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IGF1R deficiency mitigates acute lung injury by promoting anti-inflammatory transcriptional profiles. IGF1R缺乏通过促进抗炎转录谱减轻急性肺损伤。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-22 DOI: 10.1186/s12931-025-03339-x
Alfredo Urtubia, Sergio Piñeiro-Hermida, Elvira Alfaro-Arnedo, Judith Beni-Ledesma, Marta Canalejo, María de Toro, José García Pichel, Icíar P López
{"title":"IGF1R deficiency mitigates acute lung injury by promoting anti-inflammatory transcriptional profiles.","authors":"Alfredo Urtubia, Sergio Piñeiro-Hermida, Elvira Alfaro-Arnedo, Judith Beni-Ledesma, Marta Canalejo, María de Toro, José García Pichel, Icíar P López","doi":"10.1186/s12931-025-03339-x","DOIUrl":"https://doi.org/10.1186/s12931-025-03339-x","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and COVID-19 are characterized by hyperinflammation, commonly referred to as \"cytokine storm\". The insulin-like growth factor (IGF) pathway, particularly the type 1 receptor (IGF1R), plays a critical role in lung homeostasis and has been implicated in the pathogenesis of pulmonary inflammatory diseases. In mice, widespread Igf1r deficiency attenuates lung inflammation and alveolar damage in bleomycin (BLM)-induced ALI.</p><p><strong>Methods: </strong>We analyzed single-cell RNA sequencing datasets from lung tissue of COVID-19 cases and control donors as well as mouse lungs to determine Igf1r and IGF family expression across pulmonary cell types. Furthermore, we conducted bulk RNA sequencing on lungs from Igf1r-deficient mice three days after BLM or saline instillation, followed by differential expression and functional enrichment analyses. Findings were further tested through protein detection, assessment of DNA damage and methylation in lung tissues, and functional assays using Igf1r-deficient primary mouse embryonic fibroblasts (MEFs).</p><p><strong>Results: </strong>IGF1R was broadly expressed across multiple cell types in both human and mouse lungs under normal and pathological conditions. Other IGF family members showed cell-type-specific expression, which was modulated by lung injury. Transcriptomic profiling revealed differentially expressed genes between BLM-challenged and control mouse lungs, detecting biological processes and signaling pathways involved in ALI pathobiology. Igf1r deficiency in BLM-challenged mice reversed a large fraction of the transcriptional changes triggered by BLM, including \"cytokine storm\"-related gene expression. Functional enrichment analysis additionally revealed significant modulation of pathways related to DNA damage, metabolic reprogramming, mitochondrial homeostasis, and epigenetic regulation. In vitro, Igf1r-deficient MEFs exhibited decreased mitochondrial respiration and glycolysis, protection against BLM-induced nuclear damage and mitochondrial accumulation, and decreased histone H3 acetylation. Moreover, Igf1r-deficient mouse lungs displayed increased global DNA methylation following BLM challenge.</p><p><strong>Conclusions: </strong>IGF1R is a key modulator of the inflammatory and molecular response to ALI pathogenesis. IGF1R deficiency dampens the \"cytokine storm\", modifies transcriptional and epigenetic profiles and promotes protective cellular responses. These findings highlight IGF1R signaling as a potential therapeutic target in ARDS and related lung injuries.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"292"},"PeriodicalIF":5.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of clinical factors and season on inflammatory cytokines in biologic-treated and untreated asthma. 临床因素和季节对生物治疗和未治疗哮喘患者炎症因子的影响。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-22 DOI: 10.1186/s12931-025-03373-9
Tanawin Nopsopon, Javier Cabrera-Perez, Pui Y Lee, Kailey E Brodeur, Njira L Lugogo, Evan E Hsu, Courtney LeSon, Georg Hahn, Steven A Carr, Scott T Weiss, Ayobami Akenroye
