Respiratory Research最新文献

{"title":"Initial self-reported data on sleep and burnout in pulmonary, critical care and sleep medicine: an initiative from the Assembly on Sleep and Respiratory Neurobiology of the American Thoracic Society.","authors":"Sushmita Pamidi, Reena Mehra, Indira Gurubhagavatula, Mihaela Teodorescu","doi":"10.1186/s12931-025-03112-0","DOIUrl":"10.1186/s12931-025-03112-0","url":null,"abstract":"<p><strong>Rationale: </strong>Health worker burnout has reached crisis proportions, threatening workforce sustainability. Limited data exist on the burden of burnout in pulmonary, critical care and sleep medicine (PCCSM), a high-demand and strained specialty.</p><p><strong>Objective: </strong>At the Assembly of Sleep and Respiratory Neurobiology of the American Thoracic Society, we aimed to gather exploratory data on burnout in this group.</p><p><strong>Methods: </strong>During a dedicated series of five virtual town halls (THs), we polled the audience regarding self-reported burnout. Topics included the scope of the problem, role of sleep, impact on clinical and academic operations, contributors in vulnerable groups, and mitigation strategies.</p><p><strong>Results: </strong>A high proportion experienced burnout (45%) and 58% considered premature retirement. Insufficient sleep (53%) was common, most often due to excessive workload (57%) curtailing sleep through early morning meetings and electronic medical record (EMR) documentation. 36% also reported having a sleep disorder. Sleepiness (69%) and fatigue (58%) impaired work performance and patient care, and 54% reported a fatigue-related, personal-safety incident. Contributors to burnout in vulnerable communities included bias/discrimination (81%), harassment (44%) and assault (12%). Respondents predominantly endorsed organizational mitigating strategies: promoting a culture of \"recovery time\" (96%) and healthy sleep (86%), and periodic evaluation and accountability of leadership (86%).</p><p><strong>Conclusions: </strong>In this convenience sample of participants in a TH series regarding burnout in PCCSM, self-reported burnout was common. Sleep disturbance is a prevalent, under-recognized, but potentially modifiable contributor. The high reported rates of discrimination and harassment suggest that vulnerable groups may be at particular risk. To reduce burnout, system-level interventions aimed at transforming organizational culture and promoting leadership accountability were strongly endorsed.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"100"},"PeriodicalIF":5.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634696","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":"YAP/TAZ-mediated nuclear membrane rupture in promoting senescence of skeletal muscle associated with COPD.","authors":"Ge Gong, Shuping Shen, Shaoran Shen, Ran Wang, Tianping Zheng, Wei Xu, Jianqing Wu","doi":"10.1186/s12931-025-03170-4","DOIUrl":"10.1186/s12931-025-03170-4","url":null,"abstract":"<p><p>Patients with chronic obstructive pulmonary disease (COPD) often develop complications associated with sarcopenia; however, the underlying mechanisms remain unclear. Through a combination of in vitro and in vivo experiments, as well as bioinformatics analysis, our study identified YAP/TAZ as a key regulator of the aging phenotype in the skeletal muscle of COPD patients. In skeletal muscle affected by cigarette smoke-induced COPD, we observed significant reductions in YAP/TAZ levels, alongside markers indicative of skeletal muscle aging and dysfunction. Notably, overexpression of YAP/TAZ significantly improved these conditions. Our results suggest a novel mechanism whereby the maintenance of YAP/TAZ activity interacts with ACTR2 to preserve nuclear membrane integrity and reduce cytoplasmic dsDNA levels, thereby attenuating STING activation and cellular senescence. Additionally, we found that YAP is involved in the transcriptional regulation of the ACTR2 promoter region. Overall, preserving YAP/TAZ activity may help prevent skeletal muscle aging associated with COPD, representing a new strategy for intervening in COPD-related sarcopenia.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"98"},"PeriodicalIF":5.