{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:34:34Z","timestamp":1784396074895,"version":"3.55.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":625,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["#HI22C0610"],"award-info":[{"award-number":["#HI22C0610"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Basic Science Research Program of the National Research Foundation","award":["NRF-2014R1A6A1029617"],"award-info":[{"award-number":["NRF-2014R1A6A1029617"]}]},{"name":"Basic Science Research Program of the National Research Foundation","award":["NRF-2018R1C1B5041472"],"award-info":[{"award-number":["NRF-2018R1C1B5041472"]}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["#HI22C0610"],"award-info":[{"award-number":["#HI22C0610"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The clinical application of doxorubicin (DOX), a potent anthracycline anticancer drug that effectively treats various malignancies, is limited by its side effects, such as cardiomyopathy. Apurinic\/apyrimidinic endonuclease 1\/redox factor-1 (APE1\/Ref-1) is a multifunctional protein that can be secreted and is a promising target for the reduction of DOX-induced inflammation and oxidative stress. We aimed to investigate the protective role of secretory APE1\/Ref-1 against DOX-induced cardiac injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Designated adenoviral preprotrypsin-leading sequence APE1\/Ref-1 (Ad-PPTLS-APE1\/Ref-1) was used to overexpress secretory APE1\/Ref-1 and assess its role in preventing DOX-induced cardiomyopathy in vitro. Our findings revealed that exposure to secretory APE1\/Ref-1 significantly decreased N-terminal pro-B-type natriuretic peptide levels in DOX-treated H9C2 cells. In addition, secretory APE1\/Ref-1 reduced the severity of cardiomyocyte injury and apoptosis in both in vitro and in vivo DOX-induced cardiotoxicity models. The observed cardioprotective effects of secretory APE1\/Ref-1 were mediated via inhibition of the p53 signalling pathway and enhancement of cell viability through attenuation of oxidative stress in DOX-treated cardiomyocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provides evidence that secretory APE1\/Ref-1 has the potential to inhibit DOX-induced cardiac toxicity by inhibiting oxidative stress and p53 related apoptosis both in vitro and in vivo. These findings suggest that secretory APE1\/Ref-1 supplementation is a promising strategy to attenuate DOX-induced cardiomyocyte damage in a preclinical model. Further clinical investigations are essential to validate the therapeutic efficacy and safety of the intervention in human subjects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14686","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T22:59:17Z","timestamp":1706569157000},"page":"1182-1193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Protective Effect of Secretory APE1\/Ref-1 on Doxorubicin-Induced Cardiotoxicity via Suppression of ROS and p53 Pathway"],"prefix":"10.1093","volume":"11","author":[{"given":"Soo Yeon","family":"An","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chungnam National University Hospital, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]},{"name":"Department of Medical Sciences, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon-Ah","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chungnam National University Hospital, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]},{"name":"Research Institute for Medical Sciences, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Jeong","family":"Seo","sequence":"additional","affiliation":[{"name":"Research Institute for Medical Sciences, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Ran","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Institute for Medical Sciences, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]},{"name":"Department of Physiology, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]},{"name":"Department of Physiology, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong Hwa","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of Korea"]},{"name":"Research Institute for Medical Sciences, College of Medicine, Chungnam National University , Daejeon ,","place":["Republic of 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