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Cold storage of human precision-cut lung slices in TiProtec preserves cellular composition and transcriptional responses and enables on-demand mechanistic studies.
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-17 DOI: 10.1186/s12931-025-03132-w
M Camila Melo-Narvaez, Fee Gölitz, Eshita Jain, Janine Gote-Schniering, Mircea Gabriel Stoleriu, Wilhelm Bertrams, Bernd Schmeck, Ali Önder Yildirim, Ursula Rauen, Timo Wille, Mareike Lehmann
{"title":"Cold storage of human precision-cut lung slices in TiProtec preserves cellular composition and transcriptional responses and enables on-demand mechanistic studies.","authors":"M Camila Melo-Narvaez, Fee Gölitz, Eshita Jain, Janine Gote-Schniering, Mircea Gabriel Stoleriu, Wilhelm Bertrams, Bernd Schmeck, Ali Önder Yildirim, Ursula Rauen, Timo Wille, Mareike Lehmann","doi":"10.1186/s12931-025-03132-w","DOIUrl":"https://doi.org/10.1186/s12931-025-03132-w","url":null,"abstract":"<p><strong>Background: </strong>Human precision-cut lung slices (hPCLS) are a unique platform for functional, mechanistic, and drug discovery studies in the field of respiratory research. However, tissue availability, generation, and cultivation time represent important challenges for their usage. Therefore, the present study evaluated the efficacy of a specifically designed tissue preservation solution, TiProtec, complete or in absence (-) of iron chelators, for long-term cold storage of hPCLS.</p><p><strong>Methods: </strong>hPCLS were generated from peritumor control tissues and stored in DMEM/F-12, TiProtec, or TiProtec (-) for up to 28 days. Viability, metabolic activity, and tissue structure were determined. Moreover, bulk-RNA sequencing was used to study transcriptional changes, regulated signaling pathways, and cellular composition after cold storage. Induction of cold storage-associated senescence was determined by transcriptomics and immunofluorescence (IF). Finally, cold-stored hPCLS were exposed to a fibrotic cocktail and early fibrotic changes were assessed by RT-qPCR and IF.</p><p><strong>Results: </strong>Here, we found that TiProtec preserves the viability, metabolic activity, transcriptional profile, as well as cellular composition of hPCLS for up to 14 days. Cold storage did not significantly induce cellular senescence in hPCLS. Moreover, TiProtec downregulated pathways associated with cell death, inflammation, and hypoxia while activating pathways protective against oxidative stress. Cold-stored hPCLS remained responsive to fibrotic stimuli and upregulated extracellular matrix-related genes such as fibronectin and collagen 1 as well as alpha-smooth muscle actin, a marker for myofibroblasts.</p><p><strong>Conclusions: </strong>Optimized long-term cold storage of hPCLS preserves their viability, metabolic activity, transcriptional profile, and cellular composition for up to 14 days, specifically in TiProtec. Finally, our study demonstrated that cold-stored hPCLS can be used for on-demand mechanistic studies relevant for respiratory research.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"57"},"PeriodicalIF":5.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441851","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
Long-term trends in the burden of asthma in China: a joinpoint regression and age-period-cohort analysis based on the GBD 2021.