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617689","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":"The role of lactate metabolism and lactylation in pulmonary arterial hypertension.","authors":"Tong-Yu Peng, Jun-Mi Lu, Xia-Lei Zheng, Cheng Zeng, Yu-Hu He","doi":"10.1186/s12931-025-03163-3","DOIUrl":"10.1186/s12931-025-03163-3","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a complex and progressive disease characterized by elevated pulmonary artery pressure and vascular remodeling. Recent studies have underscored the pivotal role of metabolic dysregulation and epigenetic modifications in the pathogenesis of PAH. Lactate, a byproduct of glycolysis, is now recognized as a key molecule that links cellular metabolism with activity regulation. Recent findings indicate that, in addition to altered glycolytic activity and dysregulated. Lactate homeostasis and lactylation-a novel epigenetic modification-also play a significant role in the development of PAH. This review synthesizes current knowledge regarding the relationship between altered glycolytic activity and PAH, with a particular focus on the cumulative effects of lactate in pulmonary vascular cells. Furthermore, lactylation, an emerging epigenetic modification, is discussed in the context of PAH. By elucidating the complex interplay between lactate metabolism and lactylation in PAH, this review aims to provide insights into potential therapeutic targets. Understanding these metabolic pathways may lead to innovative strategies for managing PAH and improving patient outcomes. Future research should focus on the underlying mechanisms through which lactylation influences the pathophysiology of PAH, thereby aiding in the development of targeted interventions.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"99"},"PeriodicalIF":5.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617614","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":"High level of initial Aspergillus fumigatus-specific IgE links increased risk of exacerbation in allergic bronchopulmonary aspergillosis patients.","authors":"Hao Qian, Jia-Yan Xu, Rui Fan, Jing Shi, Hai-Wen Lu, Ling Ye, Jia-Wei Yang, Rui Jiang, Li-Sha Zhang, Yi-Fan Wu, Mei-Ling Jin, Jin-Fu Xu","doi":"10.1186/s12931-025-03171-3","DOIUrl":"10.1186/s12931-025-03171-3","url":null,"abstract":"<p><strong>Background: </strong>Elevated Aspergillus fumigatus (A. fumigatus)-specific Immunoglobulin E (IgE) is recognized as an essential diagnostic criterion for allergic bronchopulmonary aspergillosis (ABPA). However, it remains unknown whether initial A. fumigatus-specific IgE at acute stage has a role beyond diagnostic purposes.</p><p><strong>Method: </strong>This two-center retrospective study enrolled 149 acute ABPA patients. Risk factors for one-year exacerbation were analyzed using univariate and multivariate logistic regression. Participants were then divided into a discovery cohort (n = 93) to determine the optimal initial A. fumigatus-specific IgE cut-off value via receiver operating characteristic (ROC) curve, and a validation cohort (n = 56) to confirm exacerbation differences based on this cut-off value.</p><p><strong>Result: </strong>Multivariate logistic regression analysis revealed that female sex (odds ratio (OR) 2.44, 95% confidence interval (CI) 1.15-5.16, P = 0.020), A. fumigatus-specific IgE (OR 1.05, 95% CI 1.02-1.08, P = 0.002), and bronchiectasis (OR 3.61, 95% CI 1.07-12.21, P = 0.039) were independent risk factors for ABPA exacerbation. In the discovery cohort, the optimal initial cut-off value for A. fumigatus-specific IgE was calculated to be 9.88 kUA/L. And, the validation cohort confirmed that patients with A. fumigatus-specific IgE > 9.88 kUA/L were at higher risk of exacerbation (P = 0.005).</p><p><strong>Conclusion: </strong>This study highlighted the prognostic utility of initial A. fumigatus-specific IgE at acute stage and found that elevated levels, especially those exceeding 9.88 kUA/L, were associated with increased risks of exacerbation in ABPA patients.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"95"},"PeriodicalIF":5.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598121","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":"Epidemiology of idiopathic pulmonary fibrosis in central and Western Pennsylvania.","authors":"Faina Linkov, Yue-Fang Chang, Harshitha Ramanan, Richard S Morgan, Kathleen M McTigue, Anne E F Dimmock, Rebecca Bascom, Daniel J Kass","doi":"10.1186/s12931-025-03164-2","DOIUrl":"10.1186/s12931-025-03164-2","url":null,"abstract":"<p><strong>Background/rationale: </strong>Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive disease of unknown origin. Establishing the epidemiology of IPF has been challenging due to diagnostic complexity, poor survival, low prevalence, and heterogeneity of ascertainment methodologies.