Inflammation In Chronic Pulmonary Disease Research Articles

The role of the cGAS-STING pathway in chronic pulmonary inflammatory diseases

The innate immune system plays a vital role in the inflammatory process, serving as a crucial mechanism for the body to respond to infection, cellular stress, and tissue damage. The cGAS-STING signaling pathway is pivotal in the onset and progression of various autoimmune diseases and chronic inflammation. By recognizing cytoplasmic DNA, this pathway initiates and regulates inflammation and antiviral responses within the innate immune system. Consequently, the regulation of the cGAS-STING pathway has become a prominent area of interest in the treatment of many diseases. Chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis, are characterized by persistent or recurrent lung inflammation and tissue damage, leading to diminished respiratory function. This paper explores the mechanism of action of the cGAS-STING signaling pathway in these diseases, examines the development of STING inhibitors and nanomaterial applications, and discusses the potential clinical application prospects of targeting the cGAS-STING pathway in chronic inflammatory lung diseases.

Mechanisms of Lung Endothelial Cell Injury and Survival in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive, chronic, and incurable inflammatory pulmonary vascular disease characterized by significant sex bias and largely unexplored microbial-associated molecular mechanisms that may influence its development and sex prevalence across various subgroups. PAH can be subclassified as idiopathic, heritable, or associated with conditions such as connective tissue diseases, congenital heart defects, liver disease, infections, and chronic exposure to drugs or toxins. During PAH progression, lung vascular endothelial cells (ECs) undergo dramatic morphofunctional transformations in response to acute and chronic inflammation. These transformations include the appearance and expansion of abnormal vascular cell phenotypes such as those derived from apoptosis-resistant cell growth and endothelial-to-mesenchymal transition (EndoMT). Compelling evidence indicates that these endothelial phenotypes seem to be triggered by chronic lung vascular injury and dysfunction, often characterized by reduced secretion of vasoactive molecules like nitric oxide (NO) and exacerbated response to vasoconstrictors such as Endothelin-1 (ET-1); both long-term known contributors of PAH pathogenesis. This review sheds light on the mechanisms of EC dysfunction, apoptosis, and EndoMT in PAH, aiming to unravel the intricate interactions between ECs, pathogens, and other cell types that drive the onset and progression of this devastating disease. Ultimately, we hope to provide an overview of the complex functions of lung vascular ECs in PAH, inspiring novel therapeutic strategies that target these dysfunctional cells to improve the treatment landscape for PAH, particularly in the face of current and emerging global pathogenic threats.

Association of monoaminergic gene polymorphisms in chronic inflammatory pulmonary disease patients with successful smoking cessation

BackgroundAlbeit smoking cessation has unequivocal health benefits, attempts to quit are not unanimous, even in patient populations at high risk for smoking-related diseases cessation. Allelic variations of enzymes involved in dopamine metabolism are being considered as candidates for nicotine addiction. We set out to assess whether rs4680 G/A and rs2235186 G/A polymorphisms of COMT and MAO-A, respectively are associated with the ability to quit smoking in chronic inflammatory pulmonary disease patients.MethodsPatients managed for chronic inflammatory pulmonary disease by the Department of Pulmonology (University of Debrecen, Hungary), with a current or past smoking habit were included in the current analysis. The study was designed in line with the STROBE statement for cross-sectional studies and was approved by the National Center for Public Health, Hungary. Genomic DNA was extracted from peripheral blood specimens. SNPs were genotyped using TaqMan SNP genotyping assays.Resultsrs4680 COMT polymorphism showed significant effect for successful smoking cessation in patients with pulmonary disease. Accordingly, A/A subjects had lower odds for successful smoking cessation (odds ratio 0.37; 95% confidence interval 0.20–0.69, p = 0.002 (additive model). On the other hand, patients homozygous for the minor allele (A) at rs2235186 of MAO-A showed a non-significant trend toward increased odds for successful smoking cessation.ConclusionsThe presence of the minor allele for rs4680 COMT was shown to decrease the odds for successful smoking cessation, a finding that may be interpreted in view of the altered balance between tonic and phasic dopamine release.

