{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:48:58Z","timestamp":1788994138030,"version":"build-2803163510"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100016105","name":"Quzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["2024K106"],"award-info":[{"award-number":["2024K106"]}],"id":[{"id":"10.13039\/501100016105","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.bcp.2025.117402","type":"journal-article","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T00:12:06Z","timestamp":1759536726000},"page":"117402","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"P3","title":["Targeting DOT1L-mediated histone methylation by hesperetin alleviates retinal microvascular endothelial cell dysfunction and diabetic retinopathy"],"prefix":"10.1016","volume":"242","author":[{"given":"Zhu-Jun","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Xi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Lin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hua","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-6647","authenticated-orcid":false,"given":"Si-Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.bcp.2025.117402_b0005","doi-asserted-by":"crossref","first-page":"438","DOI":"10.3390\/nu10040438","article-title":"Dietary flavonoids in the prevention of T2d: an overview","volume":"10","author":"Alkhalidy","year":"2018","journal-title":"Nutrients"},{"issue":"3","key":"10.1016\/j.bcp.2025.117402_b0010","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3390\/biomedicines12030552","article-title":"Computational and experimental approaches exploring the role of hesperetin in improving autophagy in rat diabetic retinopathy","volume":"12","author":"Alshaman","year":"2024","journal-title":"Biomedicines"},{"issue":"1","key":"10.1016\/j.bcp.2025.117402_b0015","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13148-015-0095-z","article-title":"Epigenetic activities of flavonoids in the prevention and treatment of cancer","volume":"7","author":"Busch","year":"2015","journal-title":"Clin. Epigenetics"},{"issue":"1","key":"10.1016\/j.bcp.2025.117402_b0020","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13148-025-01874-4","article-title":"DNA hypermethylation of Pltp mediated by Dnmt3b aggravates vascular dysfunction in diabetic retinopathy via the Akt\/Gsk3\u03b2 signaling pathway","volume":"17","author":"Cai","year":"2025","journal-title":"Clin. Epigenetics"},{"issue":"4","key":"10.1016\/j.bcp.2025.117402_b0025","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nm.3832","article-title":"Dot1l inhibits sirt1-mediated epigenetic silencing to maintain leukemic gene expression in Mll-rearranged leukemia","volume":"21","author":"Chen","year":"2015","journal-title":"Nat. Med."},{"issue":"2","key":"10.1016\/j.bcp.2025.117402_b0030","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.preteyeres.2007.12.001","article-title":"Diabetic retinopathy and systemic vascular complications","volume":"27","author":"Cheung","year":"2008","journal-title":"Prog. Retin. Eye Res."},{"issue":"17","key":"10.1016\/j.bcp.2025.117402_b0035","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1182\/blood.2020007352","article-title":"Rerouting Dot1l inhibitors in leukemia","volume":"136","author":"Dickins","year":"2020","journal-title":"Blood"},{"issue":"7","key":"10.1016\/j.bcp.2025.117402_b0040","doi-asserted-by":"crossref","first-page":"852","DOI":"10.7150\/ijbs.19370","article-title":"Emerging roles of sirt1 in fatty liver diseases","volume":"13","author":"Ding","year":"2017","journal-title":"Int. J. Biol. Sci."},{"issue":"10","key":"10.1016\/j.bcp.2025.117402_b0045","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1111\/bph.16237","article-title":"Natural products modulating epigenetic mechanisms by affecting histone methylation\/demethylation: targeting cancer cells","volume":"182","author":"Dorna","year":"2025","journal-title":"Br. J. Pharmacol."},{"issue":"43","key":"10.1016\/j.bcp.2025.117402_b0050","doi-asserted-by":"crossref","first-page":"4562","DOI":"10.1093\/eurheartj\/ehac097","article-title":"The epigenetic enzyme dot1l orchestrates vascular smooth muscle cell-monocyte crosstalk and protects against atherosclerosis via the Nf-\u03bab pathway","volume":"43","author":"Farina","year":"2022","journal-title":"Eur. Heart J."},{"issue":"2","key":"10.1016\/j.bcp.2025.117402_b0055","doi-asserted-by":"crossref","first-page":"112","DOI":"10.7861\/clinmed.2021-0792","article-title":"Diabetic retinopathy for the non-ophthalmologist","volume":"22","author":"Fung","year":"2022","journal-title":"Clin. Med. (Lond.)"},{"issue":"5","key":"10.1016\/j.bcp.2025.117402_b0060","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nrg3173","article-title":"Histone methylation: a dynamic mark in health, disease and inheritance","volume":"13","author":"Greer","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.bcp.2025.117402_b0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.105871","article-title":"Dihydroartemisinin ameliorates retinal vascular dysfunction in diabetes mellitus via the Fasn\/Kmal-Mtor\/Srebp1 feedback loop","volume":"174","author":"Gu","year":"2021","journal-title":"Pharmacol. Res."},{"issue":"33","key":"10.1016\/j.bcp.2025.117402_b0070","doi-asserted-by":"crossref","first-page":"11925","DOI":"10.1080\/10408398.2022.2097637","article-title":"Dietary flavonoids prevent diabetes through epigenetic regulation: advance and challenge","volume":"63","author":"Han","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"10.1016\/j.bcp.2025.117402_b0075","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2024.1295967","article-title":"Unraveling the epigenetic fabric of type 2 diabetes mellitus: pathogenic mechanisms and therapeutic implications","volume":"15","author":"Jazieh","year":"2024","journal-title":"Front. Endocrinol. (Lausanne)."