</p><p><strong>Objectives: </strong>This research aimed to estimate the rates of IPF in central and western Pennsylvania and to pilot the use of capture recapture (CR) methods to estimate the disease incidence.</p><p><strong>Methods: </strong>We identified adults ≥ 30 years old diagnosed with IPF (by ICD-9/10 coding) between 2013 to 2021 from two health systems (UPMC Health System and Penn State Health) participating in the PaTH Clinical Research Network. We extracted information on patients' sex, race, date of birth and 3-digit zip code from electronic health records (EHR). Incidence rate of IPF among Pennsylvania residents was calculated using three case definitions (broad and two restricted) and piloted the use of CR in estimating IPF incidence.</p><p><strong>Results: </strong>IPF incidence rates were 8.42, 6.95 and 4.4 per 100,000 person-years for the unrestricted (n = 3148), partially restricted (n = 2598) and fully restricted (n = 1661) samples, respectively. Low case overlap between two sites resulted in a highly inflated estimate of IPF incidence, using the CR methodology.</p><p><strong>Conclusions: </strong>The rate of IPF in central and western Pennsylvania was similar to previously published statistics. The application of CR to IPF epidemiology could be further investigated in health systems with greater overlap of patients utilizing more than one system.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"97"},"PeriodicalIF":5.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598119","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":"Modulation of the Epithelial-mesenchymal transition process by Forkhead Box C2 in the repair of airway epithelium after injury.","authors":"Yudong Wang, Jun Liu","doi":"10.1186/s12931-025-03150-8","DOIUrl":"10.1186/s12931-025-03150-8","url":null,"abstract":"<p><strong>Background: </strong>Epithelial-mesenchymal transition (EMT) is regarded as a key process in repair of airway epithelium after injury. Forkhead Box C2 (FOXC2) is a transcription factor involved in EMT process, whether it is involved in repair of bronchial epithelium remains unknown.</p><p><strong>Methods: </strong>C57BL/6 mice were subjected to intraperitoneal injection with naphthalene (NAPH; 200 mg/kg) to induce airway injury model. qPCR, immunoblot and FOXC2 immunohistochemistry assays were conducted to detect the expression of FOXC2 in bronchial epithelium. To explore the function of FOXC2 in NAPH-induced airway injury, the mice were given intratracheal administration of shFOXC2- or shNC-lentivirus particles, followed by NAPH treatment. Hematoxylin-and-eosin staining was used to assess the histopathology of the bronchial epithelium. Immunofluorescence analysis of CCSP, a club cell marker confirmed the CCSP expression in bronchial epithelium. Immunoblot and immunofluorescence assays determined the expression of E-cadherin, vimentin, and N-cadherin. In mouse primary bronchial epithelial cells (PBECs), we overexpressed and silenced FOXC2 by lentivirus particles, respectively. Cell migration was analyzed using wound healing assay. Immunoblot assays determined the E-cadherin, vimentin, FN-EDA expression in TGF-β1-induced PBECs. mRNA sequencing (mRNA-seq) and FOXC2 ChIP sequencing (ChIP-seq) to reveal the downstream genes of FOXC2 in TGF-β1-induced PBECs. Luciferase assay, ChIP-PCR and functional rescue experiments were performed to confirm the interaction of FOXC2/formin binding protein 1 (FNBP1) in TGF-β1-induced PBECs.</p><p><strong>Results: </strong>FOXC2 expression was up-regulated in the lung tissues of mice at 2, 3 and 6 days post-NAPH. FOXC2 knockdown in bronchial epithelium of mice delayed CCSP⁺ club cell regeneration and normal repair of the airway epithelium within 14 days after injury. Knockdown of FOXC2 increased E-cadherin but decreased vimentin and N-cadherin, EMT markers during early phase after injury. In vitro, knockdown of endogenous FOXC2 repressed the migration of cells and increased TGF-β1-induced E-cadherin but decreased vimentin, N-cadherin and FN-EDA. Exogenous FOXC2 addition exerted opposite effects. Furthermore, mRNA-seq and FOXC2 ChIP-seq revealed that FNBP1 might be a downstream target of FOXC2. Overexpression of FNBP1 reversed the inhibitory role of FOXC2 knockdown in EMT.</p><p><strong>Conclusions: </strong>These data highlight the important function of FOXC2 as a regulator in repair of bronchial epithelium after injury.