{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:14:29Z","timestamp":1787804069495,"version":"build-2784847793"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Project of Traditional Chinese Medicine","award":["ZYY202303"],"award-info":[{"award-number":["ZYY202303"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Ulcerative colitis (UC) is a recurrent inflammatory condition of the bowel with a multifaceted pathogenesis, including programmed cell death, oxidative stress, and immune-mediated inflammation. As a recently identified type of cell death, disulfidptosis has an unclear role in UC.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We analyzed clusters of disulfidptosis-related genes (DRGs) and immune cell infiltration in 361 patients with UC from the GSE73661and GSE92415 datasets. Differentially expressed genes (DEGs) were identified using unsupervised clustering methods, and hub genes were selected using machine learning algorithms. Additionally, potential key components of potential traditional Chinese medicines for the treatment of UC were predicted based on hub genes. Finally, experimental validation was performed through qRT-PCR, western blotting, and immunohistochemistry.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>We identified two molecular clusters related to disulfidptosis, each showing significant heterogeneity in gene expression and immune profiles. Hub genes associated with disulfidptosis, CXCL1, HMGCS2, AQP8, and SLC26A2, were further screened and validated. Additionally, potential traditional Chinese medicines for UC were predicted. 3\u2019-Methoxydaidzein (MHD), a key constituent of Puerariae Radix, inhibited LPS-induced inflammatory responses in Caco2 cells and alleviated DSS-induced colonic injury in UC mice via upregulation of SLC26A2.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>DRGs demonstrate strong discriminatory power in distinguishing UC subtypes. Cluster with high expression of SLC26A2 showed a UC phenotype with a milder degree of damage. Additionally, we identified the hub gene SLC26A2 as playing a significant role in UC, and MHD demonstrates potential as a targeted therapeutic strategy for UC.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0324586","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T17:47:03Z","timestamp":1749232023000},"page":"e0324586","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Screening and validation of 3\u2019-Methoxydaidzein as a therapeutic agent in ulcerative colitis based on disulfidptosis-associated molecular 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Med"},{"issue":"10","key":"pone.0324586.ref033","article-title":"A comparative study on the effects of different sources of carboxymethyl poria polysaccharides on the repair of DSS-induced colitis in mice","volume":"24","author":"Z Tan","year":"2023","journal-title":"Int J Mol Sci"},{"key":"pone.0324586.ref034","doi-asserted-by":"crossref","first-page":"668418","DOI":"10.3389\/fphar.2021.668418","article-title":"Constituents, pharmacokinetics, and pharmacology of Gegen-Qinlian Decoction","volume":"12","author":"J-Z Lu","year":"2021","journal-title":"Front Pharmacol"},{"issue":"3","key":"pone.0324586.ref035","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.jep.2011.02.001","article-title":"Kudzu root: traditional uses and potential medicinal benefits in diabetes and cardiovascular diseases","volume":"134","author":"KH Wong","year":"2011","journal-title":"J 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Schmitt","year":"2020","journal-title":"J Crohns Colitis"},{"issue":"1","key":"pone.0324586.ref039","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/0016-5085(90)91238-2","article-title":"Enhancement of human intestinal mast cell mediator release in active ulcerative colitis","volume":"99","author":"CC Fox","year":"1990","journal-title":"Gastroenterology"},{"key":"pone.0324586.ref040","doi-asserted-by":"crossref","first-page":"109101","DOI":"10.1016\/j.jnutbio.2022.109101","article-title":"Resveratrol and resveratrol nano-delivery systems in the treatment of inflammatory bowel disease","volume":"109","author":"V Gowd","year":"2022","journal-title":"J Nutr Biochem"},{"issue":"5","key":"pone.0324586.ref041","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1080\/08923973.2020.1790595","article-title":"Dual role of sirtuin 1 in inflammatory bowel disease","volume":"42","author":"K Devi","year":"2020","journal-title":"Immunopharmacol 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Kappelman","year":"2011","journal-title":"Arch Dis Child"},{"issue":"6","key":"pone.0324586.ref045","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.3390\/antiox12061230","article-title":"NAD+ metabolism and immune regulation: new approaches to inflammatory bowel disease therapies","volume":"12","author":"C Chen","year":"2023","journal-title":"Antioxidants (Basel)"},{"issue":"12","key":"pone.0324586.ref046","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.7150\/thno.32126","article-title":"RIP3 promotes colitis-associated colorectal cancer by controlling tumor cell proliferation and CXCL1-induced immune suppression","volume":"9","author":"Z-Y Liu","year":"2019","journal-title":"Theranostics"},{"issue":"5","key":"pone.0324586.ref047","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.nut.2004.08.025","article-title":"Serum selenoprotein-P levels in patients with inflammatory bowel disease","volume":"21","author":"A Andoh","year":"2005","journal-title":"Nutrition"},{"issue":"1","key":"pone.0324586.ref048","doi-asserted-by":"crossref","first-page":"12126","DOI":"10.1038\/s41598-023-39012-w","article-title":"Biomarkers of ulcerative colitis disease activity CXCL1, CYP2R1, LPCAT1, and NEU4 and their relationship to immune infiltrates","volume":"13","author":"A Huo","year":"2023","journal-title":"Sci Rep"},{"key":"pone.0324586.ref049","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.freeradbiomed.2021.05.032","article-title":"Ketogenesis alleviates TNF\u03b1-induced apoptosis and inflammatory responses in intestinal cells","volume":"172","author":"JT Kim","year":"2021","journal-title":"Free Radic Biol Med"},{"issue":"2","key":"pone.0324586.ref050","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s00441-004-0932-4","article-title":"Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn\u2019s disease and 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