Disease-specific transcriptional programs govern airway goblet cell metaplasia

Hypersecretion of airway mucus caused by goblet cell metaplasia is a characteristic of chronic pulmonary inflammatory diseases including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD). Goblet cells originate from airway progenitor club cells. However, the molecular mechanisms and features of goblet cell metaplasia in lung disease are poorly understood. Herein, public single-cell RNA sequencing datasets of human lungs were reanalyzed to explore the transitional phase as club cells differentiate into goblet cells in asthma, CF, and COPD. We found that changes in club and goblet cells during pathogenesis and cellular transition were associated with signalling pathways related to immune response, oxidative stress, and apoptosis. Moreover, other key drivers of goblet cell specification appeared to be pathologically specific, with interleukin (IL)-13 and hypoxia inducible factor 1 (HIF-1)-induced genetic changes in asthma, cystic fibrosis transmembrane conductance regulator (CFTR) mutation being present in CF, and interactions with CD8+ T cells, mitophagy, and mitochondria-induced apoptosis in COPD. In conclusion, this study revealed the similarities and differences in goblet cell metaplasia in asthma, CF, and COPD at the transcriptome level, thereby providing insights into possible novel therapeutic approaches for these diseases.

Evaluation of vitamin D deficiency and low bone mass in children with asthma in fars province: A case-control study.

Asthma is a chronic inflammatory pulmonary disease which affects 10%-20% of children and adolescents. Inhaled corticosteroids (ICS) is one of its most effective therapies. The effect of systemic corticosteroids on decreasing bone mineral density (BMD) was investigated and proved in children; however, the influence of ICSs on bone density has still remained unclear. This study evaluates the bone mineral density of children and adolescents with asthma in southern Iran and the associated factors, for example, amount of used inhaled steroid. This case-control study enrolled 41 children and adolescents (aged 8-18 years) with asthma and their age and gender-matched controls in 2019-2020. Serum Calcium, phosphate, vitamin D, and bone mineral density were measured. Their physical activity, sun exposure, and fracture history were evaluated subjectively. Lumbar BMD and BMD Z-score in patients showed no significant difference with controls (p = 0.23, p = 0.73). Also, it showed that there was no significant difference in biochemical studies, growth, and bone densitometry parameters between patients who used ICSs for less than 3 months/year corticosteroid therapy compared to those with equal or more than 3 months/year usage. Prevalence of vitamin D deficiency was 28% and 8% in the controls and patients, respectively (p = 0.005). The present study showed that 9.46% of children and adolescents with asthma had low bone mass for chronological age, and it is not significantly higher than normal population. Dosage of inhaled steroid did not associate with osteoporosis in these patients. Prevalence of vitamin D deficiency in patients was lower than normal population, probably due to receiving vitamin D in their routine follow-ups.

Rhinovirus protease cleavage of nucleoporins: perspective on implications for airway remodeling.

Human Rhinoviruses (RV) are a major cause of common colds and infections in early childhood and can lead to subsequent development of asthma via an as yet unknown mechanism. Asthma is a chronic inflammatory pulmonary disease characterized by significant airway remodeling. A key component of airway remodeling is the transdifferentiation of airway epithelial and fibroblast cells into cells with a more contractile phenotype. Interestingly, transforming growth factor-beta (TGF-β), a well characterized inducer of transdifferentiation, is significantly higher in airways of asthmatics compared to non-asthmatics. RV infection induces TGF-β signaling, at the same time nucleoporins (Nups), including Nup153, are cleaved by RV proteases disrupting nucleocytoplasmic transport. As Nup153 regulates nuclear export of SMAD2, a key intermediate in the TGF-β transdifferentiation pathway, its loss of function would result in nuclear retention of SMAD2 and dysregulated TGF-β signaling. We hypothesize that RV infection leads to increased nuclear SMAD2, resulting in sustained TGF-β induced gene expression, priming the airway for subsequent development of asthma. Our hypothesis brings together disparate studies on RV, asthma and Nup153 with the aim to prompt new research into the role of RV infection in development of asthma.