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"96"},"PeriodicalIF":5.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598122","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":"Prediction of tumor spread through air spaces with an automatic segmentation deep learning model in peripheral stage I lung adenocarcinoma.","authors":"Cong Liu, Yu-Feng Wang, Ping Gong, Xiu-Qing Xue, Hong-Ying Zhao, Hui Qian, Chao Jia, Xiao-Feng Li","doi":"10.1186/s12931-025-03174-0","DOIUrl":"10.1186/s12931-025-03174-0","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the clinical applicability of deep learning (DL) models based on automatic segmentation in preoperatively predicting tumor spread through air spaces (STAS) in peripheral stage I lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>This retrospective study analyzed data from patients who underwent surgical treatment for lung tumors from January 2022 to December 2023. An external validation set was introduced to assess the model's generalizability. The study utilized conventional radiomic features and DL models for comparison. ROI segmentation was performed using the VNet architecture, and DL models were developed with transfer learning and optimization techniques. We assessed the diagnostic accuracy of our models via calibration curves, decision curve analysis, and ROC curves.</p><p><strong>Results: </strong>The DL model based on automatic segmentation achieved an AUC of 0.880 (95% CI 0.780-0.979), outperforming the conventional radiomics model with an AUC of 0.833 (95% CI 0.707-0.960). The DL model demonstrated superior performance in both internal validation and external testing cohorts. Calibration curves, decision curve analysis, and ROC curves confirmed the enhanced diagnostic accuracy and clinical utility of the DL approach.</p><p><strong>Conclusion: </strong>The DL model based on automatic segmentation technology shows significant promise in preoperatively predicting STAS in peripheral stage I LUAD, surpassing traditional radiomics models in diagnostic accuracy and clinical applicability. Clinical trial number The clinical trial was registered on April 22, 2024, with the registration number researchregistry10213 ( www.researchregistry.com ).</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"94"},"PeriodicalIF":5.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587669","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":"Protease-activated receptor-2 (PAR2) mutation attenuates airway fibrosis in mice during the exacerbation of house dust mite‑induced allergic lung disease by multi‑walled carbon nanotubes.","authors":"Logan J Tisch, Ryan D Bartone, Silvio Antoniak, James C Bonner","doi":"10.1186/s12931-025-03168-y","DOIUrl":"10.1186/s12931-025-03168-y","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) induces potent pro-inflammatory and pro-fibrotic responses in mouse models of allergic lung disease. We recently reported that MWCNTs exacerbated components of house dust mite (HDM)-induced allergic lung disease, including eosinophilic inflammation, mucous cell metaplasia and airway fibrosis. Protease-activated receptor 2 (PAR2) plays a significant role in the development of various respiratory diseases, including asthma and pulmonary fibrosis. However, studies investigating the function of PAR2 in allergic lung disease have produced variable results. To further define the role of PAR2 in pulmonary pathology, we investigated the effects of MWCNTs on HDM-induced allergic lung disease in PAR2-mutant mice.</p><p><strong>Methods: </strong>The PAR2-mutant mice used were previously generated by replacing a 1.8-kb region of the PAR2 coding sequence with a neomycin resistance gene, which did not entirely delete the gene. Wild-type (WT) male C57BL/6J mice and PAR2-mutant male mice were exposed to a vehicle solution, MWCNTs, HDM extract, or both via oropharyngeal aspiration six times over 3 weeks. Bronchoalveolar lavage fluid (BALF) was collected to measure changes in inflammatory cells, total protein, and lactate dehydrogenase (LDH). Lung protein and mRNA were assayed for pro-inflammatory and profibrotic mediators, and formalin-fixed lung sections were evaluated for histopathology.