, Maltby S, Essilfie AT, et al., 'Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung', PLoS Pathogens, 11 (2015) [C1]
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibio... [more]
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.
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Nova |
2015 |
Dhouib R, Pg Othman DSM, Essilfie AT, Hansbro PM, Hanson JO, McEwan AG, Kappler U, 'Maturation of molybdoenzymes and its influence on the pathogenesis of non-typeable Haemophilus influenzae', Frontiers in Microbiology, 6 (2015) [C1]
Mononuclear molybdenum enzymes of the dimethylsulfoxide (DMSO) reductase family occur exclusively in prokaryotes, and a loss of some these enzymes has been linked to a loss of bac... [more]
Mononuclear molybdenum enzymes of the dimethylsulfoxide (DMSO) reductase family occur exclusively in prokaryotes, and a loss of some these enzymes has been linked to a loss of bacterial virulence in several cases. The MobA protein catalyzes the final step in the synthesis of the molybdenum guanine dinucleotide (MGD) cofactor that is exclusive to enzymes of the DMSO reductase family. MobA has been proposed as a potential target for control of virulence since its inhibition would affect the activities of all molybdoenzymes dependent upon MGD. Here, we have studied the phenotype of a mobA mutant of the host-adapted human pathogen Haemophilus influenzae. H. influenzae causes and contributes to a variety of acute and chronic diseases of the respiratory tract, and several enzymes of the DMSO reductase family are conserved and highly expressed in this bacterium. The mobA mutation caused a significant decrease in the activities of all Mo-enzymes present, and also resulted in a small defect in anaerobic growth. However, we did not detect a defect in in vitro biofilm formation nor in invasion and adherence to human epithelial cells in tissue culture compared to the wild-type. In a murine in vivo model, the mobA mutant showed only a mild attenuation compared to the wild-type. In summary, our data show that MobA is essential for the activities of molybdenum enzymes, but does not appear to affect the fitness of H. influenzae. These results suggest that MobA is unlikely to be a useful target for antimicrobials, at least for the purpose of treating H. influenzae infections.
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Nova |
2015 |
Tay H, Kaiko G, Mattes J, Hansbro P, Foster P, 'The role of miR-328 in respiratory diseases (INM3P.410)', The Journal of Immunology, 194 127.15-127.15 (2015)
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2014 |
Starkey MR, Nguyen DH, Essilfie AT, Kim RY, Hatchwell LM, Collison AM, et al., 'Tumor necrosis factor-related apoptosis-inducing ligand translates neonatal respiratory infection into chronic lung disease.', Mucosal Immunol, 7 478-488 (2014) [C1]
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Nova |
2014 |
Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, et al., 'The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation.', Nat Immunol, 15 727-737 (2014) [C1]
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Nova |
2014 |
Olson SH, Parmley J, Soos C, Gilbert M, Latorre-Margalef N, Hall JS, et al., 'Sampling strategies and biodiversity of influenza A subtypes in wild birds', PLoS ONE, 9 (2014) [C1]
Wild aquatic birds are recognized as the natural reservoir of avian influenza A viruses (AIV), but across high and low pathogenic AIV strains, scientists have yet to rigorously id... [more]
Wild aquatic birds are recognized as the natural reservoir of avian influenza A viruses (AIV), but across high and low pathogenic AIV strains, scientists have yet to rigorously identify most competent hosts for the various subtypes. We examined 11,870 GenBank records to provide a baseline inventory and insight into patterns of global AIV subtype diversity and richness. Further, we conducted an extensive literature review and communicated directly with scientists to accumulate data from 50 non-overlapping studies and over 250,000 birds to assess the status of historic sampling effort. We then built virus subtype sample-based accumulation curves to better estimate sample size targets that capture a specific percentage of virus subtype richness at seven sampling locations. Our study identifies a sampling methodology that will detect an estimated 75% of circulating virus subtypes from a targeted bird population and outlines future surveillance and research priorities that are needed to explore the influence of host and virus biodiversity on emergence and transmission.
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Nova |
2014 |
Grafton KT, Moir LM, Black JL, Hansbro NG, Hansbro PM, Burgess JK, Oliver BG, 'LF-15 & T7, synthetic peptides derived from tumstatin, attenuate aspects of airway remodelling in a murine model of chronic OVA-induced allergic airway disease', PLoS ONE, 9 (2014) [C1]
Background: Tumstatin is a segment of the collagen-IV protein that is markedly reduced in the airways of asthmatics. Tumstatin can play an important role in the development of air... [more]
Background: Tumstatin is a segment of the collagen-IV protein that is markedly reduced in the airways of asthmatics. Tumstatin can play an important role in the development of airway remodelling associated with asthma due to its antiangiogenic properties. This study assessed the anti-angiogenic properties of smaller peptides derived from tumstatin, which contain the interface tumstatin uses to interact with the aVb3 integrin. Methods: Primary human lung endothelial cells were exposed to the LF-15, T3 and T7 tumstatin-derived peptides and assessed for cell viability and tube formation in vitro. The impact of the anti-angiogenic properties on airways hyperresponsiveness (AHR) was then examined using a murine model of chronic OVA-induced allergic airways disease. Results: The LF-15 and T7 peptides significantly reduced endothelial cell viability and attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had reduced total lung vascularity and AHR was attenuated compared to mice exposed to OVA alone. T3 peptides reduced cell viability but had no effect on any other parameters. Conclusion: The LF-15 and T7 peptides may be appropriate candidates for use as novel pharmacotherapies due to their small size and anti-angiogenic properties observed in vitro and in vivo. © 2014 Grafton et al.
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Nova |
2014 |
Simpson JL, Powell H, Baines KJ, Milne D, Coxson HO, Hansbro PM, Gibson PG, 'The Effect of Azithromycin in Adults with Stable Neutrophilic COPD: A Double Blind Randomised, Placebo Controlled Trial', PLOS ONE, 9 (2014) [C1]
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Nova |
2014 |
Rehaume LM, Mondot S, Aguirre De Cárcer D, Velasco J, Benham H, Hasnain SZ, et al., 'ZAP-70 genotype disrupts the relationship between microbiota and host, leading to spondyloarthritis and ileitis in SKG mice', Arthritis and Rheumatology, 66 2780-2792 (2014) [C1]
Objective The spondyloarthritides share genetic susceptibility, interleukin-23 (IL-23) dependence, and the involvement of microbiota. The aim of the current study was to elucidate... [more]
Objective The spondyloarthritides share genetic susceptibility, interleukin-23 (IL-23) dependence, and the involvement of microbiota. The aim of the current study was to elucidate how host genetics influence gut microbiota and the relationship between microbiota and organ inflammation in spondyloarthritides.