Nicotinic acetylcholine receptor signaling maintains epithelial barrier integrity.

Disruption of epithelial barriers is a common disease manifestation in chronic degenerative diseases of the airways, lung, and intestine. Extensive human genetic studies have identified risk loci in such diseases, including in chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases. The genes associated with these loci have not fully been determined, and functional characterization of such genes requires extensive studies in model organisms. Here, we report the results of a screen in Drosophila melanogaster that allowed for rapid identification, validation, and prioritization of COPD risk genes that were selected based on risk loci identified in human genome-wide association studies (GWAS). Using intestinal barrier dysfunction in flies as a readout, our results validate the impact of candidate gene perturbations on epithelial barrier function in 56% of the cases, resulting in a prioritized target gene list. We further report the functional characterization in flies of one family of these genes, encoding for nicotinic acetylcholine receptor (nAchR) subunits. We find that nAchR signaling in enterocytes of the fly gut promotes epithelial barrier function and epithelial homeostasis by regulating the production of the peritrophic matrix. Our findings identify COPD-associated genes critical for epithelial barrier maintenance, and provide insight into the role of epithelial nAchR signaling for homeostasis.

Biologic drugs in the treatment of chronic inflammatory pulmonary diseases: recent developments and future perspectives.

Chronic inflammatory diseases of the lung are some of the leading causes of mortality and significant morbidity worldwide. Despite the tremendous burden these conditions put on global healthcare, treatment options for most of these diseases remain scarce. Inhaled corticosteroids and beta-adrenergic agonists, while effective for symptom control and widely available, are linked to severe and progressive side effects, affecting long-term patient compliance. Biologic drugs, in particular peptide inhibitors and monoclonal antibodies show promise as therapeutics for chronic pulmonary diseases. Peptide inhibitor-based treatments have already been proposed for a range of diseases, including infectious disease, cancers and even Alzheimer disease, while monoclonal antibodies have already been implemented as therapeutics for a range of conditions. Several biologic agents are currently being developed for the treatment of asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and pulmonary sarcoidosis. This article is a review of the biologics already employed in the treatment of chronic inflammatory pulmonary diseases and recent progress in the development of the most promising of those treatments, with particular focus on randomised clinical trial outcomes.

Identification of a real-world clinical model associated with atrial fibrillation in a large french primary care database

