The evolving landscape of IL-10, IL-22 and IL-26 in pleurisy especially in tuberculous pleurisy.

Pleurisy can be categorized as primary or secondary, arising from immunological, tumorous, or microbial conditions. It often results in lung structure damage and the development of various respiratory issues. Among the different types, tuberculous pleurisy has emerged as a prominent focus for both clinical and scientific investigations. The IL-10 family, known for its anti-inflammatory properties in the human immune system, is increasingly being studied for its involvement in the pathogenesis of pleurisy. This review aims to present a detailed overview of the intricate role of IL-10 family members (specifically IL-10, IL-22, and IL-26) in human and animal pleuritic diseases or relevant animal models. These insights could serve as valuable guidance and references for further studies on pleurisy and potential therapeutic strategies.

High-Precision Microscale Particulate Matter Prediction in Diverse Environments Using a Long Short-Term Memory Neural Network and Street View Imagery.

In this study, we propose a novel long short-term memory (LSTM) neural network model that leverages color features (HSV: hue, saturation, value) extracted from street images to estimate air quality with particulate matter (PM) in four typical European environments: urban, suburban, villages, and the harbor. To evaluate its performance, we utilize concentration data for eight parameters of ambient PM (PM1.0, PM2.5, and PM10, particle number concentration, lung-deposited surface area, equivalent mass concentrations of ultraviolet PM, black carbon, and brown carbon) collected from a mobile monitoring platform during the nonheating season in downtown Augsburg, Germany, along with synchronized street view images. Experimental comparisons were conducted between the LSTM model and other deep learning models (recurrent neural network and gated recurrent unit). The results clearly demonstrate a better performance of the LSTM model compared with other statistically based models. The LSTM-HSV model achieved impressive interpretability rates above 80%, for the eight PM metrics mentioned above, indicating the expected performance of the proposed model. Moreover, the successful application of the LSTM-HSV model in other seasons of Augsburg city and various environments (suburbs, villages, and harbor cities) demonstrates its satisfactory generalization capabilities in both temporal and spatial dimensions. The successful application of the LSTM-HSV model underscores its potential as a versatile tool for the estimation of air pollution after presampling of the studied area, with broad implications for urban planning and public health initiatives.

PM10-bound trace elements in pan-European urban atmosphere.

Although many studies have discussed the impact of Europe's air quality, very limited research focused on the detailed phenomenology of ambient trace elements (TEs) in PM10 in urban atmosphere. This study compiled long-term (2013-2022) measurements of speciation of ambient urban PM10 from 55 sites of 7 countries (Switzerland, Spain, France, Greece, Italy, Portugal, UK), aiming to elucidate the phenomenology of 20 TEs in PM10 in urban Europe. The monitoring sites comprised urban background (UB, n = 26), traffic (TR, n = 10), industrial (IN, n = 5), suburban background (SUB, n = 7), and rural background (RB, n = 7) types. The sampling campaigns were conducted using standardized protocols to ensure data comparability. In each country, PM10 samples were collected over a fixed period using high-volume air samplers. The analysis encompassed the spatio-temporal distribution of TEs, and relationships between TEs at each site. Results indicated an annual average for the sum of 20 TEs of 90 ± 65 ng/m3, with TR and IN sites exhibiting the highest concentrations (130 ± 66 and 131 ± 80 ng/m3, respectively). Seasonal variability in TEs concentrations, influenced by emission sources and meteorology, revealed significant differences (p < 0.05) across all monitoring sites. Estimation of TE concentrations highlighted distinct ratios between non-carcinogenic and carcinogenic metals, with Zn (40 ± 49 ng/m3), Ti (21 ± 29 ng/m3), and Cu (23 ± 35 ng/m3) dominating non-carcinogenic TEs, while Cr (5 ± 7 ng/m3), and Ni (2 ± 6 ng/m3) were prominent among carcinogenic ones. Correlations between TEs across diverse locations and seasons varied, in agreement with differences in emission sources and meteorological conditions. This study provides valuable insights into TEs in pan-European urban atmosphere, contributing to a comprehensive dataset for future environmental protection policies.

Identification of novel biomarkers related to neutrophilic inflammation in COPD.

