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The article explores the role of miR-155-5p in regulating lung epithelial cell behavior in severe asthma. Topics include the differential expression of IL-13 receptor subunits in asthma, the impact of miR-155-5p on IL-13Ra1 and IL-13Ra2 signaling, and how miR-155-5p influences abnormal epithelial cell phenotypes in severe asthma.

The article highlights several medical research papers. Topics include the characterization of commercially available human primary alveolar epithelial cells, the role of farnesoid X receptor in protecting the lung against IL-6-induced ferroptosis, and the impact of alternative splicing on transcriptome diversity in chronic obstructive pulmonary disease . It emphasizes the importance of these studies in understanding lung physiology, disease mechanisms, and potential therapeutic strategies.

The article focuses on various studies exploring mechanisms underlying lung diseases, specifically how airway smooth muscle (ASM) phenotype, unfolded protein responses, lung hematopoietic progenitors, and aging affect lung function and pathology. It identifies how excessive serum response factor (SRF) expression in ASM cells enables a dual contractile-proliferative phenotype, potentially worsening asthma.

The article informs about highlighted papers by junior investigators in the American Journal of Respiratory Cell and Molecular Biology. The topics include the promotion of pulmonary fibrosis through the upregulation of NEAT1 by GOLM1, the amelioration of sepsis-associated lung injury through inducing IL-33-mediated type 2 immunity by lack of S1PR2 in macrophages, and the role of interstitial macrophages in mediating efferocytosis of alveolar epithelium during influenza infection.

The article presents the discussion on NIH news briefs. Topics include diverse functions of alveolar macrophages (AMØs) in the lung, highlighting their distinct roles during homeostasis and in response to lung injury such as O3 exposure; and controversy surrounding the recruitment of monocyte-derived AMØs in lung injury models, and the importance of efferocytosis in promoting resolution of inflammation.

The article offers information on bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, characterized by impaired lung development. Topics include the concept of dysanapsis in BPD, which refers to disproportionate airways and parenchymal size, and its contribution to late respiratory disease.

The article reveals that RAGE (receptor for advanced glycation end products) is a receptor for the SARS-CoV-2 N protein, as reported by Jie Xia and colleagues. Topics include evaluating novel protein phosphatase 2A (PP2A) activators for emphysema treatment, with Brian Soto and colleagues introducing a stable PP2A activator, ATUX-792, showing promising effects in models of smoke-induced and AAT deficiency-associated emphysema.

The article discusses the results of two medical studies. A study by Joseph Farahany and colleagues examined the role of CD38, an ectoenzyme expressed in macrophages, to the regulation of NLRP3 inflammasome to prevent endotoxemic lung injury. A study led by Broa Coates, Clarissa Koch and Andrew Prigge investigated host response to SARS-CoV-2 in the nasal mucosa using RNA sequencing to determine if age-related differences in the initial response to SARS-CoV-2 may impact disease severity.

An editorial is presented by the outgoing Editor of the Journal, reflecting on the past 7 years of service, achievements, and challenges. Topics include enhancing the quality and impact of the Journal, addressing emerging issues like Open Access mandates and the influence of artificial intelligence in academic publishing, and the importance of diversity and scientific integrity in journal operations.

The concurrence of chronic obstructive pulmonary disease (COPD) and lung cancer has been widely reported and extensively addressed by pulmonologists and oncologists. However, most studies have focused on shared risk factors, DNA damage pathways, immune microenvironments, inflammation, and imbalanced proteases/antiproteases. In the present review, we explore the association between COPD and lung cancer in terms of airway pluripotent cell fate determination and discuss the various cell types and signaling pathways involved in the maintenance of lung epithelium homeostasis and their involvement in the pathogenesis of co-occurring COPD and lung cancer. [ABSTRACT FROM AUTHOR]

