Search Results (1,913)

Lycopus lucidus Turcz. var. hirtus Regel (L. lucidus var. hirtus) is a medicinal herb traditionally used in Chinese folk medicine for the treatment of inflammatory disorders, joint pain, and rheumatoid arthritis (RA)-like symptoms. However, systematic research on the bioactive flavonoids of this herb in RA-related cellular models is limited. The aim of this study was to isolate the main flavonoid from this herb and evaluate its in vitro anti-inhibitory effects in TNF-α-induced human RA fibroblast-like synoviocytes (HFLS-RA). Flavonoids were extracted, purified, and isolated using chromatographic techniques. The structure was elucidated by spectroscopic analysis. The effects of the isolated compound were assessed in a TNF-α-induced HFLS-RA cell model by evaluating pro-inflammatory cytokine secretion and cell proliferation/metabolic activity. A main flavonoid was identified as formononetin. Formononetin exhibited antioxidant activity and inhibited TNF-α-provoked inflammatory responses in HFLS-RA cells under cell-safe concentrations, as evidenced by reduced secretion of IL-6, IL-8, and IL-1β and suppression of TNF-α-induced hyperproliferation. In conclusion, formononetin is a major flavonoid constituent of L. lucidus var. hirtus, and these findings provide preliminary in vitro cellular evidence that formononetin exerts in vitro anti-inflammatory inhibitory activity on TNF-α-activated human RA fibroblast-like synoviocytes. Further in vivo and mechanistic studies are required to explore its potential for anti-RA-related pharmacological application. Full article

Background: The incidence of rheumatoid arthritis is steadily increasing worldwide, resulting in a growing number of individuals who may lose the ability to perform self-care activities and professional duties, thereby reducing their quality of life. Rheumatoid arthritis represents a significant social problem, limiting the ability of the working population to lead a full life. A comprehensive approach to the treatment of patients with rheumatoid arthritis, including both pharmacological therapy and an individualized rehabilitation program, is of strategic importance for maintaining their functional status. Materials and Methods: A review of modern physiotherapy methods (physical factors) in patients with rheumatoid arthritis was conducted in the international scientific databases Web of Science, PubMed, Google Scholar, and Elibrary over a seven-year period to identify an alternative approach to the treatment of this disease. Results: The search identified 12 articles presenting the results of clinical studies (3), cross-sectional study (1) and randomized clinical trials (8). These studies investigated physiotherapy interventions in patients with RA and highlighted the potential value of exploring alternative treatment approaches for this patient population. Despite substantial heterogeneity in the interventions, treatment protocols, and combinations of physical factors used, all of the reviewed methods demonstrated positive effects. Conclusions: Physiotherapy interventions may have a positive impact on the clinical course of rheumatoid arthritis; however, the available evidence is insufficient to draw definitive conclusions regarding their effectiveness, primarily due to the lack of long-term follow-up data and substantial heterogeneity in the number and design of treatment sessions, as well as in the physical factors applied. The long-term effects of physiotherapy interventions remain insufficiently studied and warrant further research aimed at developing standardized and evidence-based treatment protocols. Full article

