Respiratory Research最新文献

{"title":"Pulmonary infectious complications associated with the addition of cryobiopsy to conventional sampling for peripheral pulmonary lesions: a retrospective study.","authors":"Tatsuya Imabayashi, Yuji Matsumoto, Keigo Uchimura, Hideaki Furuse, Takaaki Tsuchida","doi":"10.1186/s12931-026-03715-1","DOIUrl":"https://doi.org/10.1186/s12931-026-03715-1","url":null,"abstract":"<p><strong>Background: </strong>Cryobiopsy is used in addition to conventional sampling during endobronchial ultrasound (rEBUS)-guided bronchoscopy for peripheral pulmonary lesions (PPLs) to improve diagnostic yield. However, the incremental risk of procedure-related pulmonary infection remains poorly quantified in routine clinical practice.</p><p><strong>Methods: </strong>We retrospectively analyzed consecutive patients who underwent rEBUS-guided bronchoscopy for PPLs between January 2019 and March 2022. Patients were categorized into those undergoing combined conventional biopsy and cryobiopsy and those undergoing conventional biopsy alone. Pulmonary infectious complications occurring within 4 weeks after bronchoscopy were assessed. Propensity score matching was performed to adjust for baseline differences and to evaluate the impact of cryobiopsy on pulmonary infectious complications. Sensitivity analyses using overlap weighting were also conducted.</p><p><strong>Results: </strong>After propensity score matching, 756 patients were included in the matched cohort (combined cryobiopsy group: n = 252; conventional biopsy group: n = 504). Pulmonary infectious complications occurred more frequently in the combined cryobiopsy group than in the conventional biopsy group (4.8% vs. 1.8%). Adding cryobiopsy was associated with an increased risk of pulmonary infectious complications (odds ratio, 2.84; 95% confidence interval, 1.15-6.99; P = 0.023), corresponding to an absolute risk increase of 3.0% and a number needed to harm of 33. These findings were consistent in sensitivity analyses using overlap weighting.</p><p><strong>Conclusions: </strong>Adding cryobiopsy to conventional sampling in rEBUS-guided bronchoscopy is associated with a higher risk of pulmonary infectious complications. These findings provide quantitative evidence to guide patient selection and procedural planning.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857482","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}

{"title":"Development and external validation of an interpretable machine-learning model for HFpEF comorbidity risk in COPD patients.","authors":"Jing Cao, Boyu Kang, Shuangshuang Li, Yan Lei, Dan Liu, Chunmei Li, Wei Guo, Binghua Zhang, Xiaoyan Xie","doi":"10.1186/s12931-026-03711-5","DOIUrl":"https://doi.org/10.1186/s12931-026-03711-5","url":null,"abstract":"<p><strong>Background: </strong>Chronic Obstructive Pulmonary Disease (COPD) and Heart Failure with preserved Ejection Fraction (HFpEF) frequently coexist, leading to increased hospitalization, mortality, and healthcare burden. Early identification of HFpEF risk in COPD patients is critical for timely intervention.</p><p><strong>Aim: </strong>To develop and validate an interpretable machine learning (ML) model for predicting HFpEF risk in COPD patients and to identify key predictors using explainable artificial intelligence techniques.</p><p><strong>Methods: </strong>This retrospective study analyzed 1,550 COPD patients, divided into COPD-only and COPD-HFpEF groups. Feature selection was performed using LASSO regression, logistic regression, and Boruta random forest. Ten ML models were developed and evaluated on an internal test set, with the best model further validated on an external cohort (n = 69). Model interpretability was assessed using SHapley Additive exPlanations (SHAP).</p><p><strong>Results: </strong>Nine predictors were consistently selected: NT-proBNP, red blood cell count, fibrinogen, cholesterol, arterial PaO₂, inspiratory capacity (IC), IC% predicted, late diastolic mitral inflow velocity (A wave), and CAT score. The XGBoost model achieved the best performance, with an AUC of 0.898 (95% CI: 0.867-0.929) on the internal test set and 0.819 (95%CI: 0.713 - 0.924) on external validation. SHAP analysis identified NT-proBNP as the most influential predictor.</p><p><strong>Conclusion: </strong>The developed XGBoost model accurately predicts HFpEF risk in COPD patients and offers clinically interpretable insights into key predictive markers, supporting early identification and stratified management.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857435","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}

