{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:15:01Z","timestamp":1792512901535,"version":"4.5.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Int Med Res"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the cerebroprotective effects of leptin in vitro and in vivo via the Janus kinase-2 (JAK2)\/transcription factor signal transducer and activators of transcription-3 (STAT3) pathway and leptin receptors (LEPR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study used the cellular oxygen-glucose deprivation (OGD) model in PC12 cells and the middle cerebral artery occlusion (MCAO) rat model of cerebral ischaemia\u2013reperfusion injury (CIRI) to assess changes in gene expression and protein levels following leptin pretreatment. The methylated DNA immunoprecipitation (MeDIP) assay measured DNA methylation levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The optimal leptin concentration for exerting neuroprotective effects against ischaemia\u2013reperfusion injury in PC12 cells was 200\u2009ng\/ml in vitro, but excessive leptin diminished this effect. Leptin pretreatment in the MCAO rat model demonstrated a similar effect to previously reported leptin administration post-CIRI. In addition to regulating the expression of inflammation-related cytokines, Western blot analysis showed that leptin pretreatment upregulated BCL-2 and downregulated caspase 3 levels. The MeDIP analysis demonstrated that DNA methylation regulated LEPR gene expression in the MCAO rat model when leptin pretreatment was used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Exogenous leptin might bind to extra-activated LEPR by reducing the methylation level of the LEPR gene promoter region, which leads to an increase in phosphorylated JAK2\/STAT3 and apoptotic signalling pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03000605241261912","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T14:13:25Z","timestamp":1722521605000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Hypomethylated leptin receptor reduces cerebral ischaemia\u2013reperfusion injury by activating the JAK2\/STAT3 signalling pathway"],"prefix":"10.1177","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1571-044X","authenticated-orcid":false,"given":"Xuelou","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Practice, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhongnan Hospital of Wuhan 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