Background/Objectives: Rheumatoid arthritis (RA) affects a high percentage of people. This condition can lead to foot and ankle deformities frequently accompanied by severe pain and limitations in daily activities; together, these aspects reduce the quality of life. Methods: We carried out a systematic search of databases such as PubMed, Cochrane, and Scopus. We compared the outcomes of treatments with conventional disease-modifying antirheumatic drugs (DMARDs), anti-TNF biologic drugs, custom foot orthoses, and combined therapies over a six-month period. This systematic review and meta-analysis synthesized evidence from 21 included studies evaluating pharmacological, orthotic, and physical therapy interventions in adult RA patients with foot and ankle involvement. Results: Across pooled estimates, multidisciplinary interventions combining pharmacotherapy, custom foot orthoses, and structured physical therapy demonstrated substantial reductions in pain (VAS score mean reduction of: −5.0 points in VAS score) and kinesiophobia, alongside gains in health-related quality of life (EQ-5D increase of: +0.30 points). High statistical heterogeneity was observed across study designs (I^2 > 50\%). Conclusions: Early assessment of foot pathologies and multidisciplinary collaboration are recommended, while future long-term randomized controlled trials are needed to confirm component-specific efficacy. Recommendations include early assessment of foot pathologies, collaboration among multidisciplinary teams, and future studies including 12-month follow-ups using specific assessment tools such as the MFPDI. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease frequently accompanied by depression, with persistent inflammation, oxidative stress, and neuroimmune dysfunction contributing to disease progression. This study evaluated the therapeutic efficacy of a Gum Arabic-stabilized bioactive oil blend nanoemulsion and investigated its underlying mechanisms using molecular docking and network pharmacology. Methods: A lyophilized nanoemulsion prepared from grape seed oil, wheat germ oil, and avocado peel oil was characterized for physicochemical properties and phytochemical composition. Female rats with Freund’s complete adjuvant-induced rheumatoid arthritis received the nanoemulsion at two doses. Paw inflammation, behavioral performance, inflammatory cytokines, oxidative stress biomarkers, acetylcholinesterase concentration, lipid profile, and liver and kidney function were evaluated. Molecular docking and network pharmacology analyses were performed to identify potential molecular targets and signaling pathways. Results: The nanoemulsion exhibited favorable physicochemical characteristics and was rich in phenolic compounds, flavonoids, phytosterols, tocopherols, and unsaturated fatty acids. Treatment significantly reduced paw inflammation, TNF-α, IL-6, malondialdehyde, and acetylcholinesterase while enhancing catalase activity, improving metabolic parameters, and alleviating depression-like behavior. Molecular docking demonstrated favorable binding of the major phytochemicals to TNF-α, IL-6, and acetylcholinesterase. Network pharmacology identified key therapeutic targets, including TNF, AKT1, PTGS2, IL6, STAT3, ESR1, and NR3C1, and revealed enrichment of inflammatory, oxidative stress, and neuroimmune signaling pathways. Conclusions: The Gum Arabic-stabilized bioactive oil blend nanoemulsion ameliorated rheumatoid arthritis-associated depression-like behavior through a multi-component–multi-target–multi-pathway mechanism involving coordinated regulation of inflammatory, oxidative stress, cholinergic, and neuroimmune pathways. These findings support its potential as a complementary nutraceutical strategy for rheumatoid arthritis and its associated neurobehavioral complications. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive synovial inflammation, joint destruction, and metabolic abnormalities. In recent years, there has been growing interest in intermittent fasting (IF) as a potential dietary strategy for modulating inflammatory and immunometabolic processes in RA. Preliminary data suggest that IF may lead to reduced joint pain, lower inflammatory markers, improved well-being, and weight loss, but the available evidence is scattered and heterogeneous. The aim of this scoping review was to provide a comprehensive overview of the current state of knowledge regarding the effects of IF on inflammatory, immunological, and metabolic processes in patients with RA. Methods: The review was conducted in accordance with the Joanna Briggs Institute methodology and the PRISMA-ScR guidelines. The databases PubMed, Scopus, Web of Science, EBSCO, the Cochrane Library, and Google Scholar were searched (16 March to 12 April 2026) using the Population–Concept–Context model. Full-text observational and experimental studies, as well as reviews, on intermittent fasting in RA were included in the analysis. Results: Of the 137 publications identified, 9 studies were included in the review, covering populations from Iran, Luxembourg, Tunisia, Mexico, China, and Turkey. The results indicate that IF may lead to improvements in disease activity, quality of life, and selected metabolic parameters. Several studies reported a beneficial effect of IF on markers of oxidative stress and selected pro-inflammatory cytokines, although other analyses did not confirm significant changes in inflammatory biomarkers. Preclinical data have demonstrated strong anti-inflammatory and immunoregulatory effects of IF, including a reduction in pro-inflammatory cytokines and an increase in the Treg population. The heterogeneity of IF protocols, population differences, and small sample sizes limit the ability to interpret the results unequivocally. Conclusions: The available evidence suggests that intermittent fasting may represent a promising, nonpharmacological strategy to support the treatment of RA, particularly in terms of improving immunometabolic parameters and subjective disease symptoms. However, due to methodological limitations and the lack of long-term studies, further well-designed randomized clinical trials are needed to evaluate the efficacy and safety of IF in this population. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which fatigue and sleep disturbances, in addition to articular symptoms, are of significant importance. These symptoms are among the most common and burdensome complaints reported by patients; they affect their daily functioning and quality of life, and can also exacerbate one another. Currently, the treatment of RA focuses not only on reducing inflammatory activity and preventing structural damage, but also on improving outcomes that matter most to patients. In modern RA treatment, Janus kinase inhibitors (JAKis) are becoming increasingly important; by inhibiting the JAK/STAT pathway, they limit the activity of cytokines involved in the inflammatory response. This review aimed to analyse the effect of selected JAKis on fatigue and sleep quality in patients with RA. An analysis of available study results showed that baricitinib, filgotinib, tofacitinib and upadacitinib reduce fatigue severity. In many cases, improvement was observed as early as the initial stages of treatment and persisted at later follow-up points. At the same time, the extent of this improvement was not uniform and depended on the drug used, the dose, the patient population, and the assessment method adopted. Some analyses also suggested that this effect may have been partly due to reduced pain and improved disease activity. The data on sleep quality are less extensive, but the results suggest that tofacitinib and upadacitinib may also have a beneficial effect in this regard. With tofacitinib, improvements in sleep quality were observed early, affected multiple sleep domains, and, in some studies, persisted over the long term. For upadacitinib, an improvement in sleep quality appeared to be associated with disease control and remission. The smaller number of studies on sleep quality than on fatigue highlights the need to consider this parameter more thoroughly when assessing the efficacy of JAKi treatment and emphasises the importance of a more holistic approach in clinical practice. Full article

