Progression Of Respiratory Diseases Research Articles

Targeting ferroptosis using Chinese herbal compounds to treat respiratory diseases

BackgroundRespiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, and autophagy, characterised by iron, reactive oxygen species, and lipid peroxide accumulation, as well as glutathione (GSH) depletion and GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis and the onset and progression of respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, pulmonary fibrosis, and lung cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in the treatment of respiratory diseases owing to their natural properties and potential efficacy. These compounds can effectively regulate ferroptosis by modulating several key signalling pathways such as system Xc− -GSH-GPX4, NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1, thus playing a positive role in improving respiratory diseases. PurposeThis comprehensive review systematically outlines the regulatory role of ferroptosis in the onset and progression of respiratory diseases and provides evidence for treating respiratory diseases by targeting ferroptosis with TCM compounds. These insights aim to offer potential remedies for the clinical prevention and treatment of respiratory diseases. Study design and methodsWe searched scientific databases PubMed, Web of Science, Scopus, and CNKI using keywords such as “ferroptosis”,“respiratory diseases”,“chronic obstructive pulmonary disease”,“bronchial asthma”,“acute lung injury”,“pulmonary fibrosis”,“lung cancer”,“traditional Chinese medicine”,“traditional Chinese medicine compound”,“monomer”, and “natural product” to retrieve studies on the therapeutic potential of TCM compounds in ameliorating respiratory diseases by targeting ferroptosis. The retrieved data followed PRISMA criteria (preferred reporting items for systematic review). ResultsTCM compounds possess unique advantages in treating respiratory diseases, stemming from their natural origins and proven clinical effectiveness. TCM compounds can exert therapeutic effects on respiratory diseases by regulating ferroptosis, which mainly involves modulation of pathways such as system Xc− -GSH-GPX4,NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1. ConclusionTCM compounds have demonstrated promising potential in improving respiratory diseases through the regulation of ferroptosis. The identification of specific TCM-related inducers and inhibitors of ferroptosis holds great significance in developing more effective strategies. However, current research remains confined to animal and cellular studies, emphasizing the imperative for further verifications through high-quality clinical data.

MicroRNA-26a in respiratory diseases: mechanisms and therapeutic potential.

MicroRNAs (miRNAs) are short, non-coding single-stranded RNA moleculesapproximately 22 nucleotides in length, intricately involved in post-transcriptional gene expression regulation. Over recent years, researchers have focused keenly on miRNAs, delving into their mechanisms in various diseases such as cancers. Among these, miR-26a emerges as a pivotal player in respiratory ailments such as pneumonia, idiopathic pulmonary fibrosis, lung cancer, asthma, and chronic obstructive pulmonary disease. Studies have underscored the significance of miR-26a in the pathogenesis and progression of respiratory diseases, positioning it as a promising therapeutic target. Nevertheless, several challenges persist in devising medical strategies for clinical trials involving miR-26a. In this review, we summarize the regulatory role and significance of miR-26a in respiratory diseases, and we analyze and elucidate the challenges related to miR-26a druggability, encompassing issues such as the efficiency of miR-26a, delivery, RNA modification, off-target effects, and the envisioned therapeutic potential of miR-26a in clinical settings.

The aging lung: microenvironment, mechanisms, and diseases.

With the development of global social economy and the deepening of the aging population, diseases related to aging have received increasing attention. The pathogenesis of many respiratory diseases remains unclear, and lung aging is an independent risk factor for respiratory diseases. The aging mechanism of the lung may be involved in the occurrence and development of respiratory diseases. Aging-induced immune, oxidative stress, inflammation, and telomere changes can directly induce and promote the occurrence and development of lung aging. Meanwhile, the occurrence of lung aging also further aggravates the immune stress and inflammatory response of respiratory diseases; the two mutually affect each other and promote the development of respiratory diseases. Explaining the mechanism and treatment direction of these respiratory diseases from the perspective of lung aging will be a new idea and research field. This review summarizes the changes in pulmonary microenvironment, metabolic mechanisms, and the progression of respiratory diseases associated with aging.

