{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:13:54Z","timestamp":1785510834555,"version":"3.56.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.phymed.2026.158541","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:02:54Z","timestamp":1783090974000},"page":"158541","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Targeting myoferlin by 6-shogaol inhibition regulates hyperglycemia-induced retinal vascular dysfunction"],"prefix":"10.1016","volume":"159","author":[{"given":"Xiaoyu","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yau-Tuen","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruogu","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0241-670X","authenticated-orcid":false,"given":"Yibin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2026.158541_bib0001","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-48968-7","article-title":"Myoferlin silencing inhibits VEGFR2-mediated proliferation of metastatic clear cell renal cell carcinoma","volume":"9","author":"An","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.phymed.2026.158541_bib0002","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/s41589-024-01801-3","article-title":"Engineering covalent small molecule-RNA complexes in living cells","volume":"21","author":"Bereiter","year":"2025","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.phymed.2026.158541_bib0003","doi-asserted-by":"crossref","first-page":"30745","DOI":"10.1074\/jbc.M704798200","article-title":"Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function","volume":"282","author":"Bernatchez","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.phymed.2026.158541_bib0004","doi-asserted-by":"crossref","first-page":"C484","DOI":"10.1152\/ajpcell.00498.2008","article-title":"Myoferlin is critical for endocytosis in endothelial cells","volume":"297","author":"Bernatchez","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.phymed.2026.158541_bib0005","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/cvr\/cvs143","article-title":"Emerging role of PKA\/eNOS pathway in therapeutic angiogenesis for ischaemic tissue diseases","volume":"95","author":"Bir","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.phymed.2026.158541_bib0006","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.844767","article-title":"Ginger constituent 6-shogaol inhibits inflammation- and angiogenesis-related cell functions in primary human endothelial cells","volume":"13","author":"Bischoff-Kont","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158541_bib0007","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.2165\/11538130-000000000-00000","article-title":"Current approaches to the management of diabetic retinopathy and diabetic macular oedema","volume":"70","author":"Boscia","year":"2010","journal-title":"Drugs"},{"key":"10.1016\/j.phymed.2026.158541_bib0008","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1056\/NEJMct0908432","article-title":"Panretinal photocoagulation for proliferative diabetic retinopathy","volume":"365","author":"Bressler","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.phymed.2026.158541_bib0009","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1001\/jamaophthalmol.2013.4154","article-title":"Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial","volume":"131","author":"Bressler","year":"2013","journal-title":"JAMa Ophthalmol."},{"key":"10.1016\/j.phymed.2026.158541_bib0010","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s12964-024-01606-w","article-title":"Endomucin selectively regulates vascular endothelial growth factor receptor-2 endocytosis through its interaction with AP2","volume":"22","author":"Cano","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"10.1016\/j.phymed.2026.158541_bib0011","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S0140-6736(09)62124-3","article-title":"Diabetic retinopathy","volume":"376","author":"Cheung","year":"2010","journal-title":"Lancet"},{"key":"10.1016\/j.phymed.2026.158541_bib0012","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.cell.2020.08.013","article-title":"Cell types of the human retina and its organoids at single-cell resolution","volume":"182","author":"Cowan","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.phymed.2026.158541_bib0013","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1161\/01.RES.86.1.4","article-title":"Akt takes center stage in angiogenesis signaling","volume":"86","author":"Dimmeler","year":"2000","journal-title":"Circ. Res."},{"key":"10.1016\/j.phymed.2026.158541_bib0014","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jep.2009.10.004","article-title":"Comparative antioxidant and anti-inflammatory effects of 6 -gingerol, 8 -gingerol, 10 -gingerol and 6 -shogaol","volume":"127","author":"Dugasani","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2026.158541_bib0015","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1167\/iovs.02-1022","article-title":"High glucose-induced tyrosine nitration in endothelial cells: role of eNOS uncoupling and aldose reductase activation","volume":"44","author":"El-Remessy","year":"2003","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.phymed.2026.158541_bib0016","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1002\/ijc.29820","article-title":"Myoferlin plays a key role in vegfa secretion and impacts tumor-associated angiogenesis in human pancreas cancer","volume":"138","author":"Fahmy","year":"2016","journal-title":"Int. J. Cancer"},{"key":"10.1016\/j.phymed.2026.158541_bib0017","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1177\/002215540004800412","article-title":"Ultrastructural localization of the vascular permeability factor\/vascular endothelial growth factor (VPF\/VEGF) receptor-2 (FLK-1, KDR) in normal mouse kidney and in the hyperpermeable vessels induced by VPF\/VEGF-expressing tumors and adenoviral vectors","volume":"48","author":"Feng","year":"2000","journal-title":"J. Histochem. Cytochem."