Publications by authors named "Philip M Hansbro"

Background Osteoprotegerin (OPG), a decoy receptor for receptor activator of NF-kB ligand (RANKL), serves as a biomarker for liver fibrosis severity. Our recent findings show OPG production in fibrotic lung tissue, though its specific cellular source and role in pulmonary fibrosis are unknown. We hypothesized that OPG is produced by fibroblasts and serves as a marker for pulmonary fibrosis progression.

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Variations in the airway microbiome are associated with inflammatory responses in the lung and pulmonary disease outcomes. Regional changes in microbiome composition could have spatial effects on the metabolic environment, contributing to differences in the host response. Here, we profiled the respiratory microbiome (metagenome/metatranscriptome) and metabolome of a patient cohort, uncovering topographical differences in microbial function, which were further delineated using isotope probing in mice.

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Next-generation vaccines are essential to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should elicit broad protection, provide long-lasting immunity and ensure equitable access for all populations. In this study, we developed a panel of chimeric, full-length spike antigens incorporating mutations from previous, circulating and predicted SARS-CoV-2 variants.

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Background: Preeclampsia is a complex pregnancy disorder characterized by the new onset of hypertension and organ dysfunction, often leading to significant maternal and fetal morbidity and mortality. Placental dysfunction is a hallmark feature of preeclampsia, which is often caused by inappropriate trophoblast cell function in association with oxidative stress, inflammation and/or pathological hypoxia. This study explores the role of oxidative stress in trophoblast cell-based models mimicking the preeclamptic placenta and evaluates potential therapeutic strategies targeting these mechanisms.

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Females are disproportionately affected by asthma. An increased understanding of how female sex hormones influence key pathophysiological processes that underpin asthma may identify new, more effective asthma therapies, particularly for females with severe, poorly controlled asthma. We assessed the effects of oral ethinylestradiol/levonorgestrel (representing OCP use) and depot-medroxyprogesterone acetate (DMPA) and estradiol injections on key features of experimental asthma, and determined their effects on glucose transporter-1 (GLUT-1).

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Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in chronic obstructive pulmonary disease (COPD) is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1) that induced collagen and airway remodeling.

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Tobacco smoking is prevalent across the world and causes numerous diseases. Cigarette smoke (CS) compromises immunity, yet little is known of the components of CS that impact T cell function. MR1 is a ubiquitous molecule that presents bacterial metabolites to MAIT cells, which are highly abundant in the lungs.

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Article Synopsis
  • Lung cancer (LC) is the leading cause of cancer mortality, with significant implications from the interplay between human genetics and microbial cells in the body.
  • The gut-lung axis and interactions between gut and lung microbiomes are believed to influence the progression of lung cancer and other lung diseases.
  • Advances in 16s rDNA sequencing have revealed the role of the lung microbiome in tumor development and treatment responses, suggesting that microbiome-based therapies could be a promising approach for improving LC treatment outcomes.
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Purpose Of Review: Advances in DNA sequencing and analysis of the respiratory microbiome highlight its close association with bronchiectasis phenotypes, revealing fresh opportunities for diagnosis, stratification, and personalized clinical intervention. An under-recognized condition, bronchiectasis is increasingly the subject of recent large-scale, multicentre, and longitudinal clinical studies including detailed analysis of the microbiome. In this review, we summarize recent progress in our understanding of the bronchiectasis microbiome within the context of its potential use in treatment decisions.

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Article Synopsis
  • * Understanding how viruses and bacteria work helps researchers identify important biomarkers, leading to the discovery of beneficial biological molecules that can help prevent or treat these infections.
  • * The review focuses on the effectiveness of medicinal plants against infections like COVID-19, influenza A, pneumonia, and tuberculosis, emphasizing a need for further research and clinical studies to validate their use and understand how they work.
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Drug-resistant tuberculosis (DR-TB) represents a pressing global health issue, leading to heightened morbidity and mortality. Despite extensive research efforts, the escalation of DR-TB cases underscores the urgent need for enhanced prevention, diagnosis, and treatment strategies. This review delves deep into the molecular and genetic origins of different types of DR-TB, highlighting recent breakthroughs in detection and diagnosis, including Rapid Diagnostic Tests like Xpert Ultra, Whole Genome Sequencing, and AI-based tools along with latest viewpoints on diagnosis and treatment of DR-TB utilizing newer and repurposed drug molecules.

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Background And Objective: Severe asthma is a heterogeneous disease with subtype classification according to dominant airway infiltrates, including eosinophilic (Type 2 high), or non-eosinophilic asthma. Non-eosinophilic asthma is further divided into paucigranulocytic or neutrophilic asthma characterized by elevated neutrophils, and mixed Type 1 and Type 17 cytokines in the airways. Severe non-eosinophilic asthma has few effective treatments and many patients do not qualify for biologic therapies.

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Chronic obstructive pulmonary disease (COPD) is strongly linked to cigarette smoke, which contains toxins that induce oxidative stress and airway inflammation, ultimately leading to premature airway epithelial cell senescence and exacerbating COPD progression. Current treatments for COPD are symptomatic and hampered by limited efficacy and severe side effects. This highlights the need to search for an optimal therapeutic candidate to address the root causes of these conditions.

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Article Synopsis
  • Bronchiolitis is a major reason infants are hospitalized in their first year and is more common in babies born to mothers with asthma.
  • The study analyzed cord blood granulocytes (eosinophils and neutrophils) from 89 infants, examining their relationship to bronchiolitis hospitalization over the first year.
  • Results showed higher eosinophil levels in cord blood were linked to increased risk of bronchiolitis hospitalization, indicating that early immune cell profiles may affect vulnerability to this condition later on.
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Reactive oxygen species are involved in the pathogenesis of cancers and metabolic diseases, including diabetes, obesity, and fatty liver disease. Thus, inhibiting the generation of free radicals is a promising strategy to control the onset of metabolic diseases and cancer progression. Various synthetic drugs and natural product-derived compounds that exhibit antioxidant activity have been reported to have a protective effect against a range of metabolic diseases and cancer.

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Influenza A virus (IAV) infection is a major health risk during pregnancy. Although vaccination and antiviral agents are widely used and reduce IAV-induced symptoms, they are not sufficient to control IAV infections in pregnancy, especially during pandemics. Respiratory viruses like IAV exploit immune alterations that occur during pregnancy, including the upregulation of immune checkpoint proteins (ICPs) like programmed death ligand-1 (PDL1), programmed cell death receptor 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4).

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Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics.

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Curcumin, the principal curcuminoid of turmeric (Curcuma longa extract), is very well known for its multiple biological therapeutic activities, particularly its anti-inflammatory and antioxidant potential. However, due to its low water solubility, it exhibits poor bioavailability. In order to overcome this problem, in the current study, we have employed liposomal technology to encapsulate curcumin with the aim of enhancing its therapeutic efficacy.

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Respiratory viruses cause airway inflammation, resulting in epithelial injury and repair. miRNAs, including miR-149-5p, regulate different pathological conditions. We aimed to determine how miR-149-5p functions in regulating pro-inflammatory IL-6 and p63, key regulators of airway epithelial wound repair, in response to viral proteins in bronchial (BEAS-2B) and alveolar (A549) epithelial cells.

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Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due to global demographic changes. NDs are mainly represented by degeneration/loss of neurons, which is primarily accountable for severe mental illness. This neuronal degeneration leads to many neuropsychiatric problems and permanent disability in an individual.

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