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-15 DOI: 10.1186/s12931-025-03135-7
Na Li, Yuhan Xu, Xinru Xiao, Ziqi Ding, Chuang Sun, Qian Zhang
{"title":"Long-term trends in the burden of asthma in China: a joinpoint regression and age-period-cohort analysis based on the GBD 2021.","authors":"Na Li, Yuhan Xu, Xinru Xiao, Ziqi Ding, Chuang Sun, Qian Zhang","doi":"10.1186/s12931-025-03135-7","DOIUrl":"10.1186/s12931-025-03135-7","url":null,"abstract":"<p><strong>Background: </strong>To develop effective strategies for controlling asthma, a thorough assessment of its disease burden is essential. In this study, we examined long-term trends in the asthma burden in China over the past three decades and analyzed its epidemiological features.</p><p><strong>Methods: </strong>We assessed the burden of asthma in China via the global burden of disease (GBD) 2021 database, focusing on prevalence, incidence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs). Additionally, we employed joinpoint analysis and age-period-cohort (apc) methods to interpret the epidemiological characteristics of asthma. Finally, we analyzed the attributable burden of asthma to gain a comprehensive understanding of its impact.</p><p><strong>Results: </strong>The age-standardized incidence rate (ASIR) and mortality rate (ASMR) for both sexes in China shifted from 524.81 (95% UI: 421.31, 672.76) to 314.17 (95% UI: 283.22, 494.10) and from 5.82 (95% UI: 4.46, 8.50) to 1.47 (95% UI: 1.15, 1.79) per 100,000 population between 1990 and 2021. According to joinpoint analysis, the average annual percentage change (AAPC) in the age-standardized incidence rate was - 1.2 (95% CI: - 1.4, - 1.1), indicating a gradual but fluctuating decline (with significant turning points in 2005 and 2014). The apc fitting results suggest that the prevalence is now lower than it was in the past and that the relative prevalence risk is high among adolescents and middle-aged to elderly individuals, possibly due to different pathophysiological mechanisms. In 2021, the primary asthma-related burdens were metabolic risks, especially obesity.</p><p><strong>Conclusions: </strong>In conclusion, we found that the disease burden of asthma in China has significantly decreased. However, it remains a major concern among adolescents and elderly individuals. Metabolic risk factors, particularly obesity, are the main contributors to the asthma burden. It is essential to address specific risk factors and develop targeted public health strategies for different age groups.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"56"},"PeriodicalIF":5.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426534","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
A pilot study of endobronchial repairment for bronchopleural fistulas.
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-13 DOI: 10.1186/s12931-025-03128-6
Zhibing Luo, Yanghong Zheng, Guo Ye, Yuhua Ma, Tingting Lin, Chen Chen, Dongmei Liu, Qiang Li, Na Wang
{"title":"A pilot study of endobronchial repairment for bronchopleural fistulas.","authors":"Zhibing Luo, Yanghong Zheng, Guo Ye, Yuhua Ma, Tingting Lin, Chen Chen, Dongmei Liu, Qiang Li, Na Wang","doi":"10.1186/s12931-025-03128-6","DOIUrl":"10.1186/s12931-025-03128-6","url":null,"abstract":"<p><strong>Background: </strong>Bronchopleural fistulas (BPFs) are severe medical condition with high mortality. When the conventional surgical therapy failed, endobronchial intervention could function as the supplementary option. Several studies reported successful endobronchial managements of BPFs whereas the optimal strategies remain elusive.</p><p><strong>Methods: </strong>We retrospectively reviewed the medical records of patients with BPFs underwent endobronchial interventions with Vaseline gauze, shape-adjustable silicone plug, sutured silicone tube or covered metallic stent in our institution.</p><p><strong>Results: </strong>From 2018 to 2024, a total of 30 patients (11 females VS. 19 males; mean age 48.03 ± 20.33 years) with primary etiology of tumor (n = 19), empyema (n = 6), gastro-bronchial fistula (n = 1), lung infection with immune suppressed status (n = 1) and spontaneous pneumothorax (n = 3) were treated. Different occlusive materials were placed including covered metallic stent (n = 6), shape-adjustable silicone plug (n = 4), sutured silicone tube (n = 1) and Vaseline gauze(s) (n = 21). The dislocation of devices occurred in two patients with covered metallic stent occlusion. On the first day post procedure, 17 patients (56.7%) had complete resolution of the fistulas, compared with 13 patients (43.3%) had incomplete resolution. At the end of the first week post procedure, 19 patients (63.3%) showed complete resolution and 10 patients (33.3%) with partial resolution, whereas one patient (3.3%) failed to have effective closure of the fistula. The representative computer tomography images showed the closure of fistulas and ameliorated hydropneumothorax.</p><p><strong>Conclusion: </strong>Four endobronchial interventional maneuvers, the Vaseline gauze, shape-adjustable silicone plug, sutured silicone tube and covered metallic stent, showed both safe and effective managements for patients with BPFs.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"55"},"PeriodicalIF":5.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415913","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
Pathophysiological mechanisms of ARDS: a narrative review from molecular to organ-level perspectives.
