{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:12:37Z","timestamp":1789398757729,"version":"build-2803163510"},"reference-count":91,"publisher":"Portland Press Ltd.","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:p>Despite the well-known role of hypoxia-driven inflammatory mediators in the pathogenesis of hypoxic pulmonary hypertension, their involvement in high-altitude (HA) illnesses, particularly high-altitude pulmonary edema (HAPE), remains unclear. The present study uses an integrated clinical, transcriptomic, proteomic, and long noncoding RNA (lncRNA) profiling of 83 individuals, including HAPE patients segregated into mild, moderate, and severe categories, HAPE-free sojourners, and long-term HA residents, to highlight the molecular and immunological changes associated with HAPE and its severity. Clinical assessments revealed significantly reduced peripheral oxygen saturation and elevated respiratory parameters in HAPE patients. Differential gene expression and functional enrichment analyses identified 515 significantly differentially expressed genes, with marked enrichment of inflammatory and hypoxia-associated pathways. Protein\u2013protein interaction network analysis revealed eighteen hub genes, including toll-like receptor (TLR) 2 and Forkhead box O3 (FOXO3), with strong diagnostic potential. Immune cell deconvolution analysis and hematological profiling indicated a prominent increase in neutrophil proportion. Interestingly, oncostatin M (OSM), a hypoxia-regulated predominant cytokine produced by neutrophils, was revealed in the cytokine and transcriptomic profiling, highlighting its role in inflammation and extracellular matrix degradation. Co-expression network analysis notably revealed significant alterations that formed a gene module exhibiting a strong correlation with immune response, leukocyte adhesion, and ncRNA processing pathways. Interestingly, these co-expressed partners, LINC01093 and immune-regulatory genes like interleukin-18 receptor 1 and TLR5, appear to regulate the NF-\u03baB signaling pathway, one of the positively enriched pathways in our analysis. Overall, this multiomics approach highlighted a strong inflammatory signature and lncRNA-mRNA interactions associated with HAPE.<\/jats:p>","DOI":"10.1042\/bsr20253746","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T16:29:41Z","timestamp":1765556981000},"page":"733-752","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrative blood profiling uncovers inflammatory network signatures in high-altitude pulmonary edema"],"prefix":"10.1042","volume":"45","author":[{"given":"Kanika","family":"Singh","sequence":"first","affiliation":[{"name":"1Genomics and Genome Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, 110025, India"},{"name":"2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Kumar G","sequence":"additional","affiliation":[{"name":"1Genomics and Genome Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, 110025, India"},{"name":"2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manzoor","family":"Ali","sequence":"additional","affiliation":[{"name":"1Genomics and Genome Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, 110025, India"},{"name":"2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raushni","family":"Choudhary","sequence":"additional","affiliation":[{"name":"1Genomics and Genome Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, 110025, India"},{"name":"2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohit","family":"Khadia","sequence":"additional","affiliation":[{"name":"1Genomics and Genome Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, 110025, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanzen","family":"Rabyang","sequence":"additional","affiliation":[{"name":"3Department of Medicine, Sonam Norboo Memorial Hospital, Leh, 194101, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tashi","family":"Thinlas","sequence":"additional","affiliation":[{"name":"3Department of Medicine, Sonam Norboo Memorial Hospital, Leh, 194101, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Kumar","sequence":"additional","affiliation":[{"name":"4Department of Medicine, University of California San Francisco, San Francisco, California, 94143, U.S.A."},{"name":"5Lung Biology Center, Zuckerberg San Francisco General Hospital, San Francisco, California, 94143, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0403-0293","authenticated-orcid":false,"given":"Aastha","family":"Mishra","sequence":"additional","affiliation":[{"name":"1Genomics and Genome Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, 110025, India"},{"name":"2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"2025122306213180100_BSR-2025-3746C1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41580-020-0227-y","article-title":"Cellular adaptation to hypoxia through hypoxia inducible factors and beyond","volume":"21","author":"Lee","year":"2020","journal-title":"Nat. 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