},{"key":"10.1016\/j.phymed.2026.158541_bib0018","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1161\/01.ATV.0000070546.16946.3A","article-title":"Caveolin, caveolae, and endothelial cell function","volume":"23","author":"Frank","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.phymed.2026.158541_bib0019","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1096\/fasebj.9.10.7542215","article-title":"Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction","volume":"9","author":"Friesel","year":"1995","journal-title":"Faseb. J."},{"key":"10.1016\/j.phymed.2026.158541_bib0020","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1038\/s41467-019-10359-x","article-title":"Endophilin-a2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis","volume":"10","author":"Genet","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.phymed.2026.158541_bib0021","doi-asserted-by":"crossref","first-page":"W270","DOI":"10.1093\/nar\/gkr366","article-title":"Swissdock, a protein-small molecule docking web service based on eadock dss","volume":"39","author":"Grosdidier","year":"2011","journal-title":"Nucleic. Acids. Res."},{"key":"10.1016\/j.phymed.2026.158541_bib0022","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1039\/c1np00051a","article-title":"Multitargeting by curcumin as revealed by molecular interaction studies","volume":"28","author":"Gupta","year":"2011","journal-title":"Nat. Prod. Rep."},{"key":"10.1016\/j.phymed.2026.158541_bib0023","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.neuropharm.2012.03.016","article-title":"6-shogaol, a ginger product, modulates neuroinflammation: a new approach to neuroprotection","volume":"63","author":"Ha","year":"2012","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.phymed.2026.158541_bib0024","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.cell.2018.02.001","article-title":"Mapping the mouse cell atlas by microwell-seq","volume":"172","author":"Han","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.phymed.2026.158541_bib0025","doi-asserted-by":"crossref","DOI":"10.1186\/1475-2840-2-2","article-title":"Is type 2 diabetes mellitus a vascular disease (atheroscleropathy) with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress","volume":"2","author":"Hayden","year":"2003","journal-title":"Cardiovasc. Diabetol."},{"key":"10.1016\/j.phymed.2026.158541_bib0026","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1210\/endrev\/bnaa025","article-title":"Microvascular dysfunction in diabetes mellitus and cardiometabolic disease","volume":"42","author":"Horton","year":"2021","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.phymed.2026.158541_bib0027","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1001\/archophthalmol.2012.1043","article-title":"Long-term effects of ranibizumab on diabetic retinopathy severity and progression","volume":"130","author":"Ip","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"10.1016\/j.phymed.2026.158541_bib0028","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ophtha.2014.08.048","article-title":"Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy","volume":"122","author":"Ip","year":"2015","journal-title":"Ophthalmology"},{"key":"10.1016\/j.phymed.2026.158541_bib0029","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ophtha.2023.12.033","article-title":"Risk of endophthalmitis based on cumulative number of anti-VEGF intravitreal injections","volume":"131","author":"Israilevich","year":"2024","journal-title":"Ophthalmology"},{"key":"10.1016\/j.phymed.2026.158541_bib0030","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1038\/nprot.2014.138","article-title":"The cellular thermal shift assay for evaluating drug target interactions in cells","volume":"9","author":"Jafari","year":"2014","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.phymed.2026.158541_bib0031","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s00125-020-05333-y","article-title":"Overexpression of d-amino acid oxidase prevents retinal neurovascular pathologies in diabetic rats","volume":"64","author":"Jiang","year":"2021","journal-title":"Diabetologia"},{"key":"10.1016\/j.phymed.2026.158541_bib0032","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1161\/01.RES.0000089257.94002.96","article-title":"Ligand-independent activation of vascular endothelial growth factor receptor 2 by fluid shear stress regulates activation of endothelial nitric oxide synthase","volume":"93","author":"Jin","year":"2003","journal-title":"Circ. Res."},{"key":"10.1016\/j.phymed.2026.158541_bib0033","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1039\/C7FO01354J","article-title":"Occurrence, biological activity and metabolism of 6-shogaol","volume":"9","author":"Kou","year":"2018","journal-title":"Food Funct."