{"title":"The integrated analysis of PRDX3 in lung cancer: biomarker potential and therapeutic target prospects.","authors":"Qi Kong, Lei Zhang, Shuang Gong, Yue Wu, Jue Wang","doi":"10.1186/s12931-026-03703-5","DOIUrl":"https://doi.org/10.1186/s12931-026-03703-5","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains the malignant tumor with the highest global incidence and mortality, posing a severe threat to public health. Peroxiredoxin 3 (PRDX3), a well-characterized ferroptosis biomarker, has been implicated in lung cancer progression. Accumulating evidence suggests that PRDX3 may serve as a core gene and potential biomarker, which is critical for elucidating pathogenesis, improving diagnostic accuracy, and developing targeted therapeutic strategies for lung cancer.</p><p><strong>Methods: </strong>To systematically investigate the expression pattern of PRDX3 and its clinical relevance in lung cancer, we integrated multiple bioinformatics tools and public datasets to analyze PRDX3 expression across pan-cancer cohorts, major lung cancer subtypes, and patient subgroups stratified by sex, age, and clinical stage. Furthermore, we evaluated the correlation between PRDX3 expression and immunotherapeutic-related factors, and performed multivariate survival analysis to validate its independent prognostic value. Additionally, protein-protein interaction (PPI) networking and co-expression analysis were employed to explore the functional interactions of PRDX3 with core ferroptosis regulators and immune microenvironment modulators.</p><p><strong>Results: </strong>PRDX3 was significantly upregulated in multiple malignant tumors, including LUAD and LUSC, with minimal variations in expression levels across different sex, age, and clinical stage subgroups. High PRDX3 expression was independently associated with significantly poorer clinical prognosis in lung cancer, particularly in the LUAD subtype. Pathway enrichment analysis revealed that immune activation, immune inhibition, and MHC molecule-related signaling pathways were closely correlated with altered PRDX3 expression in both LUAD and LUSC, with distinct subtype-specific patterns. PPI networking demonstrated that PRDX3 exhibited positive co-expression with core ferroptosis regulators (GPX4, TXN2) and interacted with components of the thioredoxin system (TXNRD2, TXN), indicating its potential involvement in regulating cellular redox homeostasis and ferroptosis. Single-cell analysis further confirmed PRDX3 expression in lung cancer cells and key immune cell subsets (T cells, macrophages), with higher expression levels observed in LUAD than in LUSC.</p><p><strong>Conclusions: </strong>These correlative findings suggest that PRDX3 may play a pivotal role in lung cancer pathogenesis, potentially through mechanisms involving ferroptosis regulation via interaction with GPX4 and the thioredoxin system, redox homeostasis maintenance, and subtype-specific immune microenvironment modulation. Collectively, PRDX3 represents a promising independent prognostic biomarker for lung cancer, especially for LUAD, and a potential therapeutic target for ferroptosis-based and immunotherapeutic strategies.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845115","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}