{"title":"Impact of clinical factors and season on inflammatory cytokines in biologic-treated and untreated asthma.","authors":"Tanawin Nopsopon, Javier Cabrera-Perez, Pui Y Lee, Kailey E Brodeur, Njira L Lugogo, Evan E Hsu, Courtney LeSon, Georg Hahn, Steven A Carr, Scott T Weiss, Ayobami Akenroye","doi":"10.1186/s12931-025-03373-9","DOIUrl":"https://doi.org/10.1186/s12931-025-03373-9","url":null,"abstract":"<p><strong>Background: </strong>Clinical features influence cytokine profiles and can inform biomarker studies.</p><p><strong>Objectives: </strong>We assessed the impact of 13 preselected patient characteristics on the circulating levels of 15 Th-1/2/17 cytokines in moderate-to-severe asthma patients on omalizumab, anti-IL-5 (mepolizumab, benralizumab), or dupilumab (n = 76) versus controls (n = 162) not yet on biologics but meeting eligibility criteria for a T2-biologic.</p><p><strong>Methods: </strong>Plasma cytokines (Olink) were analyzed for associations with these clinical/lifestyle factors using LASSO regression and observed variance explained estimated using generalized linear models. Differential expression analysis was conducted using limma.</p><p><strong>Results: </strong>In controls, IL-6 had the highest variance explained by clinical/lifestyle factors (50% in non-allergic rhinitis patients, 22% in allergic rhinitis), with BMI and exacerbations contributing most to this. In T2-biologics users, eotaxin-1 had the highest explained variance (26.0%) and smoking was the most linked to Th1/17 cytokines. In omalizumab users: IFN-γ (51%) was most explained (exacerbations, smoking, age). In anti-IL-5 users, eotaxin-1 (58%; BMI, sex) and in dupilumab users, IL-4 (83%) was most explained (exacerbations, sex, BMI). The association between patient characteristics and cytokine levels differed by the season of sample collection. In non-biologic users, IL-6 was the cytokine with the most explained variance in the Winter (asthma admissions accounted for most of this variance) and IL-18 in the Spring/Summer/Fall. In T2-biologic users, TNF-α was the top cytokine in the Winter (smoking accounted for most of this variance); IL-4 (allergic rhinitis), IL-33 (IgE and eosinophil), and CXCL10 (allergic rhinitis and IgE) were the top cytokines in the Spring/Summer/Fall. In differential expression analyses, IL-1β was lower in biologics users than non-biologics users.</p><p><strong>Conclusions: </strong>In moderate-to-severe asthma, multiple clinical features and season are associated with cytokine levels and might impact inference from proteomics studies. Smoking and BMI are the key proinflammatory factors in biologics-treated and untreated patients.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"291"},"PeriodicalIF":5.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mass spectrometry-based peripheral blood proteomics for biomarker discovery in idiopathic pulmonary fibrosis. 基于质谱的外周血蛋白质组学在特发性肺纤维化中发现生物标志物。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-22 DOI: 10.1186/s12931-025-03377-5
Aravind A Menon, Benedikt Gansen, Hillary Mulder, Megan L Neely, Panagiotis Papavasileiou, Margaret L Salisbury, Brian D Southern, Christian Hesslinger, Thomas B Leonard, Felix Meissner, Jamie L Todd
{"title":"Mass spectrometry-based peripheral blood proteomics for biomarker discovery in idiopathic pulmonary fibrosis.","authors":"Aravind A Menon, Benedikt Gansen, Hillary Mulder, Megan L Neely, Panagiotis Papavasileiou, Margaret L Salisbury, Brian D Southern, Christian Hesslinger, Thomas B Leonard, Felix Meissner, Jamie L Todd","doi":"10.1186/s12931-025-03377-5","DOIUrl":"https://doi.org/10.1186/s12931-025-03377-5","url":null,"abstract":"<p><strong>Background: </strong>The circulating proteome may provide insights into the pathobiology of idiopathic pulmonary fibrosis (IPF) and diagnostic or prognostic biomarkers. We applied liquid chromatography coupled to mass spectrometry to quantify the peripheral blood proteome in patients with IPF and identify proteins associated with disease severity and progression.</p><p><strong>Methods: </strong>The IPF cohort comprised 299 patients from the IPF-PRO Registry. Controls (n = 99) without known lung disease had similar distributions of age, sex and smoking status to the IPF cohort. Proteins were measured in plasma collected at enrollment using an Evosep One coupled to an Orbitrap Exploris. Data were analyzed with Spectronaut 14 with a deep experimental spectral library and were log<sub>2</sub> transformed. Linear regression was used to compare protein abundances in the IPF versus control cohorts and identify proteins associated with disease severity measures at enrollment in the IPF cohort. Cox regression analyses were used to identify proteins associated with outcomes in the IPF cohort, split 75/25 into training and test sets. The false discovery rate was controlled at 5%.