Integrative Analyses of Bulk and Single-Cell RNA Seq Identified the Shared Genes in Acute Respiratory Distress Syndrome and Rheumatoid Arthritis.

Acute respiratory distress syndrome (ARDS), a progressive status of acute lung injury (ALI), is primarily caused by an immune-mediated inflammatory disorder, which can be an acute pulmonary complication of rheumatoid arthritis (RA). As a chronic inflammatory disease regulated by the immune system, RA is closely associated with the occurrence and progression of respiratory diseases. However, it remains elusive whether there are shared genes between the molecular mechanisms underlying RA and ARDS. The objective of this study is to identify potential shared genes for further clinical drug discovery through integrated analysis of bulk RNA sequencing datasets obtained from the Gene Expression Omnibus database, employing differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA). The hub genes were identified through the intersection of common DEGs and WGCNA-derived genes. The Random Forest (RF) and least absolute shrinkage and selection operator (LASSO) algorithms were subsequently employed to identify key shared target genes associated with two diseases. Additionally, RA immune infiltration analysis and COVID-19 single-cell transcriptome analysis revealed the correlation between these key genes and immune cells. A total of 59 shared genes were identified from the intersection of DEGs and gene clusters obtained through WGCNA, which analyzed the integrated gene matrix of ALI/ARDS and RA. The RF and LASSO algorithms were employed to screen for target genes specific to ALI/ARDS and RA, respectively. The final set of overlapping genes (FCMR, ADAM28, HK3, GRB10, UBE2J1, HPSE, DDX24, BATF, and CST7) all exhibited a strong predictive effect with an area under the curve (AUC) value greater than 0.8. Then, the immune infiltration analysis revealed a strong correlation between UBE2J1 and plasma cells in RA. Furthermore, scRNA-seq analysis demonstrated differential expression of these nine target genes primarily in T cells and NK cells, with CST7 showing a significant positive correlation specifically with NK cells. Beyond that, transcriptome sequencing was conducted on lung tissue collected from ALI mice, confirming the substantial differential expression of FCMR, HK3, UBE2J1, and BATF. This study provides unprecedented evidence linking the pathophysiological mechanisms of ALI/ARDS and RA to immune regulation, which offers novel understanding for future clinical treatment and experimental research.

Outcome of Human Parainfluenza Virus infection in allogeneic stem cell transplantation recipients: possible impact of ribavirin therapy.

This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess the impact of ribavirin treatment, clinical characteristics, and risk factors associated with lower respiratory tract disease (LRTD) progression and all-cause mortality. The study included 230 allo-SCT recipients diagnosed with hPIV between December 2013 and June 2023. Risk factors for the development of LRTD, disease severity, and mortality were analyzed. Ribavirin treatment was administered at physician discretion in 61 out of 230 cases (27%). Risk factors for LRTD progression in multivariate analysis were corticosteroids > 30mg/day (Odds ratio (OR) 3.5, 95% Confidence Interval (C.I.) 1.3-9.4, p = 0.013), fever at the time of hPIV detection (OR 3.89, 95% C.I. 1.84-8.2, p < 0.001), and absolute lymphocyte count (ALC) < 0.2 × 109/L (OR 4.1, 95% C.I. 1.42-11.9, p = 0.009). In addition, the study found that ribavirin therapy significantly reduced progression to LRTD [OR 0.19, 95% C.I. 0.05-0.75, p = 0.018]. Co-infections (OR 5.7, 95% C.I. 1.4-23.5, p = 0.015) and ALC < 0.2 × 109/L (OR 17.7, 95% C.I. 3.6-87.1, p < 0.001) were independently associated with higher day + 100 after hPIV detection all-cause mortality. There were no significant differences in all-cause mortality and infectious mortality at day + 100 between the treated and untreated groups. ALC, corticosteroids, and fever increased the risk for progression to LRTD while ribavirin decreased the risk. However, mortality was associated with ALC and co-infections. This study supports further research of ribavirin therapy for hPIV in the allo-HSCT setting.

