{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:33:33Z","timestamp":1777530813852,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>This study aimed to evaluate if the treatment with metformin affects the morphologic structure, endothelial function, angiogenesis, inflammation and oxidation-responsive pathways in the heart of mice with surgically induced endometriosis. B6CBA\/F1 mice (n = 37) were divided into four groups; Sham (S), Metformin (M), Endometriosis (E) and Metformin\/Endometriosis (ME). The cross-sectional area of cardiomyocytes was assessed after Hematoxylin\u2013Eosin staining and fibrosis after Picrosirius-Red staining. ET-1, nitric oxide synthases-iNOS and eNOS, and VEGF and VEGFR-2 were detected by immunofluorescence. Semi-quantification of ET-1, eNOS, VEGF, NF-kB, Ik\u03b2\u03b1 and KEAP-1 was performed by Western blotting. MIR199a, MIR16-1, MIR18a, MIR20a, MIR155, MIR200a, MIR342, MIR24-1 and MIR320a were quantified by Real-Time qPCR. The interaction of endometriosis and metformin effects was assessed by a two-way ANOVA test. Compared with the other groups, M-treated mice presented a higher cross-sectional area of cardiomyocytes. Heart fibrosis increased with endometriosis. Treatment of endometriosis with metformin in the ME group downregulates ET-1 and upregulates eNOS expression comparatively with the E group. However, metformin failed to mitigate NF-kB expression significantly incremented by endometriosis. The expression of MIR199a, MIR16-1 and MIR18a decreased with endometriosis, whereas MIR20a showed an equivalent trend, altogether reducing cardioprotection. In summary, metformin diminished endometriosis-associated endothelial dysfunction but did not mitigate the increase in NF-kB expression and cardiac fibrosis in mice with endometriosis.<\/jats:p>","DOI":"10.3390\/biomedicines10112782","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T03:36:44Z","timestamp":1667360204000},"page":"2782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0960-2991","authenticated-orcid":false,"given":"Ana Filipa","family":"Martins","sequence":"first","affiliation":[{"name":"Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5292-4390","authenticated-orcid":false,"given":"Ana Catarina","family":"Neto","sequence":"additional","affiliation":[{"name":"Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9613-1552","authenticated-orcid":false,"given":"Adriana Raquel","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), 4200-135 Porto, Portugal"}]},{"given":"Sandra Marisa","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Cl\u00e1udia","family":"Sousa-Mendes","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-3596","authenticated-orcid":false,"given":"Adelino","family":"Leite-Moreira","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Alexandra Maria","family":"Gouveia","sequence":"additional","affiliation":[{"name":"Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), 4200-135 Porto, Portugal"}]},{"given":"Henrique","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3301-8376","authenticated-orcid":false,"given":"Delminda","family":"Neves","sequence":"additional","affiliation":[{"name":"Department of Biomedicine-Experimental Biology Unit, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bpobgyn.2018.06.001","article-title":"Risk for and consequences of endometriosis: A critical epidemiologic review","volume":"51","author":"Shafrir","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0140-6736(21)00389-5","article-title":"Endometriosis is a chronic systemic disease: Clinical challenges and novel innovations","volume":"397","author":"Taylor","year":"2021","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1161\/HYPERTENSIONAHA.117.09056","article-title":"Association Between Endometriosis and Hypercholesterolemia or Hypertension","volume":"70","author":"Mu","year":"2017","journal-title":"Hypertension"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1161\/CIRCOUTCOMES.115.002224","article-title":"Endometriosis and Risk of Coronary Heart Disease","volume":"9","author":"Mu","year":"2016","journal-title":"Circul. Cardiovasc. Qual. Outcomes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3425560","DOI":"10.1155\/2021\/3425560","article-title":"Association of Inflammatory Markers\/Cytokines with Cardiovascular Risk Manifestation in Patients with Endometriosis","volume":"2021","author":"Rafi","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1093\/humupd\/dmv013","article-title":"Endometriosis: A high-risk population for major chronic diseases?","volume":"21","author":"Kvaskoff","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.rbmo.2019.05.021","article-title":"Atherosclerotic cardiovascular disease in women with endometriosis: A systematic review of risk factors and prospects for early surveillance","volume":"39","author":"Tan","year":"2019","journal-title":"Reprod. Biomed. Online"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1177\/1933719115572478","article-title":"Evidence for a hypercoagulable state in women with ovarian endometriomas","volume":"22","author":"Wu","year":"2015","journal-title":"Reprod. Sci."