{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T23:10:04Z","timestamp":1788649804985,"version":"build-2803163510"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32370837"],"award-info":[{"award-number":["32370837"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["20230484244"],"award-info":[{"award-number":["20230484244"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["BMU2023PYJH001"],"award-info":[{"award-number":["BMU2023PYJH001"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2023CX04"],"award-info":[{"award-number":["2023CX04"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"DOI":"10.1007\/s10238-025-01843-4","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T03:44:07Z","timestamp":1755747847000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The association between 4-HPR-mediated LCN2 suppression and reduced intestinal cell senescence in ulcerative colitis"],"prefix":"10.1007","volume":"25","author":[{"given":"Xiaoxue","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanwen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"issue":"10401","key":"1843_CR1","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","volume":"402","author":"C Le Berre","year":"2023","unstructured":"Le Berre C, Honap S, Peyrin-Biroulet L. Ulcerative colitis. Lancet. 2023;402(10401):571\u201384. https:\/\/doi.org\/10.1016\/S0140-6736(23)00966-2.","journal-title":"Lancet"},{"issue":"7422","key":"1843_CR2","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/nature11582","volume":"491","author":"L Jostins","year":"2012","unstructured":"Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119\u201324. https:\/\/doi.org\/10.1038\/nature11582.","journal-title":"Nature"},{"issue":"9","key":"1843_CR3","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/ng.3359","volume":"47","author":"JZ Liu","year":"2015","unstructured":"Liu JZ, van Sommeren S, Huang H, et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 2015;47(9):979\u201386. https:\/\/doi.org\/10.1038\/ng.3359.","journal-title":"Nat Genet"},{"issue":"2","key":"1843_CR4","doi-asserted-by":"publisher","first-page":"289","DOI":"10.3390\/biomedicines10020289","volume":"10","author":"C Stolfi","year":"2022","unstructured":"Stolfi C, Maresca C, Monteleone G, et al. Implication of intestinal barrier dysfunction in gut dysbiosis and diseases. Biomedicines. 2022;10(2):289. https:\/\/doi.org\/10.3390\/biomedicines10020289.","journal-title":"Biomedicines"},{"issue":"1","key":"1843_CR5","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1017\/S0954422416000019","volume":"29","author":"WM Miner-Williams","year":"2016","unstructured":"Miner-Williams WM, Moughan PJ. Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel. Nutr Res Rev. 2016;29(1):40\u201359. https:\/\/doi.org\/10.1017\/S0954422416000019.","journal-title":"Nutr Res Rev"},{"issue":"10","key":"1843_CR6","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1016\/j.tips.2024.08.003","volume":"45","author":"P Wangchuk","year":"2024","unstructured":"Wangchuk P, Yeshi K, Loukas A. Ulcerative colitis: clinical biomarkers, therapeutic targets, and emerging treatments. Trends Pharmacol Sci. 2024;45(10):892\u2013903. https:\/\/doi.org\/10.1016\/j.tips.2024.08.003.","journal-title":"Trends Pharmacol Sci"},{"issue":"1","key":"1843_CR7","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.molmed.2016.11.006","volume":"23","author":"PLJ de Keizer","year":"2017","unstructured":"de Keizer PLJ. The fountain of youth by targeting senescent cells? Trends Mol Med. 2017;23(1):6\u201317. https:\/\/doi.org\/10.1016\/j.molmed.2016.11.006.","journal-title":"Trends Mol Med"},{"issue":"5","key":"1843_CR8","doi-asserted-by":"publisher","first-page":"e167676","DOI":"10.1172\/jci.insight.167676","volume":"9","author":"Z Wang","year":"2024","unstructured":"Wang Z, Gao P, Guo K, et al. Age-related dysregulation of intestinal epithelium fucosylation is linked to an increased risk of colon cancer. JCI Insight. 2024;9(5):e167676. https:\/\/doi.org\/10.1172\/jci.insight.167676.","journal-title":"JCI Insight"},{"issue":"1","key":"1843_CR9","doi-asserted-by":"publisher","first-page":"12852","DOI":"10.1038\/s41598-025-96331-w","volume":"15","author":"TR Peng","year":"2025","unstructured":"Peng TR, Lin HH, Yang LJ, et al. The impact of inflammatory bowel disease on dementia risk: a current systematic review and meta-analysis. Sci Rep. 2025;15(1):12852. https:\/\/doi.org\/10.1038\/s41598-025-96331-w.","journal-title":"Sci Rep"},{"issue":"1","key":"1843_CR10","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41522-025-00663-4","volume":"11","author":"X Nie","year":"2025","unstructured":"Nie X, Li Q, Ji H, et al. Bifidobacterium longum NSP001-derived extracellular vesicles ameliorate ulcerative colitis by modulating T cell responses in gut microbiota-(in)dependent manners. NPJ Biofilms Microbiomes. 