Background: Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic respiratory diseases and the fourth cause of mortality globally. Neutrophilic inflammation has a vital role in the occurrence and progression of COPD. This study aimed to identify the novel hub genes involved in neutrophilic inflammation in COPD through bioinformatic prediction and experimental validation. Methods: Both the single-cell RNA sequencing (scRNA-seq) dataset (GSE173896) and the RNA sequencing (RNA-seq) dataset (GSE57148) were downloaded from the Gene Expression Omnibus (GEO) database. The Seurat package was used for quality control, dimensions reduction, and cell identification of scRNA-seq. The irGSEA package was used for scoring individual cells. The Monocle2 package was used for the trajectory analysis of neutrophils. The CIBERSORT algorithm was used for analysis of immune cell infiltration in the lungs of COPD patients and controls in RNA-seq dataset, and weighted gene co-expression network analysis (WGCNA) correlated gene modules with neutrophil infiltration. The Mendelian randomization (MR) analysis explored the causal relationship between feature DEGs and COPD. The protein-protein interaction (PPI) network of novel hub genes was constructed, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate novel hub genes in clinical specimens. Results: In scRNA-seq, the gene sets upregulated in COPD samples were related to the neutrophilic inflammatory response and TNF-α activation of the NF-κB signaling pathway. In RNA-seq, immune infiltration analysis showed neutrophils were upregulated in COPD lung tissue. We combined data from differential and modular genes and identified 51 differential genes associated with neutrophilic inflammation. Using MR analysis, 6 genes were explored to be causally associated with COPD. Meanwhile, 11 hub genes were identified by PPI network analysis, and all of them were upregulated. qRT-PCR experiments validated 9 out of 11 genes in peripheral blood leukocytes of COPD patients. Furthermore, 5 genes negatively correlated with lung function in COPD patients. Finally, a network of transcription factors for NAMPT and PTGS2 was constructed. Conclusion: This study identified nine novel hub genes related to the neutrophilic inflammation in COPD, and two genes were risk factors of COPD, which may serve as potential biomarkers for the clinical severity of COPD.

COPD patients with high blood eosinophil counts exhibit a lower rate of omicron infection and milder post-infection symptoms.

BACKGROUND: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent Omicron variant has raised concerns for chronic obstructive pulmonary disease (COPD) patients due to the potential risk of disruptions to healthcare services and unknown comorbidities between COPD and Omicron. METHOD: In this study, we conducted a follow-up investigation of 315 COPD patients during the Omicron outbreak at Shanxi Bethune Hospital to understand the impact of the pandemic on this vulnerable population. Among all patients, 228 were infected with Omicron, of which 82 needed hospitalizations. RESULT: We found that COPD patients with high blood eosinophil (EOS) counts exhibited lower susceptibility to Omicron infection and were more likely to have milder symptoms that did not require hospitalization. Conversely, patients with low EOS counts showed higher rates of infection and hospitalization. Moreover, EOS count was positively correlated with T lymphocyte counts in hospitalized patients after Omicron infection, suggesting potential associations between EOS and specific immune responses in COPD patients during viral infections. Correlation analysis revealed a positive correlation between EOS count and lymphocyte and T-cells, and a negative correlation between EOS count and age, neutrophil, and C-reactive protein. CONCLUSION: Overall, our study contributes to the knowledge of COPD management during the COVID-19 Omicron outbreak and emphasizes the importance of considering individual immune profiles to improve care for COPD patients in the face of the ongoing global health crisis.

Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease.

BACKGROUND: The interplay between airway epithelium and macrophages plays a pivotal role in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis. Exosomes, which transport miRNA cargo, have emerged as novel mediators of intercellular communication. MicroRNA-125a-5p (miR-125a-5p) has been implicated in macrophage polarization.This study aims to investigate the role of exosomal miR-125a-5p in the dysfunctional epithelium-macrophage cross-talk in cigarette smoke (CS)-induced COPD. METHODS: In cell models, THP-1 monocytic cells were differentiated into macrophages (M0). Human bronchial epithelial cells treated with CS extract (CSE) were co-cultured with M0. Exosomes were isolated from culture media using commercial kits and characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Exosomes labeled with PKH26 red fluorescent cell linker kits were incubated with macrophages. Luciferase reporter assay was used to confirm the target gene of miR-125a-5p. In mouse experiments, inhibiting miR-125a-5p was utilized to examine its role in macrophage polarization. Furthermore, the underlying mechanism was explored. RESULTS: In vitro results indicated that CSE treatment led to upregulation of miR-125a-5p in HBE cells, and exosomes contained miR-125a-5p. PKH26-labeled exosomes were internalized by macrophages. Co-culture experiments between bronchial epithelial cells and miR-125a-5p mimic resulted in significant increase in M1 macrophage markers (TNF-α, iNOS-2, IL-1ß) and decrease in M2 markers (IL-10 and Arg-1). In COPD mouse models, miR-125a-5p inhibitor reduced levels of TNF-α, IL-1ß, and IL-6. Luciferase assays revealed that miR-125a-5p inhibitors enhanced the relative luciferase activity of IL1RN. Mechanistic experiments demonstrated that HBE-derived exosomes transfected with miR-125a-5p mimics promoted upregulation of MyD88, TRAF6, p65, iNOS-2, and downregulation of Arg-1. CONCLUSION: This study suggests that exosomal miR-125a-5p may act as a mediator in the cross-talk between airway epithelium and macrophage polarization in COPD. Exosomal miR-125a-5p targeting IL1RN may promote M1 macrophage polarization via the MyD88/NF-κB pathway.