Rheumatoid arthritis (RA) is an autoimmune disease with a complex pathogenesis. It has been shown that epigenetic modifications can influence the differentiation and function of many immune system cells involved in the pathogenesis of RA. Important epigenetic factors include non-coding RNAs, such as long non-coding RNAs (lncRNAs). Non-coding RNAs can influence numerous immune processes in RA. This study aimed to evaluate the expression of lncRNAs SNHG7, SNHG12, and SNHG14 in the synovial membranes of patients with RA and to correlate these results with selected clinical parameters of the disease. This study included 46 patients diagnosed with RA and 67 healthy individuals as the control group. The expression levels of the lncRNAs SNHG7, SNHG12, and SNHG14 in synovial membranes in patients with RA were statistically higher than those in the control group. The synovial expression of SNHG14 showed a statistically significant negative correlation with C-reactive protein values. There were no statistically significant correlations between synovial expression of SNHG7, SNHG12, and clinical parameters. The study results suggest that lncRNAs may potentially play a role in the development of RA. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Cellular senescence contributes to chronic inflammation, yet key senescence-associated regulators in RA remain unclear. This study aimed to identify RA senescence-related signatures and their roles. Using GSE89408 as the training cohort, we screened hub genes by intersecting differentially expressed and senescence-related genes via WGCNA and three machine learning algorithms, with GSE55457 for external validation. Immune infiltration, regulatory network, subtyping and drug prediction were analyzed. Clinical and in vitro assays validated RIPK2 expression and function in the macrophage senescence-like phenotype, with preliminary signaling exploration. Three senescence-related hub genes (TNFAIP6, SLC2A3, RIPK2) were identified. The derived nomogram showed robust diagnostic performance (AUC = 0.988). Hub genes correlated strongly with myeloid cells, especially macrophages. Two immunologically distinct RA subtypes were identified. RIPK2 was upregulated in clinical samples; its inhibition attenuated LPS-induced macrophage senescence-like changes and inflammation. Preliminary data suggested RIPK2 may act via the NF-κB pathway. This study identifies RA senescence-associated signatures, revealing RIPK2 linking innate immunity to macrophage senescence-like changes, offering novel insights into pathogenesis and supporting it as a candidate biomarker and therapeutic target. Full article

Background: Sensorineural hearing loss (SNHL) has increasingly been recognized as an extra-articular manifestation of systemic autoimmune rheumatic disease (SARDs), but its burden and clinical characteristics remain inconsistent. This systematic review and meta-analysis evaluated the prevalence, risk, audiometric characteristics, diagnostic methods and prognostic factors of SNHL in patients with major SARDs. Methods: A systematic search of the PubMed, Scopus and Cochrane Library databases was conducted between 25 June and 3 July 2026 in accordance with PRISMA 2020 guidelines. Observational studies evaluating SNHL in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS) and systemic sclerosis (SSc) were included. Meta-analyses using a random-effects model were performed to estimate pooled prevalence and odds ratios (OR). Subgroup analyses, meta-regression, sensitivity analysis, publication bias assessment and certainty of evidence evaluation were performed. Results: Twenty-two studies met the eligibility criteria and were included. The pooled prevalence of SNHL was 50% (95% CI: 13–87%, p < 0.001) in patients with RA, 61% (95% CI: 22–95%, p < 0.001) in SLE, 31% (95% CI: 5–67%, p < 0.001) in pSS and 28% (95% CI: 14–44%, p < 0.001) in SS. Patients with RA (OR 1.92; 95% CI: 1.29–2.87) and SLE (OR 21.68; 95% CI: 4.65–100.99) had significantly increased odds of SNHL compared to healthy controls. Hearing loss was predominantly mild, bilateral, and cochlear in origin, and affected high or extended high frequencies. Longer disease duration and greater disease activity were associated with worse hearing thresholds. In exploratory analyses of RA studies, sample size, study setting, and study design were significant study-level moderators of heterogeneity. Conclusions: SNHL is reported with appreciable prevalence across several major systemic autoimmune rheumatic diseases, although prevalence estimates are highly heterogeneous and should be interpreted cautiously. Comparative evidence supports increased odds of SNHL in RA, whereas the magnitude of the association in SLE remains uncertain because of the limited and imprecise evidence. Evidence establishing increased comparative risk in pSS and SSc remains insufficient. Audiological assessment may be particularly relevant in patients with longstanding or active disease. Full article

