Occludin Is Essential to Maintain Normal Alveolar Barrier Integrity and Its Protective Role During ARDS Progression.

Acute respiratory distress syndrome (ARDS) is a severe lung condition without targeted therapy that is characterized by the disruption of epithelial and endothelial barriers. The role of the tight junction protein occludin in the pathogenesis of this disease is unknown, although it has previously been deemed redundant in some tissues. The aim of the present study is to determine whether occludin is required for lung function by controlling alveolar barrier integrity in mouse models.

Association between weight loss and mortality in idiopathic pulmonary fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease that has no cure. Many current research efforts center on diagnostic and therapeutic modalities for IPF while other risk factors affecting disease pathogenesis receive less attention. Emerging data support the clinical importance of weight loss in patients with IPF.

The Novel Small Molecule BTB Inhibits Pro-Fibrotic Fibroblast Behavior though Inhibition of RhoA Activity.

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, interstitial lung disease with a poor prognosis. Although specific anti-fibrotic medications are now available, the median survival time following diagnosis remains very low, and new therapies are urgently needed. To uncover novel therapeutic targets, we examined how biochemical properties of the fibrotic lung are different from the healthy lung.

Unifying the known and unknown microbial coding sequence space.

Genes of unknown function are among the biggest challenges in molecular biology, especially in microbial systems, where 40-60% of the predicted genes are unknown. Despite previous attempts, systematic approaches to include the unknown fraction into analytical workflows are still lacking. Here, we present a conceptual framework, its translation into the computational workflow AGNOSTOS and a demonstration on how we can bridge the known-unknown gap in genomes and metagenomes.

miR-338-3p blocks TGFβ-induced myofibroblast differentiation through the induction of PTEN.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease. The pathogenesis of IPF is not completely understood. However, numerous genes are associated with the development and progression of pulmonary fibrosis, indicating there is a significant genetic component to the pathogenesis of IPF.

The effect of air pollution on the transcriptomics of the immune response to respiratory infection.

Combustion related particulate matter air pollution (PM) is associated with an increased risk of respiratory infections in adults. The exact mechanism underlying this association has not been determined. We hypothesized that increased concentrations of combustion related PM would result in dysregulation of the innate immune system.

The self-fulfilling prophecy of pulmonary fibrosis: a selective inspection of pathological signalling loops.

Pulmonary fibrosis is a devastating, progressive disease and carries a prognosis worse than most cancers. Despite ongoing research, the mechanisms that underlie disease pathogenesis remain only partially understood. However, the self-perpetuating nature of pulmonary fibrosis has led several researchers to propose the existence of pathological signalling loops.

Reinterpreting Evidence of Rheumatoid Arthritis-Associated Interstitial Lung Disease to Understand Etiology.

Interstitial Lung Disease (ILD) is a well-known complication of rheumatoid arthritis (RA) which often results in significant morbidity and mortality. It is often diagnosed late in the disease process via descriptive criteria. Multiple subtypes of RA-ILD exist as defined by chest CT and histopathology.

The clinical impact of pneumocystis and viral PCR testing on bronchoalveolar lavage in immunosuppressed patients.

Introduction: Pulmonary infiltrates in immunosuppressed patients are common. Yields from bronchoscopy with bronchoalveolar lavage (BAL) has been reported to be between 31 and 65%. The clinical impact of pneumocystis and viral Polymerase chain reaction (PCR) testing on BAL has not been extensively evaluated in a mixed immunosuppressed patient population.

Prevention and treatment of bleomycin-induced pulmonary fibrosis with the lactate dehydrogenase inhibitor gossypol.

Pulmonary fibrosis is a chronic and irreversible scarring disease in the lung with poor prognosis. Few therapies are available; therefore it is critical to identify new therapeutic targets. Our lab has previously identified the enzyme lactate dehydrogenase-A (LDHA) as a potential therapeutic target in pulmonary fibrosis.

Development of an accurate and sensitive method for lactate analysis in exhaled breath condensate by LC MS/MS.

Exhaled breath condensate (EBC) is easily obtained for clinical diagnosis and prognosis for pulmonary diseases and has gained much interest in biomarker discovery research and studies. Lactate, a physiological material, is found in EBC and has been demonstrated to be a potential indicator of chronic obstructive pulmonary disease and other lung diseases. Several assays are available to detect lactate in human body fluids, and yet none is suitable for detecting lactate in EBC.

The Lactate Dehydrogenase Inhibitor Gossypol Inhibits Radiation-Induced Pulmonary Fibrosis.

Exposure of the lung to ionizing radiation that occurs in radiotherapy, as well as after accidental or intentional mass casualty incident can result in pulmonary fibrosis, which has few treatment options. Pulmonary fibrosis is characterized by an accumulation of extracellular matrix proteins that create scar tissue. Although the mechanisms leading to radiation-induced pulmonary fibrosis remain poorly understood, one frequent observation is the activation of the profibrotic cytokine transforming growth factor-beta (TGF-β).

