American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"Too much of a good thing: therapeutic targeting of type I interferon in superinfection.","authors":"Flavia Rago, John F Alcorn","doi":"10.1093/ajrcmb/aanag086","DOIUrl":"10.1093/ajrcmb/aanag086","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1329-1331"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832612","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":"When ZIP code matters: myeloid-specific role of TLR2 signaling in neonatal influenza.","authors":"Miša Gunjak, Ivana Mižik","doi":"10.1093/ajrcmb/aanag085","DOIUrl":"10.1093/ajrcmb/aanag085","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1327-1328"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832587","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":"Peripheral blood monocyte clusters predict radiographic severity and progression in fibrotic hypersensitivity pneumonitis.","authors":"Sonia M Leach, Brian Vestal, Beth Canono, Evans R Fernández Pérez","doi":"10.1093/ajrcmb/aanag147","DOIUrl":"10.1093/ajrcmb/aanag147","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1467-1470"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817282","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":"Piezo1 mediates stretch-induced Wnt/β-catenin signaling and extracellular matrix remodeling in aging asthmatic airway smooth muscle.","authors":"Niyati A Borkar, Daniel A Pfeffer-Kleemann, Samantha K Hamrick, Maunick L Koloko Ngassie, Michael A Thompson, Christina M Pabelick, Y S Prakash","doi":"10.1093/ajrcmb/aanag058","DOIUrl":"10.1093/ajrcmb/aanag058","url":null,"abstract":"<p><p>Asthma in the elderly (AIE) represents a unique challenge, necessitating a better understanding of the mechanisms that drive airway hyperreactivity and remodeling (thickened, fibrotic airways). Normal aging is associated with increased lung stiffness, and thus the influence of mechanical forces on bronchial airways (breathing, sighs, CPAP) likely changes, potentially increasing with AIE and resultant remodeling, overall highlighting the need to understand the importance of mechanobiology in aging and AIE. Here, mechanosensitive Piezo (Pz) channels are highly expressed in the lung, including within airway epithelium and smooth muscle (ASM), but their specific roles, particularly with aging, remain largely unexplored. In this study, we used human ASM cells from young vs old (≥65 y) non-asthmatics vs asthmatics to test the hypothesis that normal aging blunts Pz expression and functionality at baseline as well as in response to mechanical stretch, whereas asthma, particularly, AIE ASM leads to enhanced Pz expression promoting fibrosis and remodeling. Both Pz1 and Pz2 were expressed in ASM and increased in AIE. Oscillatory mechanical stretch mimicking breathing with superimposed static stretch increased Pz, especially in AIE: effects exacerbated by Pz activator Yoda1 and blunted by Pz inhibitor GsMTx4. Stretch or Yoda1 increased Wnt3a, β-catenin, and GSK3β activation, particularly in AIE, while ASM proliferation and extracellular matrix production remained preserved or even heightened in elderly ASM. Conversely, Pz1 inhibition by GsMTx4 potently reduced extracellular matrix (ECM) deposition, particularly in AIE cells, highlighting Pz1's pivotal role in modulating ECM deposition. Overall, our findings indicate Pz1 as a mechanosensitive regulator of airway remodeling in AIE.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1376-1388"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832493","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":"Refueling T cell memory in cystic fibrosis.","authors":"Michael Shlossman, Daniel P Cook","doi":"10.1093/ajrcmb/aanag060","DOIUrl":"10.1093/ajrcmb/aanag060","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1325-1326"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873126","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":"Withdrawn as duplicate: Pulmonary Blood Volumes on CT Predict Residual Pulmonary Hypertension Post-Pulmonary Endarterectomy.","authors":"Hakim Ghani, Muhunthan Thillai, David Jenkins, Elliott Bussell, Alessandro Ruggiero, Simon Walsh, Nicholas Screaton, Katherine Bunclark, John Cannon, Karen Sheares, Dolores Taboada, Martin Graves, Mark Toshner, Choo Ng, Joanna Pepke-Zaba","doi":"10.1093/ajrcmb/aanaf026","DOIUrl":"10.1093/ajrcmb/aanaf026","url":null,"abstract":"<p><p>Pulmonary blood volumes (PBV), currently not assessed by computed tomography pulmonary angiography (CTPA), could provide additional information to routine investigations performed for chronic thromboembolic pulmonary hypertension (CTEPH). We investigated