{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:23:10Z","timestamp":1778059390700,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Skeletal muscle ischaemia\/reperfusion (I\/R) injury remains a clinically significant condition characterized by muscular dystrophy. Although ozone therapy has shown protective potential against I\/R injury in animal models of various organs including skeletal muscle, its precise mechanistic underpinnings require further elucidation. This investigation evaluates the therapeutic potential of major ozonated autohemotherapy (MOAH) for skeletal muscle I\/R injury management. Utilizing a rat femoral artery ligation\/release model, we demonstrated that MOAH pretreatment substantially alleviated histopathological damage through hematoxylin\u2013eosin\/Masson staining analyzes, diminished skeletal muscle apoptosis via terminal deoxynucleotidyl transferase dUTP nick\u2010end labeling and Western blot, and reduced tissue edema as quantified by wet weight ratios. Serum biomarker assessments confirmed decreased creatine kinase and lactate dehydrogenase levels with MOAH administration. In oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R)\u2010treated L6 myoblast models, ozone pretreatment enhanced cellular proliferation capacity while attenuating apoptosis and mitochondrial dysfunction. Subsequent analyzes revealed ozone's regulatory effects on oxidative stress markers (MDA content, SOD and CAT activity) and inflammatory factors (TNF\u2010\u03b1 and IL\u20101\u03b2) across both in\u00a0vivo and in\u00a0vitro models. Mechanistic evaluations through Western blot and reverse transcription quantitative real\u2010time polymerase chain reaction techniques identified MOAH\u2010induced activation of the Nrf2\/HO\u20101 signaling pathway, with observed abolition of protective efficacy under Nrf2 knockdown conditions. These results collectively establish that MOAH mitigates skeletal muscle I\/R injury through Nrf2\/HO\u20101 pathway modulation, providing substantive mechanistic justification for its clinical implementation in I\/R injury therapeutics.<\/jats:p>","DOI":"10.1002\/kjm2.70039","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T09:40:16Z","timestamp":1747993216000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Major Ozonated Autoheamotherapy Alleviates Skeletal Muscle Ischemia\/Reperfusion Injury by Regulating Nrf2\/<scp>HO<\/scp>\u20101 Pathway"],"prefix":"10.1002","volume":"41","author":[{"given":"Hui\u2010Zhuang","family":"Guo","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Jinan University  Guangzhou China"},{"name":"Department of Radiology, The Affiliated Panyu Central Hospital Guangzhou Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng\u2010Long","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, The Affiliated Panyu Central Hospital Guangzhou Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9849-6742","authenticated-orcid":false,"given":"Han\u2010Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Jinan University  Guangzhou China"},{"name":"Panyu Health Management Center (Panyu Rehabilitation Hospital)  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2021.101082"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medcli.2023.06.005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suc.2018.05.002"},{"issue":"4","key":"e_1_2_9_5_1","first-page":"319","article-title":"Current Treatment Options in Acute Limb Ischemia","volume":"192","author":"Fluck F.","year":"2020","journal-title":"Radiology"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.0c01197"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9208949"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2022.04.040"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.02.013"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2020.198207"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.14060"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology12121512"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.187046"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27978"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.5114\/ada.2023.130522"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3562191"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2369-12-61"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-015-0240-z"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2015.01.053"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.10.094"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-48858-z"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115185"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14626"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-024-00616-7"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2005.00240.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020417"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11061213"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113033"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/08941939.2018.1473901"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.1974760"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2022.2060259"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39412-6"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41800-x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25225474"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11122377"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2018.02.010"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-73075-7"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X21666221129100308"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14130"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9626703"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14326"}],"container-title":["The Kaohsiung Journal of Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/kjm2.70039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T04:27:26Z","timestamp":1755750446000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/kjm2.70039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,23]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/kjm2.70039"],"URL":"https:\/\/doi.org\/10.1002\/kjm2.70039","archive":["Portico"],"relation":{},"ISSN":["1607-551X","2410-8650"],"issn-type":[{"value":"1607-551X","type":"print"},{"value":"2410-8650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,23]]},"assertion":[{"value":"2024-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70039"}}