{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T14:59:18Z","timestamp":1773413958571,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013076","name":"National Major Science and Technology Projects of China","doi-asserted-by":"publisher","award":["2023ZD0506205"],"award-info":[{"award-number":["2023ZD0506205"]}],"id":[{"id":"10.13039\/501100013076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300047"],"award-info":[{"award-number":["82300047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M750527"],"award-info":[{"award-number":["2024M750527"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>With the widespread use of antiretroviral therapy (ART), life expectancy among people living with human immunodeficiency virus (HIV) infection has significantly increased. However, studies on HIV\u2010associated emphysema, especially those addressing the mechanisms, remain limited. In this study, we analysed transcriptomic data from Gene Expression Omnibus (GEO) to investigate the underlying mechanisms and identify biomarkers of HIV\u2010associated emphysema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The gene expression profiling data of HIV infection (GSE76246, peripheral blood samples), emphysema (GSE11906, airway tissue samples) and HIV\u2010associated emphysema (GSE76403, peripheral blood samples) were obtained. We performed differential expression gene (DEG) analysis, functional enrichment analysis, weighted gene co\u2010expression network analysis (WGCNA), protein\u2010protein interaction (PPI) network analysis and random forest modelling to explore the mechanisms and candidate biomarkers of HIV\u2010associated emphysema. The expression of candidate biomarkers was subsequently validated in the comorbidity dataset, and immune cell infiltration was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified genes shared between HIV infection and emphysema and trait\u2010relevant modules. Functional enrichment analysis suggested that persistent immune activation, altered RNA metabolism, protein translation, enhanced oxidative stress responses and potential adverse effects of ART via P450 might contribute to HIV\u2010associated emphysema. PPI network analysis and random forest modelling identified Glutathione\u2010disulphide reductase (GSR) and Carbonyl reductase 1 (CBR1) as candidate biomarkers, which were preliminarily supported by findings from the comorbidity dataset. Immune cell infiltration analyses indicated increased proportions of memory B cells, activated dendritic cells, CD8+ T cells, gamma delta T cells and Tregs, along with decreased levels of resting mast cells and naive CD4+ T cells in HIV\u2010associated emphysema.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study suggests possible mechanisms and candidate biomarkers (GSR and CBR1) for HIV\u2010associated emphysema and also provides exploratory insights into potential immune dysregulation in affected patients. However, due to the heterogeneity of tissue sources, limited sample size and the fact that the mechanistic insights were inferred from bioinformatics analyses rather than experimental validation, the cross\u2010tissue relevance of shared genes remains speculative and the immune infiltration findings based on peripheral blood transcriptomes may not fully reflect lung immune composition. Therefore, these findings should be interpreted with caution.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hiv.70153","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T14:05:26Z","timestamp":1764338726000},"page":"373-385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of\n                    <scp>GSR<\/scp>\n                    and\n                    <scp>CBR1<\/scp>\n                    as biomarkers in\n                    <scp>HIV<\/scp>\n                    \u2010associated emphysema through transcriptomic analysis"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7316-9689","authenticated-orcid":false,"given":"Jian\u2010cheng","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010ping","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College Fudan University  Shanghai 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