{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:49:29Z","timestamp":1765954169995,"version":"3.48.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumor necrosis factor alpha (TNF\u03b1) is a key cytokine involved in the inflammatory and neurodegenerative processes underlying multiple sclerosis (MS). Its expression is finely regulated by epigenetic and post-transcriptional mechanisms, including promoter methylation and miRNA activity. The objective of this study is to investigate TNF\u03b1 expression, promoter methylation, and its regulation by miR-130a-3p in patients with relapsing\u2013remitting (RR)MS, evaluating both serum and saliva as potential diagnostic biofluids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RRMS patients in clinical remission and sex and age-matched healthy controls (HC) were enrolled. TNF\u03b1 levels were quantified in serum, peripheral blood mononuclear cell (PBMC) supernatants, and saliva using ELISA. TNF\u03b1 mRNA expression and promoter methylation were analyzed by qPCR and pyrosequencing, respectively. Bioinformatic tools (TargetScan, miRTargetLink 2.0, miEAA 2) were used to explore miRNA\u2013TNF\u03b1 interactions, and miR-130a-3p expression was evaluated in serum and saliva by qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RRMS patients showed significantly higher TNF\u03b1 mRNA and protein levels compared to HC, paralleled by significant hypomethylation of the TNF\u03b1 promoter in PBMCs. miR-130a-3p was markedly downregulated in both serum and saliva, exhibiting an inverse trend with TNF\u03b1 expression. Salivary TNF\u03b1 levels mirrored serum alterations, supporting the feasibility of saliva as a noninvasive biomarker source.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The data indicate that TNF\u03b1 upregulation in RRMS is associated with promoter hypomethylation and reduced miR-130a-3p expression, suggesting a coordinated epigenetic and post-transcriptional control of this cytokine. The parallel trends observed in saliva and serum highlight the potential use of salivary TNF\u03b1 and miR-130a-3p as minimally invasive biomarkers for MS monitoring and early diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2025.1730177","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:44:58Z","timestamp":1765953898000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TNF\u03b1 protein, DNA methylation, mRNA and miRNA expression evaluation in multiple sclerosis"],"prefix":"10.3389","volume":"12","author":[{"given":"E.","family":"Costantini","sequence":"first","affiliation":[]},{"given":"N. H.","family":"Greig","sequence":"additional","affiliation":[]},{"given":"L.","family":"Aielli","sequence":"additional","affiliation":[]},{"given":"P. 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