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-13 DOI: 10.1186/s12931-025-03137-5
Kaihuan Zhou, Qianqian Qin, Junyu Lu
{"title":"Pathophysiological mechanisms of ARDS: a narrative review from molecular to organ-level perspectives.","authors":"Kaihuan Zhou, Qianqian Qin, Junyu Lu","doi":"10.1186/s12931-025-03137-5","DOIUrl":"10.1186/s12931-025-03137-5","url":null,"abstract":"<p><strong>Background: </strong>Acute respiratory distress syndrome (ARDS) remains a life-threatening pulmonary condition with persistently high mortality rates despite significant advancements in supportive care. Its complex pathophysiology involves an intricate interplay of molecular and cellular processes, including cytokine storms, oxidative stress, programmed cell death, and disruption of the alveolar-capillary barrier. These mechanisms drive localized lung injury and contribute to systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Unlike prior reviews that primarily focus on isolated mechanisms, this narrative review synthesizes the key pathophysiological processes of ARDS across molecular, cellular, tissue, and organ levels.</p><p><strong>Main body: </strong>By integrating classical theories with recent research advancements, we provide a comprehensive analysis of how inflammatory mediators, metabolic reprogramming, oxidative stress, and immune dysregulation synergistically drive ARDS onset and progression. Furthermore, we critically evaluate current evidence-based therapeutic strategies, such as lung-protective ventilation and prone positioning, while exploring innovative therapies, including stem cell therapy, gene therapy, and immunotherapy. We emphasize the significance of ARDS subtypes and their inherent heterogeneity in guiding the development of personalized treatment strategies.</p><p><strong>Conclusions: </strong>This narrative review provides fresh perspectives for future research, ultimately enhancing patient outcomes and optimizing management approaches in ARDS.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"54"},"PeriodicalIF":5.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415916","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
Prognostic significance of pleural fluid microbiological positivity in pleural infection: a bicentric 10-year retrospective observational study.
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-13 DOI: 10.1186/s12931-025-03129-5
Charles Wong, Hon Cheung Fan, Najib M Rahman, Jeffrey Chi Chung Wong, Hei Shun Cheng, Pui Hing Chiu, Chun Wai Tong, Flora Pui Ling Miu, Loretta Yin Chun Yam
{"title":"Prognostic significance of pleural fluid microbiological positivity in pleural infection: a bicentric 10-year retrospective observational study.","authors":"Charles Wong, Hon Cheung Fan, Najib M Rahman, Jeffrey Chi Chung Wong, Hei Shun Cheng, Pui Hing Chiu, Chun Wai Tong, Flora Pui Ling Miu, Loretta Yin Chun Yam","doi":"10.1186/s12931-025-03129-5","DOIUrl":"10.1186/s12931-025-03129-5","url":null,"abstract":"<p><strong>Background: </strong>Despite its heterogeneity, there is currently limited data in pleural infection phenotyping. Using pleural fluid characteristics, pleural infection can be classified into microbiological-positive pleural infection (MPPI) and microbiological-negative pleural infection (MNPI). This study aimed to evaluate the prognostic significance of microbiological positivity in pleural infection, and to evaluate the performance of RAPID (renal, age, purulence, infection source, dietary factor) score in these subgroups.</p><p><strong>Methods: </strong>Consecutive patients hospitalized for pleural infection over a 10-year period in two acute-care hospitals in Hong Kong were evaluated. According to the pleural fluid characteristics, they were classified into MPPI and MNPI, respectively. Survival was evaluated using multivariate Cox regression analysis. Performance of RAPID score to predict mortality at 3-month and 1-year was evaluated using C-statistics.