2025;11(1):27. https:\/\/doi.org\/10.1038\/s41522-025-00663-4.","journal-title":"NPJ Biofilms Microbiomes"},{"issue":"4","key":"1843_CR11","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1254\/jphs.14060fp","volume":"125","author":"D Mori","year":"2014","unstructured":"Mori D, Watanabe N, Kaminuma O, et al. IL-17A induces hypo-contraction of intestinal smooth muscle via induction of iNOS in muscularis macrophages. J Pharmacol Sci. 2014;125(4):394\u2013405. https:\/\/doi.org\/10.1254\/jphs.14060fp.","journal-title":"J Pharmacol Sci"},{"issue":"8","key":"1843_CR12","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/s41575-024-00931-2","volume":"21","author":"PS Haque","year":"2024","unstructured":"Haque PS, Kapur N, Barrett TA, et al. Mitochondrial function and gastrointestinal diseases. Nat Rev Gastroenterol Hepatol. 2024;21(8):537\u201355. https:\/\/doi.org\/10.1038\/s41575-024-00931-2.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"1843_CR13","doi-asserted-by":"publisher","first-page":"4361043","DOI":"10.1155\/2020\/4361043","volume":"2020","author":"JC Hoving","year":"2020","unstructured":"Hoving JC, Keeton R, H\u00f6ft MA, et al. IL-4 receptor-alpha signalling of intestinal epithelial cells, smooth muscle cells, and macrophages plays a redundant role in oxazolone colitis. Mediators Inflamm. 2020;2020:4361043. https:\/\/doi.org\/10.1155\/2020\/4361043.","journal-title":"Mediators Inflamm"},{"issue":"2","key":"1843_CR14","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1007\/s10753-020-01361-3","volume":"44","author":"R de Oliveira Santos","year":"2021","unstructured":"de Oliveira Santos R, da Silva Cardoso G, da Costa Lima L, et al. L-glutamine and physical exercise prevent intestinal inflammation and oxidative stress without improving gastric dysmotility in rats with ulcerative colitis. Inflammation. 2021;44(2):617\u201332. https:\/\/doi.org\/10.1007\/s10753-020-01361-3.","journal-title":"Inflammation"},{"issue":"4","key":"1843_CR15","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1097\/MCO.0000000000000065","volume":"17","author":"Y Zhu","year":"2014","unstructured":"Zhu Y, Armstrong JL, Tchkonia T, et al. Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Curr Opin Clin Nutr Metab Care. 2014;17(4):324\u20138. https:\/\/doi.org\/10.1097\/MCO.0000000000000065.","journal-title":"Curr Opin Clin Nutr Metab Care"},{"issue":"1","key":"1843_CR16","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41392-021-00646-9","volume":"6","author":"X Zhu","year":"2021","unstructured":"Zhu X, Chen Z, Shen W, et al. Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention. Signal Transduct Target Ther. 2021;6(1):245. https:\/\/doi.org\/10.1038\/s41392-021-00646-9.","journal-title":"Signal Transduct Target Ther"},{"issue":"2","key":"1843_CR17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/j.1474-9726.2006.00199.x","volume":"5","author":"BY Lee","year":"2006","unstructured":"Lee BY, Han JA, Im JS, et al. Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell. 2006;5(2):187\u201395. https:\/\/doi.org\/10.1111\/j.1474-9726.2006.00199.x.","journal-title":"Aging Cell"},{"issue":"2","key":"1843_CR18","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","volume":"186","author":"C L\u00f3pez-Ot\u00edn","year":"2023","unstructured":"L\u00f3pez-Ot\u00edn C, Blasco MA, Partridge L, et al. Hallmarks of aging: an expanding universe. Cell. 2023;186(2):243\u201378. https:\/\/doi.org\/10.1016\/j.cell.2022.11.001.","journal-title":"Cell"},{"issue":"26","key":"1843_CR19","doi-asserted-by":"publisher","first-page":"3003","DOI":"10.2174\/138161209789058110","volume":"15","author":"M de la Fuente","year":"2009","unstructured":"de la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des. 2009;15(26):3003\u201326. https:\/\/doi.org\/10.2174\/138161209789058110.","journal-title":"Curr Pharm Des"},{"issue":"1","key":"1843_CR20","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41413-024-00375-z","volume":"12","author":"Z Han","year":"2024","unstructured":"Han Z, Wang K, Ding S, et al. Cross-talk of inflammation and cellular senescence: a new insight into the occurrence and progression of osteoarthritis. Bone Res. 2024;12(1):69. https:\/\/doi.org\/10.1038\/s41413-024-00375-z.","journal-title":"Bone Res"},{"issue":"7","key":"1843_CR21","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.3390\/pharmaceutics15071974","volume":"15","author":"AJ Martin","year":"2023","unstructured":"Martin AJ, Shackleford DM, Charman SA, et al. Increased in vivo exposure of N-(4-hydroxyphenyl) retinamide (4-HPR) to achieve plasma concentrations effective against dengue virus. Pharmaceutics. 