{"title":"Genomic characterization of DNA damage response pathway mutations reveals their adverse impact on EGFR-TKI efficacy in non-small cell lung cancer.","authors":"Lujie Yang, Jinli Cheng, Xin Guo, He Xiao, Xunjie Kuang, Yuxin Yang, Lei Zhang, Qin Zhang, Dong Wang, Yu Xu, Mengxia Li","doi":"10.1186/s12931-026-03699-y","DOIUrl":"https://doi.org/10.1186/s12931-026-03699-y","url":null,"abstract":"<p><strong>Background: </strong>Although tyrosine kinase inhibitors (TKIs) significantly improve survival outcomes in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), tumor clonal evolution under drug pressure inevitably leads to acquired resistance. DNA damage response (DDR) mutations lead to elevated genome instability, but the frequency and impact of DDR gene/pathway mutations on EGFR-TKI treatment efficacy remain unclear.</p><p><strong>Methods: </strong>A total of 790 NSCLC patients who received high-throughput targeted sequencing at Daping Hospital were retrospectively enrolled to analyze the mutation landscape of DDR genes in NSCLC. Next, 202 EGFR-mutant patients from Daping Hospital and 126 patients from the GENIE database who received first-line EGFR-TKI treatment were further enrolled to explore the association between DDR mutations and clinical outcomes.</p><p><strong>Results: </strong>DDR genes including ATM, MSH3, BRCA2 (> 5%), and pathways including the Fanconi anemia (FA), homologous recombination repair (HRR), and mismatch repair (MMR) exhibited substantial mutation rates (15%). In the Daping cohort, patients with DDR mutations had inferior outcomes when receiving EGFR-TKI treatment (median PFS: 14.9 vs. 10.8 months, P = 0.001) and higher mutation burden. Specifically, FA (HR = 2.314, 95% CI: 1.547-3.549, P < 0.001) or HRR (HR = 2.686, 95% CI: 1.786-4.039, P < 0.001) pathway mutations were independent risk factors for disease progression. Notably, patients with co-occurring TP53 and DDR mutations had the worst outcomes compared to those with either single mutations or wild-type TP53/DDR, and similar findings were validated in the GENIE cohort.</p><p><strong>Conclusion: </strong>Our study demonstrates a substantial prevalence of DDR mutations and their association with inferior EGFR-TKI efficacy, highlighting the importance of genomic profiling of DDR mutations to identify this high-risk subpopulation in EGFR-mutant NSCLC.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845077","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}

{"title":"IL-36γ enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis via the IFN-γ/HIF-1ɑ/glycolysis pathway.","authors":"Yuchi Gao, Longbin Cao, Xiuhua Huang, Guikai Duan, Bingying Lin, Junai Zhang, Wenyi Liu, Chen Chen, Junxiang Li, Mi Liu, Xiang Li, Hao Chen, Rong Liu, Juan Tang, Jing Xiao, Yuanbin Lu","doi":"10.1186/s12931-026-03700-8","DOIUrl":"https://doi.org/10.1186/s12931-026-03700-8","url":null,"abstract":"<p><strong>Background: </strong>IL-36γ coordinates macrophage activation and is essential for defense against Mycobacterium tuberculosis (Mtb), but the mechanisms remains poorly understood. Aerobic glycolysis plays a critical role in macrophages intrinsic control of Mtb infection. This study aimed to investigate the potential effects of IL-36γ on macrophages energy metabolism transformation from mitochondrial oxidative phosphorylation to aerobic glycolysis in response to Mtb infection.</p><p><strong>Methods: </strong>The expression of IL-36γ in lung tissues, PBMCs and serum was analyzed using Immunohistochemistry, ELISA and RT-qPCR, while the role and mechanism of IL-36γ on macrophages energy metabolism transformation duing Mtb infection were investigated by RT-qPCR, ELISA, Western blot and colony-forming unit assay.</p><p><strong>Results: </strong>We demonstrated IL-36γ enhanced the aerobic glycolysis, and downregulated the mitochondrial oxidative phosphorylation in Mtb infected macrophages. Furthermore, IL-36γ upregulated the expression of HIF-1α and IFN-γ in macrophages through the NF-κB/ERK/JNK signaling pathway, especially in macrophages infected with Mtb, where it induced the expression of large amounts of HIF-1α and IFN-γ. Moreover, IL-36γ promoted aerobic glycolysis through inducing the expression of HIF-1α in macrophages during Mtb infection. Meanwhile, HIF-1α was required for IL-36γ-mediated control of Mtb infection. Interestingly, the expression of IL-36γ was increased in lung tissues, PBMCs and serum from patients with active pulmonary tuberculosis and correlated with monocytes/macrophages immune response and IFN-γ levels, displayed an appreciable diagnostic value.