ArticleBiochemistry and biophysics reports2025
Therapeutic gene targets and epigenetic modifications in rheumatoid arthritis: Insights from MTX, JAK inhibitors, and LLDT-8.
Article in Biochemistry and biophysics reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Geroscience insights into difficult-to-treat rheumatoid arthritis: the role of unhealthy aging, comorbidity, and therapeutic complexity.GeroScience · 2026Review
- Immunometabolic reprogramming in rheumatoid arthritis: the epitranscriptomic role of N6-methyladenosine in innate and adaptive immunity.Frontiers in immunology · 2026Review
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13 authors.
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Abstract
Objective: This study investigates therapeutic gene targets and their epigenetic modifications in rheumatoid arthritis (RA), focusing on the molecular effects of methotrexate (MTX), Janus kinase (JAK) inhibitors, and (5R)-5-hydroxytriptolide (LLDT-8) on fibroblast-like synoviocytes (FLS). Methods: Primary FLS were isolated from synovial tissues of RA and osteoarthritis (OA) patients and treated with MTX, JAK inhibitors, and LLDT-8. RNA sequencing identified differentially expressed genes (DEGs) under each treatment. The intersection of differentially expressed genes with trend analysis identified as potential drug target genes. Functional enrichment analyses were performed to explore associated pathways. Methylation changes in key genes were examined using the GEO database (GSE46364), and clinical relevance was evaluated using RA patient data from the PEAC database. Results: Compared to the osteoarthritis FLS group, the RA FLS group showed significant differences in 5095 genes (3300 upregulated and 1795 downregulated). After JAK inhibitor treatment, 3795 significant differential genes were identified in RA FLS (1733 upregulated and 2062 downregulated). MTX treatment resulted in 3195 significant differential genes (2171 upregulated and 1023 downregulated), while LLDT-8 treatment revealed 12,993 significant differential genes (7801 upregulated and 5192 downregulated). Following trend analysis and de-duplication, we identified 45 important drug target genes that exhibited significant correlations with common clinical indices in RA patients. Among these, Conclusion: This study highlights therapeutic gene targets and their epigenetic modifications as potential mechanisms underlying the effects of MTX, JAK inhibitors, and LLDT-8 in RA treatment.
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