2023;15(7):1974. https:\/\/doi.org\/10.3390\/pharmaceutics15071974.","journal-title":"Pharmaceutics"},{"issue":"2","key":"1843_CR22","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s00280-020-04115-y","volume":"86","author":"H Zhang","year":"2020","unstructured":"Zhang H, Xu H, Zhang R, et al. Chemosensitization by 4-hydroxyphenyl retinamide-induced NF-\u03baB inhibition in acute myeloid leukemia cells. Cancer Chemother Pharmacol. 2020;86(2):257\u201366. https:\/\/doi.org\/10.1007\/s00280-020-04115-y.","journal-title":"Cancer Chemother Pharmacol"},{"issue":"4","key":"1843_CR23","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s00280-020-04224-8","volume":"87","author":"JS Thomas","year":"2021","unstructured":"Thomas JS, El-Khoueiry AB, Maurer BJ, et al. A phase I study of intravenous fenretinide (4-HPR) for patients with malignant solid tumors. Cancer Chemother Pharmacol. 2021;87(4):525\u201332. https:\/\/doi.org\/10.1007\/s00280-020-04224-8.","journal-title":"Cancer Chemother Pharmacol"},{"issue":"8044","key":"1843_CR24","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/s41586-024-08285-0","volume":"637","author":"X Zhuang","year":"2025","unstructured":"Zhuang X, Wang Q, Joost S, et al. Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis. Nature. 2025;637(8044):184\u201394. https:\/\/doi.org\/10.1038\/s41586-024-08285-0.","journal-title":"Nature"},{"key":"1843_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02126-6","author":"Q Zhu","year":"2025","unstructured":"Zhu Q, Zhang G, Cao M, et al. Microbiota-shaped neutrophil senescence regulates sexual dimorphism in bladder cancer. Nat Immunol. 2025. https:\/\/doi.org\/10.1038\/s41590-025-02126-6.","journal-title":"Nat Immunol"},{"issue":"10","key":"1843_CR26","doi-asserted-by":"publisher","first-page":"2280","DOI":"10.1038\/s41418-023-01216-y","volume":"30","author":"SY Jiang","year":"2023","unstructured":"Jiang SY, Tian T, Yao H, et al. The cGAS-STING-YY1 axis accelerates progression of neurodegeneration in a mouse model of Parkinson\u2019s disease via LCN2-dependent astrocyte senescence. Cell Death Differ. 2023;30(10):2280\u201392. https:\/\/doi.org\/10.1038\/s41418-023-01216-y.","journal-title":"Cell Death Differ"},{"issue":"5","key":"1843_CR27","first-page":"459","volume":"18","author":"B Bahmani","year":"2015","unstructured":"Bahmani B, Amiri F, Mohammadi Roushandeh A, et al. The Lcn2-engineered HEK-293 cells show senescence under stressful condition. Iran J Basic Med Sci. 2015;18(5):459\u201364.","journal-title":"Iran J Basic Med Sci"},{"issue":"7902","key":"1843_CR28","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1038\/s41586-022-04502-w","volume":"603","author":"XV Li","year":"2022","unstructured":"Li XV, Leonardi I, Putzel GG, et al. Immune regulation by fungal strain diversity in inflammatory bowel disease. Nature. 2022;603(7902):672\u20138. https:\/\/doi.org\/10.1038\/s41586-022-04502-w.","journal-title":"Nature"},{"key":"1843_CR29","doi-asserted-by":"publisher","first-page":"9064073","DOI":"10.1155\/2018\/9064073","volume":"2018","author":"K Wang","year":"2018","unstructured":"Wang K, Zhu T, Wang H, et al. Adoptive transfers of CD4+CD25+ tregs raise Foxp3 expression and alleviate mouse enteritis. Biomed Res Int. 2018;2018:9064073. https:\/\/doi.org\/10.1155\/2018\/9064073.","journal-title":"Biomed Res Int"},{"issue":"10","key":"1843_CR30","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1001\/jama.2023.15389","volume":"330","author":"B Gros","year":"2023","unstructured":"Gros B, Kaplan GG. Ulcerative colitis in adults: a review. JAMA. 2023;330(10):951\u201365. https:\/\/doi.org\/10.1001\/jama.2023.15389.","journal-title":"JAMA"}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-025-01843-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-025-01843-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-025-01843-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T06:50:40Z","timestamp":1764917440000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-025-01843-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1843"],"URL":"https:\/\/doi.org\/10.1007\/s10238-025-01843-4","relation":{},"ISSN":["1591-9528"],"issn-type":[{"value":"1591-9528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]},"assertion":[{"value":"23 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The acquisition of human samples was approved by the Ethics Committee of Peking University First Hospital. The ethic of experimental animals was approved by the Animal Experiment Center of Peking University First Hospital.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"297"}}