{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:04:37Z","timestamp":1789707877879,"version":"4.0.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tyrosine kinase inhibitors (TKIs) are potent anticancer agents; however, their clinical application is often restricted because of cardiotoxic effects. The mechanisms underlying cardiotoxicity that are shared across different TKIs remain inadequately understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed to investigate the role of sirtuin 7 (SIRT7) in regulating mitochondrial calcium homeostasis during TKI-induced cardiomyocyte injury and determine whether the SIRT7\u2013mitochondrial calcium uniporter (MCU) axis could serve as a common protective target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      AC16 cells were treated for 72\u00a0h with three TKIs: sunitinib (4.11 \u00b5M, IC\n                      <jats:sub>30<\/jats:sub>\n                      ), trametinib (12.21 \u00b5M, IC\n                      <jats:sub>30<\/jats:sub>\n                      ), and imatinib (21.84 \u00b5M, IC\n                      <jats:sub>30<\/jats:sub>\n                      ). Cell viability, cardiomyocyte injury markers (N-terminal pro-brain natriuretic peptide and cardiac troponin I), cytosolic and mitochondrial Ca\n                      <jats:sup>2+<\/jats:sup>\n                      levels, mitochondrial membrane potential, adenosine triphosphate (ATP) content, and endoplasmic reticulum\u2013mitochondria contacts assessed using transmission electron microscopy were evaluated. Proteomic analysis was performed to identify differentially expressed proteins shared across treatments. In human induced pluripotent stem cell\u2013derived cardiomyocytes (hiPSC-CMs), contraction amplitude was measured using an impedance-based system, and mitochondrial Ca\n                      <jats:sup>2+<\/jats:sup>\n                      overload was evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All three TKIs induced concentration-dependent injury in AC16 cells, accompanied by mitochondrial Ca\n                      <jats:sup>2+<\/jats:sup>\n                      overload, ATP depletion exceeding 50%, and increased mitochondria\u2013endoplasmic reticulum (ER) contacts. Proteomic analysis identified consistent SIRT7 downregulation across the three TKI treatments. SIRT7 overexpression mitigated TKI-induced cellular damage, reversed MCU upregulation and functional activation, restored mitochondrial function, and reduced excessive mitochondria\u2013ER contacts. In hiPSC-CMs, SIRT7 overexpression reduced mitochondrial Ca\n                      <jats:sup>2+<\/jats:sup>\n                      overload and prevented TKI-induced contraction inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SIRT7 upregulation protects against TKI-induced cardiotoxicity by inhibiting MCU-mediated mitochondrial calcium overload.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1929231","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:35:38Z","timestamp":1789706138000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SIRT7 upregulation protects against TKI-induced cardiotoxicity by inhibiting MCU-mediated mitochondrial calcium overload"],"prefix":"10.3389","volume":"17","author":[{"given":"Meiling","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiling","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhua","family":"Qiu","sequence":"additional","affiliation":[{"name":"Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Xu","sequence":"additional","affiliation":[{"name":"Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]},{"name":"Hebei Provincial Key Laboratory of Precision Anesthesiology and Organ Protection","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/978-1-4020-6191-2_18","article-title":"Calcium and cell death: the mitochondrial connection","volume":"45","author":"Bernardi","year":"2007","journal-title":"Sub-cellular Biochemistry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1161\/CIRCRESAHA.118.310082","article-title":"Calcium signaling and reactive oxygen species in mitochondria","volume":"122","author":"Bertero","year":"2018","journal-title":"Circ. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.yjmcc.2020.10.015","article-title":"Calcium influx through the mitochondrial calcium uniporter holocomplex, MCU(cx)","volume":"151","author":"Boyman","year":"2021","journal-title":"J. Molecular Cellular Cardiology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1007\/s00204-023-03611-3","article-title":"SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice","volume":"97","author":"Chen","year":"2023","journal-title":"Archives Toxicology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"113962","DOI":"10.1016\/j.biopha.2022.113962","article-title":"Pentraxin 3 regulates tyrosine kinase inhibitor-associated cardiomyocyte contraction and mitochondrial dysfunction via ERK\/JNK signalling pathways","volume":"157","author":"Chen","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1016\/S0140-6736(07)61865-0","article-title":"Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib","volume":"370","author":"Chu","year":"2007","journal-title":"Lancet London, Engl."