Schwann cells in the normal and pathological lung microenvironment.

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. However, although airway nerves are accepted as a mechanistically and therapeutically important feature that demands appropriate emphasizing in the context of many respiratory diseases, significantly less is known about the role of the neuroglial cells in lung physiology and pathophysiology, including lung cancer. New data have uncovered some cellular and molecular mechanisms of how Schwann cells, as fundamental components of the peripheral nervous system, may regulate lung cancer cells' survival, spreading, and invasiveness in vitro and in vivo. Schwann cells control the formation and maintenance of the lung cancer microenvironment and support metastasis formation. It was also reported that the number of lung cancer-associated Schwann cells correlates with patients' survival. Different factors secreted by Schwann cells, including microRNA, are known to sharpen the lung cancer environment by regulating the tumor-neuro-immune axis. Further clinical and experimental studies are required to elucidate the detailed role of Schwann cells in creating and maintaining pulmonary tumor-neuro-immune axis, which will advance our understanding of the pathogenesis of lung cancer and may inform therapeutic hypotheses aiming neoplasms and metastases in the lung.

Platycodon D protects human nasal epithelial cells from pyroptosis through the Nrf2/HO-1/ROS signaling cascade in chronic rhinosinusitis

BackgroundPyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis.MethodsNasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB.ResultsThe nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1β in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway.ConclusionsThe results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage.

Causal relationship between particulate matter and COVID-19 risk: A mendelian randomization study

BackgroundObservational studies have linked exposure to fine (PM2.5) and coarse (PM10) particulate matter air pollution with adverse COVID-19 outcomes, including higher incidence and mortality. However, some studies questioned the effect of air pollution on COVID-19 susceptibility, raising questions about the causal nature of these associations. To address this, a less biased method like Mendelian randomization (MR) is utilized, which employs genetic variants as instrumental variables to infer causal relationships in observational data. MethodWe performed two-sample MR analysis using public genome-wide association studies data. Instrumental variables correlated with PM2.5 concentration, PM2.5 absorbance, PM2.5-10 concentration and PM10 concentration were identified. The inverse variance weighted (IVW), robust adjusted profile score (RAPS) and generalized summary data-based Mendelian randomization (GSMR) methods were used for analysis. ResultsIVW MR analysis showed PM2.5 concentration [odd ratio (OR) = 3.29, 95% confidence interval (CI) 1.48–7.35, P-value = 0.0036], PM2.5 absorbance (OR = 5.62, 95%CI 1.98–15.94, P-value = 0.0012), and PM10 concentration (OR = 3.74, 95%CI 1.52–9.20, P-value = 0.0041) increased the risk of COVID-19 severity after Bonferroni correction. Further validation confirmed PM2.5 absorbance was associated with heightened COVID-19 severity (OR = 6.05, 95%CI 1.99–18.38, P-value = 0.0015 for RAPS method; OR = 4.91, 95%CI 1.65–14.59, P-value = 0.0042 for GSMR method) and hospitalization (OR = 3.15, 95%CI 1.54–6.47, P-value = 0.0018 for RAPS method). No causal links were observed between particulate matter exposure and COVID-19 susceptibility. ConclusionsOur study established a causal relationship between smaller particle pollution, specifically PM2.5, and increased risk of COVID-19 severity and hospitalization. These findings highlight the importance of improving air quality to mitigate respiratory disease progression.

Paediatric Thoracic Imaging in Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Conductance Regulator Modulation.

Cystic fibrosis (CF) is one of the most common progressive life-shortening genetic conditions worldwide. Ground-breaking translational research has generated therapies that target the primary cystic fibrosis transmembrane conductance regulator (CFTR) defect, known as CFTR modulators. A crucial aspect of paediatric CF disease is the development and progression of irreversible respiratory disease in the absence of clinical symptoms. Accurate thoracic diagnostics have an important role to play in this regard. Chest radiographs are non-specific and insensitive in the context of subtle changes in early CF disease, with computed tomography (CT) providing increased sensitivity. Recent advancements in imaging hardware and software have allowed thoracic CTs to be acquired in paediatric patients at radiation doses approaching that of a chest radiograph. CFTR modulators slow the progression of CF, reduce the frequency of exacerbations and extend life expectancy. In conjunction with advances in CT imaging techniques, low-dose thorax CT will establish a central position in the routine care of children with CF. International guidelines regarding the choice of modality and timing of thoracic imaging in children with CF are lagging behind these rapid technological advances. The continued progress of personalised medicine in the form of CFTR modulators will promote the emergence of personalised radiological diagnostics.

