{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:40:20Z","timestamp":1776440420751,"version":"3.51.2"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ek0109281"],"award-info":[{"award-number":["JP19ek0109281"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ek0109418"],"award-info":[{"award-number":["JP19ek0109418"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20ek0109488"],"award-info":[{"award-number":["JP20ek0109488"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H00527"],"award-info":[{"award-number":["JP20H00527"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients older than 50\u2009years of age. sIBM is hardly responds to any immunosuppressing theraphies, and its pathophysiology remains elusive. This study aims to explore pathogenic pathways underlying sIBM and identify novel therapeutic targets using metabolomic and transcriptomic analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this retrospective observational study, we analyzed biopsied muscle samples from 14 sIBM patients and six non\u2010diseased subjects to identify metabolic profiles. Frozen muscle samples were used to measure metabolites with cation and anion modes of capillary electrophoresis time of flight mass spectrometry. We validated the metabolic pathway altered in muscles of sIBM patients through RNA sequencing and histopathological studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 198 metabolites were identified. Metabolomic and transcriptomic analyses identified specific metabolite changes in sIBM muscle samples. The pathways of histamine biosynthesis and certain glycosaminoglycan biosynthesis were upregulated in sIBM patients, whereas those of carnitine metabolism and creatine metabolism were downregulated. Histopathological examination showed infiltration of mast cells and deposition of chondroitin sulfate in skeletal muscle samples, supporting the results of metabolomic and transcriptomic analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We identified alterations of several metabolic pathways in muscle samples of sIBM patients. These results suggest that mast cells, chondroitin sulfate biosynthesis, carnitine, and creatine play roles in sIBM pathophysiology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51657","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T17:00:19Z","timestamp":1663261219000},"page":"1602-1615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis"],"prefix":"10.1002","volume":"9","author":[{"given":"Ayuka","family":"Murakami","sequence":"first","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Neurology National Hospital Organization Suzuka Hospital  Suzuka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiya","family":"Noda","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Neurology National Hospital Organization Suzuka Hospital  Suzuka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Kazuta","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Neurology National Hospital Organization Suzuka Hospital  Suzuka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Neurology National Hospital Organization Suzuka Hospital  Suzuka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seigo","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Neurology National Hospital Organization Suzuka Hospital  Suzuka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotaka","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Neurology Yokkaichi Municipal Hospital  Yokkaichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Neurology Kariya Toyota General Hospital  Kariya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koyo","family":"Tsujikawa","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madoka","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruki","family":"Koike","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuma","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Institute for Glyco\u2010Core Research (iGCORE), Nagoya University  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichiro","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Genetics Research Institute of Environmental Medicine (RLeM), Nagoya University  Nagoya Japan"},{"name":"Department of Human Genetics and Molecular Biology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Kuru","sequence":"additional","affiliation":[{"name":"Department of Neurology National Hospital Organization Suzuka Hospital  Suzuka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Kadomatsu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Institute for Glyco\u2010Core Research (iGCORE), Nagoya University  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teppei","family":"Shimamura","sequence":"additional","affiliation":[{"name":"Division of Systems Biology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoo","family":"Ogi","sequence":"additional","affiliation":[{"name":"Department of Genetics Research Institute of Environmental Medicine (RLeM), Nagoya University  Nagoya Japan"},{"name":"Department of Human Genetics and Molecular Biology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9453-9311","authenticated-orcid":false,"given":"Masahisa","family":"Katsuno","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Clinical Research Education Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199111213252107"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.52.8910"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-011-6185-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12627"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr213"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.08.007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/112.3.727"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23840"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000129"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001862"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24847"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809091"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.55.6706"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac990976y"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr034020m"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-009-0178-y"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3122"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2486-6"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0344-0338(81)80137-9"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-015-7680-0"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.11"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.125799"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2018.64.1.1"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4512"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/1559325815616351"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1996.tb00901.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00633.2016"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1139\/H10-055"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2016.08.023"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25405"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.336925"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(77)90075-2"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2017.09.005"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1107"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199909)22:9<1228::AID-MUS9>3.0.CO;2-6"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.324"},{"key":"e_1_2_8_41_1","first-page":"CD004760","article-title":"Creatine for treating muscle disorders","volume":"2013","author":"Kley RA","year":"2013","journal-title":"Cochrane Database Syst Rev"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51657","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51657","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51657","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T12:54:35Z","timestamp":1692622475000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,15]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/acn3.51657"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51657","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,15]]},"assertion":[{"value":"2022-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}