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Nova |
2014 |
Keely S, Hansbro PM, 'Lung-Gut Cross Talk A Potential Mechanism for Intestinal Dysfunction in Patients With COPD', CHEST, 145 199-200 (2014) [C3]
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2014 |
Jaffer J, Unger S, Corte TJ, Keller M, Wolters PJ, Richeldi L, et al., 'Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis', CHEST, 146 1055-1063 (2014) [C1]
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Nova |
2014 |
Hansbro PM, Hamilton MJ, Fricker M, Gellatly SL, Jarnicki AG, Zheng D, et al., 'Importance of mast cell Prss31/transmembrane tryptase/tryptase- in lung function and experimental chronic obstructive pulmonary disease and colitis', Journal of Biological Chemistry, 289 18214-18227 (2014) [C1]
Protease serine member S31 (Prss31)/transmembrane tryptase/tryptase-¿ is a mast cell (MC)-restricted protease of unknown function that is retained on the outer leaflet of the plas... [more]
Protease serine member S31 (Prss31)/transmembrane tryptase/tryptase-¿ is a mast cell (MC)-restricted protease of unknown function that is retained on the outer leaflet of the plasma membrane when MCs are activated. We determined the nucleotide sequences of the Prss31 gene in different mouse strains and then used a Cre/loxP homologous recombination approach to create a novel Prss31 -/- C57BL/6 mouse line. The resulting animals exhibited no obvious developmental abnormality, contained normal numbers of granulated MCs in their tissues, and did not compensate for their loss of the membrane tryptase by increasing their expression of other granule proteases. When Prss31-null MCs were activated with a calcium ionophore or by their high affinity IgE receptors, they degranulated in a pattern similar to that of WT MCs. Prss31-null mice had increased baseline airway reactivity to methacholine but markedly reduced experimental chronic obstructive pulmonary disease and colitis, thereby indicating both beneficial and adverse functional roles for the tryptase. In a cigarette smokeinduced model of chronic obstructive pulmonary disease, WT mice had more pulmonary macrophages, higher histopathology scores, and more fibrosis in their small airways than similarly treated Prss31-null mice. In a dextran sodium sulfate-induced acute colitis model, WT mice lost more weight, had higher histopathology scores, and contained more Cxcl-2 and IL-6 mRNA in their colons than similarly treated Prss31-null mice. The accumulated data raise the possibility that inhibitors of this membrane tryptase may provide additional therapeutic benefit in the treatment of humans with these MC-dependent inflammatory diseases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
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2014 |
Chevalier N, Thorburn AN, Macia L, Tan J, Juglair L, Yagita H, et al., 'Inflammation and lymphopenia trigger autoimmunity by suppression of il-2-controlled regulatory t cell and increase of il-21-mediated effector t cell expansion', Journal of Immunology, 193 4845-4858 (2014) [C1]
The dynamic interplay between regulatory T cells (Tregs) and effector T cells (Teffs) governs the balance between tolerance and effector immune responses. Perturbations of Treg fr... [more]
The dynamic interplay between regulatory T cells (Tregs) and effector T cells (Teffs) governs the balance between tolerance and effector immune responses. Perturbations of Treg frequency and function or imbalances in Treg/Teff levels are associated with the development of autoimmunity. The factors that mediate these changes remain poorly understood and were investigated in this study in murine autoimmune arthritis. Tregs displayed a stable phenotype in arthritic mice and were fully functional in in vitro suppression assays. However, their expansion was delayed relative to Teffs (T follicular helper cells and Th17 cells) during the early stages of autoimmune reactivity. This imbalance is likely to have led to insufficient Treg control of Teffs and induced autoimmunity. Moreover, a counterregulatory and probably IL-7-driven increase in thymic Treg production and recruitment to inflamed tissues was too slow for disease prevention. Increased Teff over Treg expansion was further aggravated by inflammation and lymphopenia. Both these conditions contribute to autoimmune pathogenesis and were accompanied by decreases in the availability of IL-2 and increases in levels of IL-21. IL-2 neutralization or supplementation was used to show that Treg expansion mainly depended on this cytokine. IL-21R2/2 cells were used to demonstrate that IL-21 promoted the maintenance of Teffs. Thus, at inflammatory sites in experimental arthritis, a deficit in IL-2 hampers Treg proliferation, whereas exaggerated IL-21 levels overwhelm Treg control by supporting Teff expansion. This identifies IL-2 and IL-21 as targets for manipulation in therapies for autoimmunity.
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Nova |
2014 |
Fricker M, Walker MM, Talley NJ, Keely S, Hansbro P, 'Tu1732 Colon Pathology in a Mouse Model of Cigarette Smoke Induced Chronic Obstructive Pulmonary Disease (COPD) -A Model for Induction of Crohn's Disease?', Gastroenterology, 146 (2014)
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2014 |
McIlroy DJ, Jarnicki AG, Au GG, Lott N, Smith DW, Hansbro PM, Balogh ZJ, 'Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery', Journal of Critical Care, 29 1133.e1-1133.e5 (2014) [C1]
Introduction: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondri... [more]
Introduction: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondrial DNA (mtDNA) under certain conditions, which is potently proinflammatory. We hypothesized that injury and orthopedic trauma surgery would induce NET production with mtDNA as a structural component. Methods: Neutrophils were isolated 8 trauma patients requiring orthopedic surgery postinjury and up to 5 days postoperatively. Four healthy volunteers provided positive and negative controls. Total hip replacement patients acted as an uninjured surgical control group. Neutrophil extracellular traps were visualized with DNA (Hoechst 33342TM/Sytox Green/MitoSox/MitoTracker) stains using live cell fluorescence microscopy with downstream quantitative polymerase chain reaction analysis of DNA composition. Results: Neutrophil extracellular traps were present after injury in all 8 trauma patients. They persisted for 5 days postoperatively. Delayed surgery resulted in NET resolution, but they reformed postoperatively. Total hip replacement patients developed NETs postoperatively, which resolved by day 5. Quantitative polymerase chain reaction analysis of NET-DNA composition revealed that NETs formed after injury and surgery were made of mtDNA with no detectable nuclear DNA component. Conclusions: Neutrophil extracellular traps formed after major trauma and subsequent surgery contain mtDNA and represent a novel marker of heightened innate immune activation. They could be considered when timing surgery after trauma to prevent systemic NET-induced inflammatory complications.
