{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:13:30Z","timestamp":1792638810481,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002947","name":"Anhui Medical University","doi-asserted-by":"publisher","award":["2022xkfyts06"],"award-info":[{"award-number":["2022xkfyts06"]}],"id":[{"id":"10.13039\/501100002947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002947","name":"Anhui Medical University","doi-asserted-by":"publisher","award":["2022xkfyhz03"],"award-info":[{"award-number":["2022xkfyhz03"]}],"id":[{"id":"10.13039\/501100002947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002947","name":"Anhui Medical University","doi-asserted-by":"publisher","award":["2023xkfytszd02"],"award-info":[{"award-number":["2023xkfytszd02"]}],"id":[{"id":"10.13039\/501100002947","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":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Atrophy of the masseter muscle can result in an aged facial appearance and diminished chewing function. Electrical stimulation (ES) is known for its ability to facilitate tissue healing and functional recovery, but its precise role in the repair of atrophic masseter muscles remains incompletely understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We induced masseter muscle atrophy in rats through botulinum toxin (BTX) injection and subsequently treated the animals with or without ES. Single\u2010nucleus sequencing (sn\u2010RNA seq) was conducted to analyse the changes in macrophages of masseter muscles between control, BTX and BTX\u2009+\u2009ES groups. The role and mechanism of macrophage phenotypic transformation in the process of ES promoting the recovery of atrophied masseter muscles were both verified through in\u00a0vivo and in\u00a0vitro experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results indicate that ES treatment within defined current parameters significantly ameliorated muscle condition by reducing atrophy\u2010related gene expression (<jats:italic>MuRF1<\/jats:italic>: BTX: 10.15\u2009\u00b1\u20091.69; BTX\u2009+\u2009ES: 1.05\u2009\u00b1\u20090.06; <jats:italic>Fbxo32<\/jats:italic>: BTX: 8.62\u2009\u00b1\u20091.19, BTX\u2009+\u2009ES: 1.19\u2009\u00b1\u20090.07, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and enhancing vascularisation (Vegf positive area: BTX: 6.60\u2009\u00b1\u20092.87%, BTX\u2009+\u2009ES: 27.23\u2009\u00b1\u20091.70%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Analysis conducted with sn\u2010RNA seq demonstrated increased infiltration of M1 macrophages during muscle atrophy, with a subsequent transition to M2 macrophages following ES treatment (M1 macrophage portion: Ctrl: 15.2%, BTX: 25.8%, BTX\u2009+\u2009ES: 14.7%; M2 macrophages: Ctrl: 67.9%, BTX: 46.9%, BTX\u2009+\u2009ES: 70.5%). Further investigations demonstrated that ES reduced M1 macrophage infiltration (five\u2010fold lower of CD86<jats:sup>+<\/jats:sup> cell number, BTX: 30\u2009\u00b1\u20092; BTX\u2009+\u2009ES: 6\u2009\u00b1\u20092, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) while increasing M2 macrophage presence (3.3\u2010fold higher of CD163<jats:sup>+<\/jats:sup>cell, BTX: 10\u2009\u00b1\u20093; BTX\u2009+\u2009ES: 33\u2009\u00b1\u20098, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), potentially via activation of the PI3K\u2010Akt pathway (p\u2010Akt\/Akt ratio, BTX:0.58\u2009\u00b1\u20090.20%; BTX\u2009+\u2009ES:1.03\u2009\u00b1\u20090.07%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Depletion of macrophages using clodronate liposomes reversed the beneficial effects of ES on induced masseter atrophy (<jats:italic>MuRF1<\/jats:italic>: BTX\u2009+\u2009ES: 2.20\u2009\u00b1\u20090.16; BTX\u2009+\u2009ES\u2009+\u2009CL: 12.93\u2009\u00b1\u20090.98, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), highlighting the involvement of macrophages in the therapeutic process. In\u00a0vitro studies demonstrated that ES promoted the transition from M1 to M2 macrophages and enhanced proliferation and differentiation of myogenic cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that ES can enhance masseter muscle tissue repair by modulating macrophage polarisation, offering valuable insights into the potential of ES in noninvasive tissue regeneration strategies for treating masseter muscle atrophy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.70048","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T05:55:57Z","timestamp":1755323757000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Atrophy Masseter Recovery by Electrical Stimulation Mediated M2\u2010Like Macrophage Polarisation via JAK\/PI3K\/AKT Pathway"],"prefix":"10.1002","volume":"16","author":[{"given":"Chuan","family":"Wu","sequence":"first","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyun","family":"Zheng","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingchun","family":"Li","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Song","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quancheng","family":"Han","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfeng","family":"Fu","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Mei","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Liu","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Xu","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology, Anhui Medical University Key Lab. of Oral Diseases Research of Anhui Province  Hefei China"},{"name":"Department of Periodontics Stomatological Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital Capital Medical University  Beijing China"},{"name":"Department of VIP Dental Service, School of Stomatology Capital Medical University  Beijing China"},{"name":"Laboratory for Oral and General Health Integration and Translation, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-6820","authenticated-orcid":false,"given":"Tingting","family":"Wu","sequence":"additional","affiliation":[{"name":"College &amp; 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