{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:16:55Z","timestamp":1788257815556,"version":"build-2803163510"},"reference-count":70,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002512","name":"Kookmin University","doi-asserted-by":"publisher","award":["S2026-0028"],"award-info":[{"award-number":["S2026-0028"]}],"id":[{"id":"10.13039\/501100002512","id-type":"DOI","asserted-by":"publisher"}]},{"award":["S2026-0028"],"award-info":[{"award-number":["S2026-0028"]}],"id":[{"id":"https:\/\/ror.org\/0049erg63","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Cirsium japonicum Fisch. ex DC. has long been used in traditional East Asian medicine and has attracted increasing attention because of its diverse pharmacological activities, including antioxidant, anti-inflammatory, antifibrotic, metabolic regulatory, and anticancer effects. Although numerous studies have investigated its phytochemical composition and biological activities, current evidence has largely been organized according to individual compounds or disease categories, providing limited insight into the shared molecular mechanisms underlying its pleiotropic actions. In this review, we critically re-evaluate the molecular pharmacology of C. japonicum using an evidence-oriented framework that distinguishes experimentally supported mechanisms from pharmacological associations and emerging hypotheses. Rather than accepting changes in signaling proteins or downstream biomarkers as sufficient evidence of mechanism, we assess the strength of evidence based on reproducibility, pathway-specific interventions, genetic or pharmacological validation, and direct target engagement. Current evidence indicates that nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant responses and nuclear factor kappa B (NF-\u03baB)-associated inflammatory responses represent the most consistently observed pathway associations, although direct molecular targets and causal pathway dependency remain insufficiently established. Evidence for AMPK\/PI3K-Akt-associated metabolic regulation and TGF-\u03b2\/Smad-associated antifibrotic responses is comparatively more limited. In contrast, modulation of apoptosis and autophagy is currently supported primarily by indirect or context-dependent observations. We further discuss how multiple phytochemicals converge on interconnected signaling networks regulating oxidative stress, inflammation, metabolism, tissue remodeling, and cell fate, thereby providing a systems-level explanation for the broad therapeutic potential of C. japonicum. Finally, we highlight the need for standardized phytochemical characterization, rigorous target validation, multi-omics integration, and artificial intelligence-assisted systems biology to establish causal molecular mechanisms and accelerate the translational development of evidence-based phytopharmaceuticals.<\/jats:p>","DOI":"10.3390\/ijms27177717","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Claims to Evidence: Re-Evaluating the Molecular Pharmacology of Cirsium japonicum"],"prefix":"10.3390","volume":"27","author":[{"given":"Kyung-Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Applied Chemistry, School of Science and Technology, Kookmin University, Seoul 02707, Republic of Korea"},{"name":"Antibody Research Institute, Kookmin University, Seoul 02707, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Kyung","family":"Yeo","sequence":"additional","affiliation":[{"name":"Oculi Korean Medicine Hospital, Seoul 05655, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3738-3239","authenticated-orcid":false,"given":"Hwa-Seung","family":"Yoo","sequence":"additional","affiliation":[{"name":"East West Cancer Center, Daejeon Korean Medicine Hospital, Daejeon University, Daejeon 34520, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byong Chul","family":"Yoo","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd4510","article-title":"The re-emergence of natural products for drug discovery in the genomics era","volume":"14","author":"Harvey","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.cell.2007.08.021","article-title":"Molecular understanding and modern application of traditional medicines: Triumphs and trials","volume":"130","author":"Corson","year":"2007","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"de Menezes, I.R.A., Coutinho, H.D.M., Wanderley, A.G., Ribeiro-Filho, J., Quintans-J\u00fanior, L., Almeida, J.R.G.D.S., and Picot, L. (2026). Advances in natural products and their biological activities. Molecules, 31.","DOI":"10.3390\/molecules31111849"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nakadate, K., Ito, N., and Kawakami, K. (2026). Repositioning natural products in modern drug discovery: Technological innovation, systems pharmacology, and pathological validation. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27104330"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nchembio.118","article-title":"Network pharmacology: The next paradigm in drug discovery","volume":"4","author":"Hopkins","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network medicine: A network-based approach to human disease","volume":"12","author":"Gulbahce","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3724\/SP.J.1009.2013.00110","article-title":"Traditional Chinese medicine network pharmacology: Theory, methodology and application","volume":"11","author":"Li","year":"2013","journal-title":"Chin. J. Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.5483\/BMBRep.2022.55.9.102","article-title":"Systems pharmacology approaches in herbal medicine research: A brief review","volume":"55","author":"Lee","year":"2022","journal-title":"BMB Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"122050","DOI":"10.1016\/j.jep.2026.122050","article-title":"Cirsium japonicum Fisch. ex DC.: A review of ethnomedicine, botany, phytochemistry, pharmacology and pharmacokinetics","volume":"371","author":"Zhu","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ye, Y., Chen, Z., Wu, Y., Gao, M., Zhu, A., Kuai, X., Luo, D., Chen, Y., and Li, K. (2022). Purification process and in vitro and in vivo bioactivity evaluation of pectolinarin and linarin from Cirsium japonicum. Molecules, 27.","DOI":"10.3390\/molecules27248695"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1080\/14786410701494686","article-title":"Anticancer activity and quantitative analysis of flavone of Cirsium japonicum DC","volume":"21","author":"Liu","year":"2007","journal-title":"Nat. Prod. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2174\/1872312814666210726112910","article-title":"Biological importance, therapeutic benefit and analytical aspects of bioactive flavonoid pectolinarin in the nature","volume":"14","author":"Patel","year":"2021","journal-title":"Drug Metab. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1016\/j.bmcl.2017.05.051","article-title":"Anti-inflammatory effects and corresponding mechanisms of cirsimaritin extracted from Cirsium japonicum var. maackii Maxim","volume":"27","author":"Shin","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ejphar.2014.05.024","article-title":"Protective effect of linarin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure","volume":"738","author":"Kim","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"156601","DOI":"10.1016\/j.phymed.2025.156601","article-title":"Cirsium japonicum leaf extract attenuated lipopolysaccharide-induced acute respiratory distress syndrome in mice via suppression of the NLRP3 and HIF1alpha pathways","volume":"140","author":"Lim","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pang, Q.Q., Lee, S., Cho, E.J., and Kim, J.H. (2023). Protective effects of Cirsium japonicum var. maackii flower on amyloid beta(25-35)-treated C6 glial cells. Life, 13.","DOI":"10.3390\/life13071453"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cho, M., Kim, Y., You, S., Hwang, D.Y., and Jang, M. (2023). Chlorogenic acid of Cirsium japonicum resists oxidative stress caused by aging and prolongs healthspan via SKN-1\/Nrf2 and DAF-16\/FOXO in Caenorhabditis elegans. Metabolites, 13.","DOI":"10.3390\/metabo13020224"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.yexcr.2012.04.004","article-title":"Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6\/STAT3 pathway","volume":"318","author":"Lamy","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"110461","DOI":"10.1016\/j.neuropharm.2025.110461","article-title":"Luteolin attenuates trimethyltin chloride-induced hippocampal neurotoxicity through SIRT3\/NRF2\/HO-1 activation","volume":"274","author":"Ding","year":"2025","journal-title":"Neuropharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.2147\/DDDT.S433591","article-title":"Linarin protects against CCl(4)-induced acute liver injury via activating autophagy and inhibiting the inflammatory response: Involving the TLR4\/MAPK\/Nrf2 pathway","volume":"17","author":"Li","year":"2023","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1248\/bpb.31.760","article-title":"Pectolinarin and pectolinarigenin of Cirsium setidens prevent the hepatic injury in rats caused by D-galactosamine via an antioxidant mechanism","volume":"31","author":"Yoo","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13346","DOI":"10.1021\/jf203490a","article-title":"Antiadipogenic effect of dietary apigenin through activation of AMPK in 3T3-L1 cells","volume":"59","author":"Ono","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","first-page":"2965","article-title":"Apigenin reduces the excessive accumulation of lipids induced by palmitic acid via the AMPK signaling pathway in HepG2 cells","volume":"18","author":"Lu","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.2174\/1389201021666200320140908","article-title":"Apigenin