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Nova |
2014 |
Prieto-García A, Castells MC, Hansbro PM, Stevens RL, 'Mast cell-restricted tetramer-forming tryptases and their beneficial roles in hemostasis and blood coagulation', Immunology and Allergy Clinics of North America, 34 263-281 (2014) [C1]
Tetramer-forming tryptase (hTryptase-ß) was recently discovered to have a prominent role in preventing the internal accumulation of life-threatening fibrin deposits and fibrin-pla... [more]
Tetramer-forming tryptase (hTryptase-ß) was recently discovered to have a prominent role in preventing the internal accumulation of life-threatening fibrin deposits and fibrin-platelet clots. The anticoagulant activity of hTryptase-ß is an explanation for the presence of hemorrhagic disorders in some patients with anaphylaxis or mastocytosis. The fragments of hFibrinogen formed by the proteolysis of this prominent protein by hTryptase-ß could be used as biomarkers in the blood and/or urine for the identification and monitoring of patients with mast cell-dependent disorders. Recombinant hTryptase-ß has potential to be used in clinical settings where it is desirable to inhibit blood coagulation. © 2014 Elsevier Inc.
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2014 |
Hallstrand TS, Hackett TL, Altemeier WA, Matute-Bello G, Hansbro PM, Knight DA, 'Airway epithelial regulation of pulmonary immune homeostasis and inflammation', Clinical Immunology, 151 1-15 (2014) [C1]
Recent genetic, structural and functional studies have identified the airway and lung epithelium as a key orchestrator of the immune response. Further, there is now strong evidenc... [more]
Recent genetic, structural and functional studies have identified the airway and lung epithelium as a key orchestrator of the immune response. Further, there is now strong evidence that epithelium dysfunction is involved in the development of inflammatory disorders of the lung. Here we review the characteristic immune responses that are orchestrated by the epithelium in response to diverse triggers such as pollutants, cigarette smoke, bacterial peptides, and viruses. We focus in part on the role of epithelium-derived interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), as well as CC family chemokines as critical regulators of the immune response. We cite examples of the function of the epithelium in host defense and the role of epithelium dysfunction in the development of inflammatory diseases. © 2013 Elsevier Inc.
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Nova |
2014 |
Hirota JA, Alexis NE, Pui M, Wong S, Fung E, Hansbro P, et al., 'PM10-stimulated airway epithelial cells activate primary human dendritic cells independent of uric acid: Application of an in vitro model system exposing dendritic cells to airway epithelial cell-conditioned media', Respirology, 19 881-890 (2014) [C1]
Background and objective Airway epithelial cells represent the first line of defence against inhaled insults, including air pollution. Air pollution can activate innate immune sig... [more]
Background and objective Airway epithelial cells represent the first line of defence against inhaled insults, including air pollution. Air pollution can activate innate immune signalling in airway epithelial cells leading to the production of soluble mediators that can influence downstream inflammatory cells. Our objective was to develop and validate a model of dendritic cell exposure to airway epithelial cell-conditioned media. After establishing the model, we explored how soluble mediators released from airway epithelial cells in response to air pollution influenced the phenotype of dendritic cells. Methods Human airway epithelial cells were cultured under control and urban particulate matter (PM10) exposure conditions with or without pharmacological inhibitors of the uric acid pathway. Culture supernatants were collected for conditioned media experiments with peripheral blood mononuclear cell-derived dendritic cells analysed by flow cytometry. Results Monocytes derived from peripheral blood mononuclear cells cultured in interleukin-4 and granulocyte macrophage colony stimulating factor differentiated into immature dendritic cells that phenotypically differentiated into mature dendritic cells in response to conditioned media from phorbol myristate acetate-activated THP-1 monocytes. Exposure of immature dendritic cells to conditioned media from airway epithelial cells exposed to PM10 resulted in dendritic cell maturation that was independent of uric acid. Conclusions We present a conditioned media model useful for interrogating the contribution of soluble mediators produced by airway epithelial cells to dendritic cell phenotype and function. Furthermore, we demonstrate that PM10 exposure induces airway epithelial cell production of soluble mediators that induce maturation of dendritic cells independent of uric acid. We developed and validated a model of airway epithelial cell conditioned media exposure to primary human dendritic cells. Using this model, we then tested the hypothesis that urban particulate matter exposure to airway epithelial cells resulted in production of soluble mediators capable of inducing dendritic cell maturation. © 2014 Asian Pacific Society of Respirology.
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Nova |
2014 |
Fricker M, Deane A, Hansbro PM, 'Animal models of chronic obstructive pulmonary disease', Expert Opinion on Drug Discovery, 9 629-645 (2014) [C1]
Introduction: Chronic obstructive pulmonary disease (COPD) is a leading global cause of mortality and chronic morbidity. Inhalation of cigarette smoke is the principal risk factor... [more]
Introduction: Chronic obstructive pulmonary disease (COPD) is a leading global cause of mortality and chronic morbidity. Inhalation of cigarette smoke is the principal risk factor for development of this disease. COPD is a progressive disease that is typically characterised by chronic pulmonary inflammation, mucus hypersecretion, airway remodelling and emphysema that collectively reduce lung function. There are currently no therapies that effectively halt or reverse disease progression. It is hoped that the development of animal models that develop the hallmark features of COPD, in a short time frame, will aid in the identifying and testing of new therapeutic approaches. Areas covered: The authors review the recent developments in mouse models of chronic cigarette smoke-induced COPD as well as the principal findings. Furthermore, the authors discuss the use of mouse models to understand the pathogenesis and the contribution of infectious exacerbations. They also discuss the investigations of the systemic co-morbidities of COPD (pulmonary hypertension, cachexia and osteoporosis). Expert opinion: Recent advances in the field mark a point where animal models recapitulate the pathologies of COPD patients in a short time frame. They also reveal novel insights into the pathogenesis and potential treatment of this debilitating disease. © 2014 Informa UK, Ltd.
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Nova |
2014 |
O'Reilly M, Hansbro PM, Horvat JC, Beckett EL, Harding R, Sozo F, 'Bronchiolar Remodeling in Adult Mice Following Neonatal Exposure to Hyperoxia: Relation to Growth', Anatomical Record, 297 758-769 (2014) [C1]
Preterm infants who receive supplemental oxygen for prolonged periods are at increased risk of impaired lung function later in life. This suggests that neonatal hyperoxia induces ... [more]
Preterm infants who receive supplemental oxygen for prolonged periods are at increased risk of impaired lung function later in life. This suggests that neonatal hyperoxia induces persistent changes in small conducting airways (bronchioles). Although the effects of neonatal hyperoxia on alveolarization are well documented, little is known about its effects on developing bronchioles. We hypothesized that neonatal hyperoxia would remodel the bronchiolar walls, contributing to altered lung function in adulthood. We studied three groups of mice (C57BL/6J) to postnatal day 56 (P56; adulthood) when they either underwent lung function testing or necropsy for histological analysis of the bronchiolar wall. One group inhaled 65% O2 from birth until P7, after which they breathed room air; this group experienced growth restriction (HE+GR group). We also used a group in which hyperoxia-induced GR was prevented by dam rotation (HE group). A control group inhaled room air from birth. At P56, the bronchiolar epithelium of HE mice contained fewer Clara cells and more ciliated cells, and the bronchiolar wall contained ~25% less collagen than controls; in HE+GR mice the bronchiolar walls had ~13% more collagen than controls. Male HE and HE+GR mice had significantly thicker bronchiolar epithelium than control males and altered lung function (HE males: greater dynamic compliance; HE+GR males: lower dynamic compliance). We conclude that neonatal hyperoxia remodels the bronchiolar wall and, in adult males, affects lung function, but effects are altered by concomitant growth restriction. Our findings may partly explain the reports of poor lung function in ex-preterm children and adults. Anat Rec, 297:758-769, 2014. © 2014 Wiley Periodicals, Inc.
