{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:17:47Z","timestamp":1785428267311,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Balikesir University Scientific Research Project Unit","award":["2021\/131"],"award-info":[{"award-number":["2021\/131"]}]},{"award":["2021\/131"],"award-info":[{"award-number":["2021\/131"]}],"id":[{"id":"https:\/\/ror.org\/02tv7db43","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Circulating microRNAs (miRNAs) are emerging as accessible biomarkers for multiple sclerosis (MS). In experimental models, miR-221 and miR-222 have been linked to immune and Th17-related pathways, while interleukin-23 (IL-23) is a cytokine driving autoimmune inflammation. This observational study evaluated the expression of circulating miR-221\/222 and serum IL-23 concentrations in treatment-naive adult patients with MS. Materials and Methods: This prospective, cross-sectional case\u2013control study included 43 untreated adult patients with MS (36 with relapsing\u2013remitting MS and 7 with primary progressive MS) and 37 healthy controls. Demographic features, Expanded Disability Status Scale (EDSS) scores, magnetic resonance imaging involvement, initial symptoms, serum IL-23 concentration, and miR-221\/222 expression were recorded. Total RNA, including small RNAs, was isolated; complementary DNA was synthesized by reverse transcription from RNA templates; and reverse transcription\u2013quantitative real-time PCR (RT-qPCR) was performed using RNU6-2 as the endogenous small RNA reference. Individual \u0394\u0394Ct values were specified as the primary inferential scale, while 2\u2212\u0394\u0394Ct fold-change was retained only for descriptive reporting. Results: The relative expression (2\u2212\u0394\u0394Ct) of miR-221 and miR-222 was higher in patients than in controls. Within the patient group, miR-221 and miR-222 relative expression did not differ by age, sex, EDSS, time since MS diagnosis, MRI involvement area, or initial symptoms. No statistically significant difference in IL-23 levels was observed between the patient and control groups. Conclusions: The presence of unaltered IL-23 levels alongside significantly elevated miR-221 and miR-222 expressions in treatment-naive MS patients during the remission phase suggests their potential utility as biomarkers for immune regulation. Given the cross-sectional design of this study, no causal or regulatory relationship between miR-221\/222 and IL-23 can be inferred.<\/jats:p>","DOI":"10.3390\/medicina62081468","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:16:52Z","timestamp":1785313012000},"page":"1468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating miR-221\/222 and Serum IL-23 in Treatment-Na\u00efve Multiple Sclerosis: A Case\u2013Control Study"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5303-3621","authenticated-orcid":false,"given":"Ummu Serpil","family":"Sar\u0131","sequence":"first","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Balikesir University, 10145 Balikesir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4148-2539","authenticated-orcid":false,"given":"Nermin","family":"Tepe","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Balikesir University, 10145 Balikesir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1521-7152","authenticated-orcid":false,"given":"Ayla","family":"Solmaz Avc\u0131kurt","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Balikesir University, 10145 Balikesir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9815-1039","authenticated-orcid":false,"given":"Saliha","family":"Uysal","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Balikesir University, 10145 Balikesir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6574-8149","authenticated-orcid":false,"given":"Hilmi","family":"Bolat","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Balikesir University, 10145 Balikesir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7129-948X","authenticated-orcid":false,"given":"Figen","family":"E\u015fmeli","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Izmir University of Economics, 35330 Izmir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3390\/sclerosis1020011","article-title":"Roles of extracellular vesicles in multiple sclerosis: From pathogenesis to potential tools as biomarkers and therapeutics","volume":"1","author":"Pistono","year":"2023","journal-title":"Sclerosis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cca.2021.01.020","article-title":"MicroRNA in multiple sclerosis","volume":"516","author":"Gao","year":"2021","journal-title":"Clin. 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