Restoring the epigenetic landscape of lung microbiome: potential therapeutic approach for chronic respiratory diseases.

Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and bronchiectasis, present significant threats to global health. Recent studies have revealed the crucial role of the lung microbiome in the development of these diseases. Pathogens have evolved complex strategies to evade the immune response, with the manipulation of host cellular epigenetic mechanisms playing a pivotal role. There is existing evidence regarding the effects of Pseudomonas on epigenetic modifications and their association with pulmonary diseases. Therefore, this study aims to directly assess the connection between Pseudomonas abundance and chronic respiratory diseases. We hope that our findings will shed light on the molecular mechanisms behind lung pathogen infections. We analyzed data from 366 participants, including individuals with COPD, acute exacerbations of COPD (AECOPD), bronchiectasis, and healthy individuals. Previous studies have given limited attention to the impact of Pseudomonas on these groups and their comparison with healthy individuals. Two independent datasets from different ethnic backgrounds were used for external validation. Each dataset separately analyzed bacteria at the genus level. The study reveals that Pseudomonas, a bacterium, was consistently found in high concentrations in all chronic lung disease datasets but it was present in very low abundance in the healthy datasets. This suggests that Pseudomonas may influence cellular mechanisms through epigenetics, contributing to the development and progression of chronic respiratory diseases. This study emphasizes the importance of understanding the relationship between the lung microbiome, epigenetics, and the onset of chronic pulmonary disease. Enhanced recognition of molecular mechanisms and the impact of the microbiome on cellular functions, along with a better understanding of these concepts, can lead to improved diagnosis and treatment.

Home-spirometry exacerbation profiles in children with cystic fibrosis.

Pulmonary exacerbations (PEx) are strong predictors of respiratory disease progression in children with cystic fibrosis (CwCF) and may be associated with persistent decreased lung function after acute management. Telemonitoring devices can be used for early detection and monitoring of PEx, but its utility is debated. Which symptoms and telemonitoring spirometry characterics are related to outcome dynamics following initial PEx management? This retrospective study included CwCF followed at Bordeaux University Hospital, France. All severe PEx episodes treated with intravenous (IV) antibiotics (ATB) between 1 January 2017 and 31 December 2021 in CwCF using home telemonitoring were analyzed. Symptoms and home spirometry data were collected 45 days before and up to 60 days after each IV ATB course. We defined three response profiles based on terciles of baseline forced expiratory volume in 1 s (FEV1 ) recovery. A total of 346 IV ATB courses for PEx were administered to 65 CwCF during the study period. The drop in FEV1 became significant 8 days before IV ATB initiation. Forty-one percent of IV ATB courses failed to restore baseline FEV1 . The magnitude of FEV1 drop and a greater delay in the initiation of treatment correlated with a low response level. On the 14th day of the IV treatment, a FEV1 recovery less than 94% of baseline was associated with a nonresponder profile. Home spirometry may facilitate the early recognition of PEx to implement earlier interventions. This study also provides an outcome lung function threshold which identifies low responders to IV ATB.

Microphysiological Models of Lung Epithelium-Alveolar Macrophage Co-Cultures to Study Chronic Lung Disease.