CTPA-based PBV in evaluating hemodynamic outcome from pulmonary endarterectomy (PEA) surgery. A deep learning-based CTPA vascular segmentation model, differentiating arteries and veins, was applied for automated PBV measurements in CTEPH patients who underwent PEA at U.K.'s national CTEPH service. Pulmonary arteries were compartmentalised into \"central\" (main pulmonary and proximal lobar) and \"intrapulmonary\". Mean pulmonary arterial pressure >30 mmHg post-PEA defined \"clinically relevant\" residual PH. Logistic regression models applying CTPA-based PBV to identify residual PH were trained and tested on the discovery and validation cohorts respectively. Paired pre- and postoperative CTPA, in the discovery (n = 71) and validation (n = 102) cohorts showed that central pulmonary artery volume and total artery to vein volume ratio (A-VR) decreased and pulmonary vein volume increased with hemodynamic improvement post-PEA. Preoperative central pulmonary artery volume and A-VR helped identify patients at risk for clinically relevant residual PH post-PEA (AUROC 0.88 and 0.82 in the discovery and validation cohorts). Postoperative central pulmonary artery volume, A-VR and pulmonary vein volume helped to non-invasively identify patients without clinically relevant residual PH (AUROC 0.91 and 0.88 in the discovery and validation cohorts). Automated quantification of CTPA-based PBV at diagnosis can help stratify risk for residual PH in patients managed with PEA. Utilizing CTPA-derived PBV post-PEA to identify patients without residual PH can potentially reduce the need for routine postoperative right heart catheterization.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"e1-e39"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832426","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":"Furin inhibition protects against acute lung injury in a mouse model of Pseudomonas aeruginosa infection.","authors":"Olivier Bernard, Michael Kwon, Mark R Looney, Mélia Magnen, Michelle A Yu","doi":"10.1093/ajrcmb/aanag024","DOIUrl":"10.1093/ajrcmb/aanag024","url":null,"abstract":"<p><p>Pseudomonas aeruginosa (PA) is responsible for significant morbidity and mortality, particularly in patients with chronic lung diseases such as chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, as well as hospital-acquired pneumonia and ventilator-associated pneumonia. The rise of antibiotic-resistant PA strains necessitates alternative treatment strategies. Among the different toxins secreted by PA, Exotoxin-A (Exo-A) becomes cytotoxic when cleaved by furin. This study investigates the therapeutic potential of furin inhibitor BOS-318 in mitigating acute lung injury induced by Exo-A and PA infection. Furin inhibition significantly improved survival rates and reduced lung injury in mouse pneumonia models using Exo-A and PA103. Additionally, BOS-318 accelerated bacterial clearance in vivo, and increased phagocytosis by alveolar macrophages. Bulk RNA-sequencing done on whole lung homogenate at 6 hours revealed an immune profile with decreased natural killer cell signaling in the BOS-318-treated group, possibly because of a decrease in natural killer recruitment observed at 24 hours, suggesting a role of furin in shaping the immune response. Moreover, administration of BOS-318 as a therapeutic strategy results in a protection of the lung epithelium. Overall, our findings demonstrate that furin inhibition protects against PA-induced acute lung injury and hastens bacterial clearance. These results are the first to characterize furin inhibition in animal models and supports its potential use as an adjunctive therapeutic strategy for treating PA infections.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1364-1375"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281767","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":"Viral replication and interferon responses in bronchial epithelia is enhanced by Th17 cells.","authors":"Weston T Powell, Tomasz J Janczyk, Patricia C Dela Cruz, Basilin Benson, Nyssa B Samanas, Elizabeth R Vanderwall, Camille R Gates, Lucille M Rich, Teal S Hallstrand, Matthew C Altman, Jason S Debley","doi":"10.1093/ajrcmb/aanag070","DOIUrl":"10.1093/ajrcmb/aanag070","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"1463-1466"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832598","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":"Role of carbonic anhydrases 9 and 12 in hypoxia and non-hypoxia associated pulmonary hypertension.","authors":"Aleksandar Petrovic, Oleg Pak, Jan Niklas Schneider, Jan Ewert, Franz Loeffler, Daniel Gerd Bermes, Astrid Weiss, Christina Pilz, Stefan Hadzic, Marija