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Bristol Myers Squibb and Pfizer. Background Undiagnosed atrial fibrillation (AF) is associated with a higher risk of stroke and mortality. To date, the 2020 European Society of Cardiology (ESC) guidelines recommend opportunistic screening for AF in patients ≥65 years (Class I), or with hypertension (HTN) (Class I), or obstructive sleep apnea (OSA) (IIa), and systematic ECG screening in patients ≥75 years or at high risk of stroke defined by the CHA2DS2-VASc score (Class IIa).1 However, in a primary care practice, these criteria cover a large number of patients. Purpose Evaluate the performance of several clinical markers or combination of clinical markers to identify patients at high-risk of AF in a primary care database. Methods This retrospective national study used patients’ data from the French electronic health records THIN® database of 2 000 General Practitioners (GP). Patients included had visited their GP in 2019 and were followed for ≥ 3 years, were aged ≥ 50 with ≥ 1 risk markers potentially associated with AF (HTN, diabetes, obesity, dyslipidaemia, smoking, alcohol dependence, cardiopathy, heart failure (HF), vascular disease, OSA, chronic obstructive pulmonary disease, inflammatory disease, thyroid or renal dysfunction). Non-AF patients with anticoagulant treatment were excluded. The tested variables and models included the 2020 ESC guidelines criteria for AF screening (age ≥65, age ≥ 75, high stroke risk defined as CHA2DS2-VASc ≥ 2 (male) or ≥ 3 (female), HTN, OSA), the CHA2DS2-VASc taken as a score as well as the multivariate analysis of its components (congestive HF, HTN, age ≥ 75, diabetes, stroke, vascular disease, age 65-74, female sex), and an ad hoc model based on the combination of risk markers associated with AF (15 variables based on cardiovascular and non-cardiovascular comorbidities; Figure 1). Multivariate models were performed with logistical regression. Results Among 573 539 screened patients (mean follow-up 13.5 years), 30 476 had AF (5.3%). The ad hoc model using the 15 variables showed the highest performance with AUC 0.80 (Se 69%, Sp 77%) (Figure 1). In this model, all variables were significantly associated with AF except diabetes, dyslipidaemia, and HIV. Age ≥ 75, HF, age 65-74 and male sex were the most significant risk markers associated with AF (Figure 1). In the CHA2DS2-VASc model, AUC was 0.78 for multivariate analysis (Se 69%; Sp 72%), and 0.71 for the score result (Se 77%, Sp 56%). Regarding the ESC guidelines criteria, age ≥ 75 years had the best performance with AUC 0.69 (Se 62%, Sp 75%), then age ≥65 (AUC 0.67), high stroke risk (AUC 0.66), versus AUC < 0.60 for HTN and OSA. Conclusion In this study on a large primary care database, the ad hoc model had the highest performance, sensitivity and specificity. In the future, it might help GPs to identify patients at high-risk of AF in clinical practice and to propose targeted preventive interventions and screening.

Prevalence and Associated Factors of Osteoporosis in Chronic Obstructive Pulmonary Disease Patients

Background: Chronic Obstructive Pulmonary Disease (COPD) is a lifestyle-related chronic inflammatory pulmonary disease and a major cause of morbidity and mortality globally. In this study, we evaluated the prevalence and associated factors of osteopenia and osteoporosis in COPD patients.
 Methods:A total of 91 COPD patients were recruited from October 2017 and December 2018. Lung function test, CAT score, 6-minutes’ walk test, Modified Medical Research Council (MMRC) dyspnea score and body mass index, air flow obstruction, dyspnea, and exercise capacity (BODE index) were evaluated in the patients. Bone Mineral Density (BMD) measurements of the femoral neck, total femur (including femoral neck, trochanter, and intertrochanter area), and lumbar spine were conducted using dual-energy X-ray absorptiometry. A T-score which was 2.5 standard deviations (SDs) below the average value was indicative of osteoporosis, in accordance with the World Health Organization criteria. We excluded COPD patients who had asthma, malignancy, and fracture.
 Results: There were 86 males (mean age ± SD: 66.49±9.40 years) and 5 females (mean age±SD: 65.40±12.40 years). Among all the patients, 46 (51.1 %) patients had osteopenia and 36 (40 %) had osteoporosis. Comparing COPD grades showed grade 2 was a more prevalent grade (41.1 %). There was no statistically association between femoral neck T score (mean±SD: -2.21±0.89) and COPD grade (P= 0.58), while lumber spine T score (mean±SD: -2.13±1.11) was statistically decreased with increasing severity of COPD (p= 0.02).
 Conclusion: The results of our study demonstrated that osteoporosis is common among COPD patients. Moreover, we found significant correlations between BMI, walking test, FEV1, MMRC, and BODE index.

