{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:01:04Z","timestamp":1790319664178,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703508"],"award-info":[{"award-number":["81703508"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetic cardiomyopathy (DCM) is one of the most severe cardiovascular complications of diabetes mellitus (DM), yet effective treatment strategies remain lacking. Cellular senescence is a principal risk factor for multiple cardiovascular diseases, contributing significantly to cardiac dysfunction and disease progression. Melatonin, an endogenous hormone primarily secreted by the pineal gland, exerts cardioprotective effects against DCM. However, the underlying molecular mechanism remains incompletely understood, particularly whether melatonin ameliorates DCM by suppressing cardiomyocyte senescence. In this study, a streptozotocin (STZ)\u2011induced diabetic mouse model in vivo and an in vitro model of high\u2011glucose (HG)\u2011treated primary neonatal rat cardiomyocytes (NRCMs) were established. Melatonin ameliorated cardiac dysfunction in diabetic mice and alleviated the senescence phenotype in cardiomyocytes. Suppressing oxidative stress with the ROS scavenger N\u2010acetylcysteine (NAC) effectively attenuated cardiomyocyte senescence, confirming the causal role of oxidative stress in senescence progression under HG conditions. Mechanistically, melatonin effectively upregulated the expression of melatonin receptor 1B (MT2), thereby activating the SIRT1\/Nrf2 signaling pathway and promoting Nrf2 nuclear translocation. Notably, genetic ablation of\n                    <jats:italic>Nrf2<\/jats:italic>\n                    in diabetic mice, as well as pharmacological inhibition of MT2, SIRT1, or Nrf2 in NRCMs, substantially abolished the protective effects of melatonin. Collectively, melatonin alleviates DCM by attenuating oxidative stress\u2010induced cellular senescence through activation of the MT2\/SIRT1\/Nrf2 signaling pathway. These findings uncover a novel mechanism underlying the cardioprotective action of melatonin against DCM.\n                  <\/jats:p>","DOI":"10.1111\/jpi.70185","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:47:54Z","timestamp":1789544874000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melatonin Alleviates Diabetic Cardiomyopathy by Inhibiting Cellular Senescence via Activation of the MT2\/SIRT1\/Nrf2 Signaling Pathway"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9359-3943","authenticated-orcid":false,"given":"Fang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailing","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Li","sequence":"additional","affiliation":[{"name":"Institution of Drug Clinical Trial, Second Affiliated Hospital, Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2446-8834","authenticated-orcid":false,"given":"Xue","family":"Fan","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, Longgang District Maternity &amp; Child Healthcare Hospital of Shenzhen City Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danmei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1179-6142","authenticated-orcid":false,"given":"Yanmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4144-8891","authenticated-orcid":false,"given":"Fenfei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binger","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Division of Pharmacy, First Affiliated Hospital, Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9170-7882","authenticated-orcid":false,"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102182"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311586"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314665"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0339-2"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00542-2"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110747"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-023-01747-1"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/db25-0077"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.02.001"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.122.000622"},{"issue":"4","key":"e_1_2_13_12_1","first-page":"279","article-title":"Single\u2010Nucleus Transcriptomics Reveals a Gatekeeper Role for FOXP1 in Primate Cardiac Aging","volume":"14","author":"Zhang Y.","year":"2023","journal-title":"Protein & Cell"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-024-02520-8"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00624-2"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00007.2022"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052245"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00233-1"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/13510002.2023.2246720"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.22117"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2025.123973"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.122993"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103939"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.78654"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-025-01145-0"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001550"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2025.05.427"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8882130"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122108"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2026.178541"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155805"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12491"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X2550082X"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117568"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.822640"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2025.07.024"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-025-02170-5"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00015.2024"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01378-8"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-023-02078-x"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e06474"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12698"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-025-02720-5"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176961"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00775-3"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102824"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.645593"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00727-x"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.005"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-021-00121-8"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-4934-x"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2015.12.005"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.03.046"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.02.008"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00800-5"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/11.3.298"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12490"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0130-1"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12571"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2022.101763"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107779"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2025.111494"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-025-03345-z"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114591"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-024-00886-1"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2026.103035"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.2337\/db23-0901"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.70185","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jpi.70185","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.70185","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:48:04Z","timestamp":1790318884000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.70185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":65,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/jpi.70185"],"URL":"https:\/\/doi.org\/10.1111\/jpi.70185","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70185"}}