{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:35:09Z","timestamp":1791837309229,"version":"4.3.4"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National High Level Hospital Clinical Research Funding","award":["2023HQ10"],"award-info":[{"award-number":["2023HQ10"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201553"],"award-info":[{"award-number":["82201553"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101469"],"award-info":[{"award-number":["82101469"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We aimed to identify new biomarkers of muscle pathological changes via a large-scale histopathology-based multi-omics study of dystrophinopathies.<\/jats:p>\n               <jats:p>We performed a comparative pathological analysis of 121 Duchenne muscular dystrophy (DMD) and 114 Becker muscular dystrophy (BMD) patients to determine muscle pathological similarities and differences between DMD and BMD that have not been investigated systematically. Customized bioinformatic analyses of bulk muscle RNA-sequencing data derived from 35 DMD patients, 39 BMD patients and 21 controls were performed to identify gene signatures associated with pathological changes. Validation experiments, including single-nucleus RNA-sequencing, RNAscope in situ hybridization and immunofluorescence staining, were performed in a subset of DMD and BMD patients and on 27 patients with other acquired and inherited myopathies.<\/jats:p>\n               <jats:p>Systematic pathological analyses revealed that the percentages of necrotic, regenerating and hypercontractive myofibres and the degree of muscle fibrosis were greater in DMD patients than in BMD patients. In both DMD and BMD patients, the percentages of necrotic, regenerating and hypercontractive myofibres, respectively, increased in the early stage and decreased in later disease stages, whereas muscle fibrosis worsened progressively with disease progression. Comparative transcriptomic analysis indicated that inflammatory responses were significantly activated in DMD patients compared with BMD patients, which was confirmed by immunohistochemistry analyses. Our customized bioinformatic analyses identified the gene set of MYH3, MYH8, IL17B, TNNT2, MYMK and TDO2 as the most associated gene signature for muscle necrosis and regeneration. Muscle quantitative reverse transcription\u2013PCR analyses confirmed significantly increased levels of IL17B and TNNT2 mRNA expression in both DMD and BMD patients compared with controls. Muscle IL17B mRNA expression was significantly correlated with histological muscle regeneration and negatively correlated with the age of patients with dystrophinopathy. Single-nucleus RNA-sequencing and RNAscope in situ hybridization demonstrated that IL17B mRNA was expressed in regenerating myofibres of patients with DMD and BMD and in various acquired and inherited myopathies. Immunofluorescence staining further confirmed that interleukin-17B was expressed in regenerating myofibres of DMD and BMD patients.<\/jats:p>\n               <jats:p>Our study provides evidence that interleukin-17B is a new biomarker of muscle regeneration in dystrophinopathies.<\/jats:p>","DOI":"10.1093\/brain\/awaf058","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T18:07:46Z","timestamp":1739297266000},"page":"2579-2591","source":"Crossref","is-referenced-by-count":7,"title":["Interleukin-17B is a new biomarker of human muscle regeneration in dystrophinopathies"],"prefix":"10.1093","volume":"148","author":[{"given":"Chang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, Peking University First Hospital , Beijing 100034 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3484-7720","authenticated-orcid":false,"given":"Zhihao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, North Sichuan Medical College , Nanchong 610041 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyue","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital , Beijing 100034 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital , Beijing 100034 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital , Beijing 100034 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1742-9877","authenticated-orcid":false,"given":"Zhaoxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital , Beijing 100034 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingchao","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital , Beijing 100034 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3282-9123","authenticated-orcid":false,"given":"Yun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital , Beijing 100034 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creatine\/creatinine ratio, and myostatin as monitoring biomarkers in Becker muscular dystrophy","volume":"100","author":"van de Velde","year":"2023","journal-title":"Neurology"},{"key":"2025070715520244300_awaf058-B3","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1136\/jmedgenet-2020-107113","article-title":"Practical approach to the genetic diagnosis of unsolved dystrophinopathies: A stepwise strategy in the genomic era","volume":"58","author":"Xie","year":"2021","journal-title":"J Med Genet"},{"key":"2025070715520244300_awaf058-B4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00439-022-02485-2","article-title":"RNA-seq analysis, targeted long-read sequencing and in silico prediction to unravel pathogenic intronic events and complicated splicing abnormalities in dystrophinopathy","volume":"142","author":"Okubo","year":"2023","journal-title":"Hum 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