Respiratory Research最新文献

{"title":"TCF7 enhances pulmonary hypertension by boosting stressed natural killer cells and their interaction with pulmonary arterial smooth muscle cells.","authors":"Li-Wei Wu, Min Chen, Dai-Ji Jiang, Chen-Yu Jiang, Yi-Wei Liu, Bei Feng, Chen-Fei Shi, Xu Huang, Xu Zhang, Xiao-He Xu, Xing-Liang Zhou, Yi Shen, Tian-Yu Liu, Lin-Cai Ye, Yang-Yang He, Hao Zhang, Yi Yan","doi":"10.1186/s12931-025-03276-9","DOIUrl":"https://doi.org/10.1186/s12931-025-03276-9","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a life-threatening cardio-pulmonary disorder. Whether natural killer (NK) cells could act as participants in PH and the mechanism by which NK cells moderate pulmonary vascular remodeling has not been fully elucidated.</p><p><strong>Methods: </strong>Single-cell RNA sequencing data from lungs of human pulmonary arterial hypertension (PAH) patients and monocrotaline (MCT)-induced PH rat model were retrieved from GEO database or UCSC Cell Browser. Tcf7 conditional knockout mice and TCF7 overexpression following adeno-associated virus 6 (AAV6) intratracheal delivery in rats were generated. The NK92 cell line and primary human pulmonary artery smooth muscle cells (hPASMCs) were used for in vitro experiments.</p><p><strong>Results: </strong>Stressed NK cells were much higher in lungs from human PAH and MCT-induced PH compared to corresponding controls. Of note, TCF7 topped the list differentiating high-stressed from low-stressed human NK cells. TCF7-expressing NK cells displayed higher stress profile than TCF7-deficient cells. Tcf7-deficient NK cells exhibited lower Hsp90aa1 and Hsp90ab1 at transcriptional level and Hsp90 at protein level than Tcf7-expressing cells 24 h post-hypoxia. Mechanistically, TCF7-overexpressing NK cells secrete more SPP1 compared to control NK cells, thus promoting the proliferation and migration of hPASMCs 48 h post-hypoxia. TCF7 overexpression in rats aggravated PH features, while Tcf7 deficiency in mice alleviated pulmonary remodeling possibly due to the manipulation of HSP90 level in NK cells and SPP1 in the microenvironment.</p><p><strong>Conclusions: </strong>TCF7 contributes to the immunopathology of PH possibly through upregulation of stressed NK cells. Under stress conditions, NK cells promote the proliferation and migration of hPASMC through paracrine effects, thereby further promoting vascular remodeling.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"202"},"PeriodicalIF":5.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183277","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 novelty of profilin 2 in regulating pyruvate kinase M2 nuclear translocation and promoting tumor angiogenesis in lung adenocarcinoma.","authors":"Xiaohui Du, Chi Ma, Yingyan Wang, Mingxin Xu, Yanbin Kuang, Mengyun Li, Shuang Wen, Peipei He, Hui Zhao, Qi Wang","doi":"10.1186/s12931-025-03281-y","DOIUrl":"https://doi.org/10.1186/s12931-025-03281-y","url":null,"abstract":"<p><strong>Background: </strong>Profilin 2 (PFN2), indispensable in all organisms, is important for cancer initiation and progression. Here, we found PFN2 highly overexpressed in tumor tissues with poor prognosis of Lung adenocarcinoma (LUAD) patients had a novel role in remodulating angiogenesis. However, the mechanism of PFN2-mediated LUAD angiogenesis remains unelucided.</p><p><strong>Methods: </strong>Immunohistochemistry and western blotting were used to detected the expression levels of related proteins in tissue or lung cancer cells. To elucidate the underlying mechanisms, we identified binding partners of PFN2 through mass spectrometry, co-immunoprecipitation, and molecular modeling techniques. Additionally, we investigated the angiogenic-promoting function of PFN2 utilizing a three-dimensional droplet-based angiogenesis model capable of simulating the tumor hypoxic microenvironment.</p><p><strong>Results: </strong>Our finding reveal that PFN2 was overexpressed in tumors compared with the adjacent nontumor tissues. Its knockdown markedly impaired the proliferation, and angiogenesis of LUAD cells via hypoxia-related NF-κB/HIF-1α signaling pathway, with vascular endothelial growth Factor (VEGF) decrease. Additionally, pyruvate kinase M2 (PKM2), a pivotal enzyme in glycolysis, is a novel binding partner of PFN2. The nuclear translocation of PKM2 was observed to be dependent on PFN2 expression and their interaction, which functionally modulates angiogenesis in lung cancer.</p><p><strong>Conclusions: </strong>Our study revealed oncogene PFN2 promoted tumor angiogenesis in LUAD through regulating PKM2 nuclear translocation, providing novel molecular therapy targets for LUAD treatment.