</p><p><strong>Results: </strong>In total, 381 patients with pleural infection were included. They were classified into MPPI (n = 169) and MNPI (n = 212), respectively. The MPPI group had more elderly home residence and use of large-bore chest tube, and higher Charlson comorbidity index and RAPID score, compared to the MNPI group. Length-of-stay, the need of surgery and intensive care were similar between the two groups. MPPI was associated with significantly increased risk of mortality (adjusted hazard ratio [aHR] 1.46, 95% CI 1.08-1.98). Three-month mortality was significantly higher in MPPI compared to MNPI (24.9% vs. 10.4%, p < 0.001; adjusted odd ratio 2.05, 95% CI 1.11-3.80). The trend continued at 1, 3, 5 and 7 years. RAPID score predicted 3-month and 1-year mortality in both groups (C-statistics, MPPI 0.71, 0.75; MNPI 0.84, 0.81). In the MPPI group, presence of Staphylococcus aureus (aHR 2.26, 95% CI 1.43-3.57) and Gram-negative organisms other than Enterobacteriaceae (aHR 2.00, 95% CI 1.10-3.61) were associated with worse survival, while presence of Streptococcus anginosus group was associated better survival (aHR 0.50, 95% CI 0.32-0.78), when compared to their absence.</p><p><strong>Conclusions: </strong>Pleural fluid microbiological positivity is independently associated with increased mortality in patients with pleural infections. This finding should complement the RAPID score in risk stratification and inform future research aimed at improving outcomes in this patient population.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"53"},"PeriodicalIF":5.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415921","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
The large language model diagnoses tuberculous pleural effusion in pleural effusion patients through clinical feature landscapes. 大语言模型通过临床特征景观诊断胸腔积液患者的结核性胸腔积液。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-12 DOI: 10.1186/s12931-025-03130-y
Chaoling Wu, Wanyi Liu, Pengfei Mei, Yunyun Liu, Jian Cai, Lu Liu, Juan Wang, Xuefeng Ling, Mingxue Wang, Yuanyuan Cheng, Manbi He, Qin He, Qi He, Xiaoliang Yuan, Jianlin Tong
{"title":"The large language model diagnoses tuberculous pleural effusion in pleural effusion patients through clinical feature landscapes.","authors":"Chaoling Wu, Wanyi Liu, Pengfei Mei, Yunyun Liu, Jian Cai, Lu Liu, Juan Wang, Xuefeng Ling, Mingxue Wang, Yuanyuan Cheng, Manbi He, Qin He, Qi He, Xiaoliang Yuan, Jianlin Tong","doi":"10.1186/s12931-025-03130-y","DOIUrl":"10.1186/s12931-025-03130-y","url":null,"abstract":"<p><strong>Background: </strong>Tuberculous pleural effusion (TPE) is a challenging extrapulmonary manifestation of tuberculosis, with traditional diagnostic methods often involving invasive surgery and being time-consuming. While various machine learning and statistical models have been proposed for TPE diagnosis, these methods are typically limited by complexities in data processing and difficulties in feature integration. Therefore, this study aims to develop a diagnostic model for TPE using ChatGPT-4, a large language model (LLM), and compare its performance with traditional logistic regression and machine learning models. By highlighting the advantages of LLMs in handling complex clinical data, identifying interrelationships between features, and improving diagnostic accuracy, this study seeks to provide a more efficient and precise solution for the early diagnosis of TPE.</p><p><strong>Methods: </strong>We conducted a cross-sectional study, collecting clinical data from 109 TPE and 54 non-TPE patients for analysis, selecting 73 features from over 600 initial variables. The performance of the LLM was compared with logistic regression and machine learning models (k-Nearest Neighbors, Random Forest, Support Vector Machines) using metrics like area under the curve (AUC), F1 score, sensitivity, and specificity.</p><p><strong>Results: </strong>The LLM showed comparable performance to machine learning models, outperforming logistic regression in sensitivity, specificity, and overall diagnostic accuracy. Key features such as adenosine deaminase (ADA) levels and monocyte percentage were effectively integrated into the model. We also developed a Python package ( https://pypi.org/project/tpeai/ ) for rapid TPE diagnosis based on clinical data.</p><p><strong>Conclusions: </strong>The LLM-based model offers a non-surgical, accurate, and cost-effective method for early TPE diagnosis. The Python package provides a user-friendly tool for clinicians, with potential for broader use. Further validation in larger datasets is needed to optimize the model for clinical application.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"52"},"PeriodicalIF":5.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410889","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
YAP as a potential therapeutic target for myofibroblast formation in asthma.
