{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T22:36:55Z","timestamp":1785883015990,"version":"3.56.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82170101"],"award-info":[{"award-number":["82170101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Joint Funds for the Innovation of Science and Technology, Fujian Province","award":["2023Y9024"],"award-info":[{"award-number":["2023Y9024"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-02675-8","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T08:45:45Z","timestamp":1747817145000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["2-Methoxyestradiol attenuates lung injury induced by chronic intermittent hypoxia via inhibiting the HIF1-\u03b1\/SLC7A11 pathway"],"prefix":"10.1038","volume":"15","author":[{"given":"Jia","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansheng","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiefeng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningfang","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"2675_CR1","doi-asserted-by":"crossref","unstructured":"Badran, M., Bender, S. B. & Gozal, D. Cardiovascular disease in obstructive sleep apnea: putative contributions of mineralocorticoid receptors. Int. J. Mol. Sci., 24(3). (2023).","DOI":"10.3390\/ijms24032245"},{"key":"2675_CR2","doi-asserted-by":"crossref","unstructured":"Meliante, P. G. et al. Molecular pathology, oxidative stress, and biomarkers in obstructive sleep apnea. Int. J. Mol. Sci., 24(6). (2023).","DOI":"10.3390\/ijms24065478"},{"key":"2675_CR3","doi-asserted-by":"crossref","unstructured":"Locke, B. W., Lee, J. J. & Sundar, K. M. OSA and chronic respiratory disease: mechanisms and epidemiology. Int. J. Environ. Res. Public. Health, 19(9). (2022).","DOI":"10.3390\/ijerph19095473"},{"key":"2675_CR4","doi-asserted-by":"publisher","first-page":"100475","DOI":"10.1016\/j.ajpc.2023.100475","volume":"13","author":"YH Ou","year":"2023","unstructured":"Ou, Y. H., Tan, A. & Lee, C. H. Management of hypertension in obstructive sleep apnea. Am. J. Prev. Cardiol. 13, 100475 (2023).","journal-title":"Am. J. Prev. Cardiol."},{"issue":"2","key":"2675_CR5","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1093\/sleep\/22.2.217","volume":"22","author":"C Bassetti","year":"1999","unstructured":"Bassetti, C. & Aldrich, M. S. Sleep apnea in acute cerebrovascular diseases: final report on 128 patients. Sleep 22 (2), 217\u2013223 (1999).","journal-title":"Sleep"},{"issue":"4","key":"2675_CR6","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1007\/s11325-020-02091-4","volume":"24","author":"LD Chen","year":"2020","unstructured":"Chen, L. D. et al. The role of ferroptosis in chronic intermittent hypoxia-induced liver injury in rats. Sleep. Breath. 24 (4), 1767\u20131773 (2020).","journal-title":"Sleep. Breath."},{"key":"2675_CR7","doi-asserted-by":"publisher","first-page":"767982","DOI":"10.3389\/fphar.2021.767982","volume":"12","author":"M Tang","year":"2021","unstructured":"Tang, M. et al. Risk for cardiovascular disease and One-Year mortality in patients with chronic obstructive pulmonary disease and obstructive sleep apnea syndrome overlap syndrome. Front. Pharmacol. 12, 767982 (2021).","journal-title":"Front. Pharmacol."},{"issue":"12","key":"2675_CR8","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1111\/crj.13253","volume":"14","author":"W Zhou","year":"2020","unstructured":"Zhou, W. et al. Metabolic syndrome prevalence in patients with obstructive sleep apnea syndrome and chronic obstructive pulmonary disease: relationship with systemic inflammation. Clin. Respir J. 14 (12), 1159\u20131165 (2020).","journal-title":"Clin. Respir J."},{"issue":"14","key":"2675_CR9","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1097\/CM9.0000000000000312","volume":"132","author":"J Wang","year":"2019","unstructured":"Wang, J. et al. Endothelial function and T-lymphocyte subsets in patients with overlap syndrome of chronic obstructive pulmonary disease and obstructive sleep apnea. Chin. Med. J. (Engl). 132 (14), 1654\u20131659 (2019).","journal-title":"Chin. Med. J. (Engl)"},{"issue":"7","key":"2675_CR10","doi-asserted-by":"publisher","first-page":"973","DOI":"10.5664\/jcsm.7874","volume":"15","author":"CM Fitzgibbons","year":"2019","unstructured":"Fitzgibbons, C. M. et al. Physical activity in overlap syndrome of COPD and obstructive sleep apnea: relationship with markers of systemic inflammation. J. Clin. Sleep. Med. 15 (7), 973\u2013978 (2019).","journal-title":"J. Clin. Sleep. Med."