MicroRNA (miR)-155-5p increases in innate and adaptive immune cells in response to IL-13 and is associated with the severity of asthma. However, little is known about its role in airway structural cells. Bronchial epithelial cells (BECs) isolated from healthy donors and patients with severe asthma were stimulated with IL-13. miR-155-5p expression and release were measured by real-time (RT)-PCR in BECs and in their derived exosomes. Modulation of miR-155-5p in BECs was performed using transfection of miR-155-5p inhibitor and mimic. IL-13 receptor α1 (IL-13Rα1), IL-13Rα2, MUC5AC, IL-8, and eotaxin-1 expression was measured by RT-PCR and Western blot analysis. The BEC repair process was assessed by a wound-healing assay. IL-13Rα1 and IL-13Rα2 expression and downstream pathways were evaluated by Western blot analysis. A dual luciferase assay was used to identify miR-155-5p target genes associated with IL-13R signaling. BECs from patients with severe asthma showed increased expression and exosomal release of miR-155-5p at baseline with amplification by IL-13 stimulation. BECs from patients with asthma expressed more IL-13Rα1 and less IL-13Rα2 than those from healthy donors, and IL-13Rα1 but not IL-13Rα2 induced miR-155-5p expression under IL-13 stimulation. miR-155-5p overexpression favored MUC5AC, IL-8, and Eotaxin-1 through the IL-13Rα1/SOCS1/STAT6 pathway while delaying the repair process by downregulating IL-13Rα2/MAPK14/c-Jun/c-fos signaling. The dual luciferase assay confirmed that miR-155-5p modulates both IL-13R pathways by directly targeting SOCS1, c-fos, and MAPK14. miR-155-5p is overexpressed in BECs from patients with severe asthma and regulates IL-13Rα1 and IL-13Rα2 expression and signaling, favoring expression of mucin- and eosinophil-related genes to the detriment of airway repair. These results show that miR-155-5p may contribute to airway epithelial cell dysfunction in patients with severe asthma. [ABSTRACT FROM AUTHOR]

Chronic alcohol consumption disrupts lung immunity and host defense mechanisms, rendering individuals with alcohol use disorder more susceptible to developing inflammatory lung conditions with poor prognoses. Here, we focused on investigating the molecular and cellular effects of alcohol ingestion on lung immunity in male and female subjects using population-based human lung transcriptomics analysis and an experimental mouse model of chronic alcohol drinking using the National Institute on Alcohol Abuse and Alcoholism alcohol feeding model. Flow cytometry and transcriptomics analyses in lungs revealed a sexually dimorphic effect of chronic alcohol drinking on lung immunity in both human and mouse. Male lungs were more sensitive to chronic alcohol drinking–induced dysregulation of lung immunity compared with female lungs. Furthermore, comparative transcriptomics analysis using lungs and liver samples from matched human and mouse subjects demonstrated that lungs were more sensitive than liver to the effects of alcohol in downregulating immune-related genes and pathways. Furthermore, the transcriptomics analysis provided evidence that immunometabolic change is a central driver in lung alteration by downregulating the immune pathways and upregulating metabolic pathways. Chronic alcohol consumption resulted in reduced mTOR signaling and decreased immune cell populations. The mTOR signaling axis may serve as an upstream regulator of alcohol-induced dysregulation in lung immunity. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Attenuation of Lipopolysaccharide-induced Lung Vascular Stiffening by Lipoxin Reduces Lung Inflammation" which appeared in the February 2015 issue.

The authors of "Nitric Oxide Synthase 2 Induction Promotes Right Ventricular Fibrosis" wish to retract their article that was published in the March 2019 issue.