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-12 DOI: 10.1186/s12931-025-03115-x
Yanrong Guo, Yuran Zhou, Rui Wang, Yujing Lin, Huimin Lan, Yang Li, De-Yun Wang, Jinrui Dong, Kefeng Li, Yan Yan, Yongkang Qiao
{"title":"YAP as a potential therapeutic target for myofibroblast formation in asthma.","authors":"Yanrong Guo, Yuran Zhou, Rui Wang, Yujing Lin, Huimin Lan, Yang Li, De-Yun Wang, Jinrui Dong, Kefeng Li, Yan Yan, Yongkang Qiao","doi":"10.1186/s12931-025-03115-x","DOIUrl":"10.1186/s12931-025-03115-x","url":null,"abstract":"<p><p>Myofibroblasts accumulation contributes to airway remodeling, with the mechanisms being poorly understood. It is steroid-insensitive and has not been therapeutically targeted in asthma. In this study, we explored the potential of yes-associated protein (YAP) as a therapeutic target for myofibroblasts formation in asthma, by revealing the novel role and mechanisms by which YAP activation in type II alveolar epithelial (ATII) cells promotes the fibroblast-to-myofibroblast transition in vitro and in vivo. By performing immunofluorescence staining, we showed that myofibroblasts were increased in the bronchial walls and alveolar parenchyma in clinical asthmatic and house dust mite (HDM)-induced mouse lung samples. This was accompanied by YAP overexpression and nuclear translocation in ATII cells, and connective tissue growth factor (CTGF) upregulation. In vitro, HDM or combination of rhIL-1β with rhTNF-α upregulated and activated YAP in human primary ATII cells and A549 cells, but not in the bronchial epithelial cells, BEAS-2B. This effect was mediated by F-actin polymerization and could be suppressed by pretreatment with latrunculin A but not budesonide. Inhibition of YAP/transcriptional coactivator with PDZ-binding motif (TAZ) in A549 cells by pretreatment with YAP/TAZ siRNA or verteporfin, but not budesonide, impaired the fibroblast-to-myofibroblast transition in vitro. In vivo, verteporfin partly or completely prevented HDM-induced bronchial or alveolar myofibroblast accumulation, and significantly suppressed CTGF expression and collagen deposition in mouse lungs, without profoundly affecting airway inflammation. Our results provide novel mechanistic insights into airway remodeling, and holds promise for the development of novel therapeutic strategies.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"51"},"PeriodicalIF":5.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410891","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
Neuropeptide S and its receptor aggravated asthma via TFEB dependent autophagy in bronchial epithelial cells.