},{"issue":"9","key":"10.1016\/j.bcp.2025.117402_b0080","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000190","article-title":"The histone H3k79 methyltransferase Dot1l is essential for mammalian development and heterochromatin structure","volume":"4","author":"Jones","year":"2008","journal-title":"PLoS Genet."},{"issue":"1","key":"10.1016\/j.bcp.2025.117402_b0085","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1167\/iovs.16-20691","article-title":"The effects of metformin on obesity-induced dysfunctional retinas","volume":"58","author":"Kim","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"7","key":"10.1016\/j.bcp.2025.117402_b0090","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.2337\/db09-1431","article-title":"Resveratrol inhibits neuronal apoptosis and elevated Ca2+\/calmodulin-dependent protein kinase ii activity in diabetic mouse retina","volume":"59","author":"Kim","year":"2010","journal-title":"Diabetes"},{"key":"10.1016\/j.bcp.2025.117402_b0095","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.mvr.2013.01.002","article-title":"Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats","volume":"87","author":"Kumar","year":"2013","journal-title":"Microvasc. Res."},{"key":"10.1016\/j.bcp.2025.117402_b0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155477","article-title":"Paeoniflorin promotes Ppar\u03b3 expression to suppress Hscs activation by inhibiting Ezh2-mediated histone H3k27 trimethylation","volume":"128","author":"Lan","year":"2024","journal-title":"Phytomedicine"},{"issue":"5","key":"10.1016\/j.bcp.2025.117402_b0105","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.cell.2013.01.052","article-title":"H3k4me3 interactions with Taf3 regulate preinitiation complex assembly and selective gene activation","volume":"152","author":"Lauberth","year":"2013","journal-title":"Cell"},{"issue":"9","key":"10.1016\/j.bcp.2025.117402_b0110","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.5713\/ab.23.0402","article-title":"Dot1-like histone lysine methyltransferase is critical for adult vessel maintenance and functions","volume":"37","author":"Lee","year":"2024","journal-title":"Anim Biosci."},{"issue":"10","key":"10.1016\/j.bcp.2025.117402_b0115","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1007\/s10792-022-02283-9","article-title":"C-terminal binding protein 2 promotes high-glucose-triggered cell proliferation, angiogenesis and cellular adhesion of human retinal endothelial cell line","volume":"42","author":"Li","year":"2022","journal-title":"Int. Ophthalmol."},{"key":"10.1016\/j.bcp.2025.117402_b0120","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbrc.2024.150061","article-title":"Apigenin suppresses epithelial-mesenchymal transition in high glucose-induced retinal pigment epithelial cell by inhibiting Cbp\/P300-mediated histone acetylation","volume":"717","author":"Li","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"4","key":"10.1016\/j.bcp.2025.117402_b0125","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.3390\/ijms25041956","article-title":"Sirtuins as players in the signal transduction of citrus flavonoids","volume":"25","author":"Lombardo","year":"2024","journal-title":"Int. J. Mol. Sci."},{"issue":"5","key":"10.1016\/j.bcp.2025.117402_b0130","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1080\/15592294.2019.1699991","article-title":"Dot1l: a key target in normal chromatin remodelling and in mixed-lineage leukaemia treatment","volume":"15","author":"Sarno","year":"2020","journal-title":"Epigenetics"},{"issue":"6","key":"10.1016\/j.bcp.2025.117402_b0135","doi-asserted-by":"crossref","first-page":"7839","DOI":"10.1002\/jcp.27844","article-title":"Role of histone modification and DNA methylation in signaling pathways involved in diabetic retinopathy","volume":"234","author":"Shafabakhsh","year":"2019","journal-title":"J. Cell. Physiol."},{"issue":"6","key":"10.1016\/j.bcp.2025.117402_b0140","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.2337\/db20-1110","article-title":"Dot1l regulates thermogenic adipocyte differentiation and function via modulating H3k79 methylation","volume":"70","author":"Shuai","year":"2021","journal-title":"Diabetes"},{"key":"10.1016\/j.bcp.2025.117402_b0145","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155596","article-title":"Genipin ameliorates diabetic retinopathy via the hif-1\u03b1 and ages-rage pathways","volume":"129","author":"Sun","year":"2024","journal-title":"Phytomedicine"},{"issue":"2","key":"10.1016\/j.bcp.2025.117402_b0150","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.tcm.2022.11.003","article-title":"The role of statins in diabetic retinopathy","volume":"34","author":"Tomkins-Netzer","year":"2024","journal-title":"Trends Cardiovasc. Med."