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Nova |
2014 |
Keely S, Campbell EL, Baird AW, Hansbro PM, Shalwitz RA, Kotsakis A, et al., 'Contribution of epithelial innate immunity to systemic protection afforded by prolyl hydroxylase inhibition in murine colitis', Mucosal Immunology, 7 114-123 (2014) [C1]
Pharmacological stabilization of hypoxia-inducible factor (HIF) through prolyl hydroxylase (PHD) inhibition limits mucosal damage associated with models of murine colitis. However... [more]
Pharmacological stabilization of hypoxia-inducible factor (HIF) through prolyl hydroxylase (PHD) inhibition limits mucosal damage associated with models of murine colitis. However, little is known about how PHD inhibitors (PHDi) influence systemic immune function during mucosal inflammation or the relative importance of immunological changes to mucosal protection. We hypothesized that PHDi enhances systemic innate immune responses to colitis-associated bacteremia. Mice with colitis induced by trinitrobenzene sulfonic acid were treated with AKB-4924, a new HIF-1 isoform-predominant PHDi, and clinical, immunological, and biochemical endpoints were assessed. Administration of AKB-4924 led to significantly reduced weight loss and disease activity compared with vehicle controls. Treated groups were pyrexic but did not become subsequently hypothermic. PHDi treatment augmented epithelial barrier function and led to an approximately 50-fold reduction in serum endotoxin during colitis. AKB-4924 also decreased cytokines involved in pyrogenesis and hypothermia, significantly reducing serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-a while increasing IL-10. Treatment offered no protection against colitis in epithelial-specific HIF-1a-deficient mice, strongly implicating epithelial HIF-1a as the tissue target for AKB-4924-mediated protection. Taken together, these results indicate that inhibition of prolyl hydroxylase with AKB-4924 enhances innate immunity and identifies that the epithelium is a central site of inflammatory protection afforded by PHDi in murine colitis. © 2014 Society for Mucosal Immunology.
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Nova |
2014 |
Chambers DC, Gellatly SL, Hugenholtz P, Hansbro PM, 'JTD special edition 'Hot Topics in COPD'-The microbiome in COPD', Journal of Thoracic Disease, 6 1525-1531 (2014) [C1]
The pathogenesis of chronic obstructive pulmonary disease (COPD) and its exacerbations, are intricately linked to colonisation and infection with bacteria and other microbes. Desp... [more]
The pathogenesis of chronic obstructive pulmonary disease (COPD) and its exacerbations, are intricately linked to colonisation and infection with bacteria and other microbes. Despite their undeniable importance, we have a poor understanding of the complex relationships between COPD phenotypes, physiology, cellular and molecular biology and the roles of colonising microbe or infecting pathogens. The management algorithms for the care of patients with COPD that include microbial influences, have almost exclusively been developed using microbial methods that were entirely dependent on the ability to grow bacteria on suitable media. The shortcomings of this approach are becoming clear now that it is possible to completely and accurately define the microbial ecology of ecosystems using genomic methods, which do not rely on the ability to cultivate the organisms present. Whilst our appreciation of the relationships between some bacterial ecosystems and the organ in which they reside in humans is now relatively advanced, this is not true for lung. This perspective serves to highlight the growing importance of including an accurate description of bacterial ecology in any attempt to decipher the pathobiology of COPD. While this field is in its infancy, there is significant potential to gain new insights which will translate into more rational and effective treatment algorithms for patients with COPD.
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Nova |
2014 |
Hansbro PM, Starkey MR, Mattes J, Horvat JC, 'Pulmonary immunity during respiratory infections in early life and the development of severe asthma', Annals of the American Thoracic Society, 11 S297-S302 (2014) [C1]
Asthma affects 10% of the population in Westernized countries, being most common in children. It is a heterogeneous condition characterized by chronic allergic airway inflammation... [more]
Asthma affects 10% of the population in Westernized countries, being most common in children. It is a heterogeneous condition characterized by chronic allergic airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR) to normally innocuous antigens. Combination therapies with inhaled corticosteroids and bronchodilators effectively manage mild to moderate asthma, but there are no cures, and patients with severe asthma do not respond to these treatments. The inception of asthma is linked to respiratory viral (respiratory syncytial virus, rhinovirus) and bacterial (Chlamydia, Mycoplasma) infections. The examination of mouse models of early-life infections and allergic airway disease (AAD) provides valuable insights into the mechanisms of disease inception that may lead to the development of more effective therapeutics. For example, early-life, but not adult, Chlamydia respiratory infections in mice permanently modify immunity and lung physiology. This increases the severity of AAD by promoting IL-13 expression, mucus hypersecretion, and AHR. We have identified novel roles for tumor necrosis factor-related apoptosisinducing ligand (TRAIL) and IL-13 in promoting infection-induced pathology in early life and subsequent chronic lung disease. Genetic deletion of TRAIL or IL-13 variously protected against neonatal infection-induced inflammation, mucus hypersecretion, altered lung structure, AHR, and impaired lung function. Therapeutic neutralization of these factors prevented infection-induced severe AAD. Other novel mechanisms and avenues for intervention are also being explored. Such studies indicate the immunological mechanisms that may underpin the association between early-life respiratory infections and the development of more severe asthma and may facilitate the development of tailored preventions and treatments.
