{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T07:58:14Z","timestamp":1790582294729,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Necroptosis has been demonstrated to play a role in the process of lung ischemia\u2010reperfusion injury (LIRI) in a variety of clinical conditions, including cardiopulmonary bypass and pulmonary embolism. Melatonin has been reported to exert a protective role by reducing oxidative stress and acute inflammatory reactions in LIRI. However, the effect of melatonin on necroptosis in LIRI remains unclear. The aim of this study was to investigate whether the protective effects of melatonin against H\/R\u2010induced injury are associated with modulation of necroptosis and related changes in mitochondrial function and oxidative stress. The cells were exposed to H\/R (16\/4\u2009h) or normoxia, in the absence or presence of 2.5\u2009\u00b5M melatonin. Cell viability was determined by the MTT method, while morphological changes in BEAS\u20102B cells resulting from H\/R exposure were evaluated by fluorescence microscopy using acridine orange\/ethidium bromide (AO\/EtBr) staining. Mechanistic analyses, including flow cytometry\u2010based cell cycle assessment, apoptosis detection (Annexin V\u2010FITC), mitochondrial membrane potential evaluation (JC\u20101), and reactive oxygen species (ROS) measurements, were performed on BEAS\u20102B cells. The level of the mixed lineage kinase domain\u2010like pseudokinase (MLKL), a key component of the necroptosis complex, was also quantified using an enzyme\u2010linked immunosorbent assay. In addition, the ATP, pH, and lactate levels were determined. The findings indicated that melatonin treatment reduced the H\/R\u2010induced increase in the percentage of necrotic cells and increased the percentage of viable cells (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). In addition, melatonin treatment reduced the increase in MLKL, ROS, and lactate levels, preserved mitochondrial membrane integrity, and increased intracellular ATP levels in BEAS\u20102B cells exposed to H\/R (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). In conclusion, this study suggests that melatonin protects BEAS\u20102B cells against H\/R\u2010induced injury, and that this protective effect may be associated with reduced oxidative stress, preservation of mitochondrial function, and suppression of necroptosis\u2010related signaling.\n                  <\/jats:p>","DOI":"10.1002\/cbf.70304","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:46:36Z","timestamp":1788957996000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melatonin Protects BEAS\u20102B Cells Against Hypoxia\/Reoxygenation\u2010Induced Injury By Reducing MLKL Levels, Suppressing Oxidative Stress and Preserving Mitochondrial Function"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9523-7718","authenticated-orcid":false,"given":"Zehra","family":"Yilmaz","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Harran University Sanliurfa T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0437-7206","authenticated-orcid":false,"given":"Askin","family":"Tas","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine Istanbul Ayd\u0131n University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5533-6025","authenticated-orcid":false,"given":"Ozlem","family":"Oz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Harran University Sanliurfa T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9469-4757","authenticated-orcid":false,"given":"Ismail","family":"Koyuncu","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine Harran University Sanliurfa T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8911-7763","authenticated-orcid":false,"given":"Ebru","family":"Temiz","sequence":"additional","affiliation":[{"name":"Department of Medical Presentation and Marketing, Health Services Vocational School Harran University Sanliurfa T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2058-5440","authenticated-orcid":false,"given":"Ozgur","family":"Yuksekdag","sequence":"additional","affiliation":[{"name":"Science and Technology Application and Research Centre (HUBTAM) of Harran University Sanliurfa T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1089253212458329"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8191.2009.00823.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.51.2.166"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200207-670SO"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-023-01844-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2022.05.013"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00251.2010"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.5.9910064"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13445"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/icvts\/ivx440"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11193139"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2018.04.005"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00069.2018"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-024-03056-z"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2021.01.037"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7059304"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167378"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00630-3"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2883"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.03.003"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.10.021"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2022.09.009"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2016.12.005"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2190-5"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200012109"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.175037"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1157054"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hbpd.2021.04.001"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.01.146"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2007.00459.x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079x.2002.02924.x"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000531567"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0003-4975(01)03101-0"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/01902148.2023.2213335"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12020"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2022.12666"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.111078"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1481403"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202300424"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.10.018"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166785"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12503"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd-24-188"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-016-0843-3"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-018-06848-8"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173053"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.624402"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00367.2018"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11626-019-00333-8"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11995-3"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfh007"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70304","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbf.70304","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T07:45:23Z","timestamp":1790581523000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.70304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":51,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cbf.70304"],"URL":"https:\/\/doi.org\/10.1002\/cbf.70304","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"value":"0263-6484","type":"print"},{"value":"1099-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2025-12-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70304"}}