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-10 DOI: 10.1186/s12931-025-03125-9
Zhixu Wang, Peng Zhao, Gen Yan, Aijuan Sun, Li Xu, Jiao Li, Xiaorun Zhai, Xiangcen Liu, Tingting Mei, Yinghua Xuan, Yunjuan Nie
{"title":"Neuropeptide S and its receptor aggravated asthma via TFEB dependent autophagy in bronchial epithelial cells.","authors":"Zhixu Wang, Peng Zhao, Gen Yan, Aijuan Sun, Li Xu, Jiao Li, Xiaorun Zhai, Xiangcen Liu, Tingting Mei, Yinghua Xuan, Yunjuan Nie","doi":"10.1186/s12931-025-03125-9","DOIUrl":"10.1186/s12931-025-03125-9","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a prevalent respiratory disorder with limited treatment strategy. Neuropeptide S (NPS) is a highly conserved peptide via binding to its receptor NPSR, a susceptibility gene for asthma from genomics studies. However, little is known about the role of NPS-NPSR in the pathogenesis of asthma. This study was performed to determine the effect and underlying mechanism of NPS-NPSR on asthma.</p><p><strong>Methods: </strong>NPSR knockdown was verified to affect asthma through autophagy by transcriptome sequencing and molecular biology experiments in animal models. Silencing of transcription factor EB in a bronchial epithelial cell line and validation of NPS-NPSR activation of autophagy dependent on transcription factor EB.</p><p><strong>Results: </strong>Our results showed that NPSR expression was markedly increased in asthmatic humans and mice, mainly localized in bronchial epithelial cells. Using ovalbumin (OVA) and papain-induced asthma mouse models, NPSR-deficient mice exhibited significantly alleviated asthma, with reduced small airway lesions and inflammatory infiltration compared with wild-type mice. OVA and papain promoted TFEB-mediated autophagy with increased ATG5 and LC3 II expression, and NPS effectively regulated the activation of TFEB and autophagy. In turn, specific TFEB knockdown could restore the effect of exogenous NPS and its receptor antagonist on the autophagy and cytokines secretion in bronchial epithelial cells. Furthermore, Prkcg may be the key upstream targeting of the TFEB-autophagy pathway involved in asthma.</p><p><strong>Conclusions: </strong>NPS-NPSR exacerbated asthma by regulating the TFEB-autophagy axis in airway epithelial injury, which may be a potential target for asthma therapy.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"50"},"PeriodicalIF":5.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392291","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
Association of e-cigarette and cigarette use with self-reported chronic obstructive pulmonary disease (COPD): a multivariable analysis of a large United States data set.
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-07 DOI: 10.1186/s12931-024-03087-4
Alicia J Burns, Alexander W Steinberg, James D Sargent, Jenny E Ozga, Zhiqun Tang, Cassandra A Stanton, Laura M Paulin
{"title":"Association of e-cigarette and cigarette use with self-reported chronic obstructive pulmonary disease (COPD): a multivariable analysis of a large United States data set.","authors":"Alicia J Burns, Alexander W Steinberg, James D Sargent, Jenny E Ozga, Zhiqun Tang, Cassandra A Stanton, Laura M Paulin","doi":"10.1186/s12931-024-03087-4","DOIUrl":"10.1186/s12931-024-03087-4","url":null,"abstract":"<p><strong>Background: </strong>Prior research has linked e-cigarette use with chronic obstructive pulmonary disease (COPD). We examined the relationship between e-cigarette use and COPD prevalence in older adults with varying cigarette use status.</p><p><strong>Methods: </strong>Data from the 2020 National Health Interview Survey were used to estimate the association between each of 9 exposure categories based on cigarette use (never, former, current) and e-cigarette use (never, former, current), with respondent-reported physician-diagnosed COPD prevalence in individuals 40 years and older (N = 22,997). Weighted multivariable analysis accounted for cigarette pack years, age of cigarette smoking onset, race, income-to-poverty ratio, rurality, gender, age, and medical comorbidities. Sensitivity of results was tested in 3 separate models with addition of years since quit cigarettes, smoking intensity and duration.