Litsea salicifolia Roxb. bark ethanolic extract attenuates rheumatoid arthritis by inhibiting TLR4/NF-κB and activating SIRT1-Nrf2/HO-1 signaling axis: In-vitro and in-vivo evaluations

BackgroundLitsea salicifolia Roxb. (LS) is a pioneer medicinal plant that can be found in tropical and subtropical countries like India, China and Japan. LS is traditionally used for treating chronic pulmonary inflammatory diseases like asthma and wound healing. Also, LS contains an essential oil with powerful anti-oxidant and excite-repellency properties. However, no research findings have been reported about its protective activity on chronic inflammatory disease like rheumatoid arthritis (RA) till yet. PurposeThis study aims to investigate the anti-rheumatic potential of ethanolic extract of LS (LSE) in-vitro on RAW 264.7 cells for its anti-oxidant and anti-inflammatory activities and in-vivo CFA-induced adjuvant arthritis in the rat model. MethodsThe chemical characterization of LSE was identified by using LC-MS/MS. The in-vitro effects of LSE on RAW 264.7 cells stimulated with LPS 1 µg/ml were investigated to its potential therapeutic effects. Freund's complete adjuvant (CFA) arthritis was induced by 100 µl of CFA intradermally administered to rats. LSE 100 and 200 mg/kg were administered orally from day1 to day 28. Parameters such as paw volumes measured, X-ray radiography analysis, anti-oxidant status, Gene expression studies, western blot analysis and histological analysis were performed to check the anti-oxidant and anti-inflammatory effects of LSE. ResultsOur in-vitro results revealed that LSE at 5 μg/ml and 10 μg/ml reduced the LPS-induced oxidative stress burden evidenced by reduced ROS levels and improved endogenous anti-oxidants Nrf2 and SIRT1 in RAW 264.7 cells. Also, LSE inhibited the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, PGE2, COX-2 and NO levels induced by LPS in murine macrophage cells at 5 μg/ml and 10 μg/ml in a dose dependent manner. Our in-vivo results revealed that LSE significantly attenuated the CFA-induced inflammation by restoring body weight, arthritis index, nitrosative and lipid peroxidation assays. LSE treatment significantly reduced the pannus formation and bone erosion evidenced by histopathology of joint tissues. Additionally treatment with LSE significantly reduced inflammation-mediated protein expression levels like TLR4, NF-κB, COX-2 and iNOS levels and improved the Nrf2/HO-1/SIRT1 levels in paw tissues evidenced by immunoblotting. ConclusionLSE alleviated RA through its anti-oxidant and anti-inflammatory properties by inhibiting TLR4-mediated NF-κB nuclear translocation and by activating the Nrf2/SIRT1 signaling pathways, according to our in-vitro and in-vivo findings.

Protective Effects of Herba Houttuyniae Aqueous Extract against OVA-Induced Airway Hyperresponsiveness and Inflammation in Asthmatic Mice.

Herba Houttuyniae is the well-knownfood-medicine herb with the special taste and smell. It is also widely used in south China for prevention of various chronic pulmonary inflammatory diseases including asthma. However, the active ingredients and therapeutic mechanism of this herb remain obscure. In this study, network pharmacology technology was employed to investigate the effects of Herba Houttuyniae aqueous extract (HHAE) on OVA-induced airway hyperresponsiveness and inflammation. The results showed that six compounds (isoramanone, kaempferol, 1-methyl-2-nonacosyl-4-quinolone, C09747, spinasterol, and quercetin) were found to be mainly responsible for the therapeutic effects of the herb, which totally regulated the expressions of 168 asthma-related proteins. All those targets involved in the signal transduction of the prolactin signaling pathway, central carbon metabolism in cancer, EGFR tyrosine kinase inhibitor resistance, endocrine resistance, and VEGF signaling pathway. The in vivo experiment also revealed that orally administrated with HHAE alleviated airway hyperresponsiveness and inflammation in OVA-induced asthmatic mice. It significantly decreased the counts of neutrophils, eosinophils, and lymphocytes as well as the levels of IL-1β, IL-4, IL-6, and IL-13 in BALF of asthmatic mice. Mechanically, HHAE downregulated both the mRNA and protein expressions of p38 MAPK, PI3K, AKT, and VEGF in the lung tissues of asthmatic mice. Therefore, HHAE improved OVA-induced airway hyperresponsiveness and inflammation in mice and could be a potential supplement for asthma treatment.

