{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:17:44Z","timestamp":1790713064105,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":279,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Menopause is associated with excessive weight, increased systemic inflammation, and oxidative stress. Menopause with obesity may aggravate the severity of organ damage when complicated with sepsis. This study investigated the impacts of calcitriol on acute lung injury (ALI)\u2010associated angiopoietin (Ang)\/tyrosine kinase with immunoglobulin\u2010like and epidermal growth factor\u2010like domain 2 (Tie2) dysregulation, impairment of the barrier integrity, and ion disturbance in ovariectomized mice with sepsis. 6\u2010month\u2010old female C57BL\/6 mice were divided into three groups: the OB group, which contained mice with a sham ovariectomy and high\u2010fat diet (HFD); the OVSS group, which contained mice with an ovariectomy, an HFD, cecal ligation and puncture (CLP), and an intravenous saline injection after CLP; and the OVSD group, which contained mice with an ovariectomy, an HFD, CLP, and a calcitriol injection. The HFD was fed for 12 weeks. Mice in the respective groups were sacrificed on 24 or 72\u2009h after CLP. Results showed that compared to the OB group, the OVSS group had higher oxidative stress, iron and copper overload, whereas the Ang1\/Ang2 ratio and tight junction (TJ) protein levels were lower in the lungs. Calcitriol treatment in mice with ovariectomy and CLP enhanced Tie2 levels and the Ang1\/Ang2 ratio, increased zona occludens (ZOs)\u20101, occludin, and claudin\u20105 levels. Elevated reduced glutathione (GSH) levels and glutathione peroxidase 4 (GPX4) activities, reduced iron and copper contents, and suppressed ferroptosis\u2010 and cuproptosis\u2010associated components were found in the lungs. Also, higher survival rates and lower lung injury scores were noted in the OVSD groups. These findings suggest that calcitriol treatment mitigated the dysregulated Ang\/Tie2 pathway, improved the integrity of the alveolar\u2010capillary barrier, elicited a more balanced redox status, alleviated ferroptosis and cuproptosis in the lungs in an ovariectomy model complicated with sepsis.<\/jats:p>","DOI":"10.1155\/mi\/4374164","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T06:04:09Z","timestamp":1759903449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Calcitriol Administration Attenuates Acute Lung Injury by Improving Angiopoietin\/Tie2 Dysregulation and Alveolar\u2010Capillary Barrier Integrity in a Mouse Model of Ovariectomy Complicated With Sepsis"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8245-4601","authenticated-orcid":false,"given":"Chiu-Li","family":"Yeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Ming","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Pei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hsin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1960-1423","authenticated-orcid":false,"given":"Ting-Chun","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Ming","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuen-Yuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8811-9203","authenticated-orcid":false,"given":"Ming-Hsun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Jen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Chu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Chia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Yuan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Ling","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7313-7057","authenticated-orcid":false,"given":"Ming-Tsan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/757461"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2016.1214257"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000001792"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.3945\/an.115.010207"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe058160"},{"key":"e_1_2_11_7_2","first-page":"234","article-title":"Microvascular Endothelial Activation\/Dysfunction and Dysregulation of the Angiopoietin-Tie2 System in the Pathogenesis of Life-Threatening Infections","volume":"133","author":"Liles W. 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