{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T19:30:27Z","timestamp":1792956627868,"version":"4.5.0"},"reference-count":64,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academy of Science and Technology (ASRT)","award":["jesor_5269"],"award-info":[{"award-number":["jesor_5269"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated. Aim: Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related (HSPD1\/TNF\/MMP14\/ITGB1) mRNAs and their upstream noncoding RNA regulators (miRNA-6881-5P and lnc-SPARCL1-1:2) in NASH rats. Results: High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg\/kg\/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both (HSPD1\/TNF\/MMP14\/ITGB1) mRNAs and their epigenetic regulators (miRNA-6881-5P and lnc-SPARCL1-1:2). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-\u03b1, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats. Conclusion: Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (HSPD1, TNF, MMP14, and ITGB1) mRNAs\u2014(miRNA-6881-5P\u2014(lnc-SPARCL1-1:2) RNA panel.<\/jats:p>","DOI":"10.3390\/ijms231710148","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T05:17:23Z","timestamp":1662441443000},"page":"10148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9506-3017","authenticated-orcid":false,"given":"Reda","family":"Albadawy","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology & Infectious Disease, Faculty of Medicine, Benha University, Benha 13518, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-4350","authenticated-orcid":false,"given":"Amany Helmy","family":"Hasanin","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2382-0189","authenticated-orcid":false,"given":"Sara H. A.","family":"Agwa","sequence":"additional","affiliation":[{"name":"Clinical Pathology and Molecular Genomics Unit, Medical Ain Shams Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo 11382, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7987-8777","authenticated-orcid":false,"given":"Shaimaa","family":"Hamady","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin M.","family":"Aboul-Ela","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0779-5603","authenticated-orcid":false,"given":"Mona Hussien","family":"Raafat","sequence":"additional","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaa Samir","family":"Kamar","sequence":"additional","affiliation":[{"name":"Histology and Cell Biology Department, Kasralainy Faculty of Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Othman","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahia A.","family":"Yahia","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Misr University for Science and Technology, Giza 12566, Egypt"},{"name":"Chemistry Department, School of Science and Engineering, American University in Cairo, New Cairo 11835, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6852-3954","authenticated-orcid":false,"given":"Marwa","family":"Matboli","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pouwels, S., Sakran, N., Graham, Y., Leal, A., Pintar, T., Yang, W., Kassir, R., Singhal, R., Mahawar, K., and Ramnarain, D. (2022). Non-alcoholic fatty liver disease (NAFLD): A review of pathophysiology, clinical management and effects of weight loss. BMC Endocr. Disord., 22.","DOI":"10.1186\/s12902-022-00980-1"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111781","DOI":"10.1016\/j.biopha.2021.111781","article-title":"Probiotic-prebiotic-synbiotic modulation of (YAP1, LATS1 and NF2 mRNAs\/miR-1205\/lncRNA SRD5A3-AS1) panel in NASH animal model","volume":"140","author":"Gadallah","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4254\/wjh.v14.i1.119","article-title":"Is there a role of lipid-lowering therapies in the management of fatty liver disease?","volume":"27","author":"Tzanaki","year":"2022","journal-title":"World J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Albadawy, R., Agwa, S.H.A., Khairy, E., Saad, M., El Touchy, N., Othman, M., and Matboli, M. (2021). Clinical significance of hspd1\/mmp14\/itgb1\/mir-6881-5p\/lnc-sparcl1-1:2 rna panel in nafld\/nash diagnosis: Egyptian pilot study. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091248"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1016\/j.jhep.2014.12.012","article-title":"NAFLD: A multisystem disease","volume":"62","author":"Byrne","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"G67","DOI":"10.1152\/ajpgi.00009.2021","article-title":"Sinusoidal endotheliopathy in nonalcoholic steatohepatitis: Therapeutic implications","volume":"321","author":"Ibrahim","year":"2021","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nasiri-Ansari, N., Androutsakos, T., Flessa, C., Kyrou, I., Siasos, G., Randeva, H.S., Kassi, E., and Papavassiliou, A.G. (2022). Endothelial Cell Dysfunction and Nonalcoholic Fatty Liver Disease (NAFLD): A Concise Review. Cell, 11.","DOI":"10.3390\/cells11162511"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lafoz, E., Ruart, M., Anton, A., Oncins, A., and Hern\u00e1ndez-Gea, V. (2020). The Endothelium as a Driver of Liver Fibrosis and Regeneration. Cells, 9.","DOI":"10.3390\/cells9040929"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.matbio.2015.01.004","article-title":"Matrix metalloproteinases in liver injury, repair and fibrosis","volume":"44","author":"Duarte","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3389\/fphys.2019.00279","article-title":"Regulatory non-coding RNAs network in non-alcoholic fatty liver disease","volume":"10","author":"Sulaiman","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Matboli, M., Gadallah, S.H., Rashed, W.M., Hasanin, A.H., Essawy, N., Ghanem, H.M., and Eissa, S. (2021). Mrna-mirna-lncrna regulatory network in nonalcoholic fatty liver disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136770"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e12661","DOI":"10.14814\/phy2.12661","article-title":"Novel hepatic microRNAs upregulated in human nonalcoholic fatty liver disease","volume":"4","author":"Soronen","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/iub.1442","article-title":"Genome-wide analysis of long noncoding RNA expression profiles in patients with non-alcoholic fatty liver disease","volume":"67","author":"Sun","year":"2015","journal-title":"IUBMB Life"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25399","DOI":"10.1038\/srep25399","article-title":"Salidroside improves glucose homeostasis in obese mice by repressing inflammation in white adipose tissues and improving leptin sensitivity in hypothalamus","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, K., Si, X.P., Huang, J., Han, J., Liang, X., Xu, X.B., Wang, Y.T., Li, G.Y., Wang, H.Y., and Wang, J.H. (2016). Preventive effects of Rhodiola rosea L. On bleomycin-induced pulmonary fibrosis in rats. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060879"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s12192-015-0654-4","article-title":"Salidroside protects against bleomycin-induced pulmonary fibrosis: Activation of Nrf2-antioxidant signaling, and inhibition of NF-\u03baB and TGF-\u03b21\/Smad-2\/-3 pathways","volume":"21","author":"Tang","year":"2016","journal-title":"Cell Stress Chaperones"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.fct.2017.02.009","article-title":"Altered expression of TRAIL on mouse T cells via ERK phosphorylation by Rhodiola rosea L. and its marker compounds","volume":"108","author":"Marchev","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109552","DOI":"10.1016\/j.biopha.2019.109552","article-title":"Anti-inflammatory effects of Rhodiola rosea L.: A review","volume":"121","author":"Pu","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1101\/gr.133553.111","article-title":"Discovery of hundreds of mirtrons in mouse and human small RNA data","volume":"22","author":"Ladewig","year":"2012","journal-title":"Genome Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Puengel, T., Liu, H., Guillot, A., Heymann, F., Tacke, F., and Peiseler, M. (2022). Nuclear Receptors Linking Metabolism, Inflammation, and Fibrosis in Nonalcoholic Fatty Liver Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052668"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41419-020-2283-9","article-title":"Hepatocyte apoptosis is tumor promoting in murine nonalcoholic steatohepatitis","volume":"11","author":"Hirsova","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jcmgh.2014.11.005","article-title":"Death Receptor-Mediated Cell Death and Proinflammatory Signaling in Nonalcoholic Steatohepatitis","volume":"1","author":"Hirsova","year":"2015","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Huang, Y.H., Wang, F.S., Wang, P.W., Lin, H.Y., Luo, S.D., and Yang, Y.L. (2022). Heat Shock Protein 60 Restricts Release of Mitochondrial dsRNA to Suppress Hepatic Inflammation and Ameliorate Non-Alcoholic Fatty Liver Disease in Mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010577"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3389\/fmolb.2020.00060","article-title":"Heat Shock Protein 60 in Hepatocellular Carcinoma: Insights and Perspectives","volume":"7","author":"Hoter","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1093\/cvr\/cvaa158","article-title":"Dilated cardiomyopathy-linked heat shock protein family D member 1 mutations cause up-regulation of reactive oxygen species and autophagy through mitochondrial dysfunction","volume":"117","author":"Enomoto","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6467","DOI":"10.18632\/aging.102972","article-title":"Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease","volume":"12","author":"Li","year":"2020","journal-title":"Aging"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Singh, P. (2019). Evaluation of Pro-Inflammatory Markers IL-6 and TNF-a and their Correlation with Non-Alcoholic Fatty Liver Disease. J. Adv. Res. Med., 6.","DOI":"10.24321\/2349.7181.201906"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4103\/tmj.tmj_15_18","article-title":"Effects of berberine on high-fat\/high-sucrose-induced nonalcoholic steatohepatitis in experimental rats","volume":"47","author":"Eman","year":"2019","journal-title":"Tanta Med. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.matbio.2017.12.012","article-title":"Matrix metalloproteinases and liver fibrosis (translational aspects)","volume":"68","author":"Roeb","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0168-8278(01)00177-5","article-title":"Dynamic change of cells expressing MMP-2 mRNA and MT1-MMP mRNA in the recovery from liver fibrosis in the rat","volume":"35","author":"Watanabe","year":"2001","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.jhep.2019.07.019","article-title":"Integrin \u03b21-enriched extracellular vesicles mediate monocyte adhesion and promote liver inflammation in murine NASH","volume":"71","author":"Guo","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.3748\/wjg.v24.i25.2661","article-title":"Apoptosis and non-alcoholic fatty liver diseases","volume":"24","author":"Kanda","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3389\/fendo.2019.00665","article-title":"Inhibiting ceramide synthesis attenuates hepatic steatosis and fibrosis in rats with non-alcoholic fatty liver disease","volume":"10","author":"Jiang","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1055\/s-0035-1571272","article-title":"Targeting Cell Death and Sterile Inflammation Loop for the Treatment of Nonalcoholic Steatohepatitis","volume":"36","author":"Wree","year":"2016","journal-title":"Semin. Liver Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1159\/000366394","article-title":"Aberrant hepatic MicroRNA expression in nonalcoholic fatty liver disease","volume":"34","author":"Feng","year":"2014","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.3389\/fcell.2021.736677","article-title":"Analysis of miRNAs Profiles in Serum of Patients with Steatosis and Steatohepatitis","volume":"9","author":"Vulf","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yu, J., Peng, J., Luan, Z., Zheng, F., and Su, W. (2019). MicroRNAs as a novel tool in the diagnosis of liver lipid dysregulation and fatty liver disease. Molecules, 24.","DOI":"10.3390\/molecules24020230"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12986-021-00552-5","article-title":"A comprehensive review of long non-coding RNAs in the pathogenesis and development of non-alcoholic fatty liver disease","volume":"18","author":"Shabgah","year":"2021","journal-title":"Nutr. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.7150\/ijbs.59588","article-title":"Micrornas in the pathogenesis of nonalcoholic fatty liver disease","volume":"17","author":"Fang","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_40","first-page":"24","article-title":"The role of miRNAs in the regulation of inflammatory processes during hepatofibrogenesis","volume":"4","author":"Roy","year":"2015","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kim, Y.A., Park, K.K., and Lee, S.J. (2020). LncRNAs act as a link between chronic liver disease and hepatocellular carcinoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082883"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhang, X., Wang, W., Zhu, W., Dong, J., Cheng, Y., Yin, Z., and Shen, F. (2019). Mechanisms and functions of long non-coding RNAs at multiple regulatory levels. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225573"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41580-020-00315-9","article-title":"Gene regulation by long non-coding RNAs and its biological functions","volume":"22","author":"Statello","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"489","DOI":"10.4196\/kjpp.2021.25.5.489","article-title":"5-HT1A receptors mediate the analgesic effect of rosavin in a mouse model of oxaliplatin-induced peripheral neuropathic pain","volume":"25","author":"Li","year":"2021","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/hep.27173","article-title":"Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease","volume":"60","author":"Bedossa","year":"2014","journal-title":"Hepatology"},{"key":"ref_46","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_47","first-page":"2561","article-title":"Tetramethylpyrazine reduces inflammation in the livers of mice fed a high fat diet","volume":"19","author":"Chen","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"113070","DOI":"10.1016\/j.biopha.2022.113070","article-title":"Anti-inflammatory effect of trans-anethol in a rat model of myocardial ischemia-reperfusion injury","volume":"150","author":"Matboli","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"102022","DOI":"10.1016\/j.isci.2020.102022","article-title":"Cryo-EM structure of human mitochondrial HSPD1","volume":"24","author":"Klebl","year":"2021","journal-title":"iScience"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1083\/jcb.201111077","article-title":"Crystal structure of \u03b15\u03b21 integrin ectodomain: Atomic details of the fibronectin receptor","volume":"197","author":"Nagae","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1021\/acs.jmedchem.0c01280","article-title":"Development of Orally Efficacious Allosteric Inhibitors of TNF\u03b1 via Fragment-Based Drug Design","volume":"65","author":"Dietrich","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7587","DOI":"10.1074\/jbc.M110.178434","article-title":"The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: Crystal structure and biological functions","volume":"286","author":"Tochowicz","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10600-006-0165-8","article-title":"Synthesis of the Rhodiola rosea glycoside rosavin","volume":"42","author":"Patov","year":"2006","journal-title":"Chem. Nat. Compd."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open Babel: An open chemical toolbox","volume":"3","author":"Banck","year":"2011","journal-title":"J. Cheminform."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Linares, I., P\u00e9rez-S\u00e1nchez, H., Cecilia, J.M., and Garc\u00eda, J.M. (2012). High-Throughput parallel blind Virtual Screening using BINDSURF. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-S14-S13"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"Olson AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"W530","DOI":"10.1093\/nar\/gkab294","article-title":"PLIP 2021: Expanding the scope of the protein-ligand interaction profiler to DNA and RNA","volume":"49","author":"Adasme","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1748-7188-6-26","article-title":"ViennaRNA Package 2.0","volume":"6","author":"Lorenz","year":"2011","journal-title":"Algorithms Mol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e112","DOI":"10.1093\/nar\/gks339","article-title":"Automated 3D structure composition for large RNAs","volume":"40","author":"Popenda","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_61","first-page":"737","article-title":"New functionality of RNAComposer: An application to shape the axis of miR160 precursor structure","volume":"63","author":"Antczak","year":"2016","journal-title":"Acta Biochim. Pol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7173","DOI":"10.1021\/acs.jctc.0c00798","article-title":"RLDOCK: A New Method for Predicting RNA-Ligand Interactions","volume":"16","author":"Sun","year":"2020","journal-title":"J. Chem. Theory Comput."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s11658-021-00254-z","article-title":"Targeting programmed cell death in metabolic dysfunction-associated fatty liver disease (MAFLD): A promising new therapy","volume":"26","author":"Zhao","year":"2021","journal-title":"Cell. Mol. Biol. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/10148\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:23:20Z","timestamp":1760142200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/10148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,5]]},"references-count":64,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231710148"],"URL":"https:\/\/doi.org\/10.3390\/ijms231710148","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,5]]}}}