SARS-CoV-2 spike IgG titres up to 137 days following Comirnaty mRNA COVID-19 vaccination, Israel, February to May 2021.

BackgroundData regarding the long-term protection afforded by vaccination for the SARS-CoV-2 infection are essential for allocation of scarce vaccination resources worldwide.MethodsWe conducted a retrospective cohort study aimed at studying the kinetics of IgG antibodies against SARS-CoV-2 in COVID-19-naïve patients fully vaccinated with two doses of Comirnaty mRNA COVID-19 vaccine. Geometric mean concentrations (GMCs) of antibody levels were reported. Linear models were used to assess antibody levels after full vaccination and their decline over time.ResultsThe study included 4,740 patients and 5,719 serological tests. Unadjusted GMCs peaked 28–41 days after the first dose at 10,174 AU/mL (95% CI: 9,211–11,237) and gradually decreased but remained well above the positivity cut-off. After adjusting for baseline characteristics and repeated measurements, the antibodies half-life time was 34.1 days (95% CI: 33.1–35.2), and females aged 16–39 years with no comorbidities had antibody levels of 20,613 AU/mL (95% CI: 18,526–22,934) on day 28 post-first-dose. Antibody levels were lower among males (0.736 of the level measured in females; 95% CI: 0.672–0.806), people aged 40–59 (0.729; 95% CI: 0.649–0.818) and ≥ 60 years (0.452; 95% CI: 0.398–0.513), and patients having haematological (0.241; 95% CI: 0.190–0.306) or solid malignancies (0.757; 95% CI: 0.650–0.881), chronic kidney disease with glomerular filtration rate (GFR) ≥ 30 (0.434; 95% CI: 0.354–0.532) or with GFR < 30 mL/min (0.176; 95% CI: 0.109–0.287), and immunosuppression (0.273; 95% CI: 0.235–0.317). Body mass index, cardiovascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes and inflammatory bowel diseases were not associated with antibody levels.ConclusionsVaccination with two doses resulted in persistently high levels of antibodies (≥ cut-off of 50 AU/mL) up to 137 days post-first-dose. Risk factors for lower antibody levels were identified.

Advancing Lung Immunology Research: An Official American Thoracic Society Workshop Report.

The mammalian airways and lungs are exposed to a myriad of inhaled particulate matter, allergens, and pathogens. The immune system plays an essential role in protecting the host from respiratory pathogens, but a dysregulated immune response during respiratory infection can impair pathogen clearance and lead to immunopathology. Furthermore, inappropriate immunity to inhaled antigens can lead to pulmonary diseases. A complex network of epithelial, neural, stromal, and immune cells has evolved to sense and respond to inhaled antigens, including the decision to promote tolerance versus a rapid, robust, and targeted immune response. Although there has been great progress in understanding the mechanisms governing immunity to respiratory pathogens and aeroantigens, we are only beginning to develop an integrated understanding of the cellular networks governing tissue immunity within the lungs and how it changes after inflammation and over the human life course. An integrated model of airway and lung immunity will be necessary to improve mucosal vaccine design as well as prevent and treat acute and chronic inflammatory pulmonary diseases. Given the importance of immunology in pulmonary research, the American Thoracic Society convened a working group to highlight central areas of investigation to advance the science of lung immunology and improve human health.

Tiotropium Add-On and Treatable Traits in Asthma-COPD Overlap: A Real-World Pilot Study.