},{"issue":"12","key":"2675_CR11","doi-asserted-by":"publisher","first-page":"828","DOI":"10.12998\/wjcc.v2.i12.828","volume":"2","author":"LK Troy","year":"2014","unstructured":"Troy, L. K. & Corte, T. J. Sleep disordered breathing in interstitial lung disease: A review. World J. Clin. Cases. 2 (12), 828\u2013834 (2014).","journal-title":"World J. Clin. Cases"},{"issue":"9","key":"2675_CR12","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/j.sleep.2015.04.019","volume":"16","author":"Y Wang","year":"2015","unstructured":"Wang, Y. et al. Obstructive sleep apnea exacerbates airway inflammation in patients with chronic obstructive pulmonary disease. Sleep. Med. 16 (9), 1123\u20131130 (2015).","journal-title":"Sleep. Med."},{"issue":"1","key":"2675_CR13","doi-asserted-by":"publisher","first-page":"71","DOI":"10.5664\/jcsm.27397","volume":"5","author":"M Alkhalil","year":"2009","unstructured":"Alkhalil, M., Schulman, E. & Getsy, J. Obstructive sleep apnea syndrome and asthma: what are the links? J. Clin. Sleep. Med. 5 (1), 71\u201378 (2009).","journal-title":"J. Clin. Sleep. Med."},{"issue":"2","key":"2675_CR14","doi-asserted-by":"publisher","first-page":"279","DOI":"10.4187\/respcare.03492","volume":"60","author":"QC Yang","year":"2015","unstructured":"Yang, Q. C. et al. Systematic and endothelial inflammation and endothelial progenitor cell levels in emphysematous rats exposed to intermittent hypoxia. Respir Care. 60 (2), 279\u2013289 (2015).","journal-title":"Respir Care"},{"issue":"5","key":"2675_CR15","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1161\/ATVBAHA.114.304865","volume":"35","author":"M Haslip","year":"2015","unstructured":"Haslip, M. et al. Endothelial uncoupling protein 2 regulates mitophagy and pulmonary hypertension during intermittent hypoxia. Arterioscler. Thromb. Vasc Biol. 35 (5), 1166\u20131178 (2015).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"issue":"13","key":"2675_CR16","first-page":"4325","volume":"22","author":"I Papachatzakis","year":"2018","unstructured":"Papachatzakis, I. et al. Comorbidities in coexisting chronic obstructive pulmonary disease and obstructive sleep apnea - overlap syndrome. Eur. Rev. Med. Pharmacol. Sci. 22 (13), 4325\u20134331 (2018).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"issue":"6","key":"2675_CR17","doi-asserted-by":"publisher","first-page":"e0197342","DOI":"10.1371\/journal.pone.0197342","volume":"13","author":"NT Economou","year":"2018","unstructured":"Economou, N. T. et al. Sleepiness, fatigue, anxiety and depression in chronic obstructive pulmonary disease and obstructive sleep Apnea - Overlap - Syndrome, before and after continuous positive airways pressure therapy. PLoS One. 13 (6), e0197342 (2018).","journal-title":"PLoS One"},{"issue":"7","key":"2675_CR18","doi-asserted-by":"publisher","first-page":"e0235331","DOI":"10.1371\/journal.pone.0235331","volume":"15","author":"D Adler","year":"2020","unstructured":"Adler, D. et al. Clinical presentation and comorbidities of obstructive sleep apnea-COPD overlap syndrome. PLoS One. 15 (7), e0235331 (2020).","journal-title":"PLoS One"},{"issue":"5","key":"2675_CR19","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","volume":"149","author":"SJ Dixon","year":"2012","unstructured":"Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149 (5), 1060\u20131072 (2012).","journal-title":"Cell"},{"issue":"1","key":"2675_CR20","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1186\/s12890-022-02262-x","volume":"22","author":"J Chen","year":"2022","unstructured":"Chen, J. et al. The role of ferroptosis in chronic intermittent hypoxia-induced lung injury. BMC Pulm Med. 22 (1), 488 (2022).","journal-title":"BMC Pulm Med."},{"issue":"6","key":"2675_CR21","doi-asserted-by":"publisher","first-page":"343","DOI":"10.2174\/1566524018666181109121849","volume":"18","author":"A Pezzuto","year":"2018","unstructured":"Pezzuto, A. & Carico, E. Role of HIF-1 in Cancer progression: novel insights. A review. Curr. Mol. Med. 18 (6), 343\u2013351 (2018).","journal-title":"Curr. Mol. Med."