{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:33:24Z","timestamp":1788492804503,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104732"],"award-info":[{"award-number":["82104732"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adalimumab, a TNF\u2010\u03b1 inhibitor, is widely used clinically. Recent studies suggest Adalimumab can improve muscle damage after ischemic stroke (IS), but its protective mechanisms remain unclear. This study investigates the effect of adalimumab on muscle structure post\u2010IS and the role of calcium balance in muscle strength, while validating their synergistic effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigates the effects of adalimumab and GV\u201058 on muscle structure and function in male middle cerebral artery occlusion (MCAO) rat models using behavioural, imaging, pathological and WB experiments. In\u00a0vitro mechanisms are explored with L6 and primary muscle cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results of the present study showed a significant decrease in motor function in IS\u2010induced sarcopenia (ISS) rats, as evidenced by shortened length (\u221247.56%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), reduced weight (\u221243.79%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and reduced cross\u2010sectional area of myofibroblasts (\u221238.58%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) in the soleus muscle as compared to the sham group. Inflammatory factors such as IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1 and reactive oxygen species (ROS) levels were significantly elevated in the muscles of ISS rats (3.10\u2010fold, 3.78\u2010fold, 2.29\u2010fold, 2.80\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Molecular mechanism studies showed that TNF\u2010\u03b1, MAFbx and MuRF1 protein expression was down\u2010regulated, and IL\u201010 and MyoD1 expression was up\u2010regulated in muscle tissues of ISS rats. RNA\u2010seq implicated the Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signalling pathway in ISS\u2010related muscle weakness. Muscle strength in ISS rats is associated with Ca\n                      <jats:sup>2+<\/jats:sup>\n                      content and Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channels, and key excitation\u2013contraction coupling proteins SERCA2, Cav1.1 and RYR1 expression was decreased, whereas Ca\n                      <jats:sup>2+<\/jats:sup>\n                      sensing proteins STIM1 and CAM expression were compensatory upregulated. Adalimumab treatment significantly reduced muscle inflammation and structural damage in ISS rats, significantly increasing the length (+66.88%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and weight (+43.92%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) of the soleus muscle and increasing muscle cell cross\u2010sectional area (+53.44%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Adalimumab also inhibited the expression of MAFbx, MuRF1 and promoted the expression of IL\u201010 and MyoD1. GV\u201058 treatment of L6 cells showed that combined administration with adalimumab produced a synergistic effect. Upregulation of key Ca\n                      <jats:sup>2+<\/jats:sup>\n                      protein expression such as RyR1 and SERCA1 improved the recovery of muscle strength in ISS rats while maintaining muscle structure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combination of adalimumab and GV\u201058 effectively restores muscle function after stroke by inhibiting inflammation and improving calcium channel dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70097","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T09:27:36Z","timestamp":1762766856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Muscle Structure and Function Recovery: Adalimumab\u2010Calcium Channel Synergy in Post\u2013Ischemic Stroke Sarcopenia"],"prefix":"10.1002","volume":"16","author":[{"given":"Hu","family":"Qi","sequence":"first","affiliation":[{"name":"Lab for Innovation &amp; Effective Uses of Chinese Drug Germplasm Resources Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"},{"name":"School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong\u2010Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lab for Innovation &amp; Effective Uses of Chinese Drug Germplasm Resources Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"},{"name":"School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze\u2010Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lab for Innovation &amp; Effective Uses of Chinese Drug Germplasm Resources Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"},{"name":"School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan\u2010Shan","family":"Ou","sequence":"additional","affiliation":[{"name":"Lab for Innovation &amp; Effective Uses of Chinese Drug Germplasm Resources Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"},{"name":"School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Lin","family":"Gao","sequence":"additional","affiliation":[{"name":"Lab for Innovation &amp; Effective Uses of Chinese Drug Germplasm Resources Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"},{"name":"School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Tian","sequence":"additional","affiliation":[{"name":"Acupuncture and Tuina School Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Ning","family":"Jiang","sequence":"additional","affiliation":[{"name":"Lab for Innovation &amp; 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