lung AND physiology

IMPORTANCE: Interstitial lung disease (ILD) consists of a group of pulmonary disorders characterized by inflammation and/or fibrosis of the lung parenchyma associated with progressive dyspnea that frequently results in end-stage respiratory failure. In the US, ILD affects approximately 650 000 people and causes approximately 25 000 to 30 000 deaths per year. OBSERVATIONS: The most common forms of ILD are idiopathic pulmonary fibrosis (IPF), which accounts for approximately one-third of all cases of ILD, hypersensitivity pneumonitis, accounting for 15% of ILD cases, and connective tissue disease (CTD), accounting for 25% of ILD cases...

Idiopathic pulmonary fibrosis (IPF) is marked by the activation of fibroblasts, leading to excessive production and deposition of extracellular matrix (ECM) within the lung parenchyma. Despite the pivotal role of ECM overexpression in IPF, potential negative regulators of ECM production in fibroblasts have yet to be identified. Semaphorin class 3B (SEMA3B), a secreted protein highly expressed in lung tissues, has established roles in axonal guidance and tumor suppression. However, the role of SEMA3B in ECM production by fibroblasts in the pathogenesis of IPF remains unexplored...

Bleomycin (BLM)-induced lung injury in mice is a valuable model for investigating the molecular mechanisms that drive inflammation and fibrosis and for evaluating potential therapeutic approaches to treat the disease. Given high variability in the BLM model, it is critical to accurately phenotype the animals in the course of an experiment. In the current study, we aimed to demonstrate the utility of microscopic computed tomography (µCT) imaging combined with an artificial intelligence (AI) convolutional neural network (CNN)-powered lung segmentation for rapid phenotyping of BLM mice...

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically disease patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known...

PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by increased pulmonary vascular resistance and pulmonary arterial pressure. At present, the definitive pathology of PAH has not been elucidated and its effective treatment remains lacking. Despite PAHs having multiple pathogeneses, the cancer-like characteristics of cells have been considered the main reason for PAH progression. RECENT FINDINGS: p53 protein, an important tumor suppressor, regulates a multitude of gene expressions to maintain normal cellular functions and suppress the progression of malignant tumors...

BACKGROUND: Physical activity (PA) is associated with the risk of mortality in patients with chronic obstructive pulmonary disease (COPD); however, evidence is limited to the Japanese population. This study aimed to evaluate the effects of PA on long-term mortality in Japanese patients with COPD. METHODS: We conducted a prospective observational study in a cohort of Japanese patients with COPD and assessed mortality during a 4-year follow-up period. The Cox proportional hazards model was used to evaluate the association between PA and mortality...

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence. METHODS: Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO...

RATIONALE: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. OBJECTIVES: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. METHODS: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data...

PURPOSE: Exercise before surgery, as part of prehabilitation, aiming to enhance patients' functional and physiological capacity, has become widespread, necessitating an in-depth understanding. METHODS: A systematic search was conducted on Pubmed, Cochrane, and Scopus to examine the effect of exercise as prehabilitation, alone or in combination with other interventions, in patients with cancer. Interventional studies applying a single-arm, randomized controlled, or nonrandomized design were included...

BACKGROUD: Oesophageal cancer patients are prone to early- and late-onset pneumonia after oesophagectomy. We aimed to investigate the incidence rate and impact on the long-term prognosis of late-onset pneumonia in oesophageal cancer survivors who survived for at least one year after oesophagectomy without cancer recurrence. METHODS: We retrospectively reviewed 233 patients with thoracic oesophageal cancer who underwent oesophagectomy with gastric conduit reconstruction between September 2009 and June 2019 at a tertiary referral hospital in Japan...

The pathogenesis of acute lung injury is not fully understood. Stimulator of interferon genes (STING) and ferroptosis have been implicated in various pathological and physiological processes, including acute lung injury (ALI). However, the relationship between STING and ferroptosis in lipopolysaccharide (LPS)-induced ALI is unclear. We found that LPS stimulation activated STING and ferroptosis. Furthermore, STING knockout and ferroptosis inhibitor alleviated lung inflammation and epithelial cell damage. Also, STING knockout reduced inflammation injury and ferroptosis...

