{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:36:59Z","timestamp":1786711019286,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victor Babes University of Medicine and Pharmacy Timisoara"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Environmental heat stress disrupts cellular homeostasis through coordinated molecular responses involving protein quality control, oxidative stress regulation, inflammatory signaling, and water homeostasis. Although saliva plays an essential role in maintaining oral homeostasis, the molecular pathways underlying salivary adaptation to heat stress remain insufficiently characterized. We hypothesized that integrating the human salivary proteome with systems biology approaches would identify a reproducible heat-stress-responsive molecular signature. Human salivary proteomic datasets retrieved from the Human Salivary Proteome Wiki were integrated into a non-redundant dataset comprising 15,594 protein accessions corresponding to 2540 distinct proteins. Following deduplication, functional annotation, and biological curation, proteins associated with heat stress response, oxidative stress regulation, inflammatory signaling, water homeostasis, salivary secretion, and mucosal protection were assembled into a Salivary Climate Stress Panel (SCSP). Protein\u2013protein interaction and functional enrichment analyses were performed, and the biological relevance of the identified proteins was independently evaluated using a human heat stress transcriptomic meta-analysis comprising 322 comparisons and the GEO dataset GDS3004. Functional filtering identified 2050 heat-stress-associated salivary proteins, from which a curated SCSP of 35 proteins was established. Network analysis identified HSP90AB1, HSP90AA1, and IL1B as the principal hub proteins linking heat stress, oxidative stress, inflammatory signaling, and water homeostasis pathways, while transcriptomic validation confirmed consistent activation of representative SCSP genes under heat stress conditions. These findings provide a reproducible systems-level framework for investigating heat-stress-responsive molecular pathways in the human salivary proteome and support future studies on salivary biomarkers of environmental heat exposure.<\/jats:p>","DOI":"10.3390\/ijms27167270","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:57:46Z","timestamp":1786708666000},"page":"7270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["System-Level Identification of Heat Stress-Responsive Pathways in Human Saliva"],"prefix":"10.3390","volume":"27","author":[{"given":"Cassandra","family":"Lupita","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda-Mihaela","family":"Luca","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Faculty of Dental Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6702-6463","authenticated-orcid":false,"given":"Anca-Cristina","family":"Perpelea","sequence":"additional","affiliation":[{"name":"Department of Organization, Professional Legislation and Management of the Dental Office, Faculty of Dental Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 17-23 Plevnei Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iulia","family":"Muntean","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edida","family":"Maghet","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2942-3715","authenticated-orcid":false,"given":"Oana-Ramona","family":"Lobon\u021b","sequence":"additional","affiliation":[{"name":"Finance, Business Information Systems and Modeling Department, Faculty of Economics and Business Administration, West University of Timisoara, 300115 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-4705","authenticated-orcid":false,"given":"Laura-Cristina","family":"Rusu","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Multidisciplinary Center for Research, Evaluation, Diagnosis and Therapies in Oral Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1016\/S0140-6736(23)01859-7","article-title":"The 2023 report of the Lancet Countdown on health and climate change: The imperative for a health-centred response in a world facing irreversible harms","volume":"402","author":"Romanello","year":"2023","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Intergovernmental Panel on Climate Change (IPCC) (2023). 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