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Advanced HF, characterized by an excess of extracellular matrix (ECM), is mediated by TGF- \u03b21, that activates hepatic stellate cells (HSCs) and fibroblasts. A TGF-\u03b21 receptor inhibitor, LY2157299 or Galunisertib (GLY), has shown promising results against chronic liver progression in animal models, and we show that it can be further improved by enhancing GLYs bioavailability through encapsulation in polymeric polygalacturonic-polyacrylic acid nanomicelles (GLY-NMs). GLY-NMs reduced HF in an in vivo rat model of liver fibrosis induced by intraperitoneal injection of CCl4 as shown by the morphological, biochemical, and molecular biology parameters of normal and fibrotic livers. Moreover, GLY-NM was able to induce recovery from HF better than free GLY. Indeed, the encapsulated drug reduces collagen deposition, hepatic stellate cells (HSCs) activation, prevents fatty degeneration and restores the correct lobular architecture of the liver as well as normalizes the serum parameters and expression of the genes involved in the onset of HF. In summary, GLY-NM improved the pharmacological activity of the free TGF- \u03b21 inhibitor in the in vivo HF treatment and thus is a candidate as a novel therapeutic strategy.<\/jats:p>","DOI":"10.3390\/jpm12111812","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T03:36:44Z","timestamp":1667360204000},"page":"1812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Therapeutic Effect of Polymeric Nanomicelles Formulation of LY2157299-Galunisertib on CCl4-Induced Liver Fibrosis in Rats"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4219-4272","authenticated-orcid":false,"given":"Elisa","family":"Panzarini","sequence":"first","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-7565","authenticated-orcid":false,"given":"Stefano","family":"Leporatti","sequence":"additional","affiliation":[{"name":"Consiglio Nazionale delle Ricerche (CNR) NANOTEC istituto di Nanotecnologia-Istituto di Nanotecnologia, 73100 Lecce, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardetta","family":"Tenuzzo","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1911-9864","authenticated-orcid":false,"given":"Alessandra","family":"Quarta","sequence":"additional","affiliation":[{"name":"Consiglio Nazionale delle Ricerche (CNR) NANOTEC istituto di Nanotecnologia-Istituto di Nanotecnologia, 73100 Lecce, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-6973","authenticated-orcid":false,"given":"Nemany","family":"Hanafy","sequence":"additional","affiliation":[{"name":"Nanomedicine Department, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, Kafr El Sheikh 6860404, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluigi","family":"Giannelli","sequence":"additional","affiliation":[{"name":"National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7979-4939","authenticated-orcid":false,"given":"Camilla","family":"Moliterni","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Vardanyan","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Sbarigia","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1287-9601","authenticated-orcid":false,"given":"Marco","family":"Fidaleo","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Research Center for Nanotechnology for Engineering of Sapienza (CNIS), Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Tacconi","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2633-9040","authenticated-orcid":false,"given":"Luciana","family":"Dini","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Research Center for Nanotechnology for Engineering of Sapienza (CNIS), Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.7150\/ijbs.37500","article-title":"Matrix Mechanics as Regulatory Factors and Therapeutic Targets in Hepatic Fibrosis","volume":"15","author":"Chen","year":"2019","journal-title":"Int. J. Biol. Sci."},{"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. Rev. Pathol. Mech. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mam.2018.09.002","article-title":"Liver Fibrosis: Pathophysiology, Pathogenetic Targets and Clinical Issues","volume":"65","author":"Parola","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1126\/science.1176009","article-title":"The Extracellular Matrix: Not Just Pretty Fibrils","volume":"326","author":"Hynes","year":"2009","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev-pathol-052016-100322","article-title":"The Role of Cancer-Associated Fibroblasts and Fibrosisin Liver Cancer","volume":"12","author":"Affo","year":"2017","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Baglieri, J., Brenner, D.A., and Kisseleva, T. (2019). The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071723"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7666","DOI":"10.3748\/wjg.v23.i43.7666","article-title":"Pathological Process of Liver Sinusoidal Endothelial Cells in Liver Diseases","volume":"23","author":"Ni","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1172\/JCI92823","article-title":"Building Discontinuous Liver Sinusoidal Vessels","volume":"127","author":"Griffin","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1152\/ajpgi.00167.2007","article-title":"First Published December 6","volume":"294","author":"Elvevold","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4097205","DOI":"10.1155\/2017\/4097205","article-title":"SECs (Sinusoidal Endothelial Cells), Liver Microenvironment, and Fibrosis","volume":"2017","author":"Natarajan","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/hep.27332","article-title":"Hepatic Inflammation and Fibrosis: Functional Links and Key Pathways","volume":"61","author":"Seki","year":"2015","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s12072-018-9897-3","article-title":"Antifibrotics in Liver Disease: Are We Getting Closer to Clinical Use?","volume":"13","author":"Bansal","year":"2019","journal-title":"Hepatol. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"942841","DOI":"10.3389\/fphar.2022.942841","article-title":"Treatment of Liver Fibrosis: A 20-Year Bibliometric and Knowledge-Map Analysis","volume":"13","author":"Dai","year":"2022","journal-title":"Front. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13817","DOI":"10.1038\/ncomms13817","article-title":"Hepcidin Inhibits Smad3 Phosphorylation in Hepatic Stellate Cells by Impeding Ferroportin-Mediated Regulation of Akt","volume":"7","author":"Han","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dewidar, B., Meyer, C., Dooley, S., and Meindl-Beinker, N. (2019). Tgf-\u03b2 in Hepatic Stellate Cell Activation and Liver Fibrogenesis\u2014Updated 2019. Cells, 8.","DOI":"10.3390\/cells8111419"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3389\/fonc.2018.00357","article-title":"Transforming Growth Factor-\u03b2-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis","volume":"8","author":"Fabregat","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00441-011-1246-y","article-title":"TGF-\u03b2 in Progression of Liver Disease","volume":"347","author":"Dooley","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2008.07.001","article-title":"TGF\u03b2 in Cancer","volume":"134","year":"2008","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Khomich, O., Ivanov, A.V., and Bartosch, B. (2020). Metabolic Hallmarks of Hepatic Stellate Cells in Liver Fibrosis. Cells, 9.","DOI":"10.3390\/cells9010024"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1158\/0008-5472.CAN-14-0243","article-title":"Transforming Growth Factor-\u03b2 as a Therapeutic Target in Hepatocellular Carcinoma","volume":"74","author":"Giannelli","year":"2014","journal-title":"Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1002\/cam4.3880","article-title":"Phase 1b Study of Galunisertib and Ramucirumab in Patients with Advanced Hepatocellular Carcinoma","volume":"10","author":"Harding","year":"2021","journal-title":"Cancer Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00056","DOI":"10.14309\/ctg.0000000000000056","article-title":"A Phase 2 Study of Galunisertib (TGF-B1 Receptor Type i Inhibitor) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma","volume":"10","author":"Kelley","year":"2019","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e002068","DOI":"10.1136\/jitc-2020-002068","article-title":"Safety and Activity of the TGF\u03b2 Receptor i Kinase Inhibitor Galunisertib plus the Anti-PD-L1 Antibody Durvalumab in Metastatic Pancreatic Cancer","volume":"9","author":"Melisi","year":"2021","journal-title":"J. Immunother. Cancer."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1080\/14656566.2020.1774553","article-title":"Current and Emerging Pharmacotherapeutic Interventions for the Treatment of Liver Fibrosis","volume":"21","author":"Lambrecht","year":"2020","journal-title":"Expert Opin. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Roehlen, N., Crouchet, E., and Baumert, T.F. (2020). Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells, 9.","DOI":"10.3390\/cells9040875"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1007\/s00204-018-2231-y","article-title":"Galunisertib Modifies the Liver Fibrotic Composition in the Abcb4Ko Mouse Model","volume":"92","author":"Hammad","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6997","DOI":"10.2147\/IJN.S145951","article-title":"Nanoparticles for the Treatment of Liver Fibrosis","volume":"12","author":"Surendran","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nikolova, M.P., and Chavali, M.S. (2020). Metal Oxide Nanoparticles as Biomedical Materials. Biomimetics, 5.","DOI":"10.3390\/biomimetics5020027"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1002\/hep.27936","article-title":"Specific Hepatic Delivery of Procollagen A1(I) Small Interfering RNA in Lipid-like Nanoparticles Resolves Liver Fibrosis","volume":"62","author":"Sehgal","year":"2015","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.nantod.2010.06.007","article-title":"Polymer- and Lipid-Based Nanoparticle Therapeutics for the Treatment of Liver Diseases","volume":"5","author":"Li","year":"2010","journal-title":"Nano Today"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0168-8278(00)80222-6","article-title":"Dexamethasone Coupled to Albumin Is Selectively Taken up by Rat Nonparenchymal Liver Cells and Attenuates LPS-Induced Activation of Hepatic Cells","volume":"32","author":"Melgert","year":"2000","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6699","DOI":"10.1039\/C7RA10847H","article-title":"The Diagnosis of Hepatic Fibrosis by Magnetic Resonance and Near-Infrared Imaging Using Dual-Modality Nanoparticles","volume":"8","author":"Li","year":"2018","journal-title":"RSC Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00418-018-1753-y","article-title":"Molecular Imaging with Nanoparticles: The Dwarf Actors Revisited 10 Years Later","volume":"150","author":"Thurner","year":"2018","journal-title":"Histochem. Cell. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4041415","DOI":"10.1155\/2021\/4041415","article-title":"The Emerging Role of Nanomedicine in the Management of Nonalcoholic Fatty Liver Disease: A State-of-the-Art Review","volume":"2021","author":"Moosavian","year":"2021","journal-title":"Bioinorg. Chem. Appl."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kaps, L., and Schuppan, D. (2020). Targeting Cancer Associated Fibroblasts in Liver Fibrosis and Liver Cancer Using Nanocarriers. Cells, 9.","DOI":"10.3390\/cells9092027"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.apsb.2019.07.003","article-title":"Targeted Delivery of Hyaluronic Acid Nanomicelles to Hepatic Stellate Cells in Hepatic Fibrosis Rats","volume":"10","author":"Li","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nrd2591","article-title":"Strategies in the Design of Nanoparticles for Therapeutic Applications","volume":"9","author":"Petros","year":"2010","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1021\/acs.molpharmaceut.0c00633","article-title":"SB431542-Loaded Liposomes Alleviate Liver Fibrosis by Suppressing Tgf-\u03b2 Signaling","volume":"17","author":"Zhang","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1039\/C5CS00798D","article-title":"Smart Micro\/Nanoparticles in Stimulus-Responsive Drug\/Gene Delivery Systems","volume":"45","author":"Karimi","year":"2016","journal-title":"Chem. Soc. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1021\/acs.chemrev.5b00148","article-title":"Nanochemistry and Nanomedicine for Nanoparticle-Based Diagnostics and Therapy","volume":"116","author":"Chen","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hanafy, N.A.N., Quarta, A., Ferraro, M.M., Dini, L., Nobile, C., de Giorgi, M.L., Carallo, S., Citti, C., Gaballo, A., and Cannazza, G. (2018). Polymeric Nano-Micelles as Novel Cargo-Carriers for LY2157299 Liver Cancer Cells Delivery. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030748"},{"key":"ref_42","first-page":"185","article-title":"Ideal hepatotoxicity model in rats using carbon tetrachloride (CCL 4) 1","volume":"2","author":"Alhassan","year":"2009","journal-title":"Bayero J. Pure Appl. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.3892\/mmr.2016.5673","article-title":"Fibronectin Expression Is Critical for Liver Fibrogenesis in Vivo and in Vitro","volume":"14","author":"Liu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-4939-1050-2_3","article-title":"Tissue Processing and Hematoxylin and Eosin Staining","volume":"1180","author":"Feldman","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 Years of Image Analysis HHS Public Access","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"393","DOI":"10.4048\/jbc.2017.20.4.393","article-title":"Optimization of RNA Extraction from Formalin-Fixed Paraffin-Embedded Blocks for Targeted next-Generation Sequencing","volume":"20","author":"Choi","year":"2017","journal-title":"J. Breast Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1477-5956-10-56","article-title":"An Efficient Procedure for Protein Extraction from Formalin-Fixed, Paraffin-Embedded Tissues for Reverse Phase Protein Arrays","volume":"10","author":"Guo","year":"2012","journal-title":"Proteome Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/bph.13701","article-title":"Canonical Hedgehog Signalling Regulates Hepatic Stellate Cell-Mediated Angiogenesis in Liver Fibrosis","volume":"174","author":"Zhang","year":"2017","journal-title":"Br. J. Pharm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1111\/bph.13945","article-title":"Evaluating the Antifibrotic Potency of Galunisertib in a Human Ex Vivo Model of Liver Fibrosis","volume":"174","author":"Luangmonkong","year":"2017","journal-title":"Br. J. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sim\u00f3n, J., Casado-Andr\u00e9s, M., Goikoetxea-Usandizaga, N., Serrano-Maci\u00e1, M., and Mart\u00ednez-Chantar, M.L. (2020). Nutraceutical Properties of Polyphenols against Liver Diseases. Nutrients, 12.","DOI":"10.3390\/nu12113517"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Su, M., Cao, D., Wang, Z., Duan, Y., and Huang, Y. (2022). Fatty Acid Synthase Inhibitor Platensimycin Intervenes the Development of Nonalcoholic Fatty Liver Disease in a Mouse Model. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010005"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.7150\/thno.52102","article-title":"Inhibition of TGF\u03b21 Accelerates Regeneration of Fibrotic Rat Liver Elicited by a Novel Two-Staged Hepatectomy","volume":"11","author":"Zhang","year":"2021","journal-title":"Theranostics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00204-015-1543-4","article-title":"Experimental Models of Liver Fibrosis","volume":"90","author":"Cogliati","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_54","first-page":"105","article-title":"A Review of Liver Fibrosis and Emerging Therapies","volume":"4","author":"Nathwani","year":"2019","journal-title":"EMJ"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.bbrc.2006.03.087","article-title":"The Antifibrotic Effect of TGF-\u03921 SiRNAs in Murine Model of Liver Cirrhosis","volume":"343","author":"Kim","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9163","DOI":"10.1038\/s41598-018-27427-9","article-title":"Comparison of Two Protocols of Carbon Tetrachloride-Induced Cirrhosis in Rats\u2014Improving Yield and Reproducibility","volume":"8","author":"Fortea","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.ijbiomac.2014.02.043","article-title":"Complexes of Polyglutamic Acid and Long-Chain Alkanoylcholines: Nanoparticle Formation and Drug Release","volume":"66","author":"Tolentino","year":"2014","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"73","DOI":"10.5923\/j.ajps.20120204.05","article-title":"Modification and Characterization of Polyacrylic Acid for Metal Ion Recovery","volume":"2","author":"Abdelaal","year":"2012","journal-title":"Am. J. Polym. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s42826-020-00076-8","article-title":"Impaired Liver Regeneration and Lipid Homeostasis in CCl4 Treated WDR13 Deficient Mice","volume":"36","author":"Mishra","year":"2020","journal-title":"Lab. Anim. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1139\/cjpp-2020-0165","article-title":"Cpt1a Promoted ROS-Induced Oxidative Stress and Inflammation in Liver Injury 2 via the Nrf2\/HO-1 and NLRP3 Inflammasome Signaling Pathway Running Title: Cpt1a Promoted ROS-Induced Oxidative Stress and Inflammation in Xigang Luo","volume":"99","author":"Luo","year":"2021","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"511","DOI":"10.5604\/01.3001.0011.7396","article-title":"bin HCBP6 Is Involved in the Development of Hepatic Steatosis Induced by High-Fat Diet and CCL4 in Rats","volume":"17","author":"Zheng","year":"2018","journal-title":"Ann. Hepatol."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/11\/1812\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:08:53Z","timestamp":1760144933000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/11\/1812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":61,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["jpm12111812"],"URL":"https:\/\/doi.org\/10.3390\/jpm12111812","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]}}}