The interactions between immune cells and epithelial cells influence the progression of many respiratory diseases, such as chronic obstructive pulmonary disease (COPD). In vitro models allow for the examination of cells in controlled environments. However, these models lack the complex 3D architecture and vast multicellular interactions between the lung resident cells and infiltrating immune cells that can mediate cellular response to insults. In this study, three complementary microphysiological systems are presented to delineate the effects of cigarette smoke and respiratory disease on the lung epithelium. First, the Transwell system allows the co-culture of pulmonary immune and epithelial cells to evaluate cellular and monolayer phenotypic changes in response to cigarette smoke exposure. Next, the human and mouse precision-cut lung slices system provides a physiologically relevant model to study the effects of chronic insults like cigarette smoke with the dissection of specific interaction of immune cell subtypes within the structurally complex tissue environment. Finally, the lung-on-a-chip model provides an adaptable system for live imaging of polarized epithelial tissues that mimic the in vivo environment of the airways. Using a combination of these models, a complementary approach is provided to better address the intricate mechanisms of lung disease.

Effects of Hormone Replacement Therapy on Women's Lung Health and Disease.

This review provides an overview of menopausal hormone therapy and pulmonary disease risk, with a focus on the effect of hormone replacement therapy (HRT) on pulmonary function and its relation to lung diseases. This summary is based on authors' knowledge in the field of HRT and supplemented by a PubMed search using the terms "menopause hormone therapy," "asthma", "lung cancer", "chronic obstructive pulmonary disease", "lung function", and "pulmonary hypertension". Available evidence indicates that there is limited research on the role of sex hormones in the susceptibility, severity, and progression of chronic respiratory diseases. However, some studies suggest that the hormonal changes that occur during the menopausal transition may have an impact on pulmonary function and respiratory diseases. Women are in need of convenient access to a safe and effective modality for personalized HRT based on an artificial intelligence (AI)-driven platform that will enable them to receive personalized hormonal treatment through frequent, convenient, and accurate measurements of hormone levels in peripheral blood.

Downregulation of NOX4 improves airway remodeling and inflammation by the TGF-β1-Smad2/3 pathway in asthma.

Asthma is a respiratory inflammatory disease, and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is involved in the progression of respiratory diseases. However, the role of NOX4 in asthma remains unclear. In the present study, we aimed to explore the effects of NOX4 on airway remodeling and inflammation. NOX4 expression was measured using immunocytochemistry (IHC), western blot, and real-time PCR (qPCR). Lung tissues were stained using the H&E assay. ELISA was used to examine the levels of airway remodeling-related indicators, and qPCR was used to detect airway inflammatory factors. The results indicated that NOX4 is highly expressed in lung tissues, bronchoalveolar lavage fluid (BALF), and serum of OVA-treated mice. Inhibition of NOX4 alleviated OVA-induced airway remodeling and inflammation. Similarly, TGF-β1 was also upregulated in BALF and serum OVA-induced mice. Inhibition of TGF-β1 signaling also improved airway remodeling and inflammation induced by OVA. Moreover, the downregulation of NOX4 inactivated the TGF-β1-Smad2/3 pathway, and TGF-β1 decreased Smad2/3 expression. Moreover, inhibition of the TGF-β1 was enhanced, while TGF-β1 reversed the effects on airway remodeling and inflammation induced by NOX4 inhibition. Taken together, the downregulation of NOX4 improves airway remodeling and inflammation via inactivation of the TGF-β1-Smad2/3 pathway in asthma mice, suggesting that NOX4 may be a therapeutic target for asthma.

Risk factors for severity in seasonal respiratory viral infections and how they guide management in hematopoietic cell transplant recipients.

Seasonal respiratory virus infections (RVIs) often progress to severe diseases in hematopoietic cell transplant (HCT) recipients. This review summarizes the current evidence on risk factors for the severity of RVIs in this high-risk population and provides clinical management. The likelihood of the respiratory viral disease progression depends on the immune status of the host and the type of virus. Conventional host factors, such as the immunodeficiency scoring index and the severe immunodeficiency criteria, have been utilized to estimate the risk of progression to severe disease, including mortality. Recent reports have suggested nonconventional risk factors, such as hyperglycemia, hypoalbuminemia, prior use of antibiotics with broad anaerobic activity, posttransplant cyclophosphamide, and pulmonary impairment after RVIs. Identifying novel and modifiable risk factors is important with the advances of novel therapeutic and preventive interventions for RVIs. Validation of recently identified risk factors for severe RVIs in HCT recipients is required. The development of innovative interventions along with appropriate risk stratification is critical to improve outcomes in this vulnerable population.