Kynurenine acts as a signaling molecule to attenuate pulmonary fibrosis by enhancing the AHR-PTEN axis.

INTRODUCTION: Pulmonary fibrosis (PF) is a fatal fibrotic lung disease without any options to halt disease progression. Feasible evidence suggests that aberrant metabolism of amino acids may play a role in the pathoetiology of PF. However, the exact impact of kynurenine (Kyn), a metabolite derived from tryptophan (Trp) on PF is yet to be addressed. OBJECTIVES: This study aims to elucidate the role of kynurenine in both the onset and advancement of PF. METHODS: Liquid chromatography-tandem mass spectrometry was employed to assess Kyn levels in patients with idiopathic PF and PF associated with Sjögren's syndrome. Additionally, a mouse model of PF induced by bleomycin was utilized to study the impact of Kyn administration. Furthermore, cell models treated with TGF-ß1 were used to explore the mechanism by which Kyn inhibits fibroblast functions. RESULTS: We demonstrated that high levels of Kyn are a clinical feature in both idiopathic PF patients and primary Sjögren syndrome associated PF patients. Further studies illustrated that Kyn served as a braking molecule to suppress fibroblast functionality, thereby protecting mice from bleomycin-induced lung fibrosis. The protective effects depend on AHR, in which Kyn induces AHR nuclear translocation, where it upregulates PTEN expression to blunt TGF-ß mediated AKT/mTOR signaling in fibroblasts. However, in fibrotic microenviroment, the expression of AHR is repressed by methyl-CpG-binding domain 2 (MBD2), a reader interpreting the effect of DNA methylation, which results in a significantly reduced sensitivity of Kyn to fibroblasts. Therefore, exogenous administration of Kyn substantially reversed established PF. CONCLUSION: Our studies not only highlighted a critical role of Trp metabolism in PF pathogenesis, but also provided compelling evidence suggesting that Kyn could serve as a promising metabolite against PF.

Variability of ambient air ammonia in urban Europe (Finland, France, Italy, Spain, and the UK).

This study addressed the scarcity of NH3 measurements in urban Europe and the diverse monitoring protocols, hindering direct data comparison. Sixty-nine datasets from Finland, France, Italy, Spain, and the UK across various site types, including industrial (IND, 8), traffic (TR, 12), urban (UB, 22), suburban (SUB, 12), and regional background (RB, 15), are analyzed to this study. Among these, 26 sites provided 5, or more, years of data for time series analysis. Despite varied protocols, necessitating future harmonization, the average NH3 concentration across sites reached 8.0 ± 8.9 µg/m3. Excluding farming/agricultural hotspots (FAHs), IND and TR sites had the highest concentrations (4.7 ± 3.2 and 4.5 ± 1.0 µg/m3), followed by UB, SUB, and RB sites (3.3 ± 1.5, 2.7 ± 1.3, and 1.0 ± 0.3 µg/m3, respectively) indicating that industrial, traffic, and other urban sources were primary contributors to NH3 outside FAH regions. When referring exclusively to the FAHs, concentrations ranged from 10.0 ± 2.3 to 15.6 ± 17.2 µg/m3, with the highest concentrations being reached in RB sites close to the farming and agricultural sources, and that, on average for FAHs there is a decreasing NH3 concentration gradient towards the city. Time trends showed that over half of the sites (18/26) observed statistically significant trends. Approximately 50 % of UB and TR sites showed a decreasing trend, while 30 % an increasing one. Meta-analysis revealed a small insignificant decreasing trend for non-FAH RB sites. In FAHs, there was a significant upward trend at a rate of 3.51[0.45,6.57]%/yr. Seasonal patterns of NH3 concentrations varied, with urban areas experiencing fluctuations influenced by surrounding emissions, particularly in FAHs. Diel variation showed differing patterns at urban monitoring sites, all with higher daytime concentrations, but with variations in peak times depending on major emission sources and meteorological patterns. These results offer valuable insights into the spatio-temporal patterns of gas-phase NH3 concentrations in urban Europe, contributing to future efforts in benchmarking NH3 pollution control in urban areas.

