{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:25:45Z","timestamp":1787124345334,"version":"build-2736575974"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Radiotherapy for head and neck cancer commonly induces salivary gland dysfunction, resulting in xerostomia that substantially impairs quality of life after treatment. To identify protective strategies, we established the irradiation\u2010induced submandibular glands (SMG) injury mice model and performed integrated proteomic and metabolomic profiling of gland tissue and saliva. Spermidine levels were significantly altered in irradiated SMG during the postradiotherapy recovery phase. Oral spermidine supplementation restored salivary flow, preserved acinar aquaporin\u20105 expression, and attenuated vacuolization, apoptosis, and fibrosis in vivo; these effects were validated in SMG organoids. Single\u2010cell RNA transcriptomic analysis further showed that spermidine increased the proportion of acinar cells, enhanced Golgi\u2010mediated secretory gene expression, and suppressed inflammatory cytokine signaling. In the randomized, double\u2010blind, proof\u2010of\u2010concept clinical trial, oral spermidine supplementation during peri\u2010radiotherapy significantly reduced the incidence of xerostomia at 3 months compared with placebo (48.28\u00a0vs. 79.31%,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0391), while increasing salivary output and improving quality of life without serious adverse events. These findings highlight the potential of spermidine as a safe, metabolite\u2010based strategy for preserving salivary gland function and alleviating radiation\u2010induced xerostomia.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Clinical trial registration<\/jats:bold>\n                    : The RCT has been registered in Clinical. gov (NCT07035626).\n                  <\/jats:p>","DOI":"10.1002\/mco2.70862","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:07:34Z","timestamp":1784099254000},"source":"Crossref","is-referenced-by-count":0,"title":["Oral Spermidine Supplementation Preserves Submandibular Gland Function After Radiotherapy: Mechanistic Insights and Use in a Phase II Randomized Clinical Trial"],"prefix":"10.1002","volume":"7","author":[{"given":"Yu","family":"Min","sequence":"first","affiliation":[{"name":"Department of Biotherapy Cancer Center West China Hospital Sichuan University  Chengdu China"},{"name":"Sichuan Provincial Key Laboratory of Nuclear Physics and Medical Research Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Oncology Cancer Center West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingtong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University  Chengdu 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