},{"key":"B6","doi-asserted-by":"publisher","first-page":"107970","DOI":"10.1016\/j.phrs.2025.107970","article-title":"Sirtuin-mediated modulation of cardiac fibrosis: emerging molecular insights and therapeutic perspectives","volume":"221","author":"Cozzolino","year":"2025","journal-title":"Pharmacol. Research"},{"key":"B7","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1161\/01.RES.0000148666.20729.1c","article-title":"Sir-viving cardiac stress: cardioprotection mediated by a longevity gene","volume":"95","author":"Crow","year":"2004","journal-title":"Circulation Research"},{"key":"B8","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.cmet.2013.04.020","article-title":"MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca2+ uniporter","volume":"17","author":"Csord\u00e1s","year":"2013","journal-title":"Cell Metab."},{"key":"B9","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.freeradbiomed.2025.08.017","article-title":"Targeting PDK4 to mitigate osimertinib-induced cardiotoxicity: insights into mitochondria-endoplasmic reticulum crosstalk and necroptosis","volume":"240","author":"Deng","year":"2025","journal-title":"Free Radical Biology and Medicine"},{"key":"B10","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1161\/CIRCRESAHA.124.325440","article-title":"Roles of sirtuins in cardiovascular diseases: mechanisms and therapeutics","volume":"136","author":"Ding","year":"2025","journal-title":"Circulation Research"},{"key":"B11","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1042\/cs20200305","article-title":"Cardiotoxic effects of angiogenesis inhibitors","volume":"135","author":"Dobbin","year":"2021","journal-title":"Clin. Science Lond. Engl. 1979"},{"key":"B12","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/nrd3252","article-title":"Cardiotoxicity of kinase inhibitors: the prediction and translation of preclinical models to clinical outcomes","volume":"10","author":"Force","year":"2011","journal-title":"Nat. Reviews Drug Discovery"},{"key":"B13","doi-asserted-by":"publisher","first-page":"152027","DOI":"10.1016\/j.bbrc.2025.152027","article-title":"Tyrosine kinase inhibitors induce cardiotoxicity by causing Ca(2+) overload through the inhibition of phosphoinositide 3-kinase activity","volume":"771","author":"Gao","year":"2025","journal-title":"Biochem. Biophysical Research Communications"},{"key":"B14","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nrclinonc.2015.213","article-title":"Kinase inhibitors and monoclonal antibodies in oncology: clinical implications","volume":"13","author":"Gharwan","year":"2016","journal-title":"Nat. Reviews Clin. Oncology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.yjmcc.2021.02.014","article-title":"Computational model of cardiomyocyte apoptosis identifies mechanisms of tyrosine kinase inhibitor-induced cardiotoxicity","volume":"155","author":"Grabowska","year":"2021","journal-title":"J. Molecular Cellular Cardiology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1093\/cvr\/cvm005","article-title":"Heart mitochondria: gates of life and death","volume":"77","author":"Gustafsson","year":"2008","journal-title":"Cardiovasc. Research"},{"key":"B17","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1054\/ceca.2000.0169","article-title":"Control of apoptosis by IP(3) and ryanodine receptor driven calcium signals","volume":"28","author":"Hajn\u00f3czky","year":"2000","journal-title":"Cell Calcium"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1002\/1878-0261.13808","article-title":"Respiratory complex I-mediated NAD(+) regeneration regulates cancer cell proliferation through the transcriptional and translational control of p21(Cip1) expression by SIRT3 and SIRT7","volume":"19","author":"Higurashi","year":"2025","journal-title":"Mol. Oncology"},{"key":"B19","first-page":"2009","volume-title":"Biological Evaluation of Medical Devices Part 5: Tests for","year":"1994"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.15252\/embr.201643748","article-title":"High-affinity cooperative Ca(2+) binding by MICU1-MICU2 serves as an on-off switch for the uniporter","volume":"18","author":"Kamer","year":"2017","journal-title":"EMBO Reports"},{"key":"B21","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1752-8062.2008.00090.x","article-title":"Sunitinib-induced cardiotoxicity is mediated by off-target inhibition of AMP-activated protein kinase","volume":"2","author":"Kerkela","year":"2009","journal-title":"Clin. Translational Science"},{"key":"B22","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.abb.2018.09.026","article-title":"Regulation of cardiac calcium by mechanotransduction: role of mitochondria","volume":"659","author":"Kim","year":"2018","journal-title":"Archives Biochemistry Biophysics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1161\/CIRCRESAHA.117.310083","article-title":"Calcium signaling and cardiac arrhythmias","volume":"120","author":"Landstrom","year":"2017","journal-title":"Circ. Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1159\/000529260","article-title":"Off-target effects of cancer therapy on development of therapy-induced arrhythmia: a review","volume":"148","author":"Leiva","year":"2023","journal-title":"Cardiology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1007\/s00204-019-02448-z","article-title":"Upregulation of phosphoinositide 3-kinase prevents sunitinib-induced cardiotoxicity in vitro and in vivo","volume":"93","author":"Li","year":"2019","journal-title":"Arch. Toxicol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1177003","DOI":"10.3389\/fphar.2023.1177003","article-title":"Acute osimertinib exposure induces electrocardiac changes by synchronously inhibiting the currents of cardiac ion channels","volume":"14","author":"Li","year":"2023","journal-title":"Front. Pharmacology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1161\/circresaha.120.318562","article-title":"MCU overexpression rescues inotropy and reverses heart failure by reducing SR Ca(2+) leak","volume":"128","author":"Liu","year":"2021","journal-title":"Circulation Research"},{"key":"B28","doi-asserted-by":"publisher","first-page":"110766","DOI":"10.1016\/j.clinbiochem.2024.110766","article-title":"Plasma levels of sirtuin 7 are decreased in patients with essential hypertension","author":"Liu","year":"2024","journal-title":"Clin. Biochemistry"},{"key":"B29","doi-asserted-by":"publisher","first-page":"131ra50","DOI":"10.1126\/scitranslmed.3003623","article-title":"Suppression of phosphoinositide 3-kinase signaling and alteration of multiple ion currents in drug-induced long QT syndrome","volume":"4","author":"Lu","year":"2012","journal-title":"Sci. Translational Medicine"},{"key":"B30","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s10495-023-01911-8","article-title":"The Flt3-inhibitor quizartinib augments apoptosis and promotes maladaptive remodeling after myocardial infarction in mice","volume":"29","author":"Monogiou Belik","year":"2024","journal-title":"Apoptosis An International Journal Programmed Cell Death."},{"key":"B31","doi-asserted-by":"publisher","first-page":"4342","DOI":"10.1111\/bph.13213","article-title":"Effects of acute and chronic sunitinib treatment on cardiac function and calcium\/calmodulin-dependent protein kinase II","volume":"172","author":"Mooney","year":"2015","journal-title":"Br. Journal Pharmacology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.yjmcc.2014.08.015","article-title":"Molecular identity of the mitochondrial permeability transition pore and its role in ischemia-reperfusion injury","volume":"78","author":"Morciano","year":"2015","journal-title":"J. Molecular Cellular Cardiology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1038\/ncb2868","article-title":"The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter","volume":"15","author":"Pan","year":"2013","journal-title":"Nat. Cell Biology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.jacc.2013.08.1647","article-title":"FLT3 activation improves post-myocardial infarction remodeling involving a cytoprotective effect on cardiomyocytes","volume":"63","author":"Pfister","year":"2014","journal-title":"J. U. S. A. Coll. Cardiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.bbabio.2008.05.449","article-title":"The versatility of mitochondrial calcium signals: from stimulation of cell metabolism to induction of cell death","volume":"1777","author":"Rimessi","year":"2008","journal-title":"Biochimica biophysica acta"},{"key":"B37","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/j.cmet.2014.08.001","article-title":"A SIRT7-dependent acetylation switch of GABP\u03b21 controls mitochondrial function","volume":"20","author":"Ryu","year":"2014","journal-title":"Cell Metab."},{"key":"B38","doi-asserted-by":"publisher","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. U. S. A."