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"203"},"PeriodicalIF":5.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181514","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":"ITIH4 attenuates acute lung injury by Fe-containing particulate matter in mice via Hippo pathway in type II alveolar epithelial cells.","authors":"Vincent Laiman, Syue-Wei Peng, Lina Choridah, Didik Setyo Heriyanto, Fara Silvia Yuliani, Kang-Yun Lee, Ching-Huang Lai, Jer-Hwa Chang, Yueh-Lun Lee, Shu-Chuan Ho, Sheng-Ming Wu, Chia-Li Han, Cheng-Wei Lin, Kian Fan Chung, Hsiao-Chi Chuang","doi":"10.1186/s12931-025-03256-z","DOIUrl":"https://doi.org/10.1186/s12931-025-03256-z","url":null,"abstract":"<p><strong>Background: </strong>Metals in particulate matter (PM), like iron (Fe), were associated with lung injury. Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) was suggested to inhibit lung inflammation. However, the effect of metals in PM, particularly Fe, on lung inflammation involving ITIH4 remained unclear.</p><p><strong>Methods: </strong>We investigated the effects of recombinant ITIH4 (rITIH4) against acute lung injury in C57BL/6JNarl and B6.Sftpc-CreER^T2;Ai14(RCL-tdT)-D mice exposed to Fe-containing PM. Mice were exposed to diesel exhaust particles (DEP) or soluble iron (FeCl₃) via intratracheal instillation, while rITIH4 treatment was administered intranasally after exposure. Lung function, Fe levels (both bulk and single-cell by inductively-coupled plasma mass spectrometry (ICP-MS) and single-cell ICP-MS, respectively), inflammatory cell infiltration, and Hippo pathway regulation in type II alveolar epithelial cells (AECII) were assessed.</p><p><strong>Results: </strong>We observed correlation between lung function changes and Fe levels, both in bulk and single-cell Fe in peripheral blood mononuclear cells. Single-cell RNA sequencing of the control group identified AECII-related cells characterized by high Sftpc, Sftpa1, Mzb1, B3 gnt5, Cacna1e, and Agbl1 expression. rITIH4 treatment in DEP-exposed mice restored Hippo pathway Cdh1, Itih4, Pdpn, Wwtr1, and Yap1 in AECII. rITIH4 reversed DEP- and Fe-induced increases in neutrophil infiltration, neutrophil-to-lymphocyte ratio, and monocyte depletion in bronchoalveolar lavage fluid (BALF). rITIH4 reduced BALF CXCL1/KC levels by DEP and serum 8-isoprostane levels by Fe. rITIH4 also reduced DEP-induced lung damage, increased ⍺-catenin and p-YAP in Fe-exposed mice, and pTAZ/TAZ ratio in both DEP- and Fe-exposed mice. rITIH4 increased pYAP/YAP ratio in DEP-exposed mice while decreasing LC3BII/I ratio in Fe-exposed mice.</p><p><strong>Conclusion: </strong>ITIH4 attenuated acute lung injury in mice exposed to PM, specifically Fe, by modulating the Hippo pathway in AECII.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"201"},"PeriodicalIF":5.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175142","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":"FlexO2: A patient-controlled oxygen flow selector improving autonomy and daily function in long-term oxygen therapy (LTOT).","authors":"Michael Runold, Ingegerd Karlsson, Magda Borén","doi":"10.1186/s12931-025-03274-x","DOIUrl":"10.1186/s12931-025-03274-x","url":null,"abstract":"<p><strong>Background: </strong>Chronic respiratory insufficiency associated with severe resting hypoxemia necessitates long-term oxygen therapy (LTOT), yet existing devices often impede daily activities due to cumbersome flow adjustments, increasing reliance on caregivers. FlexO2 is a novel mechanical regulator that enables switching between preset oxygen flow rates for rest and activity. This proof-of-concept study evaluated its impact on patient autonomy, physical activity, and quality of life.</p><p><strong>Methods: </strong>In a consecutive, non-randomized pre-post intervention proof-of-concept study at Karolinska University Hospital, 26 patients on LTOT (median age 77; 69% COPD) used FlexO2 for three months. The device, worn around the neck, allowed patients to self-adjust oxygen doses without accessing the concentrator. Outcomes included ease of use measured by visual analogue scale (VAS), physical activity levels, COPD Assessment Test (CAT), EQ-5D-5 L index, and frequency of dose adjustments.</p><p><strong>Results: </strong>Ease of dose adjustment increased from a VAS score of 14 to 92 (p < 0.001), with 92% of patients reporting improved ease of adjustment (baseline 7.7%; p < 0.001). Daily adjustment frequency doubled (8 to 15; p = 0.001). Patient-reported activity capacity improved from a VAS of 11 to 80 (p < 0.001). Quality-of-life scores measured by VAS increased from 19 to 61 (p < 0.001), while CAT scores decreased from a median of 26.0 to 22.5 (p = 0.05). The EQ-5D-5 L index remained stable (0.68 to 0.70; p = 0.7), although 38% of patients showed individual improvements. Device usability was high (83% satisfaction), though 15% reported tubing tangling or airflow issues.