he alveolar region of the lung is composed of two major epithelial cell types: cuboidal alveolar type 2 cells (AT2 cells), which produce surfactant proteins, and large, thin, alveolar type 1 cells (AT1 cells), specialized for efficient gas exchange. AT1 cells cover more than 95% of the alveolar surface and constitute a major barrier to the entry of pathogenic agents. Relatively few genetic tools are available for studying the development of AT1 cells, the function of genes expressed in them, and the effect of specifically killing them in vivo in the adult lung. One distinguishing feature of AT1 cells is the high level of expression of the gene Ager, encoding the advanced glycation endproduct–specific receptor, a member of the immunoglobulin superfamily of cell surface receptors. In this paper, we report the generation of a novel Ager-CreERT2 allele in which Cre recombinase is inserted into the first coding exon of the endogenous gene. After treatment with tamoxifen the allele enables Ager+ progenitor cells to be efficiently lineage labeled during late embryonic development and AT1 cells to be killed in the adult lung using a Rosa26-diphtheria toxin A allele. Significantly, adult mice in which approximately 50% of the AT1 cells are killed survive the loss; repair is associated with increased proliferation of SFTPC+ (surfactant protein C–positive) AT2 cells and the upregulation of Ager expression. The Ager-CreERT2 allele thus expands the repertoire of genetic tools for studying AT1 turnover, physiology, and repair. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) can be idiopathic or driven by a specific insult, genetic susceptibility, or disease process. Inflammation plays a role in the pathophysiology, the extent of which remains a longstanding topic of debate. More recently, there has been increasing interest in a potential inciting role for aberrant lipid metabolism. Lipids are essential for the structure and function of all cell membranes, but specifically in the lung for surfactant composition, intra- and intercellular lipid mediators, and lipofibroblasts. Clinically, there is evidence of increased lipid deposition in the subpleural space and at a whole-lung tissue level in PF. There is evidence of increased parenchymal lipid deposition and abnormal mediastinal fat shape on chest computed tomography. A protective role for cholesterol-lowering drugs, including statins and ezetimibe, has been described in PF. At a cellular level, fatty acid, phospholipid, and glucose metabolism are disordered, as is the production of lipid mediators. Here we put forward the argument that there is substantive clinical and biological evidence to support a role for aberrant lipid metabolism and lipid mediators in the pathogenesis of PF. [ABSTRACT FROM AUTHOR]

This document summarizes a study on the effects of CFTR modulators on patients with cystic fibrosis (CF) and leukocyte adhesion deficiency type IV (LAD-IV). The study found that CFTR modulators improved certain cellular functions in CF patients, suggesting that they may correct both CF and LAD-IV phenotypes. However, there were some patients who showed improvement in CF symptoms but not in LAD-IV characteristics, indicating the need for further research. The study also suggests that measuring certain cellular markers could be a useful method for monitoring patients in the long term. [Extracted from the article]

An increased intracellular Ca2+ concentration ([Ca2+]i) is a key trigger for pulmonary arterial smooth muscle cell (PASMC) proliferation and contributes greatly to pulmonary hypertension (PH). Extracellular Ca2+ influx via a store-operated Ca2+ channel, termed store-operated Ca2+ entry (SOCE), is a crucial mechanism for [Ca2+]i increase in PASMCs. Calcium release–activated calcium modulator (Orai) proteins, consisting of three members (Orai1–3), are the main components of the store-operated Ca2+ channel. Sodium houttuyfonate (SH) is a product of the addition reaction of sodium bisulfite and houttuynin and has antibacterial, antiinflammatory, and other properties. In this study, we assessed the contributions of Orai proteins to monocrotaline (MCT)–enhanced SOCE, [Ca2+]i, and cell proliferation in PASMCs and determined the effect of SH on MCT-PH and the underlying mechanism, focusing on Orai proteins, SOCE, and [Ca2+]i in PASMCs. Our results showed that: 1) Orai1 and Orai2 were selectively upregulated in the distal pulmonary arteries and the PASMCs of MCT-PH rats; 2) knockdown of Orai1 or Orai2 reduced SOCE, [Ca2+]i, and cell proliferation without affecting their expression in PASMCs in MCT-PH rats; 3) SH significantly normalized the characteristic parameters in a dose-dependent manner in the MCT-PH rat model; and 4) SH decreased MCT-enhanced SOCE, [Ca2+]i, and PASMC proliferation via Orai1 or Orai2. These results indicate that SH likely exerts its protective role in MCT-PH by inhibiting the Orai1,2–SOCE–[Ca2+]i signaling pathway. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is an aging-associated interstitial lung disease resulting from repeated epithelial injury and inadequate epithelial repair. Alveolar type II cells (AEC2s) are progenitor cells that maintain epithelial homeostasis and repair the lung after injury. In the current study, we assessed lipid metabolism in AEC2s from human lungs of patients with IPF and healthy donors, as well as AEC2s from bleomycin-injured young and old mice. Through single-cell RNA sequencing, we observed that lipid metabolism–related genes were downregulated in IPF AEC2s and bleomycin-injured mouse AEC2s. Aging aggravated this decrease and hindered recovery of lipid metabolism gene expression in AEC2s after bleomycin injury. Pathway analyses revealed downregulation of genes related to lipid biosynthesis and fatty acid β-oxidation in AEC2s from IPF lungs and bleomycin-injured, old mouse lungs compared with the respective controls. We confirmed decreased cellular lipid content in AEC2s from IPF lungs and bleomycin-injured, old mouse lungs using immunofluorescence staining and flow cytometry. Futhermore, we show that lipid metabolism was associated with AEC2 progenitor function. Lipid supplementation and PPARγ (peroxisome proliferator activated receptor γ) activation promoted progenitor renewal capacity of both human and mouse AEC2s in three-dimensional organoid cultures. Lipid supplementation also increased AEC2 proliferation and expression of SFTPC in AEC2s. In summary, we identified a lipid metabolism deficiency in AEC2s from lungs of patients with IPF and bleomycin-injured old mice. Restoration of lipid metabolism homeostasis in AEC2s might promote AEC2 progenitor function and offer new opportunities for therapeutic approaches to IPF. [ABSTRACT FROM AUTHOR]

