{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T01:56:59Z","timestamp":1784599019426,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26460492"],"award-info":[{"award-number":["26460492"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Non-alcoholic steatohepatitis (NASH) can cause liver cirrhosis and hepatocellular carcinoma (HCC), with cases increasing worldwide. To reduce the incidence of liver cirrhosis and HCC, NASH is targeted for the development of treatments, along with viral hepatitis and alcoholic hepatitis. Lactoferrin (LF) has antioxidant, anti-cancer, and anti-inflammatory activities. However, whether LF affects NASH and fibrosis remains unelucidated. We aimed to clarify the chemopreventive effect of LF on NASH progression. We used a NASH model with metabolic syndrome established using connexin 32 (Cx32) dominant negative transgenic (Cx32\u0394Tg) rats. Cx32\u0394Tg rats (7 weeks old) were fed a high-fat diet and intraperitoneally injected with dimethylnitrosamine (DMN). Rats were divided into three groups for LF treatment at 0, 100, or 500 mg\/kg\/day for 17 weeks. Lactoferrin significantly protected steatosis and lobular inflammation in Cx32\u0394Tg rat livers and attenuated bridging fibrosis or liver cirrhosis induced by DMN. By quantitative RT\u2013PCR, LF significantly down-regulated inflammatory (Tnf-\u03b1, Il-6, Il-18, and Il-1\u03b2) and fibrosis-related (Tgf-\u03b21, Timp2, and Col1a1) cytokine mRNAs. Phosphorylated nuclear factor (NF)-\u03baB protein decreased in response to LF, while phosphorylated JNK protein was unaffected. These results indicate that LF might act as a chemopreventive agent to prevent hepatic injury, inflammation, and fibrosis in NASH via NF-\u03baB inactivation.<\/jats:p>","DOI":"10.3390\/nu14010042","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T21:40:21Z","timestamp":1640295621000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Lactoferrin Prevents Hepatic Injury and Fibrosis via the Inhibition of NF-\u03baB Signaling in a Rat Non-Alcoholic Steatohepatitis Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Yoshinaga","family":"Aoyama","sequence":"first","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"},{"name":"Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0828-2033","authenticated-orcid":false,"given":"Aya","family":"Naiki-Ito","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang","family":"Xiaochen","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Komura","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5888-6217","authenticated-orcid":false,"given":"Hiroyuki","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Nagayasu","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Inaguma","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Nanotoxicology Project, Nagoya City University, Nagoya 467-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Tomita","sequence":"additional","affiliation":[{"name":"Dairy Techno Inc., Tokyo 105-0014, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Takiguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8139-8158","authenticated-orcid":false,"given":"Satoru","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1053\/j.gastro.2012.04.001","article-title":"The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology","volume":"142","author":"Chalasani","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-alcoholic fatty liver disease\u2014A global public health perspective","volume":"70","author":"Younossi","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrgastro.2013.41","article-title":"Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis","volume":"10","author":"Anstee","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/09687680210139839","article-title":"Gap junctions: Structure and function (Review)","volume":"19","author":"Evans","year":"2002","journal-title":"Mol. Membr. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1152\/physrev.1981.61.4.829","article-title":"Junctional intercellular communication: The cell-to-cell membrane channel","volume":"61","author":"Loewenstein","year":"1981","journal-title":"Physiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1093\/carcin\/11.7.1051","article-title":"Gap junctional intercellular communication and carcinogenesis","volume":"11","author":"Yamasaki","year":"1990","journal-title":"Carcinogenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1667\/0033-7587(2001)155[0175:ROSCAG]2.0.CO;2","article-title":"Role of stem cells and gap junctional intercellular communication in human carcinogenesis","volume":"155","author":"Trosko","year":"2001","journal-title":"Radiat. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1083\/jcb.103.1.123","article-title":"Molecular cloning of cDNA for rat liver gap junction protein","volume":"103","author":"Paul","year":"1986","journal-title":"J. Cell Biol."