{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:06:58Z","timestamp":1789016818530,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Regular bathing is a common habit worldwide, yet bath additives have been characterized almost exclusively at the physiological level, while their molecular effects on human cells remain largely unexplored. We previously showed by RNA sequencing (RNA-seq) that the complex bath additive Karada Totonou ProBath (KTPB) induced the expression of EGR1 and hyaluronic acid synthase genes in human keratinocytes and fibroblasts, which represent the vascular endothelial growth factor (VEGF)-producing side of the cutaneous angiogenic axis; whether the VEGF-receiving endothelium responds to KTPB was unknown. Here, human vascular endothelial cells were exposed to KTPB and profiled by RNA-seq, and cytotoxicity was assessed using resazurin and Hoechst assays. KTPB altered gene expression in a time-dependent manner, and the differentially expressed genes were classified into three clusters with distinct temporal profiles: a late-repressed cluster, a transiently induced cell cycle-associated cluster, and a late-induced cluster enriched for blood vessel development and VEGFA-VEGFR2 signaling. The angiogenesis-related genes ID1, ID3, and EDN1 were markedly upregulated, peaking at 1\u20132 h. KTPB showed no detectable cytotoxicity in this cell model at any of the tested concentrations, which spanned the recommended use range. These results indicate that KTPB elicits an angiogenesis-associated transcriptional program in vascular endothelial cells without compromising viability and highlight transcriptomics\u2019 value for characterizing bath additives.<\/jats:p>","DOI":"10.3390\/cimb48090895","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:08:43Z","timestamp":1788275323000},"page":"895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Bath Additive KTPB Induces an Angiogenesis-Associated Transcriptional Program Without Detectable Cytotoxicity in Human Vascular Endothelial Cells"],"prefix":"10.3390","volume":"48","author":[{"given":"Norihiro","family":"Otani","sequence":"first","affiliation":[{"name":"Doctoral Program in Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan"},{"name":"X-PLOSION LLC, 2F Yamazaki CA Building, 3-8-11 Ougicho, Naka-ku, Yokohama 231-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieu D. M.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Human Biology Program, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3523-3360","authenticated-orcid":false,"given":"Kiyoshi","family":"Maehara","sequence":"additional","affiliation":[{"name":"Doctoral Program in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2264-6510","authenticated-orcid":false,"given":"Jiawei","family":"Wan","sequence":"additional","affiliation":[{"name":"Laboratory of Sports Medicine, Department of Clinical Medicine, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Hirokawa","sequence":"additional","affiliation":[{"name":"College of Medicine, School of Medicine and Health Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehito","family":"Sugasawa","sequence":"additional","affiliation":[{"name":"Laboratory of Sports Medicine, Department of Clinical Medicine, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan"},{"name":"Center for Cyber Medicine Research, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","unstructured":"The Business Research Company (2026, June 30). 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