</p><p><strong>Results: </strong>Overall, 761 protein groups corresponding to 736 unique genes were detected. Of these, 168 protein groups were significantly different in abundance in the IPF versus control cohorts, of which 39 were ≥ 1.3-fold different. Among the top differentially expressed proteins were surfactant protein B (SFTPB), secretoglobin family 3A member 1, intercellular adhesion molecule 1, thrombospondin 1 and platelet factor 4. In patients with IPF, greater abundance of apolipoprotein A-1 was statistically significantly associated with higher forced vital capacity % predicted at enrollment, while greater abundance of fibulin-1 was statistically significantly associated with lower diffusing capacity of the lungs for carbon monoxide % predicted. Multivariable models selected 4 proteins (SERPINA7, SFTPB, alpha 2 HS glycoprotein, kininogen 1) and 3 clinical factors that best discriminated the risk of respiratory death or lung transplant in patients with IPF, with a C-index of 0.78 in the training set and 0.72 in the test set.</p><p><strong>Conclusions: </strong>Mass spectrometry-based proteomic analysis of data from the IPF-PRO Registry confirmed proteins previously associated with the presence, severity and progression of IPF and revealed new candidate biomarkers.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov; No: NCT01915511; registered August 5, 2013; URL: www.</p><p><strong>Clinicaltrials: </strong>gov .</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"294"},"PeriodicalIF":5.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dual-energy computed tomography derived pulmonary blood volume: association with pulmonary blood flow. 双能计算机断层扫描得出的肺血容量:与肺血流量的关系。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-22 DOI: 10.1186/s12931-025-03374-8
Jakob Wittenstein, Rudi Apolle, Martin Scharffenberg, Carolin Rothmann, Sabine Müller, Ralf-Thorsten Hoffmann, Esther G C Troost, Thea Koch, Marcelo Gama de Abreu, Robert Huhle
{"title":"Dual-energy computed tomography derived pulmonary blood volume: association with pulmonary blood flow.","authors":"Jakob Wittenstein, Rudi Apolle, Martin Scharffenberg, Carolin Rothmann, Sabine Müller, Ralf-Thorsten Hoffmann, Esther G C Troost, Thea Koch, Marcelo Gama de Abreu, Robert Huhle","doi":"10.1186/s12931-025-03374-8","DOIUrl":"https://doi.org/10.1186/s12931-025-03374-8","url":null,"abstract":"<p><strong>Background: </strong>Distribution of ventilation and pulmonary perfusion are the major determinants of pulmonary gas exchange. To study and compare strategies of mechanical ventilation in respiratory research accurate and high-resolution methods are needed to derive distribution of ventilation and perfusion with minimal additional intervention or radiation allowing repeated measurements. Dual-energy computed tomography (DECT) is an imaging technique allowing for the derivation of regional pulmonary perfused blood volume, as a surrogate for pulmonary perfusion (PP<sub>DECT</sub>). Here accuracy of PP<sub>DECT</sub> is evaluated in comparison to pulmonary blood flow measured with fluorescence-labeled microspheres (PP<sub>FLM</sub>). Its feasibility of repeated measurements is evaluated.</p><p><strong>Methods: </strong>Agreement between PP<sub>FLM</sub> and PP<sub>DECT</sub> was assessed by regression as well as Bland-Altman analysis in three anesthetized pigs using DECT and fluorescence labelled microspheres, respectively. Measurements were performed in two-lung and, after right sided thoracotomy, at one-lung ventilation with inhaled nitric oxide. PP<sub>FLM</sub> and PP<sub>DECT</sub> were assessed in three different regions of interest (ROI): the right (non-ventilated) and left (ventilated) upper and lower lung, yielding a total of 45 paired measurements over four hours. Persistent iodine accumulation was assessed by additional DECT scans before each contrast administration.