</p><p><strong>Conclusion: </strong>IL-36γ enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis via the IFN-γ/HIF-1α/ glycolysis pathway. IL-36γ may be a potential treatment target and useful biomarker for tuberculosis.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822642","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}

{"title":"Qualitative beta-2-adrenoceptor signaling in the regulation of human airway epithelia mucin and cytokine production.","authors":"Fred Graumuller, Diana Cervantes, Tung O Chan, Niccolette Schaunaman, Dominic R Villalba, Burton F Dickey, Julia K L Walker, Hong Wei Chu, Raymond B Penn","doi":"10.1186/s12931-026-03693-4","DOIUrl":"https://doi.org/10.1186/s12931-026-03693-4","url":null,"abstract":"<p><strong>Background: </strong>Numerous in vivo studies have demonstrated beta-2-adrenoceptor (β₂AR) -agonism as permissive in the development of allergic lung inflammation, and have implicated the arrestin-dependent signaling arm of the β₂AR in mediating this effect. However, the specific cell type(s) mediating β₂AR regulation of allergic lung inflammation remain unestablished.</p><p><strong>Methods: </strong>To explore the potential contribution of airway epithelia in this phenomenon, we compared the ability of ractopamine (RP), recently identified as a Gs-biased beta-agonist, to that of the unbiased/balanced beta-agonist albuterol (ALB), on IL-13-stimulated mucin and cytokine production in human airway epithelia cultures in air-liquid interface (HAE).</p><p><strong>Results: </strong>ALB, which activates both the β₂AR-arrestin and -Gs signaling pathways significantly augmented IL-13-induced mucin production in HAE. RP, which preferentially signals via Gs/PKA, did not. Although IL-13 stimulated production of numerous cytokines, including IL-1α, IL-1RA, MDC, TGF-α, and GROα, ALB-mediated augmentation of these cytokines was highly variable and not statistically significant. Similarly, RP did not augment the induction of cytokines stimulated by IL-13. Moreover, in contrast to previous studies that reported a requirement of concomitant β₂AR agonism for IL-13 to stimulate cytokine production, such a requirement was observed only in minority of the (12) cultures examined.</p><p><strong>Conclusions: </strong>These data implicate arrestin-dependent β₂AR signaling augmenting airway epithelial mucin production as a contributor to the previously-demonstrated pro-inflammatory effects of β₂AR agonism in vivo. Moreover, they suggest that beta-agonist effects on the cytokine profile in the allergen-inflamed lung may be influenced by specific asthmatic endotypes and involve cooperativity among multiple cell types.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822708","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}

{"title":"Contribution of host-related immune factors to frequency and severity of infections in lung transplant recipients.","authors":"Jiri Kufa, Petra Schneiderova, Samuel Genzor, Marketa Trajerova, Petr Jakubec, Jan Mizera, Monika Zurkova, Eva Kriegova","doi":"10.1186/s12931-026-03685-4","DOIUrl":"https://doi.org/10.1186/s12931-026-03685-4","url":null,"abstract":"<p><strong>Background: </strong>Lung transplantation (LTx) is associated with an increased risk of infection, causing notable morbidity and mortality at all phases post-transplantation. The contribution of host-related immune factors to susceptibility to post-LTx infections is not fully understood.</p><p><strong>Methods: </strong>The circulating blood profile, serum cytokine profiles and 28 functional single nucleotide polymorphisms in cytokine genes were investigated in 103 lung transplant recipients (LTRs) (men/women: 65/38; mean [95% confidence interval {CI}]: 5.4 [4.7-6.1] years post-LTx) using cytometry and MassARRAY genotyping; the frequency and severity of viral, bacterial and fungal infections were evaluated.