{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:46:16Z","timestamp":1791830776805,"version":"4.3.4"},"reference-count":201,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multi-factorial mitochondrial damage exhibits a \u201cvicious circle\u201d that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.<\/jats:p>","DOI":"10.3390\/ijms22168649","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T21:48:12Z","timestamp":1628718492000},"page":"8649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Protective Effects of Flavonoids Against Mitochondriopathies and Associated Pathologies: Focus on the Predictive Approach and Personalized Prevention"],"prefix":"10.3390","volume":"22","author":[{"given":"Lenka","family":"Koklesova","sequence":"first","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Liskova","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2545-7694","authenticated-orcid":false,"given":"Marek","family":"Samec","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2556-5641","authenticated-orcid":false,"given":"Kevin","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine in Qatar, Education City, Qatar Foundation, Doha 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8828-0160","authenticated-orcid":false,"given":"Raghad Khalid","family":"AL-Ishaq","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine in Qatar, Education City, Qatar Foundation, Doha 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Bugos","sequence":"additional","affiliation":[{"name":"Lambda Life JSC, 851 01 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslava","family":"\u0160udomov\u00e1","sequence":"additional","affiliation":[{"name":"Museum of Literature in Moravia, Kl\u00e1\u0161ter 1, 664 61 Rajhrad, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3471-0508","authenticated-orcid":false,"given":"Kamil","family":"Biringer","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Pec","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Adamkov","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3922-2738","authenticated-orcid":false,"given":"Sherif T. S.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kam\u00fdck\u00e1 129, 165 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4530-8706","authenticated-orcid":false,"given":"Luciano","family":"Saso","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cVittorio Erspamer\u201d, Faculty of Pharmacy and Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A.","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universit\u00e4t Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-3366","authenticated-orcid":false,"given":"Dietrich","family":"B\u00fcsselberg","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine in Qatar, Education City, Qatar Foundation, Doha 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4312-5076","authenticated-orcid":false,"given":"Peter","family":"Kubatka","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia"},{"name":"European Association for Predictive, Preventive and Personalised Medicine, EPMA, 1150 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Golubnitschaja","sequence":"additional","affiliation":[{"name":"European Association for Predictive, Preventive and Personalised Medicine, EPMA, 1150 Brussels, Belgium"},{"name":"Predictive, Preventive, Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universit\u00e4t Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1800404","DOI":"10.1002\/pmic.201800404","article-title":"Mitochondrial Dysfunction in Age-Related Metabolic Disorders","volume":"20","author":"Natarajan","year":"2020","journal-title":"Proteom."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/ng1776","article-title":"Systematic identification of human mitochondrial disease genes through integrative genomics","volume":"38","author":"Calvo","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_3","first-page":"147","article-title":"Mitochondrial diseases","volume":"145","author":"Molnar","year":"2018","journal-title":"Hum. Hypothal. Neuropsychiatr. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13167-020-00206-1","article-title":"Anniversary of the European Association for Predictive, Preventive and Personalised (3P) Medicine\u2013EPMA World Congress Supplement 2020","volume":"11","author":"Golubnitschaja","year":"2020","journal-title":"EPMA J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s13167-020-00226-x","article-title":"Cell-free nucleic acid patterns in disease prediction and monitoring\u2014hype or hope?","volume":"11","author":"Crigna","year":"2020","journal-title":"EPMA J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e711","DOI":"10.1016\/j.clbc.2020.05.009","article-title":"Aberrantly Methylated cfDNA in Body Fluids as a Promising Diagnostic Tool for Early Detection of Breast Cancer","volume":"20","author":"Stastny","year":"2020","journal-title":"Clin. Breast Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/mas.21612","article-title":"Multiomic patterns in body fluids: Technological challenge with a great potential to implement the advanced paradigm of 3P medicine","volume":"39","author":"Gerner","year":"2020","journal-title":"Mass Spectrom. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1527-5299.2003.02399.x","article-title":"Drug Absorption in the Management of Congestive Heart Failure: Loop Diuretics","volume":"9","author":"Sica","year":"2003","journal-title":"Congest. Hear. Fail."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s13167-019-00188-9","article-title":"Artificial intelligence supported patient self-care in chronic heart failure: a paradigm shift from reactive to predictive, preventive and personalised care","volume":"10","author":"Barrett","year":"2019","journal-title":"EPMA J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2217\/pme.10.42","article-title":"Common origin but individual outcomes: time for new guidelines in personalized healthcare","volume":"7","author":"Golubnitschaja","year":"2010","journal-title":"Pers. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2017.09.009","article-title":"Therapies for mitochondrial diseases and current clinical trials","volume":"122","author":"Zarante","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s13167-021-00237-2","article-title":"Mitochondrial impairments in aetiopathology of multifactorial diseases: common origin but individual outcomes in context of 3P medicine","volume":"12","author":"Koklesova","year":"2021","journal-title":"EPMA J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.7150\/ijbs.37481","article-title":"Xanthohumol inhibits colorectal cancer cells via downregulation of Hexokinases II-mediated glycolysis","volume":"15","author":"Liu","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5682","DOI":"10.1039\/C8FO01397G","article-title":"Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models","volume":"9","author":"Wei","year":"2018","journal-title":"Food Funct."