},{"key":"10.1016\/j.phymed.2026.158541_bib0034","first-page":"1020","article-title":"6-shogaol ameliorates experimental colitis and colitis-associated colorectal cancer in mice through the Nrf2-Keap1 signaling pathway","author":"Li","year":"2026","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.phymed.2026.158541_bib0035","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41392-023-01400-z","article-title":"Diabetic vascular diseases: molecular mechanisms and therapeutic strategies","volume":"8","author":"Li","year":"2023","journal-title":"Sig. Transduct. Target. Ther."},{"key":"10.1016\/j.phymed.2026.158541_bib0036","doi-asserted-by":"crossref","first-page":"E5986","DOI":"10.1073\/pnas.1706778114","article-title":"Highly selective inhibition of IMPDH2 provides the basis of antineuroinflammation therapy","volume":"114","author":"Liao","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U SA"},{"key":"10.1016\/j.phymed.2026.158541_bib0037","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3390\/foods8060185","article-title":"Bioactive compounds and bioactivities of ginger (Zingiber Officinale Roscoe)","volume":"8","author":"Mao","year":"2019","journal-title":"Foods"},{"key":"10.1016\/j.phymed.2026.158541_bib0038","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ajo.2013.11.012","article-title":"Management paradigms for diabetic macular edema","volume":"157","author":"Mitchell","year":"2014","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.phymed.2026.158541_bib0039","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1161\/01.RES.0000214545.99387.e3","article-title":"Vesicular trafficking of tyrosine kinase receptors and associated proteins in the regulation of signaling and vascular function","volume":"98","author":"Mukherjee","year":"2006","journal-title":"Circ. Res."},{"key":"10.1016\/j.phymed.2026.158541_bib0040","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/aps.2013.57","article-title":"6-shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation","volume":"34","author":"Park","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.phymed.2026.158541_bib0041","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/tra.12370","article-title":"Ferlins show tissue-specific expression and segregate as plasma membrane\/late endosomal or trans-golgi\/recycling ferlins","volume":"17","author":"Redpath","year":"2016","journal-title":"Traffic"},{"key":"10.1016\/j.phymed.2026.158541_bib0042","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.phytochem.2015.07.012","article-title":"Gingerols and shogaols: important nutraceutical principles from ginger","volume":"117","author":"Semwal","year":"2015","journal-title":"Phytochemistry"},{"key":"10.1016\/j.phymed.2026.158541_bib0043","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nmeth.1373","article-title":"Proteomics strategy for quantitative protein interaction profiling in cell extracts","volume":"6","author":"Sharma","year":"2009","journal-title":"Nat. Methods"},{"key":"10.1016\/j.phymed.2026.158541_bib0044","doi-asserted-by":"crossref","first-page":"14145","DOI":"10.1074\/jbc.M500901200","article-title":"\u0391,\u03b2-unsaturated ketone is a core moiety of natural ligands for covalent binding to peroxisome proliferator-activated receptor","volume":"280","author":"Shiraki","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.phymed.2026.158541_bib0045","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.ophtha.2021.04.027","article-title":"Global prevalence of diabetic retinopathy and projection of burden through 2045 systematic review and meta-analysis","volume":"128","author":"Teo","year":"2021","journal-title":"Ophthalmology"},{"key":"10.1016\/j.phymed.2026.158541_bib0046","doi-asserted-by":"crossref","first-page":"5438","DOI":"10.1158\/0008-5472.CAN-13-1142","article-title":"Myoferlin is a key regulator of egfr activity in breast cancer","volume":"73","author":"Turtoi","year":"2013","journal-title":"Cancer Res."},{"key":"10.1016\/j.phymed.2026.158541_bib0047","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/nar\/gkac633","article-title":"Construction of a cross-species cell landscape at single-cell level","volume":"51","author":"Wang","year":"2023","journal-title":"Nucleic. Acids. Res."},{"key":"10.1016\/j.phymed.2026.158541_bib0048","doi-asserted-by":"crossref","DOI":"10.1002\/adts.202000279","article-title":"Identification of key contributive compounds in a herbal medicine: a novel mathematic-biological evaluation approach","volume":"4","author":"Zhang","year":"2021","journal-title":"Adv. Theory Simul."},{"key":"10.1016\/j.phymed.2026.158541_bib0049","doi-asserted-by":"crossref","first-page":"3726","DOI":"10.1038\/s41467-018-06179-0","article-title":"A small molecule targeting myoferlin exerts promising anti-tumor effects on breast cancer","volume":"9","author":"Zhang","year":"2018","journal-title":"Nat. Commun."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711326007749?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711326007749?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:51:03Z","timestamp":1785509463000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711326007749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":49,"alternative-id":["S0944711326007749"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2026.158541","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting myoferlin by 6-shogaol inhibition regulates hyperglycemia-induced retinal vascular dysfunction","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2026.158541","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"158541"}}