{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T04:39:28Z","timestamp":1770525568870,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"\n Abstract<\/jats:title>\n \n We employed a unique murine intensive care unit (ICU) model allowing long\u2010term studies of the ICU condition (immobilization, paralysis, sedation and mechanical ventilation). This model resulted in a substantial loss of myofibrillar protein and muscle size. We hypothesized that an inhibitor of Janus kinase (JAK) activation of transcription 3 (STAT3 (signal transducer and activator of transcription 3)) phosphorylation would help to preserve muscle mass by stimulating the rate of protein synthesis. Sprague\u2013Dawley rats were divided into a control group (CON,\n n<\/jats:italic>\n \u00a0=\u00a05) and two groups exposed to the ICU condition for 8\u00a0days. One group was treated with a JAK\/STAT3 inhibitor (JST,\n n<\/jats:italic>\n \u00a0=\u00a05) and one without a JST (immobilized group,\n n<\/jats:italic>\n \u00a0=\u00a03) inhibitor. To measure the fractional synthesis rate (FSR) of proteins across the muscle proteome,\n 2<\/jats:sup>\n H\n 2<\/jats:sub>\n O was administered as an intraparitoneal (IP) bolus followed by continuous infusion of 8%\n 2<\/jats:sup>\n H\n 2<\/jats:sub>\n O to maintain body water enrichment. Soleus, extensor digitorum longus (EDL), tibialis anterior (TA), gastrocnemius and diaphragm were obtained from all animals. Liquid chromatography\u2013mass spectrometry (LC\/MS\u2013MS) analysis was used to measure protein FSR. Compared to CON myofibrillar protein FSR was decreased 39%\u201373%, with the decrease in gastrocnemius\u00a0>\u00a0soleus\u00a0>\u00a0TA\u00a0>\u00a0diaphragm\u00a0>\u00a0EDL. Sarcoplasmic protein FSR was decreased 38%\u201369%, with the decrease in gastrocnemius\u00a0>\u00a0TA\u00a0>\u00a0EDL > soleus\u00a0>\u00a0diaphragm. Mitochondrial protein FSR was decreased 34%\u201352%, with the decrease in TA\u00a0>\u00a0soleus\u00a0>\u00a0gastrocnemius\u00a0>\u00a0EDL\u00a0>\u00a0diaphragm. The decreases in protein flux rates by ontology corresponded broadly with function and fibre types. Immobilization resulted in profound and tissue\u2010specific decreases in protein FSR, with JAK\/STAT3\u00a0showing a significant effect to preserve FSR, muscle mass and body weight.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Mechanical silencing of skeletal muscle resulted in a large lowering of protein fractional synthesis rate (FSR) in all muscles measured, the extent of which was muscle\u2010 and fibre specific.<\/jats:p>\n <\/jats:list-item>\n \n All muscle protein ontologies were affected.<\/jats:p>\n <\/jats:list-item>\n \n A Janus kinase (JAK)\/STAT inhibitor had a positive effect on body mass, muscle size and protein FSR.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp288982","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T19:44:17Z","timestamp":1759520657000},"page":"7029-7047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of inhibition of Janus kinase signalling during controlled mechanical ventilation on the rate of skeletal muscle protein synthesis"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6757-1471","authenticated-orcid":false,"given":"William J.","family":"Evans","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences and Toxicology University of California, Berkeley Berkeley California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9138-9610","authenticated-orcid":false,"given":"Mahalakshmi","family":"Shankaran","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences and Toxicology University of California, Berkeley Berkeley California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3722-035X","authenticated-orcid":false,"given":"Lars","family":"Larsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences SLU Uppsala Sweden"},{"name":"Muscle Biology Program Viron Molecular Medicine Institute Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Cacciani","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences SLU Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvette","family":"Hedstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences SLU Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1676-4905","authenticated-orcid":false,"given":"James 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