{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T07:40:01Z","timestamp":1777016401281,"version":"3.51.4"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["20K18724"],"award-info":[{"award-number":["20K18724"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cancer cachexia causes skeletal muscle atrophy, impacting the treatment and prognosis of patients with advanced cancer, but no treatment has yet been established to control cancer cachexia. We demonstrated that transcutaneous application of carbon dioxide (CO<jats:sub>2<\/jats:sub>) could improve local blood flow and reduce skeletal muscle atrophy in a fracture model. However, the effects of transcutaneous application of CO<jats:sub>2<\/jats:sub> in cancer-bearing conditions are not yet known. In this study, we calculated fat-free body mass (FFM), defined as the skeletal muscle mass, and evaluated the expression of muscle atrophy markers and uncoupling protein markers as well as the cross-sectional area (CSA) to investigate whether transcutaneous application of CO<jats:sub>2<\/jats:sub> to skeletal muscle could suppress skeletal muscle atrophy in cancer-bearing mice. Human oral squamous cell carcinoma was transplanted subcutaneously into the upper dorsal region of nude mice, and 1 week later, CO<jats:sub>2<\/jats:sub> gas was applied to the legs twice a week for 4 weeks and FFM was calculated by bioimpedance spectroscopy. After the experiment concluded, the quadriceps were extracted, and muscle atrophy markers (muscle atrophy F-box protein (MAFbx), muscle RING-finger protein 1 (MuRF-1)) and uncoupling protein markers (uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3)) were evaluated by real-time polymerase chain reaction and immunohistochemical staining, and CSA by hematoxylin and eosin staining. The CO<jats:sub>2<\/jats:sub>-treated group exhibited significant mRNA and protein expression inhibition of the four markers. Furthermore, immunohistochemical staining showed decreased MAFbx, MuRF-1, UCP2, and UCP3 in the CO<jats:sub>2<\/jats:sub>-treated group. In fact, the CSA in hematoxylin and eosin staining and the FFM revealed significant suppression of skeletal muscle atrophy in the CO<jats:sub>2<\/jats:sub>-treated group. We suggest that transcutaneous application of CO<jats:sub>2<\/jats:sub> to skeletal muscle suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.<\/jats:p>","DOI":"10.1371\/journal.pone.0302194","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T17:31:29Z","timestamp":1713375089000},"page":"e0302194","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcutaneous carbon dioxide suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma"],"prefix":"10.1371","volume":"19","author":[{"given":"Aki","family":"Sasaki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5878-8871","authenticated-orcid":true,"given":"Daisuke","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hotaka","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Tadokoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aki","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanae","family":"Yatagai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satomi","family":"Arimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Nagatsuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaya","family":"Akashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7349-7084","authenticated-orcid":true,"given":"Takumi","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"issue":"5","key":"pone.0302194.ref001","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: an international consensus","volume":"12","author":"K Fearon","year":"2011","journal-title":"Lancet Oncol"},{"issue":"6","key":"pone.0302194.ref002","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.clnu.2008.06.013","article-title":"Cachexia: a new definition","volume":"27","author":"WJ Evans","year":"2008","journal-title":"Clin Nutr"},{"issue":"16","key":"pone.0302194.ref003","doi-asserted-by":"crossref","first-page":"8491","DOI":"10.3390\/ijms22168491","article-title":"Cancer Cachexia: Its Mechanism and Clinical Significance","volume":"22","author":"H Nishikawa","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"21","key":"pone.0302194.ref004","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1200\/JCO.20.00611","article-title":"Management of Cancer Cachexia: ASCO Guideline","volume":"38","author":"EJ Roeland","year":"2020","journal-title":"J Clin Oncol"},{"issue":"11","key":"pone.0302194.ref005","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: understanding the molecular basis","volume":"14","author":"JM Argil\u00e9s","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"pone.0302194.ref006","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.semcancer.2016.01.002","article-title":"F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities","volume":"36","author":"A Sukari","year":"2016","journal-title":"Semin Cancer Biol"},{"issue":"5547","key":"pone.0302194.ref007","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1126\/science.1065874","article-title":"Identification of ubiquitin ligases required for skeletal muscle atrophy","volume":"294","author":"SC Bodine","year":"2001","journal-title":"Science"},{"key":"pone.0302194.ref008","doi-asserted-by":"crossref","first-page":"51608","DOI":"10.18632\/oncotarget.9958","article-title":"Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice","volume":"7","author":"MC. 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