{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:07:20Z","timestamp":1789020440868,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"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"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Keratinocytes coordinate re\u2010epithelialization, barrier restoration, inflammatory control, and matrix remodeling during cutaneous repair. Although betanin has reported cytoprotective and antioxidant properties, its wound\u2010relevant transcriptional program in keratinocytes remains incompletely defined. This study therefore asked whether betanin engages barrier, inflammatory, and remodeling\u2010related keratinocyte programs under inflammatory conditions, and whether existing wound\u2010healing databases can account for the resulting transcriptional pattern. Scratch closure was quantified by ImageJ measurement and by an independent rule\u2010based automated image\u2010analysis pipeline with first\u2010order kinetic modeling; transcriptional responses in IFN\u2010\u03b3\/TNF\u2010\u03b1\u2010stimulated HaCaT cells were interpreted through database\u2010weighted evidence scoring and machine learning\u2010based stress testing. Betanin (20\u2009\u03bcg\/mL) significantly reduced residual wound area at 24\u2009h (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.020) and 48\u2009h (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.035) by ImageJ quantification, and automated image analysis with kinetic modeling yielded an approximately 1.5\u2010fold higher first\u2010order closure rate constant relative to the vehicle\u2010treated wounded control. Betanin partially restored\n                    <jats:italic>FLG<\/jats:italic>\n                    , reduced\n                    <jats:italic>KRT14<\/jats:italic>\n                    , and selectively attenuated inflammatory mediators including\n                    <jats:italic>IL1B<\/jats:italic>\n                    ,\n                    <jats:italic>ICAM1<\/jats:italic>\n                    ,\n                    <jats:italic>CCL22<\/jats:italic>\n                    , and\n                    <jats:italic>CXCL8<\/jats:italic>\n                    . Among remodeling\u2010associated genes,\n                    <jats:italic>TGFB1<\/jats:italic>\n                    ,\n                    <jats:italic>COL1A1<\/jats:italic>\n                    , and\n                    <jats:italic>VEGFA<\/jats:italic>\n                    were suppressed while\n                    <jats:italic>COL3A1<\/jats:italic>\n                    was partially restored.\n                    <jats:italic>NFE2L2<\/jats:italic>\n                    and\n                    <jats:italic>HMOX1<\/jats:italic>\n                    were only modestly affected, indicating a dominant anti\u2010inflammatory and barrier\u2010modulating response rather than canonical antioxidant axis activation. Database\u2010weighted evidence scoring stably prioritized\n                    <jats:italic>FLG<\/jats:italic>\n                    ,\n                    <jats:italic>COL3A1<\/jats:italic>\n                    ,\n                    <jats:italic>COL1A1<\/jats:italic>\n                    , and\n                    <jats:italic>ICAM1<\/jats:italic>\n                    , corroborated by betanin\u2010specific experimental responses. Three architecturally distinct machine learning models showed no evidence that database\u2010derived wound\u2010healing features predict betanin\u2010induced transcriptional responses, indicating that the selected prior\u2010knowledge annotations were insufficient to account for the observed pattern in this 15\u2010gene, single\u2010context dataset.\n                  <\/jats:p>","DOI":"10.1002\/biof.70151","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:43:03Z","timestamp":1789018983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Betanin Promotes Wound Closure and Drives a Context\u2010Specific Transcriptional Repair Program in\n                    <scp>HaCaT<\/scp>\n                    Keratinocytes: A Multi\u2010Evidence\n                    <scp>AI<\/scp>\n                    \u2010Guided Prioritization Study"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5065-1686","authenticated-orcid":false,"given":"Sun Young","family":"Park","sequence":"first","affiliation":[{"name":"Research Institute of Human Ecology Yeungnam University  Gyeongsan Gyeongbuk Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0030-3560","authenticated-orcid":false,"given":"Youjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Energy &amp; Environmental Engineering The Catholic University of Korea  Bucheon\u2010si Gyeonggi\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1089\/wound.2013.0473","article-title":"Epithelialization in Wound Healing: A Comprehensive Review","volume":"3","author":"Pastar I.","year":"2014","journal-title":"Advances in Wound Care"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","DOI":"10.4110\/in.2018.18.e9","article-title":"Optimization of Cytokine Milieu to Reproduce Atopic Dermatitis\u2010Related Gene Expression in HaCaT Keratinocyte Cell Line","volume":"18","author":"Kim H. 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