{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:16:16Z","timestamp":1790612176008,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gansu Province Research Program for Traditional Chinese Medicine","award":["GZKZ-2024-22"],"award-info":[{"award-number":["GZKZ-2024-22"]}]},{"name":"Major Project of the Huixian Science and Technology Bureau of Gansu Province","award":["25ZDHK03"],"award-info":[{"award-number":["25ZDHK03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Ulcerative colitis (UC) is a complex chronic inflammatory bowel disease, and its pathogenesis is closely related to immune imbalance, intestinal flora disorder and intestinal barrier damage. In recent years, a novel form of programmed cell death, PANoptosis, has been confirmed to play a core role in the pathological process of UC. PANoptosis is driven by the PANoptosome complex, which is assembled by key molecules such as ZBP1, NLRP3, and RIPK1, which can simultaneously activate pyroptosis, apoptosis, and necroptosis. This not only leads to damage to the intestinal epithelial barrier, but it also aggravates the dysfunction of immune cells by releasing a large amount of pro-inflammatory cytokines and damage-associated molecular patterns (DAMPs), thus forming a vicious cycle of \u201ccell death and inflammation\u201d. Given the complexity of the PANoptosis signaling network, the efficacy of single-target inhibitors is limited. This review systematically expounds the mechanism of action of PANoptosis in UC and focuses on discussing multi-target combination treatment strategies represented by smart hydrogels loaded with multiple inhibitors (such as MCC950, GSK772, VX-765, disulfiram, etc.). This strategy achieves synergy through \u201cvertical blocking\u201d and \u201chorizontal coverage\u201d, and in combination with targeted delivery to the lesion, provides a highly promising innovative direction for fundamentally breaking the pathological cycle of UC. Future research should focus on the development of new inhibitors, the optimization of delivery systems, and in-depth clinical translation to promote this strategy as a breakthrough therapy for refractory UC.<\/jats:p>","DOI":"10.3390\/biom16050624","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:54:08Z","timestamp":1776862448000},"page":"624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Review on the Mechanism of and Therapies Targeting PANoptosis in Ulcerative Colitis"],"prefix":"10.3390","volume":"16","author":[{"given":"Mi","family":"Zhao","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8807-655X","authenticated-orcid":false,"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Tian","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Ren","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Jing","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China"},{"name":"Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5623-6432","authenticated-orcid":false,"given":"Zhaofeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China"},{"name":"Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/S0140-6736(12)60150-0","article-title":"Ulcerative colitis","volume":"380","author":"Ordas","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41575-024-01035-7","article-title":"Understanding the therapeutic toolkit for inflammatory bowel disease","volume":"22","author":"Vieujean","year":"2025","journal-title":"Nat. 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