},{"issue":"10","key":"2675_CR22","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/nrc1187","volume":"3","author":"GL Semenza","year":"2003","unstructured":"Semenza, G. L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer. 3 (10), 721\u2013732 (2003).","journal-title":"Nat. Rev. Cancer"},{"issue":"10","key":"2675_CR23","doi-asserted-by":"publisher","first-page":"5042","DOI":"10.1172\/JCI137560","volume":"130","author":"NR Prabhakar","year":"2020","unstructured":"Prabhakar, N. R., Peng, Y. J. & Nanduri, J. Hypoxia-inducible factors and obstructive sleep apnea. J. Clin. Invest. 130 (10), 5042\u20135051 (2020).","journal-title":"J. Clin. Invest."},{"issue":"7","key":"2675_CR24","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.1007\/s10571-023-01388-8","volume":"43","author":"X Gao","year":"2023","unstructured":"Gao, X. et al. The mechanisms of ferroptosis under hypoxia. Cell. Mol. Neurobiol. 43 (7), 3329\u20133341 (2023).","journal-title":"Cell. Mol. Neurobiol."},{"issue":"11","key":"2675_CR25","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1007\/s13238-021-00841-y","volume":"12","author":"G Lei","year":"2021","unstructured":"Lei, G. et al. Ferroptosis, radiotherapy, and combination therapeutic strategies. Protein Cell. 12 (11), 836\u2013857 (2021).","journal-title":"Protein Cell."},{"issue":"1","key":"2675_CR26","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1038\/s41467-019-09277-9","volume":"10","author":"Y Zou","year":"2019","unstructured":"Zou, Y. et al. A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nat. Commun. 10 (1), 1617 (2019).","journal-title":"Nat. Commun."},{"key":"2675_CR27","doi-asserted-by":"publisher","first-page":"968124","DOI":"10.3389\/fphar.2022.968124","volume":"13","author":"XX Fan","year":"2022","unstructured":"Fan, X. X. et al. Honokiol improves depression-like behaviors in rats by HIF-1\u03b1- VEGF signaling pathway activation. Front. Pharmacol. 13, 968124 (2022).","journal-title":"Front. Pharmacol."},{"key":"2675_CR28","doi-asserted-by":"publisher","first-page":"596376","DOI":"10.3389\/fimmu.2021.596376","volume":"12","author":"WI Liao","year":"2021","unstructured":"Liao, W. I. et al. 2-Methoxyestradiol protects against lung ischemia\/reperfusion injury by upregulating Annexin A1 protein expression. Front. Immunol. 12, 596376 (2021).","journal-title":"Front. Immunol."},{"key":"2675_CR29","doi-asserted-by":"publisher","first-page":"117743","DOI":"10.1016\/j.lfs.2020.117743","volume":"255","author":"MA Elzayat","year":"2020","unstructured":"Elzayat, M. A. et al. Ameliorative effect of 2-methoxyestradiol on radiation-induced lung injury. Life Sci. 255, 117743 (2020).","journal-title":"Life Sci."},{"key":"2675_CR30","doi-asserted-by":"crossref","unstructured":"Yaman, O. M. et al. Protective effect of thymosin \u03924 against abdominal aortic Ischemia-Reperfusion-Induced acute lung injury in rats. Med. (Kaunas), 55(5). (2019).","DOI":"10.3390\/medicina55050187"},{"key":"2675_CR31","doi-asserted-by":"publisher","first-page":"3755","DOI":"10.2147\/DDDT.S262922","volume":"14","author":"S Miao","year":"2020","unstructured":"Miao, S. et al. The potential effects of Aliskiren on atrial remodeling induced by chronic intermittent hypoxia in rats. Drug Des. Devel Ther. 14, 3755\u20133764 (2020).","journal-title":"Drug Des. Devel Ther."},{"issue":"1","key":"2675_CR32","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1007\/s00018-024-05474-y","volume":"81","author":"W Xuan","year":"2024","unstructured":"Xuan, W. et al. Gut microbiota-derived acetic acids promoted sepsis-induced acute respiratory distress syndrome by delaying neutrophil apoptosis through FABP4. Cell. Mol. Life Sci. 81 (1), 438 (2024).","journal-title":"Cell. Mol. Life Sci."},{"issue":"1","key":"2675_CR33","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1080\/13880209.2022.2034893","volume":"60","author":"Y Li","year":"2022","unstructured":"Li, Y. et al. Pterostilbene pre-treatment reduces LPS-induced acute lung injury through activating NR4A1. Pharm. Biol. 60 (1), 394\u2013403 (2022).","journal-title":"Pharm. Biol."},{"issue":"4","key":"2675_CR34","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","volume":"22","author":"X Jiang","year":"2021","unstructured":"Jiang, X., Stockwell, B. R. & Conrad, M. Ferroptosis: mechanisms, biology and role in disease. Nat. Rev. Mol. Cell. Biol. 22 (4), 266\u2013282 (2021).