{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:48:44Z","timestamp":1785293324117,"version":"3.55.0"},"reference-count":58,"publisher":"Portland Press Ltd.","issue":"5","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/501100004043","name":"Kanazawa Medical University","doi-asserted-by":"crossref","award":["RP 2017-05"],"award-info":[{"award-number":["RP 2017-05"]}],"id":[{"id":"10.13039\/501100004043","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,3,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Metabolic dysfunction-associated steatohepatitis (MASH) is always accompanied with hepatic fibrosis that could potentially progress to liver cirrhosis and hepatocellular carcinoma. Employing a rat model, we evaluated the role of human placental extract (HPE) to arrest the progression of hepatic fibrosis to cirrhosis in patients with MASH. SHRSP5\/Dmcr rats were fed with a high-fat and high-cholesterol diet for 4 weeks and evaluated for the development of steatosis. The animals were divided into control and treated groups and received either saline or HPE (3.6 ml\/kg body weight) subcutaneously thrice a week. A set of animals were killed at the end of 6th, 8th, and 12th weeks from the beginning of the experiment. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatic malondialdehyde (MDA), and glutathione content were measured. Immunohistochemical staining was performed for \u03b1-smooth muscle actin (\u03b1-SMA), 4-hydroxy-2-nonenal (4-HNE), collagen type I, and type III. Control rats depicted progression of liver fibrosis at 6 weeks, advanced fibrosis and bridging at 8 weeks, and cirrhosis at 12 weeks, which were significantly decreased in HPE-treated animals. Treatment with HPE maintained normal levels of MDA and glutathione in the liver. There was marked decrease in the staining intensity of \u03b1-SMA, 4-HNE, and collagen type I and type III in HPE treated rats compared with control animals. The results of the present study indicated that HPE treatment mediates immunotropic, anti-inflammatory, and antioxidant responses and attenuates hepatic fibrosis and early cirrhosis. HPE depicts therapeutic potential to arrest the progression of MASH towards cirrhosis.<\/jats:p>","DOI":"10.1042\/cs20230533","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T18:42:00Z","timestamp":1708540920000},"page":"327-349","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Therapeutic implication of human placental extract to prevent liver cirrhosis in rats with metabolic dysfunction-associated steatohepatitis"],"prefix":"10.1042","volume":"138","author":[{"given":"Mitsuyoshi","family":"Yamagata","sequence":"first","affiliation":[{"name":"1Department of Hepatology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsumi","family":"Tsuchishima","sequence":"additional","affiliation":[{"name":"1Department of Hepatology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Saito","sequence":"additional","affiliation":[{"name":"1Department of Hepatology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikihiro","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"1Department of Hepatology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"},{"name":"2Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"George","sequence":"additional","affiliation":[{"name":"1Department of Hepatology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan"},{"name":"2Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Ishikawa 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"2024030507403174000_B1","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1056\/NEJMoa2029349","article-title":"NASH Clinical Research Network (CRN). 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