{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:05:29Z","timestamp":1791471929854,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2022R1F1A1076114"],"award-info":[{"award-number":["NRF-2022R1F1A1076114"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2023R1A2C1006384"],"award-info":[{"award-number":["NRF-2023R1A2C1006384"]}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Science, ICT, and Future Planning","doi-asserted-by":"publisher","award":["NRF-2022R1F1A1076114"],"award-info":[{"award-number":["NRF-2022R1F1A1076114"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Science, ICT, and Future Planning","doi-asserted-by":"publisher","award":["NRF-2023R1A2C1006384"],"award-info":[{"award-number":["NRF-2023R1A2C1006384"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Non-alcoholic steatohepatitis (NASH) is becoming an increasingly serious global health threat, distinguished by hepatic lipid accumulation, inflammation, and fibrosis. There is a lack of approved pharmaceutical interventions for this disease, highlighting the urgent need for effective treatment. This study explores the hepatoprotective potential of 6-shogaol, a natural compound derived from ginger, in a methionine- and choline-deficient (MCD) dietary mouse model of NASH. Male C57BL\/6J mice were subjected to the MCD diet for 4 weeks to induce NASH, with concurrent intraperitoneal administration of 6-shogaol (20 mg\/kg) three times a week. While 6-shogaol did not impact body weight, liver weight, or hepatic lipid accumulation, it effectively mitigated liver injury, inflammation, and fibrosis in MCD diet-fed mice. Mechanistically, 6-shogaol inhibited lipid and DNA oxidation, restored hepatic glutathione levels, and regulated the expression of pro-oxidant and antioxidant enzymes. Furthermore, 6-shogaol inhibited apoptosis and necroptosis, as indicated by a decrease in TUNEL-stained cells and downregulation of apoptosis- and necroptosis-associated proteins. Additionally, 6-shogaol alleviated endoplasmic reticulum (ER) stress, as demonstrated by decreased expression of molecules associated with unfolded protein response pathways. These findings underscore the potential of 6-shogaol as a therapeutic intervention for NASH by targeting pathways related to oxidative stress, cell death, and ER stress.<\/jats:p>","DOI":"10.3390\/molecules29020419","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T11:15:01Z","timestamp":1705317301000},"page":"419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["6-Shogaol Ameliorates Liver Inflammation and Fibrosis in Mice on a Methionine- and Choline-Deficient Diet by Inhibiting Oxidative Stress, Cell Death, and Endoplasmic Reticulum Stress"],"prefix":"10.3390","volume":"29","author":[{"given":"Ah Young","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiryeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Hee","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2329-4374","authenticated-orcid":false,"given":"Jaechan","family":"Leem","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Eun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.metabol.2016.01.012","article-title":"Epidemiology and natural history of non-alcoholic fatty liver disease","volume":"65","author":"Fazel","year":"2016","journal-title":"Metabolism"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Guo, X., Yin, X., Liu, Z., and Wang, J. (2022). Non-Alcoholic Fatty Liver Disease (NAFLD) Pathogenesis and Natural Products for Prevention and Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415489"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Arroyave-Ospina, J.C., Wu, Z., Geng, Y., and Moshage, H. (2021). Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy. Antioxidants, 10.","DOI":"10.3390\/antiox10020174"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Shojaie, L., Iorga, A., and Dara, L. (2020). Cell Death in Liver Diseases: A Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249682"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jhep.2018.06.008","article-title":"Endoplasmic reticulum stress signaling and the pathogenesis of non-alcoholic fatty liver disease","volume":"69","author":"Lebeaupin","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s13020-023-00839-0","article-title":"Anticancer perspective of 6-shogaol: Anticancer properties, mechanism of action, synergism and delivery system","volume":"18","author":"Jia","year":"2023","journal-title":"Chin. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bischoff-Kont, I., and F\u00fcrst, R. (2021). Benefits of Ginger and Its Constituent 6-Shogaol in Inhibiting Inflammatory Processes. Pharmaceuticals, 14.","DOI":"10.3390\/ph14060571"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"809621","DOI":"10.3389\/fnut.2022.809621","article-title":"Potential Role of Ginger (Zingiber officinale Roscoe) in the Prevention of Neurodegenerative Diseases","volume":"9","author":"Arcusa","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gwon, M.-G., Gu, H., Leem, J., and Park, K.-K. (2021). Protective Effects of 6-Shogaol, an Active Compound of Ginger, in a Murine Model of Cisplatin-Induced Acute Kidney Injury. Molecules, 26.","DOI":"10.3390\/molecules26195931"},{"key":"ref_11","first-page":"7371","article-title":"Therapeutic effect of 6-shogaol on acetaminophen-induced hepatotoxicity in mice: An experimental study","volume":"26","author":"Tekin","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Guo, X., Qiu, J., and Qian, Y. (2021). 