</p><p><strong>Results: </strong>In total, 62 (60.2%) LTRs had frequent/severe infections requiring inpatient care (FSI) and 41 (39.8%) had infrequent infections managed in the outpatient setting (IO). We identified rs1800587 AA (IL1A), rs1143634 AA (IL1B), rs16944 GG (IL1B), rs1800795 CG/GG (IL6) and rs1800797 AG/GG (IL6) as being associated with susceptibility to frequent/severe infections in LTRs. A combination of ≥ 2 IL1/IL6 risk variants was present in 53.2% of patients with frequent/severe infections compared with 17.1% with infrequent infections, increasing the likelihood of severe/frequent infections 5.5-fold (95% CI 2.17-13.6; p < 0.001). Moreover, patients with severe/frequent infections exhibited distinct changes in immune cell composition and cytokine profiles between 6- and 12-months post-LTx compared with others.</p><p><strong>Conclusion: </strong>Our data demonstrated that LTRs carrying IL1/IL6 risk variants and exhibiting limited post-LTx immune reconstitution were substantially more susceptible to frequent/severe infections. These findings highlight the value of combining immunogenetic profiling with longitudinal immune monitoring to improve infection risk stratification and guide personalised post-LTx care.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822625","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}

{"title":"Blood eosinophil counts and postoperative outcomes in early-stage lung cancer: a retrospective cohort study.","authors":"Everglad Mugutso, Ophir Freund, Isabelle Pitrou, Ankita Ghatak, Cédric Roux, Samantha Jacobson, Jonathan-Raphaël Stetco, Sara Kutzkel, Amir Bar-Shai, Benjamin Smith, Nicole Ezer","doi":"10.1186/s12931-026-03672-9","DOIUrl":"https://doi.org/10.1186/s12931-026-03672-9","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer resection is curative but associated with postoperative morbidity and mortality. This study evaluated whether elevated blood eosinophil count (BEC) was associated with postoperative outcomes in early-stage lung cancer.</p><p><strong>Methods: </strong>This was a retrospective cohort study of consecutive adult patients undergoing lung resection for stage I and II non-small cell lung cancer in a large tertiary referral center from September 2017 to June 2021. Data were drawn from the institution's Data Warehouse. The primary outcome was 90-day healthcare utilization defined as emergency department visit or hospital readmission. Secondary outcomes were postoperative complications, index hospitalization length of stay, and 1-year survival. Preoperative 90-day BEC was categorized by a threshold of 200 cells/µL. Covariates were age, sex, smoking status, Charlson Comorbidity Index, chronic obstructive pulmonary disease (COPD), asthma, tumor size, nodal status, surgical approach, and blood results (white blood cells, hemoglobin, and creatinine). The main analyses were validated by a second international cohort. Log-Poisson with robust variance estimation and Cox proportional hazards regression models were fit for primary and secondary outcomes. Analyses were replicated for BEC thresholds of 150 and 300 cells/µL.</p><p><strong>Results: </strong>Among 715 patients undergoing lung resection (median age = 69 years, 42% male, 29% with COPD), 146 patients (20%) had high preoperative BEC ≥ 200 cells/µL. BEC ≥ 200 cells/µL was associated with a higher rate of 90-day healthcare utilization:19% vs. 14% for BEC < 200 cells/µL. This association remained after adjustment (Risk Ratio [RR], 1.52; 95% Confidence Interval [CI], 1.02-2.25) and the validation cohort (RR, 2.23; 95% CI, 1.06-4.69). BEC as a continuous measure was also associated with the primary outcome in both cohorts: RR, 2.15 (95% CI, 1.49-3.12) and RR, 1.42 (95% CI, 1.10-1.94), respectively. BEC ≥ 200 cells/µL was associated with higher probability of death 1 year post-surgery (adjusted Hazard Ratio, 2.41; 95% CI, 1.08-5.35). There was no difference in the risk of postoperative pulmonary complications between high and low BEC (RR, 0.86; 95% CI, 0.58-1.27).</p><p><strong>Conclusions: </strong>Elevated preoperative BEC was associated with higher risk of postoperative healthcare utilization and lower 1-year survival after lung cancer resection among patients with or without respiratory disease.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822645","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}