},{"key":"B39","doi-asserted-by":"publisher","first-page":"6726","DOI":"10.7150\/thno.100667","article-title":"Targeting sirtuins for cancer therapy: epigenetics modifications and beyond","volume":"14","author":"Shen","year":"2024","journal-title":"Theranostics"},{"key":"B40","doi-asserted-by":"publisher","first-page":"651","DOI":"10.3389\/fphys.2017.00651","article-title":"Mechanistic systems modeling to improve understanding and prediction of cardiotoxicity caused by targeted cancer therapeutics","volume":"8","author":"Shim","year":"2017","journal-title":"Front. Physiology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/s41392-023-01469-6","article-title":"Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management","volume":"8","author":"Shyam","year":"2023","journal-title":"Signal Transduction Targeted Therapy"},{"key":"B42","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1093\/cvr\/cvz006","article-title":"Ponatinib-induced cardiotoxicity: delineating the signalling mechanisms and potential rescue strategies","volume":"115","author":"Singh","year":"2019","journal-title":"Cardiovasc. Research"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.7150\/thno.19551","article-title":"Cardiac metabolic deregulation induced by the tyrosine kinase receptor inhibitor sunitinib is rescued by endothelin receptor antagonism","volume":"7","author":"Sourdon","year":"2017","journal-title":"Theranostics"},{"key":"B44","doi-asserted-by":"publisher","first-page":"3830","DOI":"10.7150\/thno.49837","article-title":"Sunitinib-induced cardiac hypertrophy and the endothelin axis","volume":"11","author":"Sourdon","year":"2021","journal-title":"Theranostics"},{"key":"B45","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.jacbts.2017.12.007","article-title":"Increased afterload augments sunitinib-induced cardiotoxicity in an engineered cardiac microtissue model","volume":"3","author":"Truitt","year":"2018","journal-title":"JACC Basic Translational Science"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e15545","DOI":"10.7554\/eLife.15545","article-title":"Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex","volume":"5","author":"Tsai","year":"2016","journal-title":"eLife"},{"key":"B47","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1161\/CIRCRESAHA.107.164558","article-title":"Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice","volume":"102","author":"Vakhrusheva","year":"2008","journal-title":"Circulation Research"},{"key":"B48","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1002\/cpt.787","article-title":"Practical recommendations for therapeutic drug monitoring of kinase inhibitors in oncology","volume":"102","author":"Verheijen","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"B49","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s12916-023-02838-2","article-title":"Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes","volume":"21","author":"Wang","year":"2023","journal-title":"BMC Medicine"},{"key":"B50","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.yjmcc.2014.10.019","article-title":"Mitochondrial calcium and the regulation of metabolism in the heart","volume":"78","author":"Williams","year":"2015","journal-title":"J. Molecular Cellular Cardiology"},{"key":"B51","doi-asserted-by":"publisher","first-page":"3404","DOI":"10.1093\/eurheartj\/ehv290","article-title":"Protective effects of sirtuins in cardiovascular diseases: from bench to bedside","volume":"36","author":"Winnik","year":"2015","journal-title":"Eur. Heart Journal"},{"key":"B52","doi-asserted-by":"publisher","first-page":"153830","DOI":"10.1016\/j.tox.2024.153830","article-title":"Phosphoproteomics reveals a novel mechanism underlying the proarrhythmic effects of nilotinib, vandetanib, and mobocertinib","volume":"505","author":"Wu","year":"2024","journal-title":"Toxicology"},{"key":"B53","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.bbabio.2016.03.019","article-title":"Analysis of the structure and function of EMRE in a yeast expression system","volume":"1857","author":"Yamamoto","year":"2016","journal-title":"Biochimica biophysica acta"},{"key":"B54","doi-asserted-by":"publisher","first-page":"3249","DOI":"10.1007\/s00204-019-02573-9","article-title":"Sirt3 promotes sensitivity to sunitinib-induced cardiotoxicity via inhibition of GTSP1\/JNK\/autophagy pathway in vivo and in vitro","volume":"93","author":"Yang","year":"2019","journal-title":"Archives Toxicology"},{"key":"B55","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1002\/jcb.22169","article-title":"Effects of resveratrol on H(2)O(2)-induced apoptosis and expression of SIRTs in H9c2 cells","volume":"107","author":"Yu","year":"2009","journal-title":"J. Cellular Biochemistry"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1929231\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:35:45Z","timestamp":1789706145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1929231\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":55,"alternative-id":["10.3389\/fphar.2026.1929231"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1929231","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"article-number":"1929231"}}