},{"key":"ref_10","first-page":"100108","article-title":"Atherosclerosis-related biomarkers in women with endometriosis: The effects of dienogest and oral contraceptive therapy","volume":"7","author":"Maeda","year":"2020","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol. X"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.cardiores.2007.06.004","article-title":"The importance of endothelin-1 for vascular dysfunction in cardiovascular disease","volume":"76","author":"Bohm","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/ejp.1133","article-title":"Bradykinin system is involved in endometriosis-related pain through endothelin-1 production","volume":"22","author":"Yoshino","year":"2018","journal-title":"Eur. J. Pain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.atherosclerosis.2011.08.005","article-title":"Increased asymmetric dimethylarginine and enhanced inflammation are associated with impaired vascular reactivity in women with endometriosis","volume":"219","author":"Kinugasa","year":"2011","journal-title":"Atherosclerosis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1113\/JP270538","article-title":"Ageing, metabolism and cardiovascular disease","volume":"594","author":"Costantino","year":"2016","journal-title":"J. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis\u2014An Inflammatory Disease","volume":"340","author":"Ross","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.gmit.2015.05.001","article-title":"Endometriosis and possible inflammation markers","volume":"4","author":"Wu","year":"2015","journal-title":"Gynecol. Minim. Invasive Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"859619","DOI":"10.1155\/2013\/859619","article-title":"Angiogenesis and Endometriosis","volume":"2013","author":"Rocha","year":"2013","journal-title":"Obstet. Gynecol. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1161\/CIRCULATIONAHA.105.535294","article-title":"Role of Angiogenesis in Cardiovascular Disease","volume":"112","author":"Khurana","year":"2005","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.1002\/jcp.27486","article-title":"An overview of microRNAs: Biology, functions, therapeutics, and analysis methods","volume":"234","author":"Saliminejad","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"557.e1","DOI":"10.1016\/j.ajog.2020.02.050","article-title":"Accurate diagnosis of endometriosis using serum microRNAs","volume":"223","author":"Moustafa","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.fertnstert.2016.04.013","article-title":"Serum microRNAs as diagnostic markers of endometriosis: A comprehensive array-based analysis","volume":"106","author":"Cosar","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2456340","DOI":"10.1155\/2020\/2456340","article-title":"Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis","volume":"2020","author":"Zhang","year":"2020","journal-title":"Dis. Markers"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/ijgo.12392","article-title":"Diagnostic accuracy of serum miR-122 and miR-199a in women with endometriosis","volume":"141","author":"Maged","year":"2018","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41536-021-00128-0","article-title":"Targets identified from exercised heart: Killing multiple birds with one stone","volume":"6","author":"Wang","year":"2021","journal-title":"npj Regen. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/nrcardio.2014.207","article-title":"MicroRNAs in myocardial infarction","volume":"12","author":"Boon","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1161\/CIRCULATIONAHA.108.814145","article-title":"MicroRNA-320 Is Involved in the Regulation of Cardiac Ischemia\/Reperfusion Injury by Targeting Heat-Shock Protein 20","volume":"119","author":"Ren","year":"2009","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s10456-018-9632-7","article-title":"Regulation of angiogenesis by microRNAs in cardiovascular diseases","volume":"21","author":"Kir","year":"2018","journal-title":"Angiogenesis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/jb\/mvab047","article-title":"MiR-20a-5p overexpression prevented diabetic cardiomyopathy via inhibition of cardiomyocyte apoptosis, hypertrophy, fibrosis and JNK\/NF-\u03baB signalling pathway","volume":"170","author":"Liu","year":"2021","journal-title":"J. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.3892\/ijmm.2016.2719","article-title":"Overexpression of miR-200a protects cardiomyocytes against hypoxia-induced apoptosis by modulating the kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 signaling axis","volume":"38","author":"Sun","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1080\/14656566.2018.1494154","article-title":"Current and emerging treatment options for endometriosis","volume":"19","author":"Ferrero","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1186\/s12905-021-01545-5","article-title":"Treatment of endometriosis: A review with comparison of 8 guidelines","volume":"21","author":"Kalaitzopoulos","year":"2021","journal-title":"BMC Women Health"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1172\/JCI73939","article-title":"mTOR: A pharmacologic target for autophagy regulation","volume":"125","author":"Kim","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_33","first-page":"47","article-title":"Differential expression of mTOR components in endometriosis and ovarian cancer: Effects of rapalogues and dual kinase inhibitors on mTORC1 and mTORC2 stoichiometry","volume":"43","author":"Kumar","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kimber-Trojnar, \u017b., D\u0142uski, D.F., Wierzchowska-Opoka, M., Rusza\u0142a, M., and Leszczy\u0144ska-Gorzelak, B. (2022). Metformin as a potential treatment option for endometriosis. Cancers, 14.","DOI":"10.3390\/cancers14030577"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"368.e1","DOI":"10.1016\/j.ajog.2009.10.873","article-title":"Metformin regresses endometriotic implants in rats by improving implant levels of superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of metalloproteinase-2, and matrix metalloproteinase-9","volume":"202","author":"Yilmaz","year":"2010","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1161\/CIRCRESAHA.116.308445","article-title":"Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status","volume":"119","author":"Cameron","year":"2016","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1038\/ncomms3192","article-title":"Metformin improves healthspan and lifespan in mice","volume":"4","author":"Mercken","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S0015-0282(02)04925-7","article-title":"Metformin has direct effects on human ovarian steroidogenesis","volume":"79","author":"Mansfield","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"112659","DOI":"10.1016\/j.yexcr.2021.112659","article-title":"Metformin attenuates expression of angiogenic and inflammatory genes in human endometriotic stromal cells","volume":"404","author":"Yari","year":"2021","journal-title":"Exp. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1007\/s43032-022-00869-3","article-title":"Comparative Proteomic Analysis Reveals Metformin Improves the Expression of Biomarkers of Endometrial Receptivity in Infertile Women with Minimal\/Mild Endometriosis","volume":"29","author":"Huang","year":"2022","journal-title":"Reprod. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.mefs.2012.09.001","article-title":"Metformin as a new therapy for endometriosis, its effects on both clinical picture and cytokines profile","volume":"17","author":"Foda","year":"2012","journal-title":"Middle East Fertil. Soc. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4103\/0976-500X.119726","article-title":"How to calculate sample size in animal studies?","volume":"4","author":"Charan","year":"2013","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10815-014-0390-1","article-title":"Effect of induced peritoneal endometriosis on oocyte and embryo quality in a mouse model","volume":"32","author":"Cohen","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1093\/humrep\/des062","article-title":"Endothelial dysfunction but not increased carotid intima-media thickness in young European women with endometriosis","volume":"27","author":"Santoro","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/cvr\/cvaa324","article-title":"Cardiac fibrosis","volume":"117","author":"Frangogiannis","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"622262","DOI":"10.3389\/fphar.2021.622262","article-title":"Metformin: A novel weapon against inflammation","volume":"12","author":"Bai","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"151709","DOI":"10.1016\/j.acthis.2021.151709","article-title":"Anti-cancer effect of metformin on the metastasis and invasion of primary breast cancer cells through mediating NF-kB activity","volume":"123","author":"Yenmis","year":"2021","journal-title":"Acta Histochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13293-019-0223-0","article-title":"Sex-specific influence on cardiac structural remodeling and therapy in cardiovascular disease","volume":"10","author":"Kessler","year":"2019","journal-title":"Biol. Sex Differ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41569-018-0007-y","article-title":"Mechanisms of physiological and pathological cardiac hypertrophy","volume":"15","author":"Nakamura","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/aps.2010.229","article-title":"Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation","volume":"32","author":"Fu","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1093\/eurheartj\/ehz203","article-title":"A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: The MET-REMODEL trial","volume":"40","author":"Mohan","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/jcmm.12220","article-title":"Crosstalk between AMPK activation and angiotensin II-induced hypertrophy in cardiomyocytes: The role of mitochondria","volume":"18","author":"Kuznetsov","year":"2014","journal-title":"J. Cell. Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"539","DOI":"10.3389\/fphys.2020.00539","article-title":"The histone demethylase JMJD1C regulates CAMKK2-AMPK signaling to participate in cardiac hypertrophy","volume":"11","author":"Yu","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"626011","DOI":"10.3389\/fcell.2020.626011","article-title":"Effect of metformin on cardiac metabolism and longevity in aged female mice","volume":"8","author":"Zhu","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S0015-0282(99)00466-5","article-title":"Vascular endothelial growth factor and interleukin-6 in peritoneal fluid of women with endometriosis","volume":"73","author":"Mahnke","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"637","DOI":"10.14336\/AD.2018.0513","article-title":"The anti-inflammatory and anti-oxidant mechanisms of the Keap1\/Nrf2\/ARE signaling pathway in chronic diseases","volume":"10","author":"Tu","year":"2019","journal-title":"Aging Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e00099-20","DOI":"10.1128\/MCB.00099-20","article-title":"The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway","volume":"40","author":"Baird","year":"2020","journal-title":"Mol. Cell. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wehbe, N., Nasser, S., Pintus, G., Badran, A., Eid, A., and Baydoun, E. (2019). MicroRNAs in Cardiac Hypertrophy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194714"}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/11\/2782\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:08:59Z","timestamp":1760144939000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/11\/2782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":59,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["biomedicines10112782"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines10112782","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]}}}