},{"key":"ref_10","first-page":"1539","article-title":"Connexin 32 and luteolin play protective roles in non-alcoholic steatohepatitis development and its related hepatocarcinogenesis in rats","volume":"36","author":"Sagawa","year":"2015","journal-title":"Carcinogenesis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00535-003-1386-2","article-title":"Expression of gap junction protein connexin32 in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma","volume":"39","author":"Nakashima","year":"2004","journal-title":"J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/hep.20256","article-title":"Connexin 32 dominant-negative mutant transgenic rats are resistant to hepatic damage by chemicals","volume":"40","author":"Asamoto","year":"2004","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1080\/01926230500330313","article-title":"Transgenic disruption of gap junctional intercellular communication enhances early but not late stage hepatocarcinogenesis in the rat","volume":"33","author":"Hokaiwado","year":"2005","journal-title":"Toxicol. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00232-007-9053-9","article-title":"Both early and late stages of hepatocarcinogenesis are enhanced in Cx32 dominant negative mutant transgenic rats with disrupted gap junctional intercellular communication","volume":"218","author":"Hokaiwado","year":"2007","journal-title":"J. Membr. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1007\/s00204-020-02873-5","article-title":"A novel model of non-alcoholic steatohepatitis with fibrosis and carcinogenesis in connexin 32 dominant-negative transgenic rats","volume":"94","author":"Kato","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1139\/bcb-2020-0087","article-title":"Effects of oral bovine lactoferrin on a mouse model of inflammation associated colon cancer","volume":"99","author":"Tanaka","year":"2021","journal-title":"Biochem. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1046\/j.1440-1746.2002.02868.x","article-title":"Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance","volume":"17","author":"Togawa","year":"2002","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1080\/01480545.2019.1585868","article-title":"Anti-inflammatory, anti-oxidant and hepatoprotective effects of lactoferrin in rats","volume":"44","author":"Farid","year":"2021","journal-title":"Drug Chem. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1089\/jmf.2015.3634","article-title":"Lactoferrin Increases Antioxidant Activities and Ameliorates Hepatic Fibrosis in Lupus-Prone Mice Fed with a High-Cholesterol Diet","volume":"19","author":"Chen","year":"2016","journal-title":"J. Med. Food"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3168\/jds.2010-3629","article-title":"The effect of bovine milk lactoferrin on human breast cancer cell lines","volume":"94","author":"Duarte","year":"2011","journal-title":"J. Dairy Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.3168\/jds.2009-2926","article-title":"Apoptosis of stomach cancer cell SGC-7901 and regulation of Akt signaling way induced by bovine lactoferrin","volume":"93","author":"Xu","year":"2010","journal-title":"J. Dairy Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8683","DOI":"10.1158\/1078-0432.CCR-04-0988","article-title":"Lactoferrin down-regulates G1 cyclin-dependent kinases during growth arrest of head and neck cancer cells","volume":"10","author":"Xiao","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1158\/1940-6207.CAPR-08-0208","article-title":"Effect of orally administered bovine lactoferrin on the growth of adenomatous colorectal polyps in a randomized, placebo-controlled clinical trial","volume":"2","author":"Kozu","year":"2009","journal-title":"Cancer Prev. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1177\/0192623312441402","article-title":"Age-dependent carcinogenic susceptibility in rat liver is related to potential of gap junctional intercellular communication","volume":"40","author":"Kato","year":"2012","journal-title":"Toxicol. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1053\/j.gastro.2005.09.004","article-title":"NF-kappaB activation, rather than TNF, mediates hepatic inflammation in a murine dietary model of steatohepatitis","volume":"129","author":"Leclercq","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-beta signaling and hepatic fibrosis","volume":"13","author":"Seki","year":"2007","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1111\/j.1572-0241.2007.01774.x","article-title":"Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis","volume":"103","author":"Wieckowska","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/s41575-019-0169-z","article-title":"NAFLD in children: New genes, new diagnostic modalities and new drugs","volume":"16","author":"Nobili","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.jhep.2004.05.008","article-title":"Association of non-alcoholic steatohepatitis without significant fibrosis with hepatocellular carcinoma","volume":"41","author":"Bullock","year":"2004","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1002\/hep.1840360609","article-title":"NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States","volume":"36","author":"Marrero","year":"2002","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1053\/j.gastro.2008.06.047","article-title":"Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis","volume":"135","author":"Aithal","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1053\/j.gastro.2008.03.078","article-title":"Rosiglitazone for nonalcoholic steatohepatitis: One-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial","volume":"135","author":"Ratziu","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1056\/NEJMoa0907929","article-title":"Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis","volume":"362","author":"Sanyal","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1111\/j.1572-0241.2003.08699.x","article-title":"Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis","volume":"98","author":"Harrison","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1016\/S0140-6736(10)61272-X","article-title":"Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: A post-hoc analysis","volume":"376","author":"Athyros","year":"2010","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1056\/NEJMoa072761","article-title":"Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes","volume":"356","author":"Nissen","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s40265-015-0437-3","article-title":"Non-Alcoholic Steatohepatitis: Limited Available Treatment Options but Promising Drugs in Development and Recent Progress Towards a Regulatory Approval Pathway","volume":"75","author":"Filozof","year":"2015","journal-title":"Drugs"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1159\/000491535","article-title":"Decreased Hepatic Lactotransferrin Induces Hepatic Steatosis in Chronic Non-Alcoholic Fatty Liver Disease Model","volume":"47","author":"Lee","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Min, Q.Q., Qin, L.Q., Sun, Z.Z., Zuo, W.T., Zhao, L., and Xu, J.Y. (2018). Effects of Metformin Combined with Lactoferrin on Lipid Accumulation and Metabolism in Mice Fed with High-Fat Diet. Nutrients, 10.","DOI":"10.3390\/nu10111628"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4328","DOI":"10.1039\/C8FO00317C","article-title":"Lactoferrin attenuates high-fat diet-induced hepatic steatosis and lipid metabolic dysfunctions by suppressing hepatic lipogenesis and down-regulating inflammation in C57BL\/6J mice","volume":"9","author":"Xiong","year":"2018","journal-title":"Food Funct."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, Y.C., and Hsieh, C.C. (2014). Lactoferrin dampens high-fructose corn syrup-induced hepatic manifestations of the metabolic syndrome in a murine model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097341"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"97","DOI":"10.5650\/jos.62.97","article-title":"Bovine lactoferrin reduces visceral fat and liver triglycerides in ICR mice","volume":"62","author":"Morishita","year":"2013","journal-title":"J. Oleo Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/j.1572-0241.1999.01377.x","article-title":"Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions","volume":"94","author":"Brunt","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrgastro.2017.38","article-title":"Mechanisms of hepatic stellate cell activation","volume":"14","author":"Tsuchida","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1002\/iub.1884","article-title":"Heat shock protein 47 as indispensible participant in liver fibrosis: Possible protective effect of lactoferrin","volume":"70","author":"Rizk","year":"2018","journal-title":"IUBMB Life"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3889\/oamjms.2015.038","article-title":"Lactoferrin Enhanced Apoptosis and Protected Against Thioacetamide-Induced Liver Fibrosis in Rats","volume":"3","author":"Hessin","year":"2015","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.pharep.2019.04.019","article-title":"Regulation of PKB\/Akt-pathway in the chemopreventive effect of lactoferrin against diethylnitrosamine-induced hepatocarcinogenesis in rats","volume":"71","author":"Hegazy","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/tox.22773","article-title":"Antihepatocarcinogenic activity of whey protein concentrate and lactoferrin in diethylnitrosamine-treated male albino mice","volume":"34","author":"Mohammed","year":"2019","journal-title":"Environ. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6228","DOI":"10.1038\/onc.2008.300","article-title":"NF-kappaB signaling, liver disease and hepatoprotective agents","volume":"27","author":"Sun","year":"2008","journal-title":"Oncogene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1172\/JCI121842","article-title":"STING-mediated inflammation in Kupffer cells contributes to progression of nonalcoholic steatohepatitis","volume":"129","author":"Yu","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.jhep.2020.03.051","article-title":"TGF-beta-driven reduction of cytoglobin leads to oxidative DNA damage in stellate cells during non-alcoholic steatohepatitis","volume":"73","author":"Okina","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Liu, C., Yuan, X., Tao, L., Cheng, Z., Dai, X., Sheng, X., and Xue, D. (2015). Xia-yu-xue decoction (XYXD) reduces carbon tetrachloride (CCl4)-induced liver fibrosis through inhibition hepatic stellate cell activation by targeting NF-kappaB and TGF-beta1 signaling pathways. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0733-1"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/1\/42\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:52:19Z","timestamp":1760169139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/1\/42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["nu14010042"],"URL":"https:\/\/doi.org\/10.3390\/nu14010042","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,23]]}}}