{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:55:57Z","timestamp":1790520957910,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects 5 million people globally. YTH N6\u2010methyladenosine RNA binding protein C (YTHDC1) is a critical regulator in various biological processes, yet its role in UC remains undefined. This study aims to investigate the regulatory function of YTHDC1 in UC pathogenesis. An in vivo UC model was established in C57BL\/6 mice using 3% dextran sulfate sodium (DSS). To establish an in vitro UC model, Caco\u20102 cells were exposed to 10\u2009\u03bcg\/mL lipopolysaccharide (LPS). Quantitative real\u2010time PCR (qRT\u2010PCR) was employed to detect mRNA expression levels of YTHDC1 and X\u2010box binding protein 1 (XBP1). Protein expression was analyzed by Western blot analysis assay. Haematoxylin and eosin staining was used to assess colonic pathology. Enzyme\u2010linked immunosorbent assay was performed to measure the levels of TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2. Immunohistochemistry assay was used to determine the LC3II\u2010positive expression rate. m6A methylated RNA immunoprecipitation assay and RNA immunoprecipitation assay were used to analyze the association between YTHDC1 and XBP1. An actinomycin D assay was performed to evaluate the effect of YTHDC1 overexpression on XBP1 mRNA stability. The study showed YTHDC1 and XBP1 expression were downregulated in colonic tissues from UC patients. Overexpression of YTHDC1 increased colon length and body weight in DSS\u2010induced mice and inhibited DSS\u2010triggered production of TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2. Additionally, the upregulation of YTHDC1 counteracted the suppressive impact of DSS treatment on autophagy in colon tissues. In Caco\u20102 cells, LPS treatment promoted TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2 production, whereas these effects were attenuated after YTHDC1 overexpression. Moreover, LPS\u2010induced Caco\u20102 cells showed decreases in the ratio of LC3II to LC3I and beclin1 protein expression and an increase in P62 protein expression, however, YTHDC1 overexpression relieved these effects. In addition, the results showed that the treatment with AMPK inhibit or attenuated YTHDC1 overexpression\u2010induced effects in LPS\u2010treated Caco\u20102 cells. Furthermore, YTHDC1 was found to stabilize the expression of XBP1 and activate the AMPK\/mTOR pathway. Thus, YTHDC1 overexpression inhibited inflammation and promoted autophagy to ameliorate UC through the XBP1\/AMPK\/mTOR pathway. These findings highlight YTHDC1 as apotential therapeutic target for UC treatment.<\/jats:p>","DOI":"10.1002\/jbt.70434","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T11:40:10Z","timestamp":1754566810000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["YTHDC1 Overexpression Inhibits Inflammation and Promotes Autophagy to Ameliorate Ulcerative Colitis Through the XBP1\/AMPK\/mTOR Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Lijun","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Henan Medical University Xinxiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7894-7416","authenticated-orcid":false,"given":"Yanli","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Henan Medical University Xinxiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Henan Medical University Xinxiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Henan Medical University Xinxiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiyuan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Henan Medical University Xinxiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Henan Medical University Xinxiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1916-5699","authenticated-orcid":false,"given":"Xiaohe","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Henan Medical University Xinxiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2021-0080"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0205-x"},{"issue":"4","key":"e_1_2_8_4_1","first-page":"406","article-title":"Ulcerative Colitis: Rapid Evidence Review","volume":"105","author":"Adams S. 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