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1039\/C9FO00001A","article-title":"Naringenin improves mitochondrial function and reduces cardiac damage following ischemia-reperfusion injury: the role of the AMPK-SIRT3 signaling pathway","volume":"10","author":"Yu","year":"2019","journal-title":"Food Funct."},{"key":"ref_16","first-page":"1477","article-title":"Luteolin attenuates sepsis-induced myocardial injury by enhancing autophagy in mice","volume":"45","author":"Wu","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.neuroscience.2013.01.032","article-title":"Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson\u2019s disease in rats","volume":"236","author":"Karuppagounder","year":"2013","journal-title":"Neuroscience"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10458","DOI":"10.1111\/jcmm.15658","article-title":"Protective effects of isoquercitrin on streptozotocin-induced neurotoxicity","volume":"24","author":"Chen","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3389\/fchem.2020.00829","article-title":"Apigenin as Tumor Suppressor in Cancers: Biotherapeutic Activity, Nanodelivery, and Mechanisms With Emphasis on Pancreatic Cancer","volume":"8","author":"Ashrafizadeh","year":"2020","journal-title":"Front. Chem."},{"key":"ref_20","first-page":"1","article-title":"Mitochondrial Aging and Age-Related Dysfunction of Mitochondria","volume":"2014","author":"Chistiakov","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1071\/RD17408","article-title":"The mitochondrial genome: how it drives fertility","volume":"30","author":"John","year":"2018","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/290457a0","article-title":"Sequence and organization of the human mitochondrial genome","volume":"290","author":"Anderson","year":"1981","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbabio.2017.01.004","article-title":"Mitochondrial dysfunction and mitochondrial dynamics-The cancer connection","volume":"1858","author":"Srinivasan","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA) Bioenerg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0027-5107(02)00220-8","article-title":"Mitochondrial DNA repair and aging","volume":"509","author":"Mandavilli","year":"2002","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-15051-z","article-title":"Electron transport chain activity is a predictor and target for venetoclax sensitivity in multiple myeloma","volume":"11","author":"Bajpai","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.pnpbp.2017.06.036","article-title":"The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression","volume":"80","author":"Czarny","year":"2018","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1002\/jcb.25103","article-title":"Base Excision Repair in the Mitochondria","volume":"116","author":"Prakash","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1097-2765(04)00179-0","article-title":"Mitochondrial Signaling: The Retrograde Response","volume":"14","author":"Avadhani","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1001\/jamaneurol.2016.1676","article-title":"Disentangling (Epi)Genetic and Environmental Contributions to the Mitochondrial 3243A>G Mutation Phenotype","volume":"73","author":"Picard","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nrg1606","article-title":"Mitochondrial DNA mutations in human disease","volume":"6","author":"Taylor","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/13779","article-title":"Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA","volume":"23","author":"Andrews","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.bbadis.2017.02.017","article-title":"Mitochondrial DNA maintenance defects","volume":"1863","author":"Craigen","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_33","first-page":"113","article-title":"Respiratory function decline and DNA mutation in mitochondria, oxidative stress and altered gene expression during aging","volume":"32","author":"Wei","year":"2009","journal-title":"Chang. Gung Med. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ymgme.2019.09.003","article-title":"Resolving complexity in mitochondrial disease: Towards precision medicine","volume":"128","author":"Boggan","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/bjc.2015.85","article-title":"Mitochondrial apoptosis: killing cancer using the enemy within","volume":"112","author":"Lopez","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Pfeffer, C.M., and Singh, A.T.K. (2018). Apoptosis: A Target for Anticancer Therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020448"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/science.124.3215.269","article-title":"On respiratory impairment in cancer cells","volume":"124","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1042\/BST20160094","article-title":"The Warburg effect: 80 years on","volume":"44","author":"Potter","year":"2016","journal-title":"Biochem. Soc. Trans."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8501","DOI":"10.1002\/jcb.27078","article-title":"Protein kinase CK2 modulation of pyruvate kinase M isoforms augments the Warburg effect in cancer cells","volume":"119","author":"Yang","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/gcc.20326","article-title":"Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer","volume":"45","author":"Tseng","year":"2006","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/(SICI)1098-2264(199602)15:2<95::AID-GCC3>3.0.CO;2-Z","article-title":"Novel mitochondrial DNA deletion found in a renal cell carcinoma","volume":"15","author":"Horton","year":"1996","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1073\/pnas.0408894102","article-title":"mtDNA mutations increase tumorigenicity in prostate cancer","volume":"102","author":"Petros","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1126\/science.1112125","article-title":"Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging","volume":"309","author":"Kujoth","year":"2005","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nrc3365","article-title":"Mitochondria and cancer","volume":"12","author":"Wallace","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.molmed.2011.06.001","article-title":"Revisiting the TCA cycle: signaling to tumor formation","volume":"17","author":"Raimundo","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.trsl.2018.07.013","article-title":"Targeting mitochondria in cancer: current concepts and immunotherapy approaches","volume":"202","author":"Pustylnikov","year":"2018","journal-title":"Transl. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.biochi.2017.02.008","article-title":"Genetic alterations in Krebs cycle and its impact on cancer pathogenesis","volume":"135","author":"Sajnani","year":"2017","journal-title":"Biochimie"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"117570","DOI":"10.1016\/j.lfs.2020.117570","article-title":"Targeting of cellular redox metabolism for mitigation of radiation injury","volume":"250","author":"Farhood","year":"2020","journal-title":"Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"a011411","DOI":"10.1101\/cshperspect.a011411","article-title":"Relevance of Mitochondrial Genetics and Metabolism in Cancer Development","volume":"5","author":"Gasparre","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.coph.2019.04.014","article-title":"Flavonoids in hypertension: a brief review of the underlying mechanisms","volume":"45","author":"Maaliki","year":"2019","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.biocel.2009.05.004","article-title":"Dynamic organization of mitochondria in human heart and in myocardial disease","volume":"41","author":"Hoppel","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-3-319-55330-6_5","article-title":"Mitochondrial Mutations in Cardiac Disorders","volume":"982","author":"Lee","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1615\/CritRevEukaryotGeneExpr.2019028579","article-title":"Mitochondria and Cardiovascular Disease: A Brief Account","volume":"29","author":"Pecoraro","year":"2019","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1113\/JP271301","article-title":"Mitochondrial dynamics, mitophagy and cardiovascular disease","volume":"594","author":"Pennanen","year":"2016","journal-title":"J. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/embor.2008.242","article-title":"Mouse models of mitochondrial DNA defects and their relevance for human disease","volume":"10","author":"Tyynismaa","year":"2009","journal-title":"EMBO Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-59631-x","article-title":"The role of control region mitochondrial DNA mutations in cardiovascular disease: stroke and myocardial infarction","volume":"10","author":"Umbria","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_57","first-page":"1","article-title":"Tanshinone IIA and Cryptotanshinone Prevent Mitochondrial Dysfunction in Hypoxia-Induced H9c2 Cells: Association to Mitochondrial ROS, Intracellular Nitric Oxide, and Calcium Levels","volume":"2013","author":"Jin","year":"2013","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11883-017-0678-6","article-title":"Oxidative Stress in Atherosclerosis","volume":"19","author":"Kattoor","year":"2017","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1089\/ars.2012.4729","article-title":"Mitochondria as a Source of Reactive Oxygen and Nitrogen Species: From Molecular Mechanisms to Human Health","volume":"18","author":"Figueira","year":"2013","journal-title":"Antioxidants Redox Signal."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1136\/hrt.2005.068270","article-title":"Oxidative stress and redox signalling in cardiac hypertrophy and heart failure","volume":"93","author":"Seddon","year":"2007","journal-title":"Heart"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1161\/CIRCRESAHA.117.311349","article-title":"Mitochondrial Cardiomyopathy Caused by Elevated Reactive Oxygen Species and Impaired Cardiomyocyte Proliferation","volume":"122","author":"Zhang","year":"2018","journal-title":"Circ. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ijcard.2019.01.017","article-title":"Cardiomyopathy in children with mitochondrial disease: Prognosis and genetic background","volume":"279","author":"Kishita","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.freeradbiomed.2018.09.019","article-title":"Targeting mitochondrial dysfunction and oxidative stress in heart failure: Challenges and opportunities","volume":"129","author":"Kiyuna","year":"2018","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11389","DOI":"10.1073\/pnas.1513047112","article-title":"Mitochondrial calcium overload is a key determinant in heart failure","volume":"112","author":"Santulli","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e95","DOI":"10.1016\/j.ddmec.2010.07.002","article-title":"Regulation of mitochondrial processes: A target for heart failure","volume":"7","author":"Palaniyandi","year":"2010","journal-title":"Drug Discov. Today: Dis. Mech."},{"key":"ref_66","first-page":"1544","article-title":"Cardiac mitochondrial energy metabolism in heart failure: Role of cardiolipin and sirtuins","volume":"1861","author":"Dolinsky","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5411","DOI":"10.1242\/jcs.02745","article-title":"The axonal transport of mitochondria","volume":"118","author":"Hollenbeck","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.4103\/1673-5374.280300","article-title":"Green tea catechins inhibit microglial activation which prevents the development of neurological disorders","volume":"15","author":"Samarghandian","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2013.03.018","article-title":"Mitochondrial Diseases of the Brain","volume":"63","author":"Chaturvedi","year":"2013","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.tox.2017.06.011","article-title":"Mitochondrial dysfunction in glial cells: Implications for neuronal homeostasis and survival","volume":"391","author":"Rose","year":"2017","journal-title":"Toxicology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.freeradbiomed.2012.11.014","article-title":"Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease","volume":"62","author":"Yan","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Liskova, A., Samec, M., Koklesova, L., Kudela, E., Kubatka, P., and Golubnitschaja, O. (2021). Mitochondriopathies as a Clue to Systemic Disorders\u2014Analytical Tools and Mitigating Measures in Context of Predictive, Preventive, and Personalized (3P) Medicine. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042007"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"613","DOI":"10.14348\/molcells.2017.0096","article-title":"Molecular and Cellular Basis of Neurodegeneration in Alzheimer\u2019s Disease","volume":"40","author":"Jeong","year":"2017","journal-title":"Mol. Cells"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fnins.2018.00163","article-title":"The Association of Tau With Mitochondrial Dysfunction in Alzheimer\u2019s Disease","volume":"12","author":"Cheng","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1126\/science.1132814","article-title":"A Century of Alzheimer\u2019s Disease","volume":"314","author":"Goedert","year":"2006","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1073\/pnas.83.11.4044","article-title":"Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease","volume":"83","author":"Kosik","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","article-title":"Amyloid plaque core protein in Alzheimer disease and Down syndrome","volume":"82","author":"Masters","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"a006296","DOI":"10.1101\/cshperspect.a006296","article-title":"The Genetics of Alzheimer Disease","volume":"2","author":"Tanzi","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nrn2620","article-title":"Apolipoprotein E and its receptors in Alzheimer\u2019s disease: pathways, pathogenesis and therapy","volume":"10","author":"Bu","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.14108","article-title":"Parkinson disease","volume":"27","author":"Balestrino","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/jnc.13731","article-title":"Mitochondrial dysfunction in Parkinson\u2019s disease","volume":"139","author":"Bose","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/162750","article-title":"Chemistry and Biological Activities of Flavonoids: An Overview","volume":"2013","author":"Kumar","year":"2013","journal-title":"Sci. World J."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Kopustinskiene, D.M., Jakstas, V., Savickas, A., and Bernatoniene, J. (2020). Flavonoids as anticancer agents. Nutrients, 12.","DOI":"10.3390\/nu12020457"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: an overview","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ninomiya, M., and Koketsu, M. (2013). Minor Flavonoids (Chalcones, Flavanones, Dihydrochalcones, and Aurones). Nat. Prod., 1867\u20131900.","DOI":"10.1007\/978-3-642-22144-6_62"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Liskova, A., Koklesova, L., Samec, M., Smejkal, K., Samuel, S.M., Varghese, E., Abotaleb, M., Biringer, K., Kudela, E., and Danko, J. (2020). Flavonoids in Cancer Metastasis. Cancers, 12.","DOI":"10.3390\/cancers12061498"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Cium\u0103rnean, L., Milaciu, M.V., Runcan, O., Vesa, S.C., R\u0103chi\u0219an, A.L., Negrean, V., Pern\u00e9, M.-G., Donca, V.I., Alexescu, T.-G., and Para, I. (2020). The effects of favonoids in cardiovascular diseases. Molecules, 25.","DOI":"10.3390\/molecules25184320"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Abotaleb, M., Samuel, S.M., Varghese, E., Varghese, S., Kubatka, P., L\u00ed\u0161kov\u00e1, A., and B\u00fcsselberg, D. (2018). Flavonoids in Cancer and Apoptosis. Cancers, 11.","DOI":"10.3390\/cancers11010028"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Yahfoufi, N., Alsadi, N., Jambi, M., and Matar, C. (2018). The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients, 10.","DOI":"10.3390\/nu10111618"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ejmech.2016.05.026","article-title":"Antidepressant-like effects and mechanisms of flavonoids and related analogues","volume":"121","author":"Guan","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Mirossay, L., Varinsk\u00e1, L., and Moj\u017ei\u0161, J. (2017). Antiangiogenic Effect of Flavonoids and Chalcones: An Update. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010027"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.2174\/1389450119666180326125252","article-title":"Flavonoids and its Neuroprotective Effects on Brain Ischemia and Neurodegenerative Diseases","volume":"19","author":"Manish","year":"2018","journal-title":"Curr. Drug Targets"},{"key":"ref_93","first-page":"79","article-title":"Flavonoids--food sources and health benefits","volume":"65","year":"2014","journal-title":"Rocz. Pa\u0144stw. Zak\u0142. Hig."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Prochazkova, D., Bou\u0161ov\u00e1, I., and Wilhelmov\u00e1, N. (2011). Antioxidant and prooxidant properties of flavonoids. Fitoterapia, Elsevier.","DOI":"10.1016\/j.fitote.2011.01.018"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.2174\/0929867325666180209132125","article-title":"Flavonoids in the Treatment of Alzheimer\u2019s and Other Neurodegenerative Diseases","volume":"25","author":"Airoldi","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"634","DOI":"10.2174\/156800908786241050","article-title":"Luteolin, a Flavonoid with Potential for Cancer Prevention and Therapy","volume":"8","author":"Lin","year":"2008","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/jbt.20367","article-title":"Prooxidant activity of fisetin: Effects on energy metabolism in the rat liver","volume":"25","author":"Constantin","year":"2010","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/761264","article-title":"Oxidative Stress, Prooxidants, and Antioxidants: The Interplay","volume":"2014","author":"Rahal","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1021\/tx060157q","article-title":"Pro-Oxidant Activity of Flavonoids Induces EpRE-Mediated Gene Expression","volume":"19","author":"Boerboom","year":"2006","journal-title":"Chem. Res. Toxicol."},{"key":"ref_100","first-page":"1446","article-title":"In vitro antioxidant\/prooxidant effects of combined use of flavonoids","volume":"32","author":"Ince","year":"2017","journal-title":"Nat. Prod. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3945\/ajcn.116.136051","article-title":"The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids","volume":"105","author":"Cassidy","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Garc\u00eda, C., S\u00e1nchez-Quesada, C., and Gaforio, J.J. (2019). Dietary Flavonoids as Cancer Chemopreventive Agents: An Updated Review of Human Studies. Antioxidants, 8.","DOI":"10.3390\/antiox8050137"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.tplants.2005.03.002","article-title":"Flavonoids: a colorful model for the regulation and evolution of biochemical pathways","volume":"10","author":"Koes","year":"2005","journal-title":"Trends Plant. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Rees, A., Dodd, G.F., and Spencer, J.P.E. (2018). The Effects of Flavonoids on Cardiovascular Health: A Review of Human Intervention Trials and Implications for Cerebrovascular Function. Nutrients, 10.","DOI":"10.3390\/nu10121852"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"8136","DOI":"10.1021\/acs.jafc.7b02757","article-title":"Apigenin Restrains Colon Cancer Cell Proliferation via Targeted Blocking of Pyruvate Kinase M2-Dependent Glycolysis","volume":"65","author":"Shan","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.lfs.2018.07.027","article-title":"Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction","volume":"208","author":"Jia","year":"2018","journal-title":"Life Sci."},{"key":"ref_107","first-page":"1","article-title":"Shikonin Inhibits Tumor Growth in Mice by Suppressing Pyruvate Kinase M2-mediated Aerobic Glycolysis","volume":"8","author":"Zhao","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Siu, M.K.Y., Jiang, Y.-X., Wang, J.-J., Leung, T.H.Y., Han, C.Y., Tsang, B.K., Cheung, A.N.Y., Ngan, H.Y.S., and Chan, K.K.L. (2019). Hexokinase 2 Regulates Ovarian Cancer Cell Migration, Invasion and Stemness via FAK\/ERK1\/2\/MMP9\/NANOG\/SOX9 Signaling Cascades. Cancers, 11.","DOI":"10.3390\/cancers11060813"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10863-007-9094-x","article-title":"Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers\u2019 most common phenotypes, the \u201cWarburg Effect\u201d, i.e., elevated glycolysis in the presence of oxygen","volume":"39","author":"Pedersen","year":"2007","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2002874","DOI":"10.1002\/advs.202002874","article-title":"OTUD1 Activates Caspase-Independent and Caspase-Dependent Apoptosis by Promoting AIF Nuclear Translocation and MCL1 Degradation","volume":"8","author":"Luo","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Hou, S., Song, Y., Sun, D., Zhu, S., and Wang, Z. (2021). Xanthohumol-Induced Rat Glioma C6 Cells Death by Triggering Mitochondrial Stress. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094506"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"962","DOI":"10.7150\/jca.34330","article-title":"Pyruvate dehydrogenase kinase 1 interferes with glucose metabolism reprogramming and mitochondrial quality control to aggravate stress damage in cancer","volume":"11","author":"Deng","year":"2020","journal-title":"J. Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"111082","DOI":"10.1016\/j.biopha.2020.111082","article-title":"Licochalcone A inhibits hypoxia-inducible factor-1\u03b1 accumulation by suppressing mitochondrial respiration in hypoxic cancer cells","volume":"133","author":"Park","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Phan, T.N., Kim, O., Ha, M.T., Hwangbo, C., Min, B.-S., and Lee, J.-H. (2020). Albanol B from Mulberries Exerts Anti-Cancer Effect through Mitochondria ROS Production in Lung Cancer Cells and Suppresses In Vivo Tumor Growth. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249502"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"109500","DOI":"10.1016\/j.cbi.2021.109500","article-title":"Lysionotin induces apoptosis of hepatocellular carcinoma cells via caspase-3 mediated mitochondrial pathway","volume":"344","author":"Yang","year":"2021","journal-title":"Chem. Interact."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"108728","DOI":"10.1016\/j.biopha.2019.108728","article-title":"Flavonoids from the Amazon plant Brosimum acutifolium induce C6 glioma cell line apoptosis by disrupting mitochondrial membrane potential and reducing AKT phosphorylation","volume":"113","author":"Alves","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Won, Y.-S., Kim, J.-H., Lizardo, R.C.M., Min, H.-J., Cho, H.-D., Hong, S.-M., and Seo, K.-I. (2020). The Flavonol Isoquercitrin Promotes Mitochondrial-Dependent Apoptosis in SK-Mel-2 Melanoma Cell via the PI3K\/AKT\/mTOR Pathway. Nutrients, 12.","DOI":"10.3390\/nu12123683"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11010-020-03885-6","article-title":"Myricetin: versatile plant based flavonoid for cancer treatment by inducing cell cycle arrest and ROS\u2013reliant mitochondria-facilitated apoptosis in A549 lung cancer cells and in silico prediction","volume":"476","author":"Rajendran","year":"2021","journal-title":"Mol. Cell. Biochem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.31557\/APJCP.2020.21.7.1877","article-title":"Silibinin Triggers the Mitochondrial Pathway of Apoptosis in Human Oral Squamous Carcinoma Cells","volume":"21","author":"Iyangar","year":"2020","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Ivanova, I.G., and Perkins, N.D. (2019). Hypoxia induces rapid, STAT3 and ROS dependent, mitochondrial translocation of RelA(p65) and I\u03baB\u03b1. Biosci. Rep., 39.","DOI":"10.1042\/BSR20192101"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00394-011-0240-1","article-title":"Aronia melanocarpa fruit extract exhibits anti-inflammatory activity in human aortic endothelial cells","volume":"51","author":"Bryk","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.freeradbiomed.2016.06.023","article-title":"PPAR\u03b3 as a therapeutic target to rescue mitochondrial function in neurological disease","volume":"100","author":"Corona","year":"2016","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.phymed.2014.09.005","article-title":"The protective effect of the Cornus mas fruits (cornelian cherry) on hypertriglyceridemia and atherosclerosis through PPAR\u03b1 activation in hypercholesterolemic rabbits","volume":"21","author":"Kucharska","year":"2014","journal-title":"Phytomedicine"},{"key":"ref_124","first-page":"1","article-title":"Amelioration of High Fructose-Induced Cardiac Hypertrophy by Naringin","volume":"8","author":"Park","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e12542","DOI":"10.1111\/jpi.12542","article-title":"Melatonin attenuates myocardial ischemia-reperfusion injury via improving mitochondrial fusion\/mitophagy and activating the AMPK-OPA1 signaling pathways","volume":"66","author":"Zhang","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.freeradbiomed.2019.09.033","article-title":"Brain-derived neurotrophic factor mimetic, 7,8-dihydroxyflavone, protects against myocardial ischemia by rebalancing optic atrophy 1 processing","volume":"145","author":"Wang","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.freeradbiomed.2018.11.024","article-title":"Activation