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Nova |
2014 |
Sobinoff AP, Sutherland JM, Beckett EL, Stanger SJ, Johnson R, Jarnicki AG, et al., 'Damaging legacy: maternal cigarette smoking has long-term consequences for male offspring fertility.', Hum Reprod, 29 2719-2735 (2014) [C1]
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Nova |
2013 |
Starkey MR, Nguyen DH, Kim RY, Nair PM, Brown AC, Essifie A-T, et al., 'Programming of the Lung in Early Life by Bacterial Infections Predisposes to Chronic Respiratory Disease', CLINICAL OBSTETRICS AND GYNECOLOGY, 56 566-576 (2013) [C1]
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2013 |
Hansbro P, Beckett E, Stevens R, Jarnicki A, Wark P, Foster P, 'A short-term model of COPD identifies a role for mast cell tryptase', EUROPEAN RESPIRATORY JOURNAL, 42 (2013) [C3]
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2013 |
Thorburn AN, Brown AC, Nair PM, Chevalier N, Foster PS, Gibson PG, Hansbro PM, 'Pneumococcal Components Induce Regulatory T Cells That Attenuate the Development of Allergic Airways Disease by Deviating and Suppressing the Immune Response to Allergen', JOURNAL OF IMMUNOLOGY, 191 4112-4120 (2013) [C1]
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Nova |
2013 |
Vijaykrishna D, Deng Y-M, Su YCF, Fourment M, Iannello P, Arzey GG, et al., 'The Recent Establishment of North American H10 Lineage Influenza Viruses in Australian Wild Waterfowl and the Evolution of Australian Avian Influenza Viruses', JOURNAL OF VIROLOGY, 87 10182-10189 (2013) [C1]
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Nova |
2013 |
Fung KY, Mangan NE, Cumming H, Horvat JC, Mayall JR, Stifter SA, et al., 'Interferon-epsilon Protects the Female Reproductive Tract from Viral and Bacterial Infection', SCIENCE, 339 1088-1092 (2013) [C1]
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Nova |
2013 |
Sobinoff AP, Beckett EL, Jarnicki AG, Sutherland JM, McCluskey A, Hansbro PM, McLaughlin EA, 'Scrambled and fried: Cigarette smoke exposure causes antral follicle destruction and oocyte dysfunction through oxidative stress', TOXICOLOGY AND APPLIED PHARMACOLOGY, 271 156-167 (2013) [C1]
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2013 |
Beckett EL, Stevens RL, Jarnicki AG, Kim RY, Hanish I, Hansbro NG, et al., 'A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis', The Journal of Allergy and Clinical Immunology, 131 752-762 (2013) [C1]
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Nova |
2013 |
Foster PS, Plank MW, Collison AM, Tay HL, Kaiko GE, Li J, et al., 'The emerging role of microRNAs in regulating immune and inflammatory responses in the lung', Immunological Reviews, 253 198-215 (2013) [C1]
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Nova |
2013 |
Balogh ZJ, McIlroy DJ, Smith DW, Hansbro PM, 'The origin and the role of mitochondrial DNA in postinjury inflammation', Journal of Critical Care, 28 1099-1100 (2013) [C3]
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Nova |
2013 |
Hansbro P, Horvat J, Essilfie A-T, Kim R, Mayall J, Starkey M, Foster P, 'Macrolides suppress key features of experimental steroid-sensitive and steroid-resistant asthma (P6229)', The Journal of Immunology, 190 62.13-62.13 (2013)
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2013 |
Griekspoor P, Colles FM, Mccarthy ND, Hansbro PM, Ashhurst-Smith C, Olsen B, et al., 'Marked host specificity and lack of phylogeographic population structure of Campylobacter jejuni in wild birds', MOLECULAR ECOLOGY, 22 1463-1472 (2013) [C1]
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Nova |
2013 |
Simpson JL, McDonald VM, Baines KJ, Oreo KM, Wang F, Hansbro PM, Gibson PG, 'Influence of Age, Past Smoking, and Disease Severity on TLR2, Neutrophilic Inflammation, and MMP-9 Levels in COPD', MEDIATORS OF INFLAMMATION, 2013 (2013) [C1]
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Nova |
2013 |
Hansbro PM, Knight DA, 'Are Lymphoid Follicles Important in the Pathogenesis of Chronic Obstructive Pulmonary Disease?', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 188 267-269 (2013) [C3]
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Nova |
2013 |
Hansbro PM, Scott GV, Essilfie A-T, Kim RY, Starkey MR, Nguyen D, et al., 'Th2 cytokine antagonists: Potential treatments for severe asthma', Expert Opinion on Investigational Drugs, 22 49-69 (2013) [C1]
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Nova |
2013 |
Starkey MR, Jarnicki AG, Essilfie A-T, Gellatly SL, Kim RY, Brown AC, et al., 'Murine models of infectious exacerbations of airway inflammation', CURRENT OPINION IN PHARMACOLOGY, 13 337-344 (2013) [C1]
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2013 |
Harding R, O'Reilly M, Sozo F, Hansbro P, Horvat J, Beckett E, 'Persistent effects of neonatal hyperoxia on bronchioles and lung function in adult mice: additional effects of concomitant growth restriction', Paediatric Respiratory Reviews, 14 S69-S69 (2013)
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2013 |
Li JJ, Tay HL, Plank M, Essilfie A-T, Hansbro PM, Foster PS, Yang M, 'Activation of Olfactory Receptors on Mouse Pulmonary Macrophages Promotes Monocyte Chemotactic Protein-1 Production', PLOS ONE, 8 (2013) [C1]
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2013 |
Starkey MR, Essilfie A-T, Horvat JC, Kim RY, Nguyen DH, Beagley KW, et al., 'Constitutive production of IL-13 promotes early-life Chlamydia respiratory infection and allergic airway disease', Mucosal Immunology, 6 569-579 (2013) [C1]
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Nova |
2012 |
Wynne OL, Horvat JC, Smith R, Hansbro PM, Clifton VL, Hodgson DM, 'Effect of neonatal respiratory infection on adult BALB/c hippocampal glucocorticoid and mineralocorticoid receptors', Developmental Psychobiology, 54 568-575 (2012) [C1]
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Nova |
2012 |
Prieto-Garcia A, Zheng D, Adachi R, Xing W, Xing W, Chung K, et al., 'Mast cell restricted mouse and human tryptase-heparin complexes hinder thrombin-induced coagulation of plasma and the generation of fibrin by proteolytically destroying fibrinogen', Journal of Biological Chemistry, 287 7834-7844 (2012) [C1]
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Nova |
2012 |
Thorburn AN, Foster PS, Gibson PG, Hansbro PM, 'Components of streptococcus pneumoniae suppress allergic airways disease and NKT cells by inducing regulatory T cells', The Journal of Immunology, 188 4611-4620 (2012) [C1]
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Nova |
2012 |
Essilfie A-T, Simpson JL, Dunkley ML, Morgan LC, Oliver BG, Gibson PG, et al., 'Combined haemophilus influenzae respiratory infection and allergic airways disease drives chronic infection and features of neutrophilic asthma', Thorax, 67 588-599 (2012) [C1]
