Rheumatoid arthritis: pathogenesis and therapeutic advances

MedComm, Год журнала: 2024, Номер 5(3)

Опубликована: Март 1, 2024

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the unresolved synovial inflammation for tissues‐destructive consequence, which remains one of significant causes disability and labor loss, affecting about 0.2–1% global population. Although treatments with disease‐modifying antirheumatic drugs (DMARDs) are effective to control decrease bone destruction, overall remission rates RA still stay at low level. Therefore, uncovering pathogenesis expediting clinical transformation imminently in need. Here, we summarize immunological basis, inflammatory pathways, genetic epigenetic alterations, metabolic disorders RA, highlights on abnormality immune cells atlas, epigenetics, immunometabolism. Besides an overview first‐line medications including conventional DMARDs, biologics, small molecule agents, discuss depth promising targeted therapies under or preclinical trials, especially regulators. Additionally, prospects precision medicine based biopsy RNA‐sequencing cell mesenchymal stem chimeric antigen receptor T‐cell also looked forward. The advancements innovations accelerates progress treatments.

Язык: Английский

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Deciphering Immunometabolic Landscape in Rheumatoid Arthritis: Integrative Multiomics, Explainable Machine Learning and Experimental Validation

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 637 - 652

Опубликована: Янв. 1, 2025

Immunometabolism is pivotal in rheumatoid arthritis (RA) pathogenesis, yet the intricacies of its pathological regulatory mechanisms remain poorly understood. This study explores complex immunometabolic landscape RA to identify potential therapeutic targets. We integrated genome-wide association (GWAS) data involving 1,400 plasma metabolites, 731 immune cell traits, and outcomes from over 58,000 participants. Mendelian randomization (MR) mediation analyses were applied evaluate causal relationships among cells, RA. further analyzed single-cell bulk transcriptomes investigate differential gene expression, interactions, relevant biological processes. Machine learning models identified hub genes, which validated via quantitative real-time PCR (qRT-PCR). Then, small-molecule drugs screened using Connectivity Map (CMAP) molecular docking. Finally, a phenome-wide (PheWAS) was conducted side effects targeting genes. Causalities found between six five cells genetically determined levels. Notably, DC mediated 18% protective effect PE on Autophagy-related scores elevated both subsets PE-associated Through observation functional differences cellular interactions clusters, DCs with high autophagy may process such as necroptosis activation Jak-STAT signaling pathway contributing pathogenesis Explainable machine learning, PPI network analysis, qPCR jointly four genes (PFN1, SRP14, S100A11, SAP18). CMAP, docking, PheWAS analysis highlighted vismodegib promising candidate. clarifies key RA, pinpointing paths for better prevention, diagnosis, treatment.

Язык: Английский

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JAK Inhibitors in Rheumatoid Arthritis: Immunomodulatory Properties and Clinical Efficacy

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8327 - 8327

Опубликована: Июль 30, 2024

Rheumatoid arthritis (RA) is a highly prevalent autoimmune disorder. The pathogenesis of the disease complex and involves various cellular populations, including fibroblast-like synoviocytes, macrophages, T cells, among others. Identification signalling pathways molecules that actively contribute to development crucial understanding mechanisms involved in chronic inflammatory environment present affected joints. Recent studies have demonstrated Janus kinase/signal transducer activator transcription (JAK/STAT) pathway regulates behaviour immune cells contributes progression RA. Several JAK inhibitors, such as tofacitinib, baricitinib, upadacitinib, filgocitinib, been developed, their efficacy safety patients with RA comprehensively investigated number clinical trials. Consequently, inhibitors approved registered treatment for In this review, we discuss involvement JAK/STAT summarise potential beneficial effects implicated disease. Moreover, most important phase 3 trials evaluated use these agents patients.

Язык: Английский

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Lactate: A key regulator of the immune response

Immunity, Год журнала: 2025, Номер 58(3), С. 535 - 554

Опубликована: Март 1, 2025

SummaryLactate, the end product of both anaerobic and aerobic glycolysis in proliferating growing cells—with latter process known as Warburg effect—is historically considered a mere waste cell tissue metabolism. However, research over past ten years has unveiled multifaceted functions lactate that critically shape impact cellular biology. Beyond serving fuel source, is now to influence gene expression through histone modification function signaling molecule impacts wide range activities. These properties have been particularly studied context adaptive innate immune responses. Here, we review diverse roles regulation system during homeostasis disease pathogenesis (including cancer, infection, cardiovascular diseases, autoimmunity). Furthermore, describe recently proposed therapeutic interventions for manipulating metabolism human diseases.