</p><p><strong>Conclusion: </strong>FlexO2 significantly improved the ease of oxygen dose adjustment and physical activity capacity, potentially enhancing patient autonomy in LTOT. While overall patient-reported quality-of-life scores improved, objective quality-of-life outcomes remained stable. Further studies are warranted to explore long-term clinical outcomes and the potential impact on caregiver burden.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"200"},"PeriodicalIF":5.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152651","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}

{"title":"Digital mindfulness-based intervention for people with COPD - a multicentre pilot and feasibility RCT.","authors":"Hannah Tschenett, Florian Vafai-Tabrizi, Ralf Harun Zwick, Arschang Valipour, Georg-Christian Funk, Urs M Nater","doi":"10.1186/s12931-025-03243-4","DOIUrl":"https://doi.org/10.1186/s12931-025-03243-4","url":null,"abstract":"<p><strong>Background: </strong>Mindfulness-based interventions (MBIs) are effective in improving mental and physical health in various chronic conditions. While the GOLD 2024 report recommends MBIs for chronic obstructive pulmonary disease (COPD), scientific evidence in this specific population is scarce. This prospective randomised controlled pilot study investigated the feasibility of an 8-week digital MBI and its preliminary effects on mental and physical health in COPD.</p><p><strong>Methods: </strong>Psychologically burdened COPD patients (63 ± 7 years, 61% female, FEV1% 41 ± 19) were randomly allocated to the MBI group (n = 14; daily 10-15-minute audio-guided meditation via smartphone) or a waitlist control group (n = 16). Primary outcomes included the intervention's feasibility (dropouts, MBI usage rates, interview and questionnaire responses) and its preliminary effects on symptoms of anxiety and depression (Hospital Anxiety and Depression Scale, HADS). Secondary outcomes included its preliminary effects on the COPD Assessment Test (CAT), Chronic Respiratory Disease Questionnaire (CRQ-SAS), Perceived Stress Scale (PSS-10), and biological stress markers. Exploratory outcomes included momentary subjective stress, anxiety, and dyspnoea after meditating.</p><p><strong>Results: </strong>The results indicated that the intervention was feasible (81% usage rate; 93% and 71% found the MBI enjoyable and helpful, respectively), with 21% dropout. A statistically significant intervention (time x group) effect was found for anxiety (HADS-A, p =.010, η_p² = 0.11) and emotional functioning (CRQ-SAS, p =.004, η_p² = 0.14), but not for depression (HADS-D, p =.060, η_p² = 0.06) or any other secondary outcome after 8 weeks. Momentary subjective stress (p <.001, η_p² = 0.75), anxiety (p =.022, η_p² = 0.75), and dyspnoea (p <.001, η_p² = 0.70) were significantly reduced after meditating.</p><p><strong>Conclusions: </strong>The digital MBI was feasible, with preliminary effects indicating improvements in anxiety and emotional functioning after 8 weeks as well as momentary outcomes after meditating. Future large-scale trials should further assess the effectiveness of digital MBIs in this context. However, the findings suggest that digital MBIs might be promising and effective low-threshold add-on treatments in clinical settings.</p><p><strong>Trial registration: </strong>The article has been preregistered at ClinicalTrials.gov (identifier: NCT04769505, date: 23rd February 2021).</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"199"},"PeriodicalIF":5.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152648","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":"Correction: Complement activity and autophagy are dysregulated in the lungs of patients with nonresolvable COVID‑19 requiring lung transplantation.","authors":"Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N LeFebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana","doi":"10.1186/s12931-025-03258-x","DOIUrl":"https://doi.org/10.1186/s12931-025-03258-x","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"198"},"PeriodicalIF":5.