{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:12:08Z","timestamp":1792858328821,"version":"4.5.0"},"reference-count":169,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2024YFF1107105-1"],"award-info":[{"award-number":["2024YFF1107105-1"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2023YFF1104503"],"award-info":[{"award-number":["2023YFF1104503"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>High-altitude exposure poses significant health challenges to mountaineers, military personnel, travelers, and indigenous residents. Altitude-related illnesses encompass acute conditions such as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE), and chronic manifestations like chronic mountain sickness (CMS). Hypobaric hypoxia induces oxidative stress and inflammatory cascades, causing alterations in multiple organ systems through co-related amplification mechanisms. Therefore, this review aims to systematically discuss the injury mechanisms and comprehensive intervention strategies involved in high-altitude diseases. In summary, these pathologies involve key damage pathways: oxidative stress activates inflammatory pathways through NF-\u03baB and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes; energy depletion impairs calcium homeostasis, leading to cellular calcium overload; mitochondrial dysfunction amplifies injury through mitochondrial permeability transition pore (mPTP) opening and apoptotic factor release. These mechanisms could be converged in organ-specific patterns\u2014blood\u2013brain barrier disruption in HACE, stress failure in HAPE, and right heart dysfunction in chronic exposure. Promising strategies include multi-level therapeutic approaches targeting oxygenation (supplemental oxygen, acetazolamide), specific pathway modulation (antioxidants, calcium channel blockers, HIF-1\u03b1 regulators), and damage repair (glucocorticoids). Notably, functional foods show significant therapeutic potential: dietary nitrates (beetroot) enhance oxygen delivery, tea polyphenols and anthocyanins (black goji berry) provide antioxidant effects, and traditional herbal bioactives (astragaloside, ginsenosides) offer multi-targeted organ protection.<\/jats:p>","DOI":"10.3390\/antiox15010036","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T08:38:14Z","timestamp":1766738294000},"page":"36","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["High-Altitude Hypoxia Injury: Systemic Mechanisms and Intervention Strategies on Immune and Inflammatory Responses"],"prefix":"10.3390","volume":"15","author":[{"given":"Jingman","family":"Zhang","sequence":"first","affiliation":[{"name":"Food Laboratory of Zhongyuan, Henan University of Technology, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujie","family":"Guo","sequence":"additional","affiliation":[{"name":"Food Laboratory of Zhongyuan, Henan University of Technology, Zhengzhou 450001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiebei","family":"Dou","sequence":"additional","affiliation":[{"name":"Food Laboratory of Zhongyuan, Luohe 462000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Food Laboratory of Zhongyuan, Luohe 462000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Wang","sequence":"additional","affiliation":[{"name":"Food Laboratory of Zhongyuan, Luohe 462000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingze","family":"Jiao","sequence":"additional","affiliation":[{"name":"Food Laboratory of Zhongyuan, Luohe 462000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwen","family":"Li","sequence":"additional","affiliation":[{"name":"Food Laboratory of Zhongyuan, Luohe 462000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Food Laboratory of Zhongyuan, Luohe 462000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6729-722X","authenticated-orcid":false,"given":"Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Food Laboratory of Zhongyuan, China Agricultural University, Beijing 100080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1056\/NEJMra2104829","article-title":"Medical Conditions and High-Altitude Travel","volume":"386","author":"Luks","year":"2022","journal-title":"N. 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