Язык: Английский

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Plasma Humanin and Non-Coding RNAs as Biomarkers of Endothelial Dysfunction in Rheumatoid Arthritis: A Pilot Study

Non-Coding RNA, Год журнала: 2025, Номер 11(1), С. 5 - 5

Опубликована: Янв. 14, 2025

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with an increased risk of cardiovascular disease (CVD), largely driven by peripheral endothelial dysfunction (ED). Humanin, mitochondrial-derived peptide, has been suggested to play protective role in function. However, the relationship between Humanin levels and ED RA, as well interaction non-coding RNAs such Long Non-Coding RNA GAS5, microRNA-21 (miR-21), microRNA-103 (miR-103), remains unclear. Objective: This study aimed investigate circulating levels, (GAS5, miR-21, miR-103), (ED) patients RA. Additionally, we explored correlation expression specific miR-103) better understand their potential vascular health. Methods: Peripheral was assessed using flow-mediated pulse amplitude tonometry, Ln-RHI values <0.51 indicating dysfunction. miR-103 were measured RA patients. Univariate multivariate analyses conducted determine these biomarkers ED. Kaplan–Meier survival analysis ROC curve used assess prognostic value Humanin. Results: Higher significantly function (OR = 0.9774, p 0.0196). demonstrated that higher correlated improved (p < 0.0001). The did not show significant associations Conclusions: biomarker for Further research needed explore context

Язык: Английский

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Effect of trace elements and nutrients on 21 autoimmune diseases: a Mendelian randomization study

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 20, 2025

Background Numerous clinical studies have observed a close relationship between serum trace elements, nutrients, and autoimmune diseases. However, whether there is genetic causal effect diseases remains unclear. Objective This study aims to investigate the effects of elements nutrients on 21 using Mendelian randomization (MR). Methods Single nucleotide polymorphisms for exposure factors (serum vitamins) were obtained from published UK Biobank database genome-wide association (GWAS) public databases. Outcome GWAS data derived FinnGen database. MR was employed explore relationships 9 6 vitamins Causal inference performed inverse variance weighted methods, Egger, median methods. Subsequently, heterogeneity tests, horizontal pleiotropy MR-PRESSO leave-one-out analyses conducted sensitivity analysis evaluate robustness results. Finally, that statistically significant in IVW method had consistent sizes odds ratios across five methods selected as with diabetes its complications. Additionally, multivariable assess combined multiple Results indicated elevated levels element copper associated an increased risk systemic lupus erythematosus (SLE) decreased ulcerative colitis. Carotene found negative adult-onset Still ’ s disease (AOSD). Elevated selenium hyperthyroidism. Calcium showed polyarteritis nodosa. MVMR results demonstrated could independently affect hyperthyroidism, separate copper. Conclusion The findings both univariable support These implications developing targeted prevention treatment strategies

Язык: Английский

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Senescent macrophages trigger a pro-inflammatory program and promote the progression of rheumatoid arthritis

International Immunopharmacology, Год журнала: 2025, Номер 149, С. 114164 - 114164

Опубликована: Фев. 3, 2025

Язык: Английский

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Association Between Inflammatory Arthritis, Genetic Risk, and the Long‐Term Risk of Degenerative Aortic Stenosis: A Prospective Cohort Study

Journal of the American Heart Association, Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Background Inflammatory arthritis is recognized to increase cardiovascular disease risk, but its association with degenerative aortic stenosis not well understood. Methods This prospective cohort study used participants from the UK Biobank, focusing on 4 major types of inflammatory arthritis, including rheumatoid ankylosing spondylitis, psoriatic and gout. The primary outcome was incidence stenosis. analysis Cox proportional hazards models evaluate between long‐term risk stenosis, as explore potential effect modifiers. Genetic evaluated using polygenic scores self‐reported family history diseases. Results included 497 567 participants, 271 129 women (54.5%) 468 015 White individuals (94.1%). median age 58 years. Over a follow‐up 12.58 years, 4571 cases (0.9%) were identified. Compared control group, gout associated increased risks by 54% (hazard ratio [HR], 1.54 [95% CI, 1.28–1.85]), 72% (HR, 1.72 1.19–2.50]), 176% 2.76 1.43–5.32]), 36% 1.36 1.20–1.54]), respectively. These associations independent genetic ( P for interaction>0.05). Additionally, we identified significant interactions sex interaction=0.036), interaction<0.001), socioeconomic status interaction=0.014) Conclusions significantly an underscoring need enhanced assessment in these populations.

Язык: Английский

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Anti-arthritic and anti-inflammatory activity of linalool against formaldehyde and complete Freund's adjuvant induced arthritis in rats

Biochemical and Biophysical Research Communications, Год журнала: 2025, Номер 752, С. 151462 - 151462

Опубликована: Фев. 12, 2025

Язык: Английский

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The Role of IL-23 in the Development of Inflammatory Diseases

Biology, Год журнала: 2025, Номер 14(4), С. 347 - 347

Опубликована: Март 27, 2025

Interleukin-23 is crucial in the initiation and progression of certain inflammatory disorders. As a key cytokine, IL-23 involved differentiation activation Th17 cells, which play role broad spectrum diseases. This review examines molecular mechanisms through contributes to pathogenesis conditions including psoriasis, rheumatoid arthritis, bowel disease, multiple sclerosis. By elucidating significant inflammation, this underscores its importance as therapeutic target for managing conditions, with particular emphasis on current emerging biologic treatments.

Язык: Английский

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