{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:25:53Z","timestamp":1790803553950,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013403","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2024YFC2310902"],"award-info":[{"award-number":["2024YFC2310902"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Special Foundation for Science and Technology of Jiangsu Province","award":["BZ2024044"],"award-info":[{"award-number":["BZ2024044"]}]},{"name":"Jiangsu Province Capability Improvement Project through Science, Technology","award":["ZDXYS202207"],"award-info":[{"award-number":["ZDXYS202207"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Schistosomiasis-induced hepatic fibrosis, a consequence of egg-induced granulomatous lesions, remains untreated by current drugs. Therefore, the development of novel antifibrosis drugs is of paramount importance. Our previous study indicated that aberrant uridine concentrations play a pivotal role in schistosomiasis-induced hepatic fibrosis. This study aimed to explore the inhibitory role of uridine in schistosomiasis-induced liver fibrosis and the regulatory mechanism of uridine on hepatic stellate cell (HSC) activation. The results indicated that uridine could inhibit schistosomiasis-induced liver fibrosis in vivo and TGF-\u03b2-induced HSC activation in vitro. Molecular docking revealed a strong interaction between uridine and the adenosine receptor A1 (ADORA1) receptor. Subsequent in vitro investigations demonstrated that uridine modulated the cAMP\/PKA\/CREB pathway, influencing HSC adipogenic differentiation and exerting an antifibrotic effect. In addition, compared with praziquantel (PZQ) alone, combined uridine and PZQ therapy resulted in a reduced fibrotic area and improved hepatic parameters in vivo. Our study reveals the antifibrosis mechanism of the uridine molecule, which may be a promising drug for the treatment of schistosomiasis-induced liver fibrosis.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013403","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T17:42:07Z","timestamp":1754502127000},"page":"e1013403","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["A novel combination therapy with Uridine and Praziquantel effectively alleviates schistosomiasis-induced hepatic fibrosis through promoting adipogenic 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