alleviates renal fibroblast activation through AMPK and ERK signaling pathways in vitro","volume":"21","author":"Li","year":"2020","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1007\/s10753-020-01245-6","article-title":"Luteolin and apigenin attenuate LPS-induced astrocyte activation and cytokine production by targeting MAPK, STAT3, and NF-kappaB signaling pathways","volume":"43","author":"Che","year":"2020","journal-title":"Inflammation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"156663","DOI":"10.1016\/j.phymed.2025.156663","article-title":"Luteolin inhibits inflammation and M1 macrophage polarization in the treatment of Pseudomonas aeruginosa-induced acute pneumonia through suppressing EGFR\/PI3K\/AKT\/NF-kappaB and EGFR\/ERK\/AP-1 signaling pathways","volume":"141","author":"Gu","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.bcp.2013.02.008","article-title":"Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by ampk activation","volume":"85","author":"Ong","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_30","first-page":"1460","article-title":"Linarin prevents LPS-induced acute lung injury by suppressing oxidative stress and inflammation via inhibition of TXNIP\/NLRP3 and NF-kappaB pathways","volume":"42","author":"Han","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/BF02976559","article-title":"The effect of linarin on LPS-induced cytokine production and nitric oxide inhibition in murine macrophages cell line RAW264.7","volume":"25","author":"Han","year":"2002","journal-title":"Arch. Pharmacal Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5369","DOI":"10.18632\/aging.202469","article-title":"Inhibiting TLR4 signaling by linarin for preventing inflammatory response in osteoarthritis","volume":"13","author":"Qi","year":"2021","journal-title":"Aging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"159666","DOI":"10.1016\/j.bbalip.2025.159666","article-title":"Linarin alleviates high-fat diet-induced NAFLD via modulating the PI3K\/Akt\/mTOR pathway, autophagy, and gut microbiota","volume":"1870","author":"Lv","year":"2025","journal-title":"Biochim. Biophys. Acta. Mol. Cell Biol. Lipids"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/carcin\/bgt316","article-title":"Apigenin inhibits prostate cancer progression in TRAMP mice via targeting PI3K\/Akt\/FoxO pathway","volume":"35","author":"Shukla","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.biopha.2018.04.072","article-title":"Inhibition of PI3K\/Akt\/mTOR pathway by apigenin induces apoptosis and autophagy in hepatocellular carcinoma cells","volume":"103","author":"Yang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fu, C., Peng, J., Ling, Y., Zhao, H., Zhao, Y., Zhang, X., Ai, M., Peng, Q., and Qin, Y. (2023). Apigenin inhibits angiogenesis in retinal microvascular endothelial cells through regulating of the miR-140-5p\/HDAC3-mediated PTEN\/PI3K\/AKT pathway. BMC Ophthalmol., 23.","DOI":"10.1186\/s12886-023-03046-5"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"tfae011","DOI":"10.1093\/toxres\/tfae011","article-title":"Apigenin promotes apoptosis of 4T1 cells through PI3K\/AKT\/Nrf2 pathway and improves tumor immune microenvironment in vivo","volume":"13","author":"Zhang","year":"2024","journal-title":"Toxicol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9420022","DOI":"10.26599\/FMH.2025.9420022","article-title":"Co-assembly strategies of natural plant compounds for improving their bioavailability","volume":"2","author":"Miao","year":"2025","journal-title":"Food Med. Homol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Li, W., Xing, Q., Liu, Z., Liu, R., Hu, Y., Yan, Q., Liu, X., and Zhang, J. (2023). The signaling pathways of traditional Chinese medicine in treating diabetic retinopathy. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1165649"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e18130","DOI":"10.1111\/jcmm.18130","article-title":"Temperature-sensitive hydrogel releasing pectolinarin facilitate scarless wound healing","volume":"28","author":"Chen","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sies, H. (2020). Oxidative stress: Concept and some practical aspects. Antioxidants, 9.","DOI":"10.3390\/antiox9090852"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41573-018-0008-x","article-title":"Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases","volume":"18","author":"Cuadrado","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1152\/physrev.00023.2017","article-title":"The KEAP1-NRF2 system: A thiol-based sensor-effector apparatus for maintaining redox homeostasis","volume":"98","author":"Yamamoto","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s11010-019-03516-9","article-title":"Chlorogenic acid isomers directly interact with Keap 1-Nrf2 signaling in Caco-2 cells","volume":"457","author":"Liang","year":"2019","journal-title":"Mol. Cell. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1093\/jpp\/rgab020","article-title":"Chlorogenic acid ameliorates mice clinical endometritis by activating Keap1\/Nrf2 and inhibiting NFkappaB signalling pathway","volume":"73","author":"Gao","year":"2021","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1038\/s41401-026-01770-4","article-title":"Chlorogenic acid promotes liver regeneration after partial hepatectomy through activating Nrf2 via directly targeting Keap1","volume":"47","author":"Xue","year":"2026","journal-title":"Acta. Pharmacol. Sin."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Kitakaze, T., Makiyama, A., Yamashita, Y., and Ashida, H. (2020). Low dose of luteolin activates Nrf2 in the liver of mice at start of the active phase but not that of the inactive phase. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231403"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ding, W., Chen, D., Li, J., Wang, Y., Chen, X., Xu, Y., Yang, Z., Liu, Z., and Zhao, H. (2025). Medicinal plants and compounds for chronic bronchitis treatment: Efficacy and action mechanisms. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1674079"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2010.02.029","article-title":"Nonresolving inflammation","volume":"140","author":"Nathan","year":"2010","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","article-title":"The nuclear factor NF-kappaB pathway in inflammation","volume":"1","author":"Lawrence","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nri3495","article-title":"Mitogen-activated protein kinases in innate immunity","volume":"13","author":"Arthur","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: A nutrient and energy sensor that maintains energy homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cmet.2004.12.003","article-title":"AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism","volume":"1","author":"Kahn","year":"2005","journal-title":"Cell Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in growth, metabolism, and disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.molcel.2017.05.032","article-title":"AMPK: Mechanisms of cellular energy sensing and restoration of metabolic balance","volume":"66","author":"Garcia","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","article-title":"AKT\/PKB signaling: Navigating the network","volume":"169","author":"Manning","year":"2017","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nm.2807","article-title":"Mechanisms of fibrosis: Therapeutic translation for fibrotic disease","volume":"18","author":"Wynn","year":"2012","journal-title":"Nat. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","article-title":"Fibrosis: From mechanisms to medicines","volume":"587","author":"Henderson","year":"2020","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneph.2016.48","article-title":"TGF-beta: The master regulator of fibrosis","volume":"12","author":"Meng","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/s41569-021-00646-w","article-title":"Transforming growth factor-beta in myocardial disease","volume":"19","author":"Frangogiannis","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.semcancer.2021.06.019","article-title":"Attacking the PI3K\/Akt\/mTOR signaling pathway for targeted therapeutic treatment in human cancer","volume":"85","author":"Yu","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological functions of autophagy genes: A disease perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41422-019-0164-5","article-title":"The molecular machinery of regulated cell death","volume":"29","author":"Tang","year":"2019","journal-title":"Cell Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41580-018-0068-0","article-title":"Linking cellular stress responses to systemic homeostasis","volume":"19","author":"Galluzzi","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1056\/NEJMra2022774","article-title":"Autophagy in human diseases","volume":"383","author":"Mizushima","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13059-017-1215-1","article-title":"Multi-omics approaches to disease","volume":"18","author":"Hasin","year":"2017","journal-title":"Genome Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41591-018-0300-7","article-title":"High-performance medicine: The convergence of human and artificial intelligence","volume":"25","author":"Topol","year":"2019","journal-title":"Nat. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7717\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:50:13Z","timestamp":1788256213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":70,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177717"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177717","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}