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Nova |
2012 |
Suthers B, Hansbro PM, Thambar S, McEvoy MA, Peel R, Attia JR, 'Pneumococcal vaccination may induce anti-oxidized low-density lipoprotein antibodies that have potentially protective effects against cardiovascular disease', Vaccine, 30 3983-3985 (2012) [C1]
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Nova |
2012 |
Yang M, Kumar RK, Hansbro PM, Foster PS, 'Emerging roles of pulmonary macrophages in driving the development of severe asthma', Journal of Leukocyte Biology, 91 557-569 (2012) [C1]
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Nova |
2012 |
Starkey M, Kim R, Horvat J, Essilfie A-T, Beagley K, Mattes J, et al., 'Constitutive IL-13 promotes respiratory chlamydial infection and infection-induced chronic airway hyper-responsiveness (175.18)', The Journal of Immunology, 188 175.18-175.18 (2012)
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2012 |
Hansbro PM, Jarnicki AG, 'Macrolides for macrophages in chronic obstructive pulmonary disease', Respirology, 17 739-740 (2012) [C3]
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Nova |
2012 |
Hsu A, See HV, Hansbro PM, Wark PA, 'Innate immunity to influenza in chronic airways diseases', Respirology, 17 1166-1175 (2012) [C1]
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Nova |
2012 |
Beckett EL, Phipps S, Starkey MR, Horvat JC, Beagley KW, Foster PS, Hansbro PM, 'TLR2, but not TLR4, is required for effective host defence against chlamydia respiratory tract infection in early life', PLOS One, 7 (2012) [C1]
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2012 |
Hsu A, Parsons KS, Barr I, Lowther S, Middleton D, Hansbro PM, Wark PA, 'Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection', PLoS One, 7 (2012) [C1]
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Nova |
2012 |
Starkey MR, Kim RY, Beckett EL, Schilter HC, Shim D, Essilfie A-T, et al., 'Chlamydia muridarum lung infection in infants alters hematopoietic cells to promote allergic airway disease in mice', PLoS One, 7 (2012) [C1]
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2012 |
Keely S, Talley NJ, Hansbro PM, 'Pulmonary-intestinal cross-talk in mucosal inflammatory disease', Mucosal Immunology, 5 7-18 (2012) [C1]
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Nova |
2012 |
Hansbro PM, Starkey MR, Kim RY, Stevens RL, Foster PS, Horvat JC, 'Programming of the lung by early-life infection', Journal of Developmental Origins of Health and Disease, 3 153-158 (2012) [C1]
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Nova |
2011 |
Essilfie A-T, Simpson JL, Horvat JC, Preston JA, Dunkley ML, Foster PS, et al., 'Haemophilus influenzae infection drives IL-17-mediated neutrophilic allergic airways disease', PLoS Pathogens, 7 e1002244 (2011) [C1]
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Nova |
2011 |
Asquith KL, Horvat JC, Kaiko GE, Carey AJ, Beagley KW, Hansbro PM, Foster PS, 'Interleukin-13 promotes susceptibility to chlamydial infection of the respiratory and genital tracts', PLoS Pathogens, 7 (2011) [C1]
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Nova |
2011 |
Temple SEL, Hansbro PM, 'New insights into the immune response to pneumococci', Current Respiratory Medicine Reviews, 7 257-261 (2011) [C1]
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Nova |
2011 |
Wang W, Hansbro PM, Foster PS, Yang M, 'An alternate STAT6-independent pathway promotes eosinophil influx into blood during allergic airway inflammation', PLoS ONE, 6 (2011) [C1]
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Nova |
2011 |
Wynne O, Horvat JC, Kim RY, Ong L, Smith R, Hansbro PM, et al., '131. Sex differences in the effect of neonatal infection and adult re-infection on hippocampal corticosterone receptors and stress response outcomes', Brain, Behavior, and Immunity, 25 S216-S217 (2011)
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2011 |
Hansbro PM, Kaiko GE, Foster PS, 'Cytokine/anti-cytokine therapy - Novel treatments for asthma?', British Journal of Pharmacology, 163 81-95 (2011) [C2]
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Nova |
2011 |
Jennings PC, Merriman-Jones JA, Beckett EL, Hansbro PM, Jones KT, 'Increased zona pellucida thickness and meiotic spindle disruption in oocytes from cigarette smoking mice', Human Reproduction, 26 878-884 (2011) [C1]
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Nova |
2011 |
Wynne OL, Horvat JC, Kim RY, Ong LK, Smith R, Hansbro PM, et al., 'Neonatal respiratory infection and adult re-infection: Effect on glucocorticoid and mineralocorticoid receptors in the hippocampus in BALB/c mice', Brain Behavior and Immunity, 25 1214-1222 (2011) [C1]
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Nova |
2011 |
Hazlewood LC, Wood LG, Hansbro PM, Foster PS, 'Dietary lycopene supplementation suppresses Th2 responses and lung eosinophilia in a mouse model of allergic asthma', Journal of Nutritional Biochemistry, 22 95-100 (2011) [C1]
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Nova |
2011 |
Wynne OL, Horvat JC, Osei-Kumah A, Smith R, Hansbro PM, Clifton VL, Hodgson DM, 'Early life infection alters adult BALB/c hippocampal gene expression in a sex specific manner', Stress-the International Journal on the Biology of Stress, 14 247-261 (2011) [C1]
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Nova |
2011 |
Preston JA, Thorburn AN, Starkey MR, Beckett EL, Horvat JC, Wade MA, et al., 'Streptococcus pneumoniae infection suppresses allergic airways disease by inducing regulatory T-cells', European Respiratory Journal, 37 53-64 (2011) [C1]
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Nova |
2011 |
Hsu A, Barr I, Hansbro PM, Wark PA, 'Human influenza is more effective than Avian influenza at antiviral suppression in airway cells', American Journal of Respiratory Cell and Molecular Biology, 44 906-913 (2011) [C1]
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Nova |
2011 |
Hansbro PM, Hurt AC, 'Influenza surveillance in wild birds in Australia', Microbiology Australia, 32 48-51 (2011) [C1] |
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Nova |
2010 |
Lau JY, Oliver BG, Baraket M, Beckett EL, Hansbro NG, Moir LM, et al., 'Fibulin-1 Is increased in asthma - A novel mediator of airway remodeling?', Plos One, 5 1-13 (2010) [C1]
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Nova |
2010 |
Horvat JC, Starkey MR, Kim RY, Beagley KW, Preston JA, Gibson PG, et al., 'Chlamydial respiratory infection during allergen sensitization drives neutrophilic allergic airways disease', Journal of Immunology, 184 4159-4169 (2010) [C1]
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Nova |
2010 |
