{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T19:53:08Z","timestamp":1787514788187,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T00:00:00Z","timestamp":1582848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agri-Bio industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA)","award":["317004-4"],"award-info":[{"award-number":["317004-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide and the majority of HCC patients occur with a background of hepatic fibrosis and cirrhosis. We have previously reported the hepatoprotective effects of steamed and freeze-dried mature silkworm larval powder (SMSP) in a chronic ethanol-treated rat model. Here, we assessed the anti-fibrotic and anti-carcinogenic effects of SMSP on diethylnitrosamine (DEN)-treated rats. Wistar rats were intraperitoneally injected with DEN once a week for 12 or 16 weeks with or without SMSP administration (0.1 and 1 g\/kg). SMSP administration significantly attenuated tumor foci formation and proliferation in the livers of the rats treated with DEN for 16 weeks. SMSP administration also inhibited hepatic fibrosis by decreasing the levels of collagen fiber and the expression of pro-collagen I and alpha-smooth muscle actin (\u03b1-SMA). Moreover, SMSP supplementation improved the major parameters of fibrosis such as transforming growth factor-\u03b2 (TGF-\u03b2), connective tissue growth factor (CTGF), tumor necrosis factor-alpha (TNF-\u03b1), plasminogen activator inhibitor-1 (PAI-1), and collagen type I (Col1A1) in the livers from the rats treated with DEN for 16 weeks. As s possible mechanisms, we investigated the effects of SMSP on the TGF-\u03b2 and signal transducer and activator of transcription 3 (STAT3)-mediated signaling cascades, which are known to promote hepatic fibrosis. We found that SMSP treatment inhibited the activation of TGF-\u03b2 and the phosphorylation of STAT3 pathway in DEN-treated rats. Moreover, SMSP administration suppressed the expressions of the target genes of TGF-\u03b2 and STAT3 induced by DEN treatment. Our findings provide experimental evidences that SMSP administration has inhibitory effects of hepatic fibrosis and HCC induced by DEN In Vivo and could be a promising strategy for the prevention or treatment of hepatic fibrosis and hepatocellular carcinogenesis.<\/jats:p>","DOI":"10.3390\/cells9030568","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T07:35:30Z","timestamp":1583134530000},"page":"568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Administration of Steamed and Freeze-Dried Mature Silkworm Larval Powder Prevents Hepatic Fibrosis and Hepatocellular Carcinogenesis by Blocking TGF-\u03b2\/STAT3 Signaling Cascades in Rats"],"prefix":"10.3390","volume":"9","author":[{"given":"Da-Young","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Mi","family":"Yun","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Young","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Deok","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Agricultural Biology, National Institute of Agricultural Science, Rural Development Administration, Wanju 55365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Gon","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Agricultural Biology, National Institute of Agricultural Science, Rural Development Administration, Wanju 55365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-0440","authenticated-orcid":false,"given":"Eun-Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/liv.13682","article-title":"Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening","volume":"38","author":"Marcellin","year":"2018","journal-title":"Liver Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. 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