</p><p><strong>Results: </strong>Regression analysis revealed a good overall association (R2 = 0.81) between PP<sub>FLM</sub> and PP<sub>DECT</sub>, with PP<sub>DECT</sub> substantially overestimating PP<sub>FLM</sub> up to 30%, with limits of agreement of -18 and 18%, Low PP<sub>FLM</sub> was underestimated, while high PP<sub>FLM</sub> was overestimated by PP<sub>DECT</sub>, indicating a higher sensitivity of the later. Changes of PP<sub>DECT</sub> and PP<sub>FLM</sub> had a concordance of 69.4% for all measurements. Agreement and concordance were highest in ventilated and lowest in non-ventilated ROIs. No persistent iodine enhancement was detected in the lung parenchyma after repetitive measurements per hour.</p><p><strong>Conclusions: </strong>Dual-energy CT based measurement of pulmonary perfusion shows promising results indicating its feasibility in translational research on strategies of mechanical ventilation.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"293"},"PeriodicalIF":5.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bronchial thermoplasty reduces ventilation heterogeneity measured by phase-resolved functional lung magnetic resonance imaging in severe asthma. 支气管热成形术降低严重哮喘患者相分辨功能肺磁共振成像测量的通气异质性。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-21 DOI: 10.1186/s12931-025-03372-w
Chuan T Foo, David Langton, Graham M Donovan, Bruce R Thompson, Peter B Noble, Francis Thien
{"title":"Bronchial thermoplasty reduces ventilation heterogeneity measured by phase-resolved functional lung magnetic resonance imaging in severe asthma.","authors":"Chuan T Foo, David Langton, Graham M Donovan, Bruce R Thompson, Peter B Noble, Francis Thien","doi":"10.1186/s12931-025-03372-w","DOIUrl":"https://doi.org/10.1186/s12931-025-03372-w","url":null,"abstract":"<p><strong>Rationale: </strong>Bronchial thermoplasty (BT) is a treatment option for patients with severe asthma. Despite demonstrated sustained symptomatic benefits, its mechanism of action remains unclear, with emerging evidence suggesting a reduction in ventilation heterogeneity.</p><p><strong>Objective: </strong>This study aims to determine if BT reduces ventilation heterogeneity as measured by phase-resolved function lung magnetic resonance imaging (PREFUL MRI).</p><p><strong>Methods: </strong>Twenty-one patients with severe asthma and 14 healthy volunteers (HV) were recruited. Patients were assessed at baseline and 6-months after BT. Data collected included asthma control questionnaire (ACQ-5), exacerbation frequency, and short-acting beta-agonist (SABA) and oral corticosteroid (OCS) use. Both HV and patients also underwent lung function tests and PREFUL MRI. Ventilation heterogeneity was assessed using ventilation defect percentage (VDP) of static regional ventilation (RVent) and dynamic flow-volume loop cross-correlation metric (FVL-CM), and interquartile distance (IQD) of the ventilation distribution.</p><p><strong>Results: </strong>At baseline, patients had a significantly higher RVent VDP (20.0 ± 14.5 vs 3.8 ± 2.2%, p < 0.001), FVL-CM VDP (23.7 ± 17.8 vs 2.4 ± 2.3%, p < 0.001), and IQD (0.61 ± 0.27 vs 0.32 ± 0.05, p < 0.001) than HV. Post BT, significant reductions in RVent VDP (15.5 ± 11.7 vs 20.0 ± 14.5%, p < 0.001), FVL-CM VDP (18.7 ± 13.9 vs 23.7 ± 17.8%, p < 0.001), and IQD (0.53 ± 0.22 vs 0.61 ± 0.27, p < 0.001) were observed in patients, along with significant improvements in ACQ-5, exacerbation frequency, SABA and OCS use. No change in lung function was seen. Significant correlations were observed between ΔACQ and ΔRVent VDP (ρ = 0.50, p = 0.02), ΔFVL-CM VDP (ρ = 0.51, p = 0.02), and ΔIQD (ρ = 0.45, p = 0.04).</p><p><strong>Conclusions: </strong>Clinical benefits post BT are accompanied by a reduction in ventilation heterogeneity that are undetected by lung function test. These findings provide valuable insights into the mechanisms of action of BT and highlight the complementary role of functional lung imaging in the study of pulmonary diseases for which traditional lung function tests may be insensitive at detecting therapeutic response.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"290"},"PeriodicalIF":5.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing atrial fibrillation risk prediction in an observational cohort of tobacco-exposed individuals: the role of pulmonary function tests, symptom scores, and imaging. 在烟草暴露个体的观察队列中增强房颤风险预测:肺功能检查、症状评分和影像学的作用