6-Shogaol Mitigates Sepsis-Associated Hepatic Injury through Transcriptional Regulation. Nutrients, 13.","DOI":"10.3390\/nu13103427"},{"key":"ref_13","first-page":"363","article-title":"6-Shogaol alleviates CCl4-induced liver fibrosis by attenuating inflammatory response in mice through the NF-\u03baB pathway","volume":"69","author":"Qiu","year":"2022","journal-title":"Acta Biochim. Pol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1111\/jgh.14122","article-title":"Mouse models of non-alcoholic steatohepatitis: A reflection on recent literature","volume":"33","author":"Haczeyni","year":"2018","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.omtn.2022.08.003","article-title":"Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation","volume":"29","author":"Latorre","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Oh, J.Y., Kim, S.H., Oh, I.J., Lee, Y.-h., Lee, K.W., Lee, W.H., and Kim, J.-H. (2020). Pharmaceutical Efficacy of Gypenoside LXXV on Non-Alcoholic Steatohepatitis (NASH). Biomolecules, 10.","DOI":"10.3390\/biom10101426"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.3390\/cimb45050279","article-title":"Protective Effects of Apamin on Acetaminophen-Induced Hepatotoxicity in Mice","volume":"45","author":"Jang","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.omtn.2021.12.017","article-title":"DRAM1 increases the secretion of PKM2-enriched EVs from hepatocytes to promote macrophage activation and disease progression in ALD","volume":"27","author":"Tan","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Park, J.-H., Leem, J., and Lee, S.-J. (2022). Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction. Antioxidants, 11.","DOI":"10.3390\/antiox11122341"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kim, J.-Y., Choi, Y., Leem, J., and Song, J.E. (2021). Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158253"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.omtn.2021.12.020","article-title":"Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver","volume":"27","author":"Ma","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jo, J., Kim, J.-Y., and Leem, J. (2022). Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury. J. Clin. Med., 11.","DOI":"10.3390\/jcm11237196"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, Y.-M., Lian, C.-F., Sun, Q.-W., Wang, T.-T., Liu, Y.-Y., Ye, J., Gao, L.-L., Yang, Y.-F., Liu, S.-N., and Shen, Z.-F. (2022). Ramulus Mori (Sangzhi) Alkaloids Alleviate High-Fat Diet-Induced Obesity and Nonalcoholic Fatty Liver Disease in Mice. Antioxidants, 11.","DOI":"10.3390\/antiox11050905"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lee, J.A., Shin, M.-R., Choi, J., Kim, M., Park, H.-J., and Roh, S.-S. (2023). Co-Treatments of Gardeniae Fructus and Silymarin Ameliorates Excessive Oxidative Stress-Driven Liver Fibrosis by Regulation of Hepatic Sirtuin1 Activities Using Thioacetamide-Induced Mice Model. Antioxidants, 12.","DOI":"10.3390\/antiox12010097"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/s41575-018-0065-y","article-title":"Apoptosis and necroptosis in the liver: A matter of life and death","volume":"15","author":"Schwabe","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/hep.32562","article-title":"Endoplasmic reticulum stress in liver diseases","volume":"77","author":"Ajoolabady","year":"2023","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.jhep.2023.04.036","article-title":"Changing epidemiology, global trends and implications for outcomes of NAFLD","volume":"79","author":"Wong","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Najmi, A., Javed, S.A., Al Bratty, M., and Alhazmi, H.A. (2022). Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents. Molecules, 27.","DOI":"10.3390\/molecules27020349"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Salvoza, N., Giraudi, P.J., Tiribelli, C., and Rosso, N. (2022). Natural Compounds for Counteracting Nonalcoholic Fatty Liver Disease (NAFLD): Advantages and Limitations of the Suggested Candidates. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052764"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3727\/105221617X15093707969658","article-title":"Updates on Dietary Models of Nonalcoholic Fatty Liver Disease: Current Studies and Insights","volume":"18","author":"Stephenson","year":"2018","journal-title":"Gene Expr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106961","DOI":"10.1016\/j.intimp.2020.106961","article-title":"Resolvin D1 mitigates non-alcoholic steatohepatitis by suppressing the TLR4-MyD88-mediated NF-\u03baB and MAPK pathways and activating the Nrf2 pathway in mice","volume":"88","author":"Li","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Machado, M.V., Michelotti, G.A., Xie, G., Pereira, T.A., Boursier, J., Bohnic, B., Gyu, C.D., and Diehl, A.M. (2015). Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132315"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1042\/BCJ20210071","article-title":"SREBP-1c and lipogenesis in the liver: An update1","volume":"478","author":"Phan","year":"2021","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lee, K.-C., Wu, K.-L., Yen, C.-K., Chen, C.-N., Chang, S.-F., and Huang, W.-S. (2021). 