Periodontopathogens Porphyromonas gingivalis and Fusobacterium nucleatum and Their Roles in the Progression of Respiratory Diseases.

The intricate interplay between oral microbiota and the human host extends beyond the confines of the oral cavity, profoundly impacting the general health status. Both periodontal diseases and respiratory diseases show high prevalence worldwide and have a marked influence on the quality of life for the patients. Accumulating studies are establishing a compelling association between periodontal diseases and respiratory diseases. Here, in this review, we specifically focus on the key periodontal pathogenic bacteria Porphyromonas gingivalis and Fusobacterium nucleatum and dissect their roles in the onset and course of respiratory diseases, mainly pneumonia, chronic obstructive pulmonary disease, lung cancer, and asthma. The mechanistic underpinnings and molecular processes on how P. gingivalis and F. nucleatum contribute to the progression of related respiratory diseases are further summarized and analyzed, including: induction of mucus hypersecretion and chronic airway inflammation; cytotoxic effects to disrupt the morphology and function of respiratory epithelial cells; synergistic pathogenic effects with respiratory pathogens like Streptococcus pneumoniae and Pseudomonas aeruginosa. By delving into the complex relationship to periodontal diseases and periodontopathogens, this review helps unearth novel insights into the etiopathogenesis of respiratory diseases and inspires the development of potential therapeutic avenues and preventive strategies.

Resveratrol mitigates miR-212-3p mediated progression of diesel exhaust-induced pulmonary fibrosis by regulating SIRT1/FoxO3

BackgroundDiesel exhaust (DE) exposure contributes to the progression of chronic respiratory diseases and is associated with dysregulation of microRNA expression. The present study aims to investigate the involvement of miRNAs and target genes in DE-induced lung fibrosis. MethodsC57BL/6 mice were divided into three groups. Group 1 mice were exposed to filtered air (Control). Group 2 mice were exposed to DE for 30 min per day, 5 days per week, for 8 weeks (DE). Group 3 mice received DE exposure along with resveratrol on alternate days for the last 2 weeks (DE + RES). Mice were sacrificed to isolate RNA from lung tissue for miRNA microarray profiling. Bronchoalveolar lavage fluid and lung tissues were collected for cell count and biochemical analysis. ResultsDE exposure resulted in differential expression of 28 miRNAs with fold change >2 (p < 0.05). The upregulated miR-212-3p was selected for further analysis. Consensus analysis revealed enrichment of SIRT1 in the FoxO pathway, along with a co-annotation of reduced body weight (p < 0.05). A549 cells transfected with a miR-212-3p inhibitor showed a dose-dependent increase in SIRT1 expression, indicating SIRT1 as a direct target. Treatment with resveratrol restored SIRT1 and miR-212-3p expression and led to a reduction in inflammatory cytokines (p < 0.05). The modulation of SIRT1 correlated negatively with macrophage infiltration, confirming its role in regulating cellular infiltration and lung inflammation. Fibronectin, alpha-SMA, and collagen levels were significantly decreased in DE + RES compared to DE group suggesting modulation of cellular functions and resolution of lung fibrosis. Furthermore, a significant decrease in FoxO3a and TGF-β gene expressions was observed upon resveratrol administration thereby downregulating pro-fibrotic pathway. ConclusionsThe present study demonstrates resveratrol treatment stabilizes SIRT1 gene expression by attenuating miR-212-3p in DE-exposed mice, leading to downregulation of TGF-β and FoxO3a expressions. The study highlights the therapeutic role of resveratrol in the treatment of DE-induced pulmonary fibrosis.

The Effectiveness of Supplementation with Key Vitamins, Minerals, Antioxidants and Specific Nutritional Supplements in COPD-A Review.