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-21 DOI: 10.1186/s12931-025-03366-8
Nicole Curtis, S Mehdi Nouraie, Jiantao Pu, Joseph K Leader, Frank C Sciurba, Jessica Bon
{"title":"Enhancing atrial fibrillation risk prediction in an observational cohort of tobacco-exposed individuals: the role of pulmonary function tests, symptom scores, and imaging.","authors":"Nicole Curtis, S Mehdi Nouraie, Jiantao Pu, Joseph K Leader, Frank C Sciurba, Jessica Bon","doi":"10.1186/s12931-025-03366-8","DOIUrl":"https://doi.org/10.1186/s12931-025-03366-8","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"287"},"PeriodicalIF":5.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of remimazolam-based sedation for intensive care unit patients undergoing fiberoptic bronchoscopy: a single-center prospective randomized controlled study. 基于雷马唑仑的镇静在重症监护病房纤维支气管镜检查患者中的疗效和安全性:一项单中心前瞻性随机对照研究。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-21 DOI: 10.1186/s12931-025-03365-9
Yufeng He, Ziyu Li, Yunshan Zou, Wenjuan Zhou, Xin Sui, Xiaomeng Yi, Yuling An
{"title":"Efficacy and safety of remimazolam-based sedation for intensive care unit patients undergoing fiberoptic bronchoscopy: a single-center prospective randomized controlled study.","authors":"Yufeng He, Ziyu Li, Yunshan Zou, Wenjuan Zhou, Xin Sui, Xiaomeng Yi, Yuling An","doi":"10.1186/s12931-025-03365-9","DOIUrl":"https://doi.org/10.1186/s12931-025-03365-9","url":null,"abstract":"<p><strong>Objectives: </strong>The analgesic and sedative strategies during fiberoptic bronchoscopy(FB) in critically ill patients are rarely studied.Remimazolam is a novel sedative whose metabolism is not affected by liver and kidney function.We did a prospective randomized controlled study to compare the efficacy and safety of remimazolam and propofol in sedation therapy for FB patients with liver and kidney dysfunction.</p><p><strong>Methods: </strong>The study was conducted in the Third Affiliated Hospital of Sun Yat-sen University (China) from September 2021 to December 2022. 120 adult patients were included, randomly assigned to two groups (the remimazolam or the propofol group) and achieved moderate sedation and successful bronchoscopy.The operation process of FB and changes in liver and kidney function indicators after FB operation were all recorded.</p><p><strong>Results: </strong>All patients successfully completed the FB with no difference between the two groups in terms of the median time to achieve the target sedation depth (5 min vs. 5 min, P > 0.05).The remimazolam group required fewer sedation rescues (3.33% vs. 16.67%, P = 0.03). The incidence of hypotension was significantly lower in the remimazolam group (3.33% vs. 20%, P = 0.01).The median time to return to the pre-test level of consciousness was similar between the two groups (7 min vs. 7 min, P > 0.05). There was no significant difference in liver and kidney function indexes between the two groups (P > 0.05).</p><p><strong>Conclusions: </strong>Remimazolam demonstrated a sedative effect that was not inferior to propofol.</p><p><strong>Trial registration: </strong>The Chinese Clinical Trial Registry (chiCTR.gov):No. ChiCTR2100050181, Date of registration: August 15, 2021. The date of enrolment of the first research participant was September 15,2021.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"289"},"PeriodicalIF":5.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serine/threonine kinase 33 mediates thrombin-induced interleukin-8 release from human lung epithelial cells in severe asthma. 丝氨酸/苏氨酸激酶33介导严重哮喘患者肺上皮细胞中凝血酶诱导的白介素-8释放。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-21 DOI: 10.1186/s12931-025-03368-6
Wun-Hao Cheng, Wen-Shan Chang, Po-Hao Feng, Kuan-Yuan Chen, Kang-Yun Lee, Yu-Chih Wu, Lee-Yuan Lin, Fara Silvia Yuliani, Chien-Huang Lin, Bing-Chang Chen