PurposeThe ‘treatable traits’ strategy for patients with chronic inflammatory airway diseases, especially asthma and chronic obstructive pulmonary disease (COPD), is a focus of interest, because it implements precision and personalized medicine. Asthma-COPD overlap (ACO), a phenotype involving both asthma and COPD, is an important disease entity because patients with ACO have significantly worse outcomes, conferring greater economical and social burdens. Some guidelines for ACO recommend add-on therapy of long-acting muscarinic antagonists to inhaled corticosteroids and long-acting β2 agonists. However, this approach is based on extrapolation from patients with asthma or COPD alone. Consequently, a ‘treatable traits’ approach suitable for ACO remains obscure.MethodsA 12-week open-label cross-over pilot study was conducted in patients with ACO to investigate the effect of tiotropium bromide (TIO) 5 µg/day add-on therapy to fluticasone propionate/formoterol fumarate (FP/FM) 500/20 µg/day compared with FP/FM 500/20 µg/day alone. A 4-week run-in period and two 4-week treatment periods were included.ResultsA total of 18 male patients with stable ACO participated in this pilot study. All patients were ex-smokers. Mean values ± standard deviation (SD) for forced expiratory volume in 1 second (FEV1) were 1.21 ± 0.49 L after the run-in period, 1.20 ± 0.51 L after the FP/FM combination therapy period, and 1.30 ± 0.48 L after the TIO add-on therapy to FP/FM period. FEV1 values after the TIO add-on therapy FP/FM period were significantly higher than those after the run-in period (p < 0.01).ConclusionTIO add-on therapy to FP/FM in patients with ACO, considered difficult to treat because of the presence of both asthma and COPD, resulted in improvements in lung function parameters in this real-world pilot study, indicating the potential value of TIO add-on therapy as a “treatable traits” option for standard treatment for ACO.

MicroRNA-629-3p Promotes Interleukin-13-Induced Bronchial Epithelial Cell Injury and Inflammation by Targeting FOXA2.

Asthma is a chronic pulmonary inflammatory disease. MicroRNA (miR)-629-3p expression is reported to be up-regulated in the sputum of asthma patients. Nonetheless, miR-629-3p's role and mechanism in asthma remain largely unknown. This study is aimed at exploring miR-629-3p's role in regulating the injury and inflammation of bronchial epithelial cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression levels of miR-629-3p and forkhead box a2 (FOXA2) mRNA in 16HBE cells treated with interleukin-13 (IL-13). 16HBE cell viability was evaluated using the cell counting kit-8 (CCK-8) assay, and cell apoptosis was analyzed by a flow cytometer. The levels of C-C motif chemokine ligand 11 (CCL11), C-C motif chemokine ligand 26 (CCL26), C-C motif ligand 2 (CCL-2)/mono-cyte chemotactic protein-1 (MCP-1), interleukin-1 beta (IL-1b), and interleukin 6 (IL-6) in 16HBE cell supernatant were detected through enzyme-linked immunosorbent assay (ELISA). The downstream target genes of miR-629-3p were predicted through bioinformatics. Besides, the targeted relationship between miR-629-3p and FOXA2 mRNA 3'-UTR was verified by dual-luciferase reporter gene assay. Western blot was utilized to determine the regulatory effects of miR-629-3p on the expression of FOXA2 protein in 16HBE cells. MiR-629-3p expression was significantly enhanced in IL-13-stimulated 16HBE cells while the FOXA2 mRNA and protein levels were significantly down-regulated. The transfection of miR-629-3p mimics inhibited 16HBE cells' viability, and promoted the apoptosis and the secretion of chemokines CCL11, CCL26, CCL-2/MCP-1, IL-1b, and IL-6 of 16HBE cells, whereas inhibiting miR-629-3p had the opposite effects. Moreover, FOXA2 was identified as a downstream miR-629-3p target, and its overexpression reversed the effects of the miR-629-3p on 16HBE cells. MiR-629-3p promotes IL-13-induced 16HBE cells' injury and inflammation by targeting FOXA2.