Nasopharyngeal viral PCR in immunosuppressed patients and its association with virus detection in bronchoalveolar lavage by PCR.

Background And Objective: Pulmonary infiltrates are common in immunosuppressed patients. Bronchoscopy with bronchoalveolar lavage (BAL) is often used to evaluate their aetiology. However, it may not always be easily performed.

Alternative Progenitor Lineages Regenerate the Adult Lung Depleted of Alveolar Epithelial Type 2 Cells.

An aberrant oxygen environment at birth increases the severity of respiratory viral infections later in life through poorly understood mechanisms. Here, we show that alveolar epithelial cell (AEC) 2 cells (AEC2s), progenitors for AEC1 cells, are depleted in adult mice exposed to neonatal hypoxia or hyperoxia. Airway cells expressing surfactant protein (SP)-C and ATP binding cassette subfamily A member 3, alveolar pod cells expressing keratin (KRT) 5, and pulmonary fibrosis were observed when these mice were infected with a sublethal dose of HKx31, H3N2 influenza A virus.

The antiSMASH database, a comprehensive database of microbial secondary metabolite biosynthetic gene clusters.

Secondary metabolites produced by microorganisms are the main source of bioactive compounds that are in use as antimicrobial and anticancer drugs, fungicides, herbicides and pesticides. In the last decade, the increasing availability of microbial genomes has established genome mining as a very important method for the identification of their biosynthetic gene clusters (BGCs). One of the most popular tools for this task is antiSMASH.

BioVeL: a virtual laboratory for data analysis and modelling in biodiversity science and ecology.

Background: Making forecasts about biodiversity and giving support to policy relies increasingly on large collections of data held electronically, and on substantial computational capability and capacity to analyse, model, simulate and predict using such data. However, the physically distributed nature of data resources and of expertise in advanced analytical tools creates many challenges for the modern scientist. Across the wider biological sciences, presenting such capabilities on the Internet (as "Web services") and using scientific workflow systems to compose them for particular tasks is a practical way to carry out robust "in silico" science.

The Global Genome Biodiversity Network (GGBN) Data Standard specification.

Genomic samples of non-model organisms are becoming increasingly important in a broad range of studies from developmental biology, biodiversity analyses, to conservation. Genomic sample definition, description, quality, voucher information and metadata all need to be digitized and disseminated across scientific communities. This information needs to be concise and consistent in today's ever-increasing bioinformatic era, for complementary data aggregators to easily map databases to one another.

MyOSD 2014: Evaluating Oceanographic Measurements Contributed by Citizen Scientists in Support of Ocean Sampling Day.

The first Ocean Sampling Day (OSD) took place on June 21, 2014. In a coordinated effort, an internationally distributed group of scientists collected samples from marine surface waters in order to study microbial diversity on a single day with global granularity. Concurrently, citizen scientists enriched the OSD initiative through the MyOSD project, providing additional oceanographic measurements crucial to the contextualization of microbial diversity.

Pharmacologic inhibition of lactate production prevents myofibroblast differentiation.

Myofibroblasts are one of the primary cell types responsible for the accumulation of extracellular matrix in fibrosing diseases, and targeting myofibroblast differentiation is an important therapeutic strategy for the treatment of pulmonary fibrosis. Transforming growth factor-β (TGF-β) has been shown to be an important inducer of myofibroblast differentiation. We previously demonstrated that lactate dehydrogenase and its metabolic product lactic acid are important mediators of myofibroblast differentiation, via acid-induced activation of latent TGF-β.

Resolvins attenuate inflammation and promote resolution in cigarette smoke-exposed human macrophages.

Inflammation is a protective response to injury, but it can become chronic, leading to tissue damage and disease. Cigarette smoke causes multiple inflammatory diseases, which account for thousands of deaths and cost billions of dollars annually. Cigarette smoke disrupts the function of immune cells, such as macrophages, by prolonging inflammatory signaling, promoting oxidative stress, and impairing phagocytosis, contributing to increased incidence of infections.

Ionizing radiation induces myofibroblast differentiation via lactate dehydrogenase.

Pulmonary fibrosis is a common and dose-limiting side-effect of ionizing radiation used to treat cancers of the thoracic region. Few effective therapies are available for this disease. Pulmonary fibrosis is characterized by an accumulation of myofibroblasts and excess deposition of extracellular matrix proteins.

Normal Human Lung Epithelial Cells Inhibit Transforming Growth Factor-β Induced Myofibroblast Differentiation via Prostaglandin E2.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with very few effective treatments. The key effector cells in fibrosis are believed to be fibroblasts, which differentiate to a contractile myofibroblast phenotype with enhanced capacity to proliferate and produce extracellular matrix. The role of the lung epithelium in fibrosis is unclear.