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152642","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":"Phenylacetylglutamine produced from injury lung alveolar epithelial cells promotes the function of BMSCs by regulating NONRATT006276.2/Mapt pathway.","authors":"Tianyun Yang, Juan Peng, Rongrong Ren, Lin Song","doi":"10.1186/s12931-025-03261-2","DOIUrl":"10.1186/s12931-025-03261-2","url":null,"abstract":"<p><p>Mesenchymal stem cell (MSC)-based therapy regenerates damaged structures of the respiratory system and restores lung function, thus providing a promising therapeutic approach for chronic obstructive pulmonary disease. Understanding the communication between injured alveolar cells and MSCs can improve the efficiency of MSC-based therapies. The present study analyzed the untargeted metabolomics of the supernatant of AEC-II injury induced by cigarette smoke extract and identified 205 differential metabolites. Phenotypic assays indicated that phenylacetylglutamine (PAG) significantly promoted the migration and mitochondrial function of bone marrow MSCs (BMSCs). Whole-transcriptome sequencing (WT-seq) was used to analyze the long noncoding RNA (lncRNA) and mRNA expression profiles of BMSCs treated with PAG. The upregulated lncNRA NONRATT006276.2 (NRT6276.2) and its trans-regulated gene, microtubule-associated protein tau (Mapt), were identified based on the lncRNA-mRNA co-expression network and bioinformatics analysis. The knockdown of NRT6276.2 or Mapt inhibited the positive effects of PAG on BMSCs. Furthermore, Mapt overexpression reversed the phenotype of BMSCs inhibited by silencing NRT6276.2. In conclusion, PAG enhanced the migration and mitochondrial function of BMSCs by regulating the NRT6276.2/Mapt pathway. This study clarified the positive effects of PAG produced by injured lung cells on transplanted MSCs, providing a potential new strategy to enhance the efficiency of MSC-based therapies.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"196"},"PeriodicalIF":5.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144160","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}

{"title":"First nomogram for predicting interstitial lung disease and pulmonary arterial hypertension in SLE: a machine learning approach.","authors":"Qian Niu, Qian Li, Shuaijun Chen, Lingyan Xiao, Jing Luo, Meng Wang, Linjie Song","doi":"10.1186/s12931-025-03273-y","DOIUrl":"10.1186/s12931-025-03273-y","url":null,"abstract":"<p><strong>Background: </strong>Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are severe, life-threatening complications of systemic lupus erythematosus (SLE). Early identification of high-risk patients remains challenging due to the lack of validated predictive tools. We aimed to develop and validate the first machine learning-based nomogram integrating routine clinical indicators to predict SLE-ILD-PAH risk.</p><p><strong>Methods: </strong>Using a retrospective cohort design, we analyzed 338 SLE patients (2007-2019), including 193 with ILD-PAH and 145 controls. Univariable and multivariable logistic regression identified independent predictors, followed by nomogram construction and random forest modeling. Model performance was assessed via calibration curves and decision curve analysis (DCA).</p><p><strong>Results: </strong>Age, C-reactive protein (CRP), anti-dsDNA, pericarditis, and SLE Disease Activity Index (SLEDAI) were independently associated with the prevalence of ILD-PAH in SLE patients. The 5 variables were selected to construct the nomogram model. Calibration curves and decision curve analysis indicated the clinical utility of the nomogram. Receiver operating characteristics (ROC) curves analysis demonstrated excellent discrimination (AUC = 0.871, 95% CI: 0.833-0.910). Forest plot analysis further confirmed the diagnostic weight of each variable.</p><p><strong>Conclusions: </strong>We developed the first nomogram incorporating age, CRP, anti-dsDNA, pericarditis, and SLEDAI to predict SLE-ILD-PAH risk. This machine learning-enhanced tool leverages routine clinical data, enabling early risk stratification and personalized monitoring. Future studies should validate its utility in guiding therapies and improving outcomes.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"197"},"PeriodicalIF":5.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144159","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}