Lung cancer is a highly lethal malignancy that poses a significant burden on public health worldwide. There have been numerous therapeutic approaches, among which cancer vaccines have emerged as a promising approach to harnessing the patient's immune system to induce long-lasting anti-tumor immunity. The current study aims to provide an overview of cancer vaccination in the context of lung cancer to establish a clearer landscape for lung cancer treatment. To provide a comprehensive review, we not only gathered the published studies of lung cancer vaccination and discussed their effectiveness and safety profile but also analyzed all the relevant clinical trials registered on www...

BACKGROUND: Validating walking trails is essential to promote physical activity (PA) safely and confidently in people with COPD. OBJECTIVES: We aimed to validate predetermined light, moderate, and vigorous intensities of walking trails in people with COPD. METHODS: This cross-sectional study included individuals with COPD walking in predetermined light, moderate and vigorous intensity trails. Activity intensity and volume outcomes were collected...

Recent advances in fatty acid analysis have highlighted the links between lipid disruption and disease development. Lipid abnormalities are well-established risk factors for many of the most common chronic illnesses, and their involvement in asthma is also becoming clear. Here, we review research demonstrating the role of abnormal lipid metabolism in asthma, with a focus on saturated fatty acids and sphingolipids. High levels of palmitic acid, the most abundant saturated fatty acid in the human body, have been found in the airways of asthmatic patients with obesity, and were shown to worsen eosinophilic airway inflammation in asthma model mice on a high-fat diet...

Evidence abounds that gut microbiome components are associated with sex disparities in the immune system. However, it remains unclear whether the observed sex disparity in asthma incidence is associated with sex-dependent differences in immune-modulating gut microbiota, and/or its influence on allergic airway inflammatory processes. Using a mouse model of house dust mite (HDM)-induced allergic inflammation and the four core genotypes (FCG) model, we have previously reported sex differences in lung inflammatory phenotypes...

Artificial intelligence is expected to help identify excellent candidates in drug discovery. However, we face a lack of data, as it is time-consuming and expensive to acquire raw data perfectly for many compounds. Hence, we tried to develop a novel quantitative structure-activity relationship (QSAR) method to predict a parameter more precisely from an incomplete data set via optimizing data handling by making use of predicted explanatory variables. As a case study we focused on the tissue-to-plasma partition coefficient (Kp), which is an important parameter for understanding drug distribution in tissues and building the physiologically based pharmacokinetic model and is a representative of small and sparse data sets...

The lungs are a key organ in the respiratory system. They are regulated by a complex network of nerves that control their development, structure, function, and response to various pathological stimuli. Accumulating evidence suggests the involvement of a neural mechanism in different pathophysiological conditions in the lungs and the development and progression of common respiratory diseases. Lung diseases are the chief source of death globally. For instance, lung cancer is the second most commonly diagnosed malignancy, after prostate cancer in men and breast cancer in women, and is the most lethal cancer worldwide...

In controlled organ donation after circulatory determination of death (cDCDD), accurate and timely death determination is critical, yet knowledge gaps persist. Further research to improve the science of defining and determining death by circulatory criteria is therefore warranted. In a workshop sponsored by the National Heart, Lung, and Blood Institute, experts identified research opportunities pertaining to scientific, conceptual, and ethical understandings of DCDD and associated technologies. This article identifies a research strategy to inform the biomedical definition of death, the criteria for its determination, and circulatory death determination in cDCDD...

BACKGROUND AND OBJECTIVE: Endothelial dysfunction has been widely recognized in chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma; however, it remains unclear in asthma-COPD overlap (ACO). Neopterin (NP), a metabolite of guanosine triphosphate, is a novel biomarker for identifying the increased risk of adverse cardiovascular events. This study aims to investigate the association of NP with endothelial dysfunction and impaired lung function in COPD, asthma, and ACO patients...

The success of lung transplantation is limited by the high rate of primary graft dysfunction due to ischemia-reperfusion injury (IRI). Lung IRI is characterized by a robust inflammatory response, lung dysfunction, endothelial barrier disruption, oxidative stress, vascular permeability, edema, and neutrophil infiltration. These events are dependent on the health of the endothelium, which is a primary target of IRI that results in pulmonary endothelial barrier dysfunction. Over the past 10 years, research has focused more on the endothelium, which is beginning to unravel the multi-factorial pathogenesis and immunologic mechanisms underlying IRI...