Currently, an increasing amount of evidence supports the notion that vitamins C, D and E, carotenoids, and omega-3 fatty acids may protect against the progression of chronic respiratory diseases. Although chronic obstructive pulmonary disease (COPD) primarily affects the lung, it is often accompanied by extrapulmonary manifestations such as weight loss and malnutrition, skeletal muscle dysfunction, and an excess of harmful oxidants, which can lead to a decline in quality of life and possible death. Recently, the role of various vitamins, minerals, and antioxidants in mitigating the effects of environmental pollution and smoking has received significant attention. Therefore, this review evaluates the most relevant and up-to-date evidence on this topic. We conducted a literature review between 15 May 2018 and 15 May 2023, using the electronic database PubMed. Our search keywords included COPD, chronic obstructive pulmonary disease, FEV1, supplementation: vitamin A, vitamin D, vitamin E, vitamin C, vitamin B, omega-3, minerals, antioxidants, specific nutrient supplementations, clinical trials, and randomized controlled trials (RCTs). We focused on studies that measured the serum levels of vitamins, as these are a more objective measure than patient self-reports. Our findings suggest that the role of appropriate dietary supplements needs to be reconsidered for individuals who are predisposed to or at risk of these conditions.

Macrophage-derived exosomal TNF-α promotes pulmonary surfactant protein expression in PM2.5-induced acute lung injury

Short-term high-concentration exposure to airborne fine particulate matter (PM2.5) is strongly associated with the risk of acute lung injury (ALI). It has been recently reported that exosomes (Exos) involve in the progression of respiratory diseases. However, the molecular mechanisms by which exosome-mediated intercellular signaling exacerbate PM2.5-induced ALI remains largely unaddressed. In the present study, we firstly investigated the effect of macrophage-derived exosomal tumor necrosis factor α (TNF-α) on pulmonary surfactant proteins (SPs) expression in epithelial MLE-12 cells after PM2.5 exposure. The higher levels of exosomes in the bronchoalveolar lavage fluid (BALF) of PM2.5-induced ALI mice were found. BALF-exosomes significantly up-regulated SPs expression in MLE-12 cells. Moreover, we found that remarkably high expression of TNF-α in exosomes secreted by PM2.5-treated RAW264.7 cells. Exosomal TNF-α promoted thyroid transcription factor-1 (TTF-1) activation and SPs expression in MLE-12 cells. Furthermore, intratracheal instillation of macrophage-derived TNF-α-containing exosomes increased epithelial cell SPs expression in the lungs of mice. Taken together, these results suggest that macrophages-secreted exosomal TNF-α can trigger epithelial cell SPs expression, which provides new insight and potential target in the mechanism of epithelial cell dysfunction in PM2.5-induced ALI.

The associations between gut microbiota and chronic respiratory diseases: a Mendelian randomization study.

Growing evidence indicates that variations in the composition of the gut microbiota are linked to the onset and progression of chronic respiratory diseases (CRDs), albeit the causal relationship between the two remains unclear. We conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the relationship between gut microbiota and five main CRDs, including chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), sarcoidosis, and pneumoconiosis. For MR analysis, the inverse variance weighted (IVW) method was utilized as the primary method. The MR-Egger, weighted median, and MR-PRESSO statistical methods were used as a supplement. To detect heterogeneity and pleiotropy, the Cochrane and Rucker Q test, MR-Egger intercept test, and MR-PRESSO global test were then implemented. The leave-one-out strategy was also applied to assess the consistency of the MR results. Based on substantial genetic data obtained from genome-wide association studies (GWAS) comprising 3,504,473 European participants, our study offers evidence that several gut microbial taxa, including 14 probable microbial taxa (specifically, 5, 3, 2, 3 and 1 for COPD, asthma, IPF, sarcoidosis, and pneumoconiosis, respectively) and 33 possible microbial taxa (specifically, 6, 7, 8, 7 and 5 for COPD, asthma, IPF, sarcoidosis, and pneumoconiosis, respectively) play significant roles in the formation of CRDs. This work implies causal relationships between the gut microbiota and CRDs, thereby shedding new light on the gut microbiota-mediated prevention of CRDs.