6-Shogaol Antagonizes the Adipocyte-Conditioned Medium-Initiated 5-Fluorouracil Resistance in Human Colorectal Cancer Cells through Controlling the SREBP-1 Level. Life, 11.","DOI":"10.3390\/life11101067"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s41575-018-0082-x","article-title":"The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"16","author":"Kazankov","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/JPER.19-0228","article-title":"6-Shogaol, an active ingredient of ginger, inhibits osteoclastogenesis and alveolar bone resorption in ligature-induced periodontitis in mice","volume":"91","author":"Kim","year":"2020","journal-title":"J. Periodontol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kawase, Y., Sunagawa, Y., Shimizu, K., Funamoto, M., Hamabe-Horiike, T., Katanasaka, Y., Shimizu, S., Hawke, P., Mori, K., and Komiyama, M. (2023). 6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure. Nutrients, 15.","DOI":"10.3390\/nu15092232"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1053\/j.gastro.2019.11.311","article-title":"Mechanisms of Fibrosis Development in Nonalcoholic Steatohepatitis","volume":"158","author":"Schwabe","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bocca, C., Protopapa, F., Foglia, B., Maggiora, M., Cannito, S., Parola, M., and Novo, E. (2022). Hepatic Myofibroblasts: A Heterogeneous and Redox-Modulated Cell Population in Liver Fibrogenesis. Antioxidants, 11.","DOI":"10.3390\/antiox11071278"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, D., Li, J., Luo, G., Zhou, J., Wang, N., Wang, S., Zhao, R., Cao, X., Ma, Y., and Liu, G. (2023). Nox4 as a novel therapeutic target for diabetic vascular complications. Redox Biol., 64.","DOI":"10.1016\/j.redox.2023.102781"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Matuz-Mares, D., V\u00e1zquez-Meza, H., and Vilchis-Landeros, M.M. (2022). NOX as a Therapeutic Target in Liver Disease. Antioxidants, 11.","DOI":"10.3390\/antiox11102038"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Sasson, A., Kristoferson, E., Batista, R., McClung, J.A., Abraham, N.G., and Peterson, S.J. (2021). The pivotal role of heme Oxygenase-1 in reversing the pathophysiology and systemic complications of NAFLD. Arch. Biochem. Biophys., 697.","DOI":"10.1016\/j.abb.2020.108679"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ryter, S.W. (2022). Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders. Antioxidants, 11.","DOI":"10.3390\/antiox11030555"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"F743","DOI":"10.1152\/ajprenal.00182.2019","article-title":"6-Shogaol protects against ischemic acute kidney injury by modulating NF-\u03baB and heme oxygenase-1 pathways","volume":"317","author":"Han","year":"2019","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yang, L., Yang, F., Teng, L., and Katayama, I. (2020). 6-Shogaol Protects Human Melanocytes against Oxidative Stress through Activation of the Nrf2-Antioxidant Response Element Signaling Pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103537"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nrm.2016.149","article-title":"Necroptosis in development, inflammation and disease","volume":"18","author":"Weinlich","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Liu, J., Li, B., Li, W., Pan, T., Diao, Y., and Wang, F. (2022). 6-Shogaol Inhibits Oxidative Stress-Induced Rat Vascular Smooth Muscle Cell Apoptosis by Regulating OXR1-p53 Axis. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.808162"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Riaz, T.A., Junjappa, R.P., Handigund, M., Ferdous, J., Kim, H.-R., and Chae, H.-J. (2020). Role of Endoplasmic Reticulum Stress Sensor IRE1\u03b1 in Cellular Physiology, Calcium, ROS Signaling, and Metaflammation. Cells, 9.","DOI":"10.3390\/cells9051160"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.redox.2015.08.010","article-title":"Calcium and ROS: A mutual interplay","volume":"6","author":"Bertram","year":"2015","journal-title":"Redox Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Cirone, M. (2021). ER Stress, UPR Activation and the Inflammatory Response to Viral Infection. Viruses, 13.","DOI":"10.3390\/v13050798"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"154577","DOI":"10.1016\/j.cyto.2018.10.018","article-title":"Crosstalk between inflammatory mediators and endoplasmic reticulum stress in liver diseases","volume":"124","author":"Duvigneau","year":"2019","journal-title":"Cytokine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1091\/mbc.E15-01-0036","article-title":"CHOP links endoplasmic reticulum stress to NF-\u03baB activation in the pathogenesis of nonalcoholic steatohepatitis","volume":"26","author":"Willy","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/415092a","article-title":"IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA","volume":"415","author":"Calfon","year":"2002","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.tibs.2014.02.008","article-title":"Getting RIDD of RNA: IRE1 in cell fate regulation","volume":"39","author":"Maurel","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"157","DOI":"10.5625\/lar.2017.33.2.157","article-title":"Comparative study of fatty liver induced by methionine and choline-deficiency in C57BL\/6N mice originating from three different sources","volume":"33","author":"Kim","year":"2017","journal-title":"Lab. Anim. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/2\/419\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:47:19Z","timestamp":1760104039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/2\/419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,15]]},"references-count":57,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["molecules29020419"],"URL":"https:\/\/doi.org\/10.3390\/molecules29020419","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,15]]}}}