{"title":"Alveolar epithelial barrier disruption by FKBP5-mediated necroptosis aggravates lung injury.","authors":"Jinfeng Cui, Wei Liu, Yue Zhou, Xinkai Qiu, Yangyang Xiao, Xiaozhi Wang, Tao Wang, Dong Zhang","doi":"10.1186/s12931-026-03696-1","DOIUrl":"https://doi.org/10.1186/s12931-026-03696-1","url":null,"abstract":"<p><p>Alveolar epithelial barrier damage is a key pathological feature of acute respiratory distress syndrome (ARDS). The glycocalyx and tight junctions are essential for maintaining epithelial barrier function, and their disruption exacerbates pulmonary edema. Although FK506-binding protein 51 (FKBP5) regulates inflammatory responses, its mechanistic role in ARDS remains unclear. Here, we show that FKBP5 levels in bronchoalveolar lavage fluid from patients with sepsis-associated ARDS are significantly elevated and positively correlated with disease severity. In a lipopolysaccharide (LPS)-induced ARDS mouse model, Fkbp5^-/- markedly attenuated lung inflammatory injury and reduced damage to the epithelial glycocalyx and tight junctions. Transcriptomic analysis revealed that FKBP5 regulates inflammatory responses through the necroptosis pathway. Both in vivo and in vitro experiments further confirmed that genetic deletion or knockdown of FKBP5 suppresses necroptosis activation, reduces NF-κB signaling, and restores glycocalyx and tight junction integrity. Mechanistically, necroptosis-driven NF-κB activation promotes excessive cytokine production, which in turn damages the epithelial glycocalyx and tight junctions. These findings identify FKBP5 as a potential therapeutic target in ARDS and redefine the alveolar epithelium as an active contributor to the inflammatory microenvironment.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822650","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}

{"title":"ERCC6L drives lung adenocarcinoma metastasis: a PJA2/p53 ubiquitination-dependent mechanism.","authors":"Lingyu Jiang, Huaihai Zhou, Shengjing Liang, Zhaoke Wen, Junqi Qin, Zhenniu Lei, Rongling Li, Yunzhi Ma, Shucong Peng, Yifan Zhou, Yonglong Zhong","doi":"10.1186/s12931-026-03692-5","DOIUrl":"https://doi.org/10.1186/s12931-026-03692-5","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is prone to metastasis and exhibits a poor prognosis. The DNA repair-related protein ERCC6L is implicated in tumorigenesis, but its role in LUAD invasion and metastasis remains unclear. The expression, function, and underlying mechanisms of ERCC6L were investigated using bioinformatics analysis, cellular assays, and animal experiments. ERCC6L was significantly upregulated in LUAD tissues and cell lines, and its high expression was associated with poor overall and recurrence-free survival. Functional experiments demonstrated that ERCC6L overexpression promoted the migration, invasion, and epithelial-mesenchymal transition (EMT) of LUAD cells. Mechanistically, ERCC6L activated the E3 ubiquitin ligase PJA2, which mediated K48-linked polyubiquitination and subsequent degradation of p53, thereby attenuating its tumor-suppressive function. In vivo studies confirmed that ERCC6L knockout suppressed tumor growth, metastasis, and EMT progression by regulating the PJA2/p53 signaling axis. ERCC6L promotes migration, invasion, and EMT in LUAD by facilitating PJA2-mediated ubiquitination and degradation of p53. The ERCC6L/PJA2/p53 axis represents a potential novel therapeutic target for inhibiting metastasis in LUAD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822688","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}