In recent years, metabolomics, the systematic study of small-molecule metabolites in biological samples, has yielded fresh insights into the molecular determinants of pulmonary diseases and critical illness. The purpose of this article is to orient the reader to this emerging field by discussing the fundamental tenets underlying metabolomics research, the tools and techniques that serve as foundational methodologies, and the various statistical approaches to analysis of metabolomics datasets. We present several examples of metabolomics applied to pulmonary and critical care medicine to illustrate the potential of this avenue of research to deepen our understanding of pathophysiology. We conclude by reviewing recent advances in the field and future research directions that stand to further the goal of personalizing medicine to improve patient care. [ABSTRACT FROM AUTHOR]

An editorial is presented on the transition in leadership of the periodical, emphasizing its unique position in respiratory sciences research. Topics discussed include the commitment to excellence, engagement strategies with the scientific community, and specific initiatives such as a new Early Career Editor Apprentice Program to enhance the visibility and support for innovative research in lung pathobiology.

A correction is presented to the article "Causation of Cigarette Smoke–induced Emphysema by p-Benzoquinone and Its Prevention by Vitamin C" which appeared in the March 2015 issue.

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive disease with elusive molecular mechanisms and limited therapeutic options. Aberrant activation of fibroblasts is a central hallmark of lung fibrosis. Here, we report that Golgi membrane protein 1 (GOLM1, also known as GP73 or GOLPH2) was increased in the lungs of patients with pulmonary fibrosis and mice with bleomycin (BLM)–induced pulmonary fibrosis. Loss of GOLM1 inhibited proliferation, differentiation, and extracellular matrix deposition of fibroblasts, whereas overexpression of GOLM1 exerted the opposite effects. Similarly, worsening pulmonary fibrosis after BLM treatment was observed in GOLM1–knock-in mice, whereas BLM-treated Golm1-knockout mice exhibited alleviated pulmonary fibrosis and collagen deposition. Furthermore, we identified long noncoding RNA NEAT1 downstream of GOLM1 as a potential mediator of pulmonary fibrosis through increased GOLM1 expression. Depletion of NEAT1 inhibited fibroblast proliferation and extracellular matrix production and reversed the profibrotic effects of GOLM1 overexpression. Additionally, we identified KLF4 as a downstream mediator of GOLM1 signaling to NEAT1. Our findings suggest that GOLM1 plays a pivotal role in promoting pulmonary fibrosis through the GOLM1–KLF4–NEAT1 signaling axis. Targeting GOLM1 and its downstream pathways may represent a novel therapeutic strategy for treating pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

The article focuses on a model of low-dose influenza A virus (IAV) infection in wild-type (WT) mice, examining factors such as weight retention, survival rates, and viral load in lung homogenates. It mentions the results show significant differences in viral load and protein content in bronchoalveolar lavage fluid (BALF) between naïve mice and those infected with IAV, highlighting the impact of the infection on various physiological parameters.