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"2675_CR35","doi-asserted-by":"crossref","unstructured":"Rochette, L. et al. Lipid peroxidation and Iron metabolism: two corner stones in the homeostasis control of ferroptosis. Int. J. Mol. Sci., 24(1). (2022).","DOI":"10.3390\/ijms24010449"},{"issue":"3","key":"2675_CR36","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1007\/s12035-023-03646-8","volume":"61","author":"D N.J","year":"2024","unstructured":", D. N.J. et al. Oxytosis\/Ferroptosis in neurodegeneration: the underlying role of master regulator glutathione peroxidase 4 (GPX4). Mol. Neurobiol. 61 (3), 1507\u20131526 (2024).","journal-title":"Mol. Neurobiol."},{"key":"2675_CR37","doi-asserted-by":"crossref","unstructured":"Bastian, P. et al. Regulation of Mitochondrial Dynamics in Parkinson\u2019s Disease-Is 2-Methoxyestradiol a Missing Piece?. Antioxid. (Basel), 10(2). (2021).","DOI":"10.3390\/antiox10020248"},{"issue":"10","key":"2675_CR38","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.5664\/jcsm.8682","volume":"16","author":"A Gabryelska","year":"2020","unstructured":"Gabryelska, A. et al. Patients with obstructive sleep apnea present with chronic upregulation of serum HIF-1\u03b1 protein. J. Clin. Sleep. Med. 16 (10), 1761\u20131768 (2020).","journal-title":"J. Clin. Sleep. Med."},{"issue":"2","key":"2675_CR39","doi-asserted-by":"publisher","first-page":"158","DOI":"10.20452\/pamw.15220","volume":"130","author":"A Gabryelska","year":"2020","unstructured":"Gabryelska, A. et al. Serum hypoxia-inducible factor-1\u03b1 protein level as a diagnostic marker of obstructive sleep apnea. Pol. Arch. Intern. Med. 130 (2), 158\u2013160 (2020).","journal-title":"Pol. Arch. Intern. Med."},{"issue":"4","key":"2675_CR40","doi-asserted-by":"publisher","first-page":"e12995","DOI":"10.1111\/jsr.12995","volume":"29","author":"A Gabryelska","year":"2020","unstructured":"Gabryelska, A. et al. Influence of one-night CPAP therapy on the changes of HIF-1\u03b1 protein in OSA patients: A pilot study. J. Sleep. Res. 29 (4), e12995 (2020).","journal-title":"J. Sleep. Res."},{"issue":"1","key":"2675_CR41","doi-asserted-by":"publisher","first-page":"e13158","DOI":"10.1111\/cpr.13158","volume":"55","author":"S Yuan","year":"2022","unstructured":"Yuan, S. et al. Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1\u03b1\/SLC7A11 pathway. Cell. Prolif. 55 (1), e13158 (2022).","journal-title":"Cell. Prolif."},{"issue":"21","key":"2675_CR42","doi-asserted-by":"publisher","first-page":"10197","DOI":"10.1111\/jcmm.16957","volume":"25","author":"Z Fan","year":"2021","unstructured":"Fan, Z. et al. Hypoxia blocks ferroptosis of hepatocellular carcinoma via suppression of METTL14 triggered YTHDF2-dependent Silencing of SLC7A11. J. Cell. Mol. Med. 25 (21), 10197\u201310212 (2021).","journal-title":"J. Cell. Mol. Med."},{"issue":"5","key":"2675_CR43","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1159\/000534393","volume":"148","author":"L Chen","year":"2024","unstructured":"Chen, L., Luo, S. & Tan, H. Penehyclidine hydrochloride improves Rhabdomyolysis-Mediated acute kidney injury by inhibiting ferroptosis through the HIF-1\u03b1\/MT1G Axis. Nephron 148 (5), 333\u2013344 (2024).","journal-title":"Nephron"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02675-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02675-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02675-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T08:45:52Z","timestamp":1747817152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-02675-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2675"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-02675-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,21]]},"assertion":[{"value":"13 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The Ethics Committee of the Fujian Medical University Laboratory Animal Center approved this study (approve number: IACUCFJMU2022-0031). We verified that the study was reported following ARRIVE guidelines, and all methods were performed in conformity with relevant guidelines and regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"17601"}}