Surfactant Protein A Polymorphism Is Associated with Susceptibility to Chronic Obstructive Pulmonary Disease in Chinese Uighur Population / 华中科技大学学报（医学）（英德文版）

This study investigated the correlation between surfactant protein-A (SP-A) polymorphism and the susceptibility of chronic obstructive pulmonary disease (COPD) in Xinjiang Uighurs.Genomic DNA was extracted from peripheral blood of 194 COPD smokers and 201 healthy smokers of Uighur who were hospitalized in or paid a visit to one of the four Xinjiang-based hospitals involved in the study,from March 2009 to December 2010.Single nucleotide polymorphisms (SNPs) were studied at aa62 (CCA/CCG rs 1136451) and aa219 (CGG/rGG,rs4253527) in SP-A.Genotypes were determined by using the TaqMan polymerase chain reaction (PCR).Our results showed that genotype frequencies were different between the COPD and normal smokers in aa62 (x2=6.852,P=0.033).There were also significant differences in allele genotype frequencies between the COPD and the control and allele G might decrease the risk COPD (x2=6.545,P=0.011; OR=0.663; 95％ CI:0.484-0.909).The result suggested that polymorphism of aa62 (CCA/CCG,rs1136451) of SP-A may be associated with the susceptibility to COPD in Xinjiang Uighurs.

Comparative Study on the Efficacy of Tiotropium Bromide Inhalation and Oral Doxofylline Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease / 华中科技大学学报（医学）（英德文版）

This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD).A multi-center,randomized,double-blind,double-dummy,parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time,2 times a day) for 12 and 24 weeks.Before and after treatment for 12 weeks and 24 weeks,respectively,pulmonary function,6-min walking distance and dyspnea index were recorded.The results showed that in both tiotropium group and doxofylline groups,after 12-week treatment,FEV1,FEV1/FVC％ and 6-min walk distance were significantly higher than those before the medication,while dyspnea index decreased as compared with that before treatment.After 24-week treatment,a slight improvement in the measures was observed as compared with that of 12-weeks treatment,but the difference was not statistically significant.With both 12-week and 24-week treatment,the effect of tiotropium was slightly better than that of doxofylline tablets,with the difference being statistically insignificant.The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9％) and 12 cases (12.9％),respectively,and no statistically significant difference was found between them.We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.

Changes of Protein Kinase Cα and Cyclin D1 Expressions in Pulmonary Arteries from Smokers with and without Chronic Obstructive Pulmonary Disease / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to investigate the changes of protein kinase Cα(PKCα)and cyclin D1 expressions in pulmonary arteries from smokers with normal lung function and smokers with mild to moderate chronic obstructive pulmonary disease(COPD).The peripheral lung tissues were obtained from 10 non-smokers with normal lung function(non-smoker group),14 smokers with normal lung function(smoker group),11 smokers with mild to moderate COPD(COPD group).The morphological changes of pulmonary arteries were observed by HE-staining.The expressions of α-smooth muscle actin(α-SMA),proliferating cell nuclear antigen(PCNA),PKCα and cyclin D1 proteins in pulmonary artery smooth muscle cells(PASMCs)were immunohistochemically determined.The percentages of PCNA-positive cells were taken as the smooth muscle cells proliferation index(PI).The mRNA expressions of PKCα and cyclin D1 in PASMCs were evaluated by real-time fluorescence PCR.Morphometrical analysis showed that the ratio of pulmonary artery wall area to total area(WA%)in smoker group and COPD group was significantly greater than that in non-smoker group(P<0.01).The PASMCs proliferation index in smoker group and COPD group was significantly higher than that in nonsmoker group(P<0.01).The protein levels of PKCα and cyclin D1 in PASMCs were significantly increased in smoker group and COPD group as compared with non-smoker group(P<0.01).The mRNA expressions of PKCa and cyclin D1 in PASMCs were significantly elevated in smoker group and COPD group as compared with non-smoker group(P<0.01).Significant correlations were found between PKCα protein and WA% or PI(P<0.01).Correlations between cyclin D1 protein and WA% or PI also existed(P<0.01).The expression of PKCα was positively correlated with the expression of cyclin D1 at both protein and mRNA levels(P<0.01).In conclusion,increased expressions of PKCα and cyclin D1 might be involved in the pathogenesis of abnormal proliferation of PASMCs in smokers with normal lung function and smokers with mild to moderate COPD.