Hypoxanthine Shuttles between Pulmonary and Intestinal Axes to Mediate Intestinal Injury in Chronic Pulmonary Inflammatory Disease: Scientific Connotation of "Lung and Large Intestine are Outside and Inside"

Hypoxanthine Shuttles between Pulmonary and Intestinal Axes to Mediate Intestinal Injury in Chronic Pulmonary Inflammatory Disease: Scientific Connotation of "Lung and Large Intestine are Outside and Inside"

Analysis and Clinical Application of Polyunsaturated Fatty Acids in Human Serum Using One-step Extraction and Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry

Omega-3 and omega-6 fatty acids are reported to alleviate various inflammatory reactions such as asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, and inflammatory bowel disease. We have developed a new method for their quantitation in serum, utilizing ultra-high-performance liquid chromatography-electrospray ionizationtandem mass spectrometry (UHPLC-ESI-MS/MS) in multiple reaction monitoring (MRM) mode, under negative ionization. MRM transitions were detected for five omega fatty acids, as follows: α-linolenic acid, m/z=277.20→277.20; eicosapentaenoic acid, m/z=301.10→257.30; docosahexaenoic acid, m/z=327.00→283.15; arachidonic acid, m/z=303.20→259.25; docosapentaenoic acid, m/z=329.10→285.25. After comparing several different solvents, we selected butanol:methanol (1:1, v/v) as the optimal extraction solvent. Chromatographic separations were carried out using an Acclaim RSLC 120 C18 column (150×2.1 mm, 2.2 μm) at 40oC. For the mobile phase, solvent A consisted of water containing 5% acetonitrile and 5% methanol, and solvent B consisted of methyl tert-butyl ether:acetonitrile:methanol (10:20:70, v/v/v) containing 2.5 mM ammonium acetate. The calibration curve showed excellent linearity within the range of 0.01-20 μg/mL (R2=0.9996-0.9999). The analytical method was validated and shown to have excellent sensitivity (LOD; 0.001-0.005 μg/mL, LOQ; 0.01-0.2 μg/mL), making it suitable for targeted analyses of omega fatty acids. Recovery ranged from 78.0 to 103.9% (RSD 0.5-5.6%). This new method uses relatively small amounts of serum and extraction solvent and is expected to be suitable for analysis of various clinical specimens, such as plasma, urine, and cerebrospinal fluid.

The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases.

As natural nanocarriers and intercellular messengers, extracellular vesicles (EVs) control communication among cells. Under physiological and pathological conditions, EVs deliver generic information including proteins and nucleic acids to recipient cells and exert regulatory effects. Macrophages help mediate immune responses, and macrophage-derived EVs may play immunomodulatory roles in the progression of chronic inflammatory diseases. Furthermore, EVs derived from various macrophage phenotypes have different biological functions. In this review, we describe the pathophysiological significance of macrophage-derived extracellular vesicles in the development of chronic inflammatory diseases, including diabetes, cancer, cardiovascular disease, pulmonary disease, and gastrointestinal disease, and the potential applications of these EVs.

Revisiting the role of pulmonary surfactant in chronic inflammatory lung diseases and environmental exposure.

Pulmonary surfactant is a crucial and dynamic lung structure whose primary functions are to reduce alveolar surface tension and facilitate breathing. Though disruptions in surfactant homeostasis are typically thought of in the context of respiratory distress and premature infants, many lung diseases have been noted to have significant surfactant abnormalities. Nevertheless, preclinical and clinical studies of pulmonary disease too often overlook the potential contribution of surfactant alterations - whether in quantity, quality or composition - to disease pathogenesis and symptoms. In inflammatory lung diseases, whether these changes are cause or consequence remains a subject of debate. This review will outline 1) the importance of pulmonary surfactant in the maintenance of respiratory health, 2) the diseases associated with primary surfactant dysregulation, 3) the surfactant abnormalities observed in inflammatory pulmonary diseases and, finally, 4) the available research on the interplay between surfactant homeostasis and smoking-associated lung disease. From these published studies, we posit that changes in surfactant integrity and composition contribute more considerably to chronic inflammatory pulmonary diseases and that more work is required to determine the mechanisms underlying these alterations and their potential treatability.