of cardiac TrkB receptor by its small molecular agonist 7,8-dihydroxyflavone inhibits doxorubicin-induced cardiotoxicity via enhancing mitochondrial oxidative phosphorylation","volume":"130","author":"Zhao","year":"2019","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_128","first-page":"1","article-title":"Dihydromyricetin Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Mice","volume":"2017","author":"Wu","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00210-020-01953-8","article-title":"Quercetin treatment increases H2O2 removal by restoration of endogenous antioxidant activity and blocks isoproterenol-induced cardiac hypertrophy","volume":"394","author":"Alexandre","year":"2021","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.biopha.2016.08.016","article-title":"Icariin attenuated oxidative stress induced-cardiac apoptosis by mitochondria protection and ERK activation","volume":"83","author":"Song","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.fct.2018.05.053","article-title":"Cyanidin ameliorates endotoxin-induced myocardial toxicity by modulating inflammation and oxidative stress through mitochondria and other factors","volume":"120","author":"Li","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_132","first-page":"1","article-title":"Tilianin Protects against Ischemia\/Reperfusion-Induced Myocardial Injury through the Inhibition of the Ca2+\/Calmodulin-Dependent Protein Kinase II-Dependent Apoptotic and Inflammatory Signaling Pathways","volume":"2020","author":"Jiang","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/9173436","article-title":"Fisetin Confers Cardioprotection against Myocardial Ischemia Reperfusion Injury by Suppressing Mitochondrial Oxidative Stress and Mitochondrial Dysfunction and Inhibiting Glycogen Synthase Kinase 3\u03b2 Activity","volume":"2018","author":"Shanmugam","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"566470","DOI":"10.3389\/fphar.2021.566470","article-title":"Fisetin Attenuates Myocardial Ischemia-Reperfusion Injury by Activating the Reperfusion Injury Salvage Kinase (RISK) Signaling Pathway","volume":"12","author":"Shanmugam","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_135","first-page":"1","article-title":"Baicalin Improves Cardiac Outcome and Survival by Suppressing Drp1-Mediated Mitochondrial Fission after Cardiac Arrest-Induced Myocardial Damage","volume":"2021","author":"Wu","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.neuro.2010.05.009","article-title":"The neurotoxicity of environmental aluminum is still an issue","volume":"31","author":"Bondy","year":"2010","journal-title":"NeuroToxicology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"636","DOI":"10.3109\/00207454.2013.785542","article-title":"Naringin protects memory impairment and mitochondrial oxidative damage against aluminum-induced neurotoxicity in rats","volume":"123","author":"Prakash","year":"2013","journal-title":"Int. J. Neurosci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brainresbull.2016.08.009","article-title":"Amyloid precursor protein processing and bioenergetics","volume":"133","author":"Wilkins","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.neuropharm.2015.01.027","article-title":"The flavonoid quercetin ameliorates Alzheimer\u2019s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer\u2019s disease model mice","volume":"93","author":"Manco","year":"2015","journal-title":"Neuropharmacol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"7116","DOI":"10.1007\/s12035-016-0203-x","article-title":"Quercetin Exerts Differential Neuroprotective Effects Against H2O2 and A\u03b2 Aggregates in Hippocampal Neurons: the Role of Mitochondria","volume":"54","author":"Lindsay","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1111\/bph.12531","article-title":"Changes in mitochondrial function are pivotal in neurodegenerative and psychiatric disorders: How important is BDNF?","volume":"171","author":"Markham","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/emboj\/21.1.53","article-title":"CREB activation induced by mitochondrial dysfunction is a new signaling pathway that impairs cell proliferation","volume":"21","author":"Arnould","year":"2002","journal-title":"EMBO J."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1111\/jnc.14033","article-title":"Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson\u2019s Disease","volume":"141","author":"Ay","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000441522","article-title":"Cholinesterase Inhibitor Donepezil Increases Mitochondrial Biogenesis through AMP-Activated Protein Kinase in the Hippocampus","volume":"73","author":"Kim","year":"2016","journal-title":"Neuropsychobiology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1096\/fj.10-157230","article-title":"Mitochondrial \u03b3-secretase participates in the metabolism of mitochondria-associated amyloid precursor protein","volume":"25","author":"Pavlov","year":"2011","journal-title":"FASEB J."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"153316","DOI":"10.1016\/j.phymed.2020.153316","article-title":"The pharmacological activity of epigallocatechin-3-gallate (EGCG) on Alzheimer\u2019s disease animal model: A systematic review","volume":"79","author":"Zhang","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/2856063","article-title":"Mangiferin and Morin Attenuate Oxidative Stress, Mitochondrial Dysfunction, and Neurocytotoxicity, Induced by Amyloid Beta Oligomers","volume":"2018","author":"Alberdi","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"11738","DOI":"10.18632\/aging.202868","article-title":"Administration of quercetin improves mitochondria quality control and protects the neurons in 6-OHDA-lesioned Parkinson\u2019s disease models","volume":"13","author":"Wang","year":"2021","journal-title":"Aging"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jff.2012.11.004","article-title":"Myricitrin attenuates 6-hydroxydopamine-induced mitochondrial damage and apoptosis in PC12 cells via inhibition of mitochondrial oxidation","volume":"5","author":"Wang","year":"2013","journal-title":"J. Funct. Foods"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.bbrc.2015.01.060","article-title":"Myricitrin alleviates MPP+-induced mitochondrial dysfunction in a DJ-1-dependent manner in SN4741 cells","volume":"458","author":"Cai","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/102741","article-title":"Neuroprotective Effects of Hesperidin, a Plant Flavanone, on Rotenone-Induced Oxidative Stress and Apoptosis in a Cellular Model for Parkinson\u2019s Disease","volume":"2013","author":"Tamilselvam","year":"2013","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.lfs.2018.11.035","article-title":"Tilianin mediates neuroprotection against ischemic injury by attenuating CaMKII-dependent mitochondrion-mediated apoptosis and MAPK\/NF-\u03baB signaling","volume":"216","author":"Jiang","year":"2018","journal-title":"Life Sci."