{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T20:22:43Z","timestamp":1775420563525,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study examined whether melatonin could decrease CD4\u2009+\u2009T cell apoptosis and reduce mortality rates in sepsis\u2010induced mice. Fifty\u2010one male C57BL\/6 mice were randomly classified into three groups: Sham, cecal ligation and puncture (CLP), and CLP plus melatonin (CLP\u2009+\u2009MLT). Mice in the CLP\u2009+\u2009MLT group were intraperitoneally administered melatonin at 30\u2009mg\/kg 10\u2009min before and 30\u2009min after CLP and then once daily for 6 days. Lymphocyte counts, cytokine levels, and apoptosis rates in CD4+ and CD8\u2009+\u2009T cells in the spleen and peripheral blood were examined using automatic blood cell analysis, enzyme\u2010linked immunosorbent assay, or flow cytometry. The results demonstrated that melatonin improved the survival of mice following CLP, decreased the levels of IFN\u2010\u03b3, IL\u20101\u03b2, and IL\u20102 in the serum, and significantly upregulated lymphocyte counts. In addition, melatonin increased the percentage of CD4\u2009+\u2009T cells and inhibited the apoptosis of these cells in the spleen and peripheral blood of mice following CLP. Melatonin protected against sepsis\u2010induced organ damage. Melatonin inhibited CD4\u2009+\u2009T cell apoptosis in vitro, possibly via the Bcl\u20102\/BAX but not through the PD\u20101 pathway. Our results suggest that melatonin could mitigate Pro\u2010inflammatory responses, attenuate organ injury, and suppress CD4\u2009+\u2009T cell apoptosis via the Bcl\u20102\/BAX pathway, thereby improving survival rates in a mouse model of sepsis. Targeted therapy to protect CD4\u2009+\u2009T cells against apoptosis could represent a new approach for sepsis treatment in the future.<\/jats:p>","DOI":"10.1111\/jpi.70071","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T10:28:01Z","timestamp":1755080881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Melatonin Inhibits CD4+T Cell Apoptosis via the Bcl\u20102\/BAX Pathway and Improves Survival Rates in Mice With Sepsis"],"prefix":"10.1111","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9646-0439","authenticated-orcid":false,"given":"Zhenggong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Intensive Care Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou 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