},{"key":"10.1016\/j.bcp.2025.117402_b0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.117010","article-title":"Histone deacetylases and inhibitors in diabetes mellitus and its complications","volume":"177","author":"Wang","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.bcp.2025.117402_b0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2025.110250","article-title":"Baicalein modulates endoplasmic reticulum stress by activating Sirt3 to attenuate the dysfunction of retinal microvascular endothelial cells under high glucose conditions","volume":"254","author":"Wang","year":"2025","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.bcp.2025.117402_b0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2025.156408","article-title":"Astragaloside Iv inhibits retinal pigment epithelial cell senescence and reduces Il-1\u03b2 Mrna stability by targeting Fto-mediated M(6)a methylation","volume":"138","author":"Wang","year":"2025","journal-title":"Phytomedicine"},{"issue":"1","key":"10.1016\/j.bcp.2025.117402_b0170","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41387-020-00130-3","article-title":"Neohesperidin enhances Pgc-1\u03b1-mediated mitochondrial biogenesis and alleviates hepatic steatosis in high fat diet fed mice","volume":"10","author":"Wang","year":"2020","journal-title":"Nutr. Diabetes"},{"key":"10.1016\/j.bcp.2025.117402_b0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2020.153454","article-title":"Inhibition of histone acetyltransferase by naringenin and hesperetin suppresses txnip expression and protects pancreatic \u0392 cells in diabetic mice","volume":"88","author":"Wang","year":"2021","journal-title":"Phytomedicine"},{"key":"10.1016\/j.bcp.2025.117402_b0180","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2021.153499","article-title":"Hesperetin promotes Dot1l degradation and reduces histone H3k79 methylation to inhibit gastric cancer metastasis","volume":"84","author":"Wang","year":"2021","journal-title":"Phytomedicine"},{"issue":"Pt B","key":"10.1016\/j.bcp.2025.117402_b0185","article-title":"Hesperetin, a Sirt1 activator, inhibits hepatic inflammation via Ampk\/Creb pathway","volume":"89","author":"Wang","year":"2020","journal-title":"Int. Immunopharmacol."},{"issue":"2","key":"10.1016\/j.bcp.2025.117402_b0190","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.diabres.2014.03.019","article-title":"Role of epigenetic mechanisms in the development of chronic complications of diabetes","volume":"105","author":"Wegner","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"issue":"8","key":"10.1016\/j.bcp.2025.117402_b0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.111703","article-title":"Dot1l regulates lipid biosynthesis and inflammatory responses in macrophages and promotes atherosclerotic plaque stability","volume":"41","author":"Willemsen","year":"2022","journal-title":"Cell Rep."},{"issue":"1","key":"10.1016\/j.bcp.2025.117402_b0200","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3390\/biom8010011","article-title":"Dot1l and H3k79 methylation in transcription and genomic stability","volume":"8","author":"Wood","year":"2018","journal-title":"Biomolecules"},{"key":"10.1016\/j.bcp.2025.117402_b0205","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.freeradbiomed.2025.03.050","article-title":"Nitric oxide mediates negative feedback on the Txnip\/Nlrp3 inflammasome pathway to prevent retinal neurovascular unit dysfunction in early diabetic retinopathy","volume":"233","author":"Yang","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.bcp.2025.117402_b0210","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/ncomms2304","article-title":"Catalytic site remodelling of the Dot1l methyltransferase by selective inhibitors","volume":"3","author":"Yu","year":"2012","journal-title":"Nat. Commun."},{"issue":"2","key":"10.1016\/j.bcp.2025.117402_b0215","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1681\/ASN.2019070739","article-title":"Loss of histone H3 K79 methyltransferase Dot1l facilitates kidney fibrosis by upregulating endothelin 1 through histone deacetylase 2","volume":"31","author":"Zhang","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.bcp.2025.117402_b0220","article-title":"Tgr5 activation ameliorates mitochondrial homeostasis via regulating the Pkc\u03b4\/Drp1-Hk2 signaling in diabetic retinopathy","volume":"9","author":"Zhang","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.bcp.2025.117402_b0225","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2022.108969","article-title":"Runx1 regulates Tff1 expression to expedite viability of retinal microvascular endothelial cells in mice with diabetic retinopathy","volume":"217","author":"Zhang","year":"2022","journal-title":"Exp. Eye Res."},{"issue":"10","key":"10.1016\/j.bcp.2025.117402_b0230","article-title":"Hyperglycemia-regulated Trna-derived fragment Trf-3001a propels neurovascular dysfunction in diabetic mice","volume":"4","author":"Zhu","year":"2023","journal-title":"Cell Rep. Med."},{"issue":"11","key":"10.1016\/j.bcp.2025.117402_b0235","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0027385","article-title":"A computational tool for quantitative analysis of vascular networks","volume":"6","author":"Zudaire","year":"2011","journal-title":"PLoS One"}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225006677?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225006677?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T15:28:06Z","timestamp":1762097286000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295225006677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":47,"alternative-id":["S0006295225006677"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2025.117402","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting DOT1L-mediated histone methylation by hesperetin alleviates retinal microvascular endothelial cell dysfunction and diabetic retinopathy","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2025.117402","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117402"}}