},{"key":"ref_153","first-page":"3009","article-title":"Neuroprotection of hydroxysafflor yellow A in experimental cerebral ischemia\/reperfusion injury via metabolic inhibition of phenylalanine and mitochondrial biogenesis","volume":"19","author":"Chen","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"153532","DOI":"10.1016\/j.phymed.2021.153532","article-title":"Hydroxysafflor yellow A alleviates cerebral ischemia reperfusion injury by suppressing apoptosis via mitochondrial permeability transition pore","volume":"85","author":"Huang","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"73","DOI":"10.5607\/en20051","article-title":"Nobiletin Exhibits Neuroprotective Effects against Mitochondrial Complex I Inhibition via Regulating Apoptotic Signaling","volume":"30","author":"Amarsanaa","year":"2021","journal-title":"Exp. Neurobiol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"41","DOI":"10.12703\/P7-41","article-title":"Chicken or the egg: Warburg effect and mitochondrial dysfunction","volume":"7","author":"Senyilmaz","year":"2015","journal-title":"F1000Prime Rep."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s13167-020-00217-y","article-title":"Flavonoids against the Warburg phenotype\u2014concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism","volume":"11","author":"Samec","year":"2020","journal-title":"EPMA J."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1249\/MSS.0000000000001854","article-title":"Aerobic Exercise Improves Microvascular Function in Older Adults","volume":"51","author":"Hurley","year":"2019","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41574-018-0126-x","article-title":"The obese adipose tissue microenvironment in cancer development and progression","volume":"15","author":"Quail","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1002\/ijc.31955","article-title":"Work stress and the risk of cancer: A meta-analysis of observational studies","volume":"144","author":"Yang","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s13167-018-0145-7","article-title":"\u201cDry mouth\u201d and \u201cFlammer\u201d syndromes\u2014neglected risks in adolescents and new concepts by predictive, preventive and personalised approach","volume":"9","author":"Kunin","year":"2018","journal-title":"EPMA J."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"662","DOI":"10.14336\/AD.2017.0713","article-title":"Aging, Metabolism, and Cancer Development: from Peto\u2019s Paradox to the Warburg Effect","volume":"8","author":"Tidwell","year":"2017","journal-title":"Aging Dis."},{"key":"ref_163","first-page":"1","article-title":"Inflammation and cancer","volume":"23","author":"Murata","year":"2018","journal-title":"Environ. Heal. Prev. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"150858","DOI":"10.1016\/j.sempedsurg.2019.150858","article-title":"Genetic predisposition to cancer: Surveillance and intervention","volume":"28","author":"Perrino","year":"2019","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"96S","DOI":"10.2967\/jnumed.107.045948","article-title":"Molecular Imaging of Metastatic Potential","volume":"49","author":"Winnard","year":"2008","journal-title":"J. Nucl. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s13167-018-0127-9","article-title":"Individualised patient profile: clinical utility of Flammer syndrome phenotype and general lessons for predictive, preventive and personalised medicine","volume":"9","author":"Golubnitschaja","year":"2018","journal-title":"EPMA J."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13167-015-0030-6","article-title":"EPMA position paper in cancer: current overview and future perspectives","volume":"6","author":"Grech","year":"2015","journal-title":"EPMA J."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s13167-019-00170-5","article-title":"Signaling pathway network alterations in human ovarian cancers identified with quantitative mitochondrial proteomics","volume":"10","author":"Li","year":"2019","journal-title":"EPMA J."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s13167-020-00224-z","article-title":"Quantitative proteomics revealed energy metabolism pathway alterations in human epithelial ovarian carcinoma and their regulation by the antiparasite drug ivermectin: data interpretation in the context of 3P medicine","volume":"11","author":"Li","year":"2020","journal-title":"EPMA J."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1093\/eurheartj\/ehn409","article-title":"Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke","volume":"29","author":"Chan","year":"2008","journal-title":"Eur. Hear. J."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1093\/aje\/kww207","article-title":"Dietary Flavonoid and Lignan Intake and Mortality in Prospective Cohort Studies: Systematic Review and Dose-Response Meta-Analysis","volume":"185","author":"Grosso","year":"2017","journal-title":"Am. J. Epidemiol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/aje\/154.6.495","article-title":"Does Tea Affect Cardiovascular Disease? A Meta-Analysis","volume":"154","author":"Peters","year":"2001","journal-title":"Am. J. Epidemiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"e232756","DOI":"10.1136\/bcr-2019-232756","article-title":"Hereditary transthyretin amyloidosis caused by the rare Phe33Leu mutation","volume":"13","year":"2020","journal-title":"BMJ Case Rep."