{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:11:40Z","timestamp":1787062300680,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003718","name":"Korea Institute of Oriental Medicine","doi-asserted-by":"publisher","award":["KSN2511030"],"award-info":[{"award-number":["KSN2511030"]}],"id":[{"id":"10.13039\/501100003718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008783","name":"National Research Council of Science and Technology","doi-asserted-by":"publisher","award":["CCL23221\u2010100"],"award-info":[{"award-number":["CCL23221\u2010100"]}],"id":[{"id":"10.13039\/501100008783","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Dry eye disease (DED) is a multifactorial ocular disorder marked by tear film instability, oxidative stress, and inflammation. Although melatonin is known to exert antioxidant and anti\u2010inflammatory effects, its precise role in regulating desiccation\u2010induced stress responses at the ocular surface has not been well defined. In particular, the involvement of the Nrf2 signalling pathway in melatonin\u2010mediated protection against corneal epithelial inflammation under tear film instability remains unexplored. In this study, we evaluated the therapeutic potential of melatonin in a human corneal epithelial cell (HCEC) model mimicking desiccation stress. Melatonin treatment significantly reduced reactive oxygen species (ROS) levels and upregulated antioxidant enzymes, including catalase (CAT) and heme oxygenase\u20101 (HO\u20101), via Nrf2 pathway activation. These effects were attenuated by Nrf2 knockdown using siRNA, confirming pathway specificity. Furthermore, melatonin markedly suppressed pro\u2010inflammatory cytokine production, suggesting a dual mechanism of action involving both redox regulation and immune modulation. Our findings provide novel insight into the Nrf2\u2010dependent effects of melatonin on ocular surface protection under desiccation conditions. These results suggest melatonin as a promising candidate for the treatment of DED through simultaneous modulation of oxidative and inflammatory pathways specific to tear film instability.<\/jats:p>","DOI":"10.1111\/jcmm.70879","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T04:05:55Z","timestamp":1760673955000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Melatonin Ameliorates Desiccation Stress\u2010Induced Ocular Inflammation in an In\u00a0Vitro Model by Activating the Nrf2 Pathway"],"prefix":"10.1111","volume":"29","author":[{"given":"Hye\u2010Sun","family":"Lim","sequence":"first","affiliation":[{"name":"Herbal Medicine Resources Research Center Korea Institute of Oriental Medicine  Naju\u2010si Jeollanam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinheung","family":"Park","sequence":"additional","affiliation":[{"name":"St. Mary\u2018s JIN Eye Center  Seoul Republic of Korea"},{"name":"Mediverse Co. Ltd.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woong\u2010Joo","family":"Whang","sequence":"additional","affiliation":[{"name":"Mediverse Co. Ltd.  Seoul Republic of Korea"},{"name":"Department of Ophthalmology, College of Medicine Yeouido St. Mary\u2018s Hospital, The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Seok","family":"Kang","sequence":"additional","affiliation":[{"name":"Central R&amp;D Center, B&amp;Tech Co., Ltd.  Naju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunoh","family":"Kim","sequence":"additional","affiliation":[{"name":"Central R&amp;D Center, B&amp;Tech Co., Ltd.  Naju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Sik","family":"Yoo","sequence":"additional","affiliation":[{"name":"Mediverse Co. Ltd.  Seoul Republic of Korea"},{"name":"Department of Ophthalmology, College of Medicine Uijeongbu St. Mary\u2018s Hospital, The Catholic University of Korea  Seoul Republic of Korea"},{"name":"IU Eye Clinic  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8911-831X","authenticated-orcid":false,"given":"Gunhyuk","family":"Park","sequence":"additional","affiliation":[{"name":"Herbal Medicine Resources Research Center Korea Institute of Oriental Medicine  Naju\u2010si Jeollanam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.18240\/ijo.2019.10.15"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10792-014-9969-x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2018.11.007"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2020.1841804"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.03.1165"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.18240\/ijo.2024.10.19"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9410952"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13040422"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7469326"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/13813455.2020.1770799"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000066"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612824666180426112832"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035122"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2016.1277247"},{"key":"e_1_2_7_16_1","first-page":"1","article-title":"Melatonin Alleviates Oral Epithelial Cell Inflammation via Keap1\/Nrf2 Signaling","volume":"39","author":"Nan Z.","year":"2025","journal-title":"International Journal of Immunopathology and Pharmacology"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70879","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:54:46Z","timestamp":1761659686000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70879"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":15,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/jcmm.70879"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70879","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70879"}}