{"title":"Serine/threonine kinase 33 mediates thrombin-induced interleukin-8 release from human lung epithelial cells in severe asthma.","authors":"Wun-Hao Cheng, Wen-Shan Chang, Po-Hao Feng, Kuan-Yuan Chen, Kang-Yun Lee, Yu-Chih Wu, Lee-Yuan Lin, Fara Silvia Yuliani, Chien-Huang Lin, Bing-Chang Chen","doi":"10.1186/s12931-025-03368-6","DOIUrl":"https://doi.org/10.1186/s12931-025-03368-6","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"288"},"PeriodicalIF":5.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oxidative stress triggers Itch-mediated TXNIP degradation and NF-κB activation promoting chronic obstructive pulmonary disease. 氧化应激触发瘙痒介导的TXNIP降解和NF-κB激活,促进慢性阻塞性肺疾病。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-17 DOI: 10.1186/s12931-025-03369-5
Pei-Yun Lin, Kang-Yun Lee, Shu-Chuan Ho, Hsiao-Chi Chuang, Bing-Hua Su, Ying-Jung Wu, Po-Chun Tseng, Tsung-Ting Tsai, Chiou-Feng Lin, Rahmat Dani Satria, Fu-Chia Shih, Chia-Ling Chen
{"title":"Oxidative stress triggers Itch-mediated TXNIP degradation and NF-κB activation promoting chronic obstructive pulmonary disease.","authors":"Pei-Yun Lin, Kang-Yun Lee, Shu-Chuan Ho, Hsiao-Chi Chuang, Bing-Hua Su, Ying-Jung Wu, Po-Chun Tseng, Tsung-Ting Tsai, Chiou-Feng Lin, Rahmat Dani Satria, Fu-Chia Shih, Chia-Ling Chen","doi":"10.1186/s12931-025-03369-5","DOIUrl":"10.1186/s12931-025-03369-5","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammatory lung diseases, including chronic obstructive pulmonary disease (COPD), are characterized by pulmonary structural changes, narrowing of the small airways, and destruction of the lung parenchyma caused by prolonged inflammation. Sustained inflammation mediated by macrophages is considered to play a critical role in COPD pathogenesis, while the inductive mechanisms of persistent inflammation remain unclear.</p><p><strong>Methods: </strong>In vitro, RAW264.7 cells were treated with cigarette smoke extract (CSE), hydrogen peroxide, and 12-O-tetradecanoylphorbol-13-acetate. Loss-of-function assays were performed using MAPK inhibitors and Itch-specific knockdown. In vivo, lung tissues from mice exposed to whole-body cigarette smoke (CS) for 12 weeks, as well as clinical samples from healthy non-smokers, a healthy smoker, and COPD patients, were analyzed.</p><p><strong>Results: </strong>Our findings demonstrated that thioredoxin-interacting protein (TXNIP) participates in CS-induced NF-κB activation in macrophages, which may contribute to pulmonary inflammation. CSE markedly inhibited TXNIP expression in RAW264.7 cells through MAPK-dependent regulation, accompanied by the induction of iNOS/NO and COX-2. The decrease in TXNIP was also detected in lung tissues and macrophages obtained from smoking mice, while higher NF-κB activation and lung inflammation occurred simultaneously. Additionally, CS-induced oxidative stress triggered MAPK-dependent proteasomal degradation of TXNIP, leading to subsequent NF-κB activation. The expression of E3 ligase Itch was elevated in smoking mouse lungs and in hydrogen peroxide-stimulated cells, whereas specific silencing Itch significantly attenuated TXNIP degradation as well as NF-κB activation. Moreover, Itch expression was increased in lung tissues, whereas TXNIP was markedly reduced in lung tissues, bronchoalveolar lavage fluid cells, and peripheral blood mononuclear cells from patients with COPD.</p><p><strong>Conclusion: </strong>Accordingly, CS-induced oxidative stress promotes Itch-mediated TXNIP degradation, leading to NF-κB-driven inflammation in macrophages and potentially contributing to COPD pathogenesis.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"286"},"PeriodicalIF":5.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Monocyte-derived macrophages support alveolar regeneration via oncostatin M post-H1N1 infection during the recovery phase. 在恢复阶段,单核细胞来源的巨噬细胞通过抑素M支持肺泡再生。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-10-08 DOI: 10.1186/s12931-025-03359-7
Xiao Shang, Ju Jia, Jiapei Yu, Shumei Zou, Zeyi Wang, Jiuyang Xu, Hui Li, Bin Cao
{"title":"Monocyte-derived macrophages support alveolar regeneration via oncostatin M post-H1N1 infection during the recovery phase.","authors":"Xiao Shang, Ju Jia, Jiapei Yu, Shumei Zou, Zeyi Wang, Jiuyang Xu, Hui Li, Bin Cao","doi":"10.1186/s12931-025-03359-7","DOIUrl":"10.1186/s12931-025-03359-7","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"285"},"PeriodicalIF":5.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12509380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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