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s00392-012-0463-z","article-title":"Green tea halts progression of cardiac transthyretin amyloidosis: an observational report","volume":"101","author":"Kristen","year":"2012","journal-title":"Clin. Res. Cardiol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1161\/01.cir.0000437738.63853.7a","article-title":"2013 ACC\/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults","volume":"129","author":"Stone","year":"2014","journal-title":"Circulation"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/365798","article-title":"Fatty Acid Oxidation and Cardiovascular Risk during Menopause: A Mitochondrial Connection?","volume":"2012","author":"Oliveira","year":"2012","journal-title":"J. Lipids"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.numecd.2018.03.007","article-title":"Soy isoflavones improve cardiovascular disease risk markers in women during the early menopause","volume":"28","author":"Sathyapalan","year":"2018","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1007\/s00018-017-2611-0","article-title":"Melatonin, mitochondria, and the metabolic syndrome","volume":"74","author":"Cardinali","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.3945\/jn.110.124701","article-title":"Blueberries Decrease Cardiovascular Risk Factors in Obese Men and Women with Metabolic Syndrome","volume":"140","author":"Basu","year":"2010","journal-title":"J. Nutr."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.nutres.2011.02.003","article-title":"Low-energy cranberry juice decreases lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome","volume":"31","author":"Basu","year":"2011","journal-title":"Nutr. Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"587","DOI":"10.3945\/ajcn.116.133132","article-title":"Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease in men","volume":"104","author":"Cassidy","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"e179","DOI":"10.1016\/j.atherosclerosis.2006.12.032","article-title":"Combination therapy of statin with flavonoids rich extract from chokeberry fruits enhanced reduction in cardiovascular risk markers in patients after myocardial infraction (MI)","volume":"194","author":"Naruszewicz","year":"2007","journal-title":"Atherosclerosis"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Lin, K.-J., Chen, S.-D., Liou, C.-W., Chuang, Y.-C., Lin, H.-Y., and Lin, T.-K. (2019). The Overcrowded Crossroads: Mitochondria, Alpha-Synuclein, and the Endo-Lysosomal System Interaction in Parkinson\u2019s Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215312"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1007\/s00018-018-2872-2","article-title":"Inhibition of protein misfolding and aggregation by natural phenolic compounds","volume":"75","author":"Dhouafli","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/S1474-4422(19)30141-3","article-title":"Safety and efficacy of epigallocatechin gallate in multiple system atrophy (PROMESA): A randomised, double-blind, placebo-controlled trial","volume":"18","author":"Levin","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.arr.2018.10.010","article-title":"Homocysteine and age-associated disorders","volume":"49","author":"Ostrakhovitch","year":"2019","journal-title":"Ageing Res. Rev."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jns.2010.08.050","article-title":"Effect of an antioxidant drink on homocysteine levels in Alzheimer\u2019s patients","volume":"299","author":"Albaladejo","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000017242","article-title":"A 26-Week Analysis of a Double-Blind, Placebo-Controlled Trial of the Ginkgo biloba Extract EGb 761\u00ae in Dementia","volume":"11","author":"Kieser","year":"2000","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00702-016-1507-8","article-title":"The PROMESA-protocol: progression rate of multiple system atrophy under EGCG supplementation as anti-aggregation-approach","volume":"123","author":"Levin","year":"2016","journal-title":"J. Neural Transm."},{"key":"ref_190","first-page":"45","article-title":"Mitochondria and Parkinson\u2019s Disease: Clinical, Molecular, and Translational Aspects","volume":"11","author":"Borsche","year":"2021","journal-title":"J. Park. Dis."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2174\/1573403X14666180222102312","article-title":"Management of Measurable Variable Cardiovascular Disease\u2019 Risk Factors","volume":"14","author":"Nola","year":"2018","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/s41416-019-0721-1","article-title":"Cancer as a disease of old age: changing mutational and microenvironmental landscapes","volume":"122","author":"Laconi","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1146\/annurev-pathmechdis-012419-032544","article-title":"Cardiovascular Disease, Aging, and Clonal Hematopoiesis","volume":"15","author":"Evans","year":"2020","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1039\/C8FO01997E","article-title":"The effects of polyphenols and other bioactives on human health","volume":"10","author":"Fraga","year":"2019","journal-title":"Food Funct."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"104625","DOI":"10.1016\/j.phrs.2019.104625","article-title":"The beneficial health effects of flavonoids on the cardiovascular system: Focus on K+ channels","volume":"152","author":"Fusi","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Maher, P. (2019). The Potential of Flavonoids for the Treatment of Neurodegenerative Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123056"},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Ashrafizadeh, M., Ahmadi, Z., Mohammadinejad, R., and Afshar, E.G. (2020). Tangeretin: a mechanistic review of its pharmacological and therapeutic effects. J. Basic Clin. Physiol. Pharmacol., 31.","DOI":"10.1515\/jbcpp-2019-0191"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s13167-020-00210-5","article-title":"Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine","volume":"11","author":"Koklesova","year":"2020","journal-title":"EPMA J."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s13167-020-00204-3","article-title":"Personality and stress influence vision restoration and recovery in glaucoma and optic neuropathy following alternating current stimulation: implications for personalized neuromodulation and rehabilitation","volume":"11","author":"Sabel","year":"2020","journal-title":"EPMA J."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s13167-019-00162-5","article-title":"Risks associated with the stroke predisposition at young age: facts and hypotheses in light of individualized predictive and preventive approach","volume":"10","author":"Polivka","year":"2019","journal-title":"EPMA J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8649\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:44:20Z","timestamp":1760165060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,11]]},"references-count":201,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168649"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168649","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,11]]}}}