{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T04:12:51Z","timestamp":1770523971070,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Wound Journal"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Random skin flap transplantation is a commonly used technique. However, ischemia and ischemia\u2013reperfusion injury always impair its therapeutic effectiveness through acclerating oxidative stress, apoptosis and suppressing angiogenesis. To survive, cells rely on mediating autophagy, DNA repair, immunoregulation to resist these cellular injuries. Thus, mediating autophagy may affect the survival of random skin flaps. The edaravone (EDA), a oxygen radicals scavenger, also possesses autophagy mediator potential, we investigated the effects of EDA on skin flap survival and its autophagy\u2010related mechanisms. In vivo, mice were administered EDA or saline intraperitoneally for 7\u2009days postoperatively. We found that EDA ameliorated the viability of random skin flaps, promoted autophagy and angiogenesis, attenuated apoptosis and oxidative stress. In vitro, mouse umbilical vascular endothelial cells (MUVECs) were administered EDA or 3\u2010methyladenine (3\u2010MA, an autophagy inhibitor) or rapacymin (Rapa, an autophagy activator) at the beginning of oxygen glucose deprivation (OGD). We found that EDA promoted cell viability, activated autophagy, enhanced angiogenesis, alleviated apoptosis and oxidative stress. On one hand, 3\u2010MA reversed the effects of EDA on cell viability, oxidative stress and apoptosis via inhibiting autophagy. On the other hand, Rapa had the similar effects of EDA. Furthermore, EDA\u2010induced autophagy was mediated through downregulating PI3K\/Akt\/mTOR signalling pathway. The findings showed that EDA ameliorated viability of random skin flaps by promoting angiogenesis, suppressing oxidative stress and apoptosis, which may be mediated by autophagic activation through downregulating PI3K\/AKT\/mTOR signalling pathway.<\/jats:p>","DOI":"10.1111\/iwj.14184","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T06:09:21Z","timestamp":1681279761000},"page":"3088-3104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Edaravone promotes viability of random skin flaps via activating <scp>PI3K<\/scp>\/Akt\/<scp>mTOR<\/scp> signalling pathway\u2010mediated enhancement of autophagy"],"prefix":"10.1111","volume":"20","author":[{"given":"Minglei","family":"Bi","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery Lanzhou University Second Hospital  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghong","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Lanzhou University Second Hospital  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangtao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Cuiying Biomedical Research Center  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanfen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Lanzhou University Second Hospital  Lanzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/2000656X.2015.1042386"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2019.111634"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21589"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100818"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S357989"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000489241"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.24272\/j.issn.2095-8137.2020.042"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2018-000221"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9208489"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370220974269"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2016.02.071"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00886"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-017-1693-0"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI132366"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12029-021-00774-z"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1704-0"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7090"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6610603"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0490"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12915"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093289"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1749490"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2017.11.003"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01017"},{"key":"e_1_2_12_26_1","article-title":"Current mechanistic concepts in ischemia and reperfusion injury","author":"Wu MY","journal-title":"Cell Physiol Biochem"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.001"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8070752"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13074"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3109\/2000656X.2014.903196"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7130"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-283"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/s18103249"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7072"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI93825"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.01.036"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006569"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2010.08.010"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/2309499019874470"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7071"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-018-1151-x"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543780802716501"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/128_2012_340"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2021.06.003"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14186"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1407-6"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.11.010"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3735"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.1c00140"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2019.07.018"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1731266"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1956105"}],"container-title":["International Wound Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iwj.14184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T10:12:12Z","timestamp":1741774332000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iwj.14184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,11]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1111\/iwj.14184"],"URL":"https:\/\/doi.org\/10.1111\/iwj.14184","archive":["Portico"],"relation":{},"ISSN":["1742-4801","1742-481X"],"issn-type":[{"value":"1742-4801","type":"print"},{"value":"1742-481X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,11]]},"assertion":[{"value":"2023-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}