{"title":"Use of quantitative CT chest imaging to derive and assess a radiographic phenotype of deployment-related constrictive bronchiolitis.","authors":"Alexander J Bell, Maria Masotti, Sundaresh Ram, Gregory Pappas, Robert F Miller, Ella A Kazerooni, Charles R Hatt, MeiLan K Han, Bradley W Richmond, Michael J Falvo, Craig J Galban, John J Osterholzer","doi":"10.1186/s12931-025-03269-8","DOIUrl":"10.1186/s12931-025-03269-8","url":null,"abstract":"<p><strong>Background: </strong>Efforts to phenotype veterans that developed respiratory symptoms following deployments to the Southwest Asia Theater of Military Operation have been limited by the insensitivity of current non-invasive testing to objectively identify deployment-related constrictive bronchiolitis and other features of chronic lung injury. In this study, we derived a quantitative CT (QCT)-based radiographic phenotype of biopsy-proven deployment-related constrictive bronchiolitis (DRCB) and assessed its ability to assist in the phenotyping of non-biopsied formerly deployed symptomatic veterans.</p><p><strong>Methods: </strong>QCT analysis combined with demographic, physiologic, symptom, and exposure data was obtained from three cohorts: military personnel with biopsy-proven deployment-related constrictive bronchiolitis (DRCB, n = 37), formerly deployed symptomatic veterans (FDSV, n = 71), and asymptomatic civilians (Control, n = 98). Differences in unadjusted QCT metrics and demographic variables between cohorts were identified and further assessed by principal component analysis. Thereafter, adjusted data from the DRCB cohort was used to derive a QCT-based radiographic phenotype of DRCB expressed as a DRCB-Probability Index (DRCB-PI). Application of the DRCB-PI to the FDSV cohort was used to assess additional phenotypic metrics associated with the DRCB phenotype (DRCB-PI > 0.5).</p><p><strong>Results: </strong>Individual unadjusted QCT metrics for functional small airways disease and high attenuation area were elevated in DRCB and FDSV cohorts (relative to Control). Primary component analysis revealed that DRCB and FDSV cohorts overlapped and were distinguished from the Control cohort. The FDSV subjects whose DRCB-PI was > 0.5 had greater evidence of small airways disease (assessed by oscillometry and QCT) and self-reported more intense immediate health effects to their exposures to military burn pit smoke, and sand and dust.</p><p><strong>Conclusions: </strong>Application of a QCT-derived radiographic phenotype of DRCB identified a subset of veterans with evidence of abnormal small airways and more severe self-reported health effects following inhalational exposures during military deployment. Future studies incorporating QCT may help establish non-invasive strategies to detect DRCB and other forms of chronic lung injury.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"195"},"PeriodicalIF":5.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121255","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}

{"title":"Autophagy and exosome dynamics in Radiation-Induced pulmonary fibrosis: the critical role of TRIB3.","authors":"Na Li, Wenyue Zhao, Jiale Li, Dengfeng Zhang, Kejun Li, Mengmeng Yang, Xinran Lu, Liqing Du, Chang Xu, Qiang Liu","doi":"10.1186/s12931-025-03271-0","DOIUrl":"10.1186/s12931-025-03271-0","url":null,"abstract":"<p><strong>Objective: </strong>Dysregulated autophagy plays a critical role in the pathogenesis of pulmonary fibrosis. The stress protein TRIB3 has been correlated with abnormal autophagy, but its specific contribution to radiation-induced pulmonary fibrosis (RIPF) remains unclear. This study aimed to elucidate the role of TRIB3 in RIPF progression.</p><p><strong>Methods: </strong>We conducted RNA-sequencing of rat RIPF lung tissue to analyze the transcriptomic profile and determine gene expression changes in murine with RIPF. We established mouse models with alveolar epithelial type II cells (AEC II)-specific knockdown or overexpression of TRIB3 to elucidate its role in RIPF progression. We utilized mRFP-GFP-LC3 fluorescent reporter cells, nanoparticle tracking analysis, immunofluorescence and immunoprecipitation assays to uncover the underlying mechanisms.</p><p><strong>Results: </strong>TRIB3 expression was elevated in irradiated AEC II. Silencing TRIB3 in AEC II mitigated RIPF in mice, whereas its overexpression exacerbated the condition. Mechanistically, TRIB3 interacted with the LC3-interacting region (LIR) motif and ubiquitin-associated (UBA) domain of sequestosome 1 (SQSTM1), an autophagic receptor protein, thereby inhibiting autophagic flux in AEC II cell line MLE12. This inhibition increased exosome secretion and facilitated crosstalk between MLE12 cells and fibroblasts, ultimately enhancing the proliferation and extracellular matrix production of lung fibroblasts.</p><p><strong>Conclusion: </strong>TRIB3 in AEC II inhibits autophagic flux by interacting with SQSTM1, thereby increasing exosome secretion, which promotes fibroblast proliferation and extracellular matrix production, contributing to RIPF progression.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"194"},"PeriodicalIF":5.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121252","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}