Li J, Wang W, Baines KJ, Bowden NA, Hansbro PM, Gibson PG, et al., 'IL-27/IFN-y induce MyD88-dependent steroid-resistant airway hyperresponsiveness by inhibiting glucocorticoid signaling in macrophages', Journal of Immunology, 185 4401-4409 (2010) [C1]
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Nova |
2010 |
Thorburn AN, O'Sullivan BJ, Thomas R, Kumar RK, Foster PS, Gibson PG, Hansbro PM, 'Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease', Thorax, 65 1053-1060 (2010) [C1]
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Nova |
2010 |
Horvat JC, Starkey MR, Kim RY, Phipps S, Gibson PG, Beagley KW, et al., 'Early-life chlamydial lung infection enhances allergic airways disease through age-dependent differences in immunopathology', Journal of Allergy and Clinical Immunology, 125 617-625 (2010) [C1]
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Nova |
2010 |
Starkey MR, Horvat JC, Kim RY, Hansbro PM, 'Reply', Journal of Allergy and Clinical Immunology, 125 1415 (2010) [C3]
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2010 |
Thorburn A, Foster P, Gibson P, Hansbro P, 'Induction of regulatory T cells by a novel immunoregulatory therapy suppresses the development of allergic airways disease', JOURNAL OF IMMUNOLOGY, 184 (2010)
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2010 |
Wood LG, Hazlewood LC, Foster PS, Hansbro PM, 'Lyprinol reduces inflammation and improves lung function in a mouse model of allergic airways disease', Clinical and Experimental Allergy, 40 1785-1793 (2010) [C1]
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Nova |
2010 |
Wang W, Li JJ, Foster PS, Hansbro PM, Yang M, 'Potential Therapeutic Targets for Steroid-Resistant Asthma', Current Drug Targets, 999 1-14 (2010)
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2010 |
Thorburn AN, Hansbro PM, 'Harnessing regulatory T cells to suppress asthma: From Potential to therapy', American Journal of Respiratory Cell and Molecular Biology, 43 511-519 (2010) [C1]
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Nova |
2010 |
Wood LG, Simpson JL, Hansbro PM, Gibson PG, 'Potentially pathogenic bacteria cultured from the sputum of stable asthmatics are associated with increased 8-isoprostane and airway neutrophilia', Free Radical Research, 44 146-154 (2010) [C1]
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Nova |
2010 |
Burgess JK, Boustany S, Moir LM, Weckmann M, Lau JY, Grafton K, et al., 'Reduction of tumstatin in asthmatic airways contributes to angiogenesis, inflammation, and hyperresponsiveness', American Journal of Respiratory and Critical Care Medicine, 181 106-115 (2010) [C1]
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Nova |
2010 |
Hansbro PM, Warner S, Tracey JP, Arzey KE, Selleck P, O'Riley K, et al., 'Surveillance and analysis of avian influenza viruses, Australia', Emerging Infectious Diseases, 16 1896-1904 (2010) [C1]
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Nova |
2010 |
Wang W, Li J, Foster PS, Hansbro PM, Yang M, 'Potential therapeutic targets for steroid-resistant asthma', Current Drug Targets, 11 957-970 (2010) [C1]
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Nova |
2009 |
Thorburn AN, Hansbro PM, Gibson PG, 'Pneumococcal vaccines for allergic airways diseases', Expert Opinion on Biological Therapy, 9 621-629 (2009) [C1]
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Nova |
2009 |
Haynes L, Arzey E, Bell C, Buchanan N, Burgess G, Cronan V, et al., 'Australian surveillance for avian influenza viruses in wild birds between July 2005 and June 2007', Australian Veterinary Journal, 87 266-272 (2009) [C1]
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Nova |
2009 |
Beagley K, Huston WM, Hansbro PM, Timms P, 'Chlamydial infection of immune cells: Altered function and implications for disease', Critical Reviews in Immunology, 29 275-305 (2009) [C1]
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Nova |
2009 |
Hansbro PM, Starkey MR, Horvat JC, Kim RY, Phipps S, Gibson PG, Foster PS, 'Early life chlamydial infection enhances allergic airways disease through age-dependent differences in immunopathology (79.20)', The Journal of Immunology, 182 79.20-79.20 (2009)
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2008 |
Wynne O, Horvat J, Smith R, Hansbro P, Clifton V, Hodgson D, '64. Impact of neonatal infection on adult hippocampal glucocorticoid receptor and mineralocorticoid receptor abundance', Brain, Behavior, and Immunity, 22 19-19 (2008)
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2008 |
Kaiko GE, Horvat JC, Beagley KW, Hansbro PM, 'Immunological decision-making: How does the immune system decide to mount a helper T-cell response?', Immunology, 123 326-338 (2008) [C1]
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Nova |
2008 |
Kaiko GE, Phipps S, Hickey DK, Lam CE, Hansbro PM, Foster PS, Beagley KW, 'Chlamydia muridarum infection subverts dendritic cell function to promote Th2 immunity and airways hyperreactivity', Journal of Immunology, 180 2225-2232 (2008) [C1]
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Nova |
2008 |
Asquith KL, Ramshaw HS, Hansbro PM, Beagley KW, Lopez AF, Foster PS, 'The IL-3/IL-5/GM-CSF common beta receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation', Journal of Immunology, 180 1199-1206 (2008) [C1]
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Nova |
2008 |
Hansbro NG, Horvat JC, Wark PA, Hansbro PM, 'Understanding the mechanisms of viral induced asthma: New therapeutic directions', Pharmacology & Therapeutics, 117 313-353 (2008) [C1]
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Nova |
2007 |
Ashhurst-Smith CIJ, Hall ST, Walker PJ, Stuart JE, Hansbro PM, Blackwell CC, 'Isolation of Alloiococcus otitidis from Indigenous and non-Indigenous Australian children with chronic otitis media with effusion', FEMS Immunology and Medical Microbiology, 51 163-170 (2007) [C1]
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2007 |
Horvat JC, Beagley KW, Wade MA, Preston JA, Hansbro NG, Hickey DK, et al., 'Neonatal chlamydial infection induces mixed T-cell responses that drive allergic airway disease', American Journal of Respiratory and Critical Care Medicine, 176 556-564 (2007) [C1]
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Nova |
2007 |
Preston JA, Essilfie AT, Horvat JC, Wade MA, Beagley KW, Gibson PG, et al., 'Inhibition of allergic airways disease by immunomodulatory therapy with whole killed Streptococcus pneumoniae', Vaccine, 25 8154-8162 (2007) [C1]
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Nova |
2006 |
Skelding KA, Hickey DK, Horvat JC, Bao SS, Roberts KG, Read JM, et al., 'Comparison of intranasal and transcutaneous immunization for induction of protective immunity against Chlamydia muridarum respiratory tract infection', Vaccine, 24 355-366 (2006) [C1]