</p><p><strong>Results: </strong>39.7% of individuals reported ever smoking cigarettes and 10.2% reported ever using e-cigarettes. Among individuals with ever e-cigarette use, 88.5% also reported current or former cigarette smoking. The weighted prevalence of COPD was 7.2%; Among those who reported former cigarette smoking, the highest risk of COPD prevalence compared to never cigarette/never e-cigarette use was in those currently using e-cigarettes (adjusted risk ratio (ARR) 2.82, 95% confidence interval (CI) [1.5, 5.3]). The ARR for former cigarette/current e-cigarette use was significantly larger than the ARR for former cigarette/never e-cigarette use (p < 0.002) in 3 out of 4 models; however, one model had the ARR attenuated to 1.35 (0.67, 2.76) when years since quitting smoking was added to the model. Other cigarette/e-cigarette combinations were also sensitive to how cigarette smoking history was modeled. For example, ARR for former cigarette/former e-cigarette (1.68 [1.00, 2.80] and current cigarette/former e-cigarette (2.50 [1.56,4.02]) were reduced to 1.05 (0.62, 1.77) and 1.04 (0.62, 1.75) respectively, when cigarette smoking duration was substituted for pack-years.</p><p><strong>Conclusions: </strong>Current e-cigarette use among former cigarette smokers was associated with significantly higher COPD prevalence compared to never e-cigarette use. However, COPD risk for most cigarette/e-cigarette combinations could be greatly attenuated by how cigarette smoking history was modeled, raising questions about the robustness of these associations in prior research and the possibility of reverse causality in prior cross-sectional research.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"49"},"PeriodicalIF":5.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371454","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
One-step diagnosis of infection and lung cancer using metagenomic sequencing. 利用元基因组测序对感染和肺癌进行一步诊断。
IF 5.8 2区 医学
Respiratory Research Pub Date : 2025-02-04 DOI: 10.1186/s12931-025-03127-7
Shaoqiang Li, Yangqing Zhan, Yan Wang, Weilong Li, Xidong Wang, Haoru Wang, Wenjun Sun, Xuefang Cao, Zhengtu Li, Feng Ye
{"title":"One-step diagnosis of infection and lung cancer using metagenomic sequencing.","authors":"Shaoqiang Li, Yangqing Zhan, Yan Wang, Weilong Li, Xidong Wang, Haoru Wang, Wenjun Sun, Xuefang Cao, Zhengtu Li, Feng Ye","doi":"10.1186/s12931-025-03127-7","DOIUrl":"10.1186/s12931-025-03127-7","url":null,"abstract":"<p><strong>Background: </strong>Traditional detection methods face challenges in meeting the diverse clinical needs for diagnosing both lung cancer and infections within a single test. Onco-mNGS has emerged as a promising solution capable of accurately identifying infectious pathogens and tumors simultaneously. However, critical evidence is still lacking regarding its diagnostic performance in distinguishing between pulmonary infections, tumors, and non-infectious, non-tumor conditions in real clinical settings.</p><p><strong>Methods: </strong>In this study, data were gathered from 223 participants presenting symptoms of lung infection or tumor who underwent Onco-mNGS testing. Patients were categorized into four groups based on clinical diagnoses: infection, tumor, tumor with infection, and non-infection-non-tumor. Comparisons were made across different groups, subtypes, and stages of lung cancer regarding copy number variation (CNV) patterns, microbiome compositions, and clinical detection indices.</p><p><strong>Results: </strong>Compared to conventional infection testing methods, Onco-mNGS demonstrates superior infection detection performance, boasting a sensitivity of 81.82%, specificity of 72.55%, and an overall accuracy of 77.58%. In lung cancer diagnosis, Onco-mNGS showcases excellent diagnostic capabilities with sensitivity, specificity, accuracy, positive predictive value, and negative predictive value reaching 88.46%, 100%, 91.41%, 100%, and 90.98%, respectively. In bronchoalveolar lavage fluid (BALF) samples, these values stand at 87.5%, 100%, 94.74%, 100%, and 91.67%, respectively. Notably, more abundant CNV mutation types and higher mutation rates were observed in adenocarcinoma (ADC) compared to squamous cell carcinoma (SCC). Concurrently, onco-mNGS data revealed specific enrichment of Capnocytophaga sputigeria in the ADC group and Candida parapsilosis in the SCC group. These species exhibited significant correlations with C reaction protein (CRP) and CA153 values. Furthermore, Haemophilus influenzae was enriched in the early-stage SCC group and significantly associated with CRP values.</p><p><strong>Conclusions: </strong>Onco-mNGS has exhibited exceptional efficiencies in the detection and differentiation of infection and lung cancer. This study provides a novel technological option for achieving single-step precise and swift detection of lung cancer.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"48"},"PeriodicalIF":5.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191089","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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