Gredic, Cheng-Yu Wu, Simon Platzek, Argen Mamazhakypov, Akylbek Sydykov, Khodr Tello, Natascha Sommer, Akpay Sarybaev, Sergey Avdeev, Clemens Ruppert, Andreas Günther, Norbert Weissmann, Hossein Ardeschir Ghofrani, Djuro Kosanovic, Ralph Theo Schermuly","doi":"10.1093/ajrcmb/aanag182","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag182","url":null,"abstract":"<p><strong>Rationale: </strong>Pulmonary hypertension (PH) is characterized by several cancer-like attributes, such as dysregulated proliferation and migration of pulmonary vascular cells. Carbonic anhydrases (CA)9 and 12 are elevated in various types of tumor tissues and play a major role in the pH regulation system of cancer cells. CA9 and 12 engagement in the pathology of PH remains unclear.</p><p><strong>Methods: </strong>Lung tissue samples from PH patients were analyzed for CA9 and 12 expression profiles. Circulating CA9 levels were measured in the plasma of PH patients and Kyrgyz highlanders. In vitro expression and functional studies were conducted in pulmonary arterial smooth muscle cells (PASMCs). Finally, two in vivo studies were carried out to investigate the therapeutic potential of the specific CA9 and 12 inhibitor S4.</p><p><strong>Results: </strong>The mRNA and protein expression of CA9 and 12 were upregulated in lungs of PH patients and during hypoxic and non-hypoxic stimulation of PASMCs. Circulating CA9 levels were elevated in both PH patients and Kyrgyz highlanders with PH. Furthermore, CA9 and 12 played an important role in the proliferation and migration of PASMCs. Our study demonstrated that CA9 and 12 are crucial for maintaining pH homeostasis in PASMCs and, subsequently, for the activation of protein kinases. Finally, pharmacological inhibition of CA9 and 12 ameliorated the development of monocrotaline-induced PH in rats and chronic hypoxia-induced PH in mice.</p><p><strong>Conclusions: </strong>Our study provides evidence that CA9 and 12 are engaged in the pathogenesis of hypoxia and non-hypoxia associated PH and may represent novel therapeutic targets in future.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079421","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":"Combination of Blastocyst Complementation and Omics Allows Fast Evaluation of Human Pathogenic Mutations in Mice.","authors":"Bingqiang Wen, Enhong Li, Dengfeng Gao, Jonathan Do, Guolun Wang, Tobias Jakobi, Tanya V Kalin, Vladimir V Kalinichenko","doi":"10.1093/ajrcmb/aanag195","DOIUrl":"https://doi.org/10.1093/ajrcmb/aanag195","url":null,"abstract":"<p><strong>Rationale: </strong>Development of in vivo animal models carrying patient-derived pathogenic gene variants is critical for dissecting molecular mechanisms critical for human lung diseases. However, generation of new murine lines is costly and time-consuming, often requiring years before mechanistic studies can begin.</p><p><strong>Objective: </strong>To establish a rapid experimental platform using a combination of blastocyst complementation and single-cell RNA sequencing (scRNA-seq) to evaluate the effects of conserved human pathogenic variants on lung development.</p><p><strong>Methods: </strong>Heterozygous S52F variant of FOXF1, identified in patients with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV), was introduced into mouse embryonic stem cells (ESCs). Differentially labeled mutant and wild type (WT) ESCs were injected into blastocysts to generate mouse chimeric embryos. Differentiation of FOXF1+/S52F and WT ESC-derived pulmonary cells was compared using immunostaining, flow cytometry and scRNA-seq. Integration of scRNA-seq datasets from mouse chimera and human ACDMPV lungs was performed to identify conserved molecular mechanisms.</p><p><strong>Measurements and main results: </strong>FOXF1+/S52F ESCs exhibited the loss of main subtypes among endothelial and mesenchymal cells during lung development. Transcriptomic profiling revealed dysregulated lineage-specific gene expression signatures similar to those observed in human ACDMPV lungs. Cross-species scRNA-seq comparisons uncovered conserved pathways, receptor-ligand interactions and novel downstream FOXF1 target genes, including Igf2, Icam2, Tiam1, Ets1, Lamb1 and Igfbp3.</p><p><strong>Conclusions: </strong>Blastocyst complementation combined with cross-species scRNA-seq provides a rapid and efficient approach to identify conserved molecular mechanisms disrupted by human pathogenic variants. Chimeric mouse embryos can serve as a powerful platform for uncovering new molecular mechanisms critical for lung development.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102962","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}