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Nova |
2006 |
Hurt AC, Hansbro PM, Selleck P, Olsen B, Minton C, Hampson AW, Barr IG, 'Isolation of avian influenza viruses from two different transhemispheric migratory shorebird species in Australia', Archives of Virology, 151 2301-2309 (2006) [C1]
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2006 |
Gasanov U, Koina CA, Beagley KW, Aitken RJ, Hansbro PM, 'Identification of the insulin-like growth factor II receptor as a novel receptor for binding and invasion by Listeria monocytogenes', Infection and Immunity, 74 566-577 (2006) [C1]
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2006 |
Sharkhuu T, Matthaei KI, Forbes E, Mahalingam S, Hogan SP, Hansbro PM, Foster PS, 'Mechanism of interleukin-25 (IL-17E)-induced pulmonary inflammation and airways hyper-reactivity', Clinical and Experimental Allergy, 36 1575-1583 (2006) [C1]
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2006 |
Yang M, Mattes J, Hansbro PM, Foster PS, 'Employment of microRNA profiles and RNA interference and antagomirs for the characterization and treatment of respiratory disease', Drug Discovery Today: Therapeutic Strategies, 3 325-332 (2006) [C1]
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Nova |
2005 |
Gasanov U, Hughes D, Hansbro PM, 'Methods for the isolation and identification of Listeria spp. and Listeria monocytogenes: a review', FEMS Microbiology Reviews, 29 851-875 (2005) [C1]
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Nova |
2005 |
Stephenson J, Budd GM, Manning J, Hansbro PM, 'Major eruption-induced changes to the McDonald Islands, southern Indian Ocean', Antarctic Science, 17 259-266 (2005) [C1]
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2004 |
Howland LJ, Hickey DK, Skelding KA, Bao S, Rendina AM, Hansbro PM, et al., 'Transcutaneous immunization with combined cholera toxin and CpG adjuvant protects against Chlamydia muridarum genital tract infection', Infection and Immunity, 72 1019-1028 (2004) [C1]
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2004 |
Hansbro PM, Beagley KW, Horvat JC, Gibson PG, 'Role of atypical bacterial infection of the lung in predisposition/protection of asthma', Pharmacology and Therapeutics, 101 193-210 (2004) [C1]
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Nova |
2004 |
Preston JA, Beagley KW, Gibson PG, Hansbro PM, 'Genetic background affects susceptibility in nonfatal pneumococcal bronchopneumonia', Eur Respir J, 23 224-231 (2004) [C1]
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Nova |
2002 |
Badcock D, Hansbro PM, Hanniffy S, Clarke V, Schofield K, Robinson K, et al., 'Identification of Pneumoccal Vaccine Antigens Using a Gram-positive Secretion Reporter Screen in Lactococcus lactis', 3rd International Symposium on Pneumococci and Pneumococcal Diseases, n/a 103 (2002) [C3] |
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2002 |
Preston JA, Beagley KW, Gibson PG, Hansbro PM, 'Development of a Pneumococcal Pneumonia Recovery Model in Mice', 3rd International Symposium on Pneumococci and Pneumococcal Diseases, n/a 91 (2002) [C3]
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2001 |
Preston JA, Beagley KW, Gibson PG, Hansbro PM, 'Effects of Infections by Streptococcus pneumoniae on Eosinophilic Immune Responses', Official Journal of the Australian Society for Microbiology, 22 A82 (2001) [C3]
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2001 |
Hansbro PM, Wells JM, Le Page RWF, Kyd J, 'Characterisation of a 37 kDa surface protein of Streptococcus pneumoniae that is protective against pneumococcal challenge', Final Program American Society for Microbiology, 101 General Meeting, 101 74 (2001) [C3] |
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2000 |
Clark-Walker GD, Hansbro PM, Gibson F, Chen XJ, 'Mutant residues suppressing rho(0)-lethality in Kluyveromyces lactis occur at contact sites between subunits of F-1-ATPase', BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 1478 125-137 (2000)
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1998 |
Chen XJ, Hansbro PM, Clark-Walker GD, 'Suppression of rho(0) lethality by mitochondrial ATP synthase F-1 mutations in Kluyveromyces lactis occurs in the absence of F-0', MOLECULAR AND GENERAL GENETICS, 259 457-467 (1998)
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1998 |
Hansbro PM, Chen XJ, Clark-Walker GD, 'Allele specific expression of the Mgi(-) phenotype on disruption of the F-1-ATPase delta-subunit gene in Kluyveromyces lactis', CURRENT GENETICS, 33 46-51 (1998)
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1995 |
O'Brien R, Taske N, Hansbro P, Matthaei K, Hogan S, Denborough M, Foster PS, 'Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha 1 subunit as frequent causes of malignant hyperthermia', Journal of Medical Genetics, 32 913-914 (1995) [C1]
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1994 |
Hansbro P, Foster PS, Hogan S, Ozaki S, Denborough M, 'Purification and characterization of D-myo-Inositol (1,4,5)/(1,3,4,5)-polyphosphate 5-phosphatase from skeletal muscle', Archives of Biochemistry and Biophysics, 311 47-54 (1994) [C1]
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1994 |
Foster PS, Hansbro P, Liu C, Potter B, Denborough M, 'Kinetic analysis of novel inhibitors of inositol polyphosphate metabolism', Biochemical and Biophysical Research Communications, 200 8-15 (1994) [C1]
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1994 |
Foster PS, Hogan S, Hansbro P, O'Brien R, Potter B, Ozaki S, Denborough M, 'The metabolism of D-myo-inositol 1,4,5-trisphosphate and D-myo-inositol 1,3,4,5-tetrakisphosphate by porcine skeletal muscle', European Journal of Biochemistry, 222 955-964 (1994) [C1]
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1994 |
Hogan S, Foster PS, Hansbro P, Ozaki S, Denborough M, 'Detection and partial purification of inositol 1,4,5-trisphosphate 3-kinase from porcine skeletal muscle', Cellular Signalling, 6 233-243 (1994) [C1]
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1992 |
HANSBRO PM, BYARD SJ, BUSHBY RJ, TURNBULL PJH, BODEN N, SAUNDERS MR, et al., 'THE CONFORMATIONAL BEHAVIOR OF PHOSPHATIDYLINOSITOL IN MODEL MEMBRANES - H-2-NMR STUDIES', BIOCHIMICA ET BIOPHYSICA ACTA, 1112 187-196 (1992)
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1990 |
BUSHBY RJ, BYARD SJ, HANSBRO PM, REID DG, 'THE CONFORMATIONAL BEHAVIOR OF PHOSPHATIDYLINOSITOL', BIOCHIMICA ET BIOPHYSICA ACTA, 1044 231-236 (1990)
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1988 |
SCHORAH CJ, BISHOP N, WALES JK, HANSBRO PM, HABIBZADEH N, 'BLOOD VITAMIN-C CONCENTRATIONS IN PATIENTS WITH DIABETES-MELLITUS', INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH, 58 312-318 (1988)
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