</p><p><strong>Results: </strong>In WT and PAR2-mutant mice, co-exposure to MWCNTs and HDM extract significantly increased eosinophilic lung inflammation, mucous cell metaplasia, increased BALF cellularity, BALF total protein, and LDH levels. These results were not significantly different between genotypes. Additionally, MWCNTs and HDM extract co-exposure significantly increased airway fibrosis in WT and PAR2-mutant mice, characterized by increased airway collagen deposition and Col1a1 mRNA expression. Quantitative morphometry revealed a significant decrease in airway fibrosis in PAR2-mutant mice compared to WT mice, accompanied by reduced Col1a1 mRNA as detected by PCR. Despite this reduction, the pro-fibrotic mediator arginase 1 (Arg-1) protein and mRNA levels were significantly upregulated in PAR2-mutant mice.</p><p><strong>Conclusion: </strong>Our study demonstrates that PAR2 mediates airway fibrosis but does not influence eosinophilic lung inflammation or mucous cell metaplasia caused by co-exposure to MWCNTs and HDM allergen.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"90"},"PeriodicalIF":5.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587736","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":"Correction to: Association of tobacco product use with chronic obstructive pulmonary disease (COPD) prevalence and incidence in waves 1 through 5 (2013-2019) of the population assessment of tobacco and health (PATH) study.","authors":"Laura M Paulin, Michael J Halenar, Kathryn C Edwards, Kristin Lauten, Cassandra A Stanton, Kristie Taylor, Dorothy Hatsukami, Andrew Hyland, Todd MacKenzie, Martin C Mahoney, Ray Niaura, Dennis Trinidad, Carlos Blanco, Wilson M Compton, Lisa D Gardner, Heather L Kimmel, Dana Lauterstein, Daniela Marshall, James D Sargent","doi":"10.1186/s12931-025-03166-0","DOIUrl":"10.1186/s12931-025-03166-0","url":null,"abstract":"","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"93"},"PeriodicalIF":5.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587619","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":"CPHNet: a novel pipeline for anti-HAPE drug screening via deep learning-based Cell Painting scoring.","authors":"De-Zhi Sun, Xi-Ru Yang, Cong-Shu Huang, Zhi-Jie Bai, Pan Shen, Zhe-Xin Ni, Chao-Ji Huang-Fu, Yang-Yi Hu, Ning-Ning Wang, Xiang-Lin Tang, Yong-Fang Li, Yue Gao, Wei Zhou","doi":"10.1186/s12931-025-03173-1","DOIUrl":"10.1186/s12931-025-03173-1","url":null,"abstract":"<p><strong>Background: </strong>High altitude pulmonary edema (HAPE) poses a significant medical challenge to individuals ascending rapidly to high altitudes. Hypoxia-induced cellular morphological changes in the alveolar-capillary barrier such as mitochondrial structural alterations and cytoskeletal reorganization, play a crucial role in the pathogenesis of HAPE. These morphological changes are critical in understanding the cellular response to hypoxia and represent potential therapeutic targets. However, there is still a lack of effective and valid drug discovery strategies for anti-HAPE treatments based on these cellular morphological features. This study aims to develop a pipeline that focuses on morphological alterations in Cell Painting images to identify potential therapeutic agents for HAPE interventions.</p><p><strong>Methods: </strong>We generated over 100,000 full-field Cell Painting images of human alveolar adenocarcinoma basal epithelial cells (A549s) and human pulmonary microvascular endothelial cells (HPMECs) under different hypoxic conditions (1%~5% of oxygen content). These images were then submitted to our newly developed segmentation network (SegNet), which exhibited superior performance than traditional methods, to proceed to subcellular structure detection and segmentation. Subsequently, we created a hypoxia scoring network (HypoNet) using over 200,000 images of subcellular structures from A549s and HPMECs, demonstrating outstanding capacity in identifying cellular hypoxia status.</p><p><strong>Results: </strong>We proposed a deep neural network-based drug screening pipeline (CPHNet), which facilitated the identification of two promising natural products, ferulic acid (FA) and resveratrol (RES). Both compounds demonstrated satisfactory anti-HAPE effects in a 3D-alveolus chip model (ex vivo) and a mouse model (in vivo).</p><p><strong>Conclusion: </strong>This work provides a brand-new and effective pipeline for screening anti-HAPE agents by integrating artificial intelligence (AI) tools and Cell Painting, offering a novel perspective for AI-driven phenotypic drug discovery.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"91"},"PeriodicalIF":5.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587622","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}