Objectives: The role of Phosphoglycerate Dehydrogenase (PHGDH), the first key enzyme in the serine biosynthesis pathway, is important in controlling cancer survival; however, its role in rheumatoid arthritis (RA) remains unknown. Here, we investigated the functional involvement of PHGDH in RA pathogenesis, as well as its underlying molecular mechanisms. Methods: mRNA and protein expression in RA fibroblast-like synoviocytes (FLS) was measured by RT-qPCR and Western blot, respectively. Immunohistochemistry (IHC) was used to detect the protein expression in RA synovium. Cellular and tissue localization of the protein was assessed using IHC and immunofluorescence. The functional role of PHGDH in RA FLS was evaluated using multiple approaches: Transwell assays to assess cell migration and invasion, Annexin V/PI staining to detect apoptosis, and EdU assays to measure cell proliferation. Key downstream targets of PHGDH were identified via RNA sequencing (RNA-seq). The therapeutic potential of PHGDH targeting was further assessed in a rat collagen-induced arthritis (CIA) model following intra-articular administration of PHGDH-shRNA. Results: PHGDH expression was markedly elevated in RA synovial tissues and FLS. Functionally, knockdown of PHGDH suppressed proliferation, migration, invasion, and inflammatory cytokine production of RA FLS. Mechanistic studies revealed that PHGDH exerts its effects, at least in part, by inhibiting the expression of adrenoceptor alpha 2A (ADRA2A). The therapeutic relevance of these findings was further supported by in vivo experiments, where intra-articular delivery of PHGDH-shRNA significantly ameliorated the severity of arthritis in rats with CIA. Conclusions: Our results indicate that the PHGDH-ADRA2A axis critically drives the inflammatory and aggressive phenotype of RA FLS, suggesting that PHGDH might be as a promising therapeutic target for RA. Full article

Objective: Siweixizangmaoru decoction (SXD), a classical Tibetan prescription documented in the medical text Four Medical Tantras, has shown therapeutic activity in experimental rheumatoid arthritis (RA). However, its candidate active constituents and underlying mechanisms remain unclear. Methods: In this study, serum-absorbed constituents following SXD administration were profiled using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), and network pharmacology was employed to identify core targets and candidate active constituents of SXD against RA. Candidate active constituents were further screened using cell-based assays, and the selected constituents were quantified using HPLC fingerprint analysis. Both in vivo (CIA rat model) and in vitro (RAW264.7 pyroptosis model) systems were used to investigate the pharmacological effects and mechanisms of SXD. Results: A total of 11 absorbed constituents were identified in the serum of SXD-treated rats, and four preliminary candidate active constituents, including chebulagic acid, kaempferol, gentiopicroside, and berberine, were screened. The combined in vivo and in vitro results showed that SXD attenuated RA progression and reduced inflammatory cytokine levels in rat serum and cell culture supernatants. At the molecular level, SXD increased Pol β expression and reduced DNA damage markers, cytosolic dsDNA accumulation, and cGAS/STING-, NF-κB-, and NLRP3-associated signaling. Pol β knockdown partially reduced the effects of SXD. Conclusions: These findings support the partial involvement of Pol β-associated processes in the anti-arthritic effects of SXD. Full article

Objective: To explore the association of glucocorticoid (GC) exposure with objectively assessed sleep architecture in patients with rheumatoid arthritis (RA). Methods: A single-center exploratory pilot study involving 20 consecutive patients with RA (9 GC users and 11 non-users; mean age 64.9 years) was conducted. Using single-channel electroencephalography (EEG) and accelerometry, objective sleep architecture and autonomic balance were evaluated. Sleep parameters included wake after sleep onset (WASO), sleep stages, and delta EEG power during the first sleep cycle, while heart rate variability, expressed as low frequency/high frequency (LF/HF) ratio, was used as an index of autonomic balance. RA disease activity was evaluated using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Associations between clinical variables and objective sleep parameters were evaluated using Spearman rank correlation analysis. Results: Disease activity, assessed by DAS28-CRP, did not differ significantly between GC users and non-users. Compared with non-users, GC users had longer WASO (p = 0.011), shorter non-rapid eye movement (NREM) stage N3 duration (p = 0.010), and lower delta power (p = 0.014) than non-users. A higher nighttime-to-daytime LF/HF ratio was also observed in GC users, although this difference did not reach statistical significance. Total sleep time, sleep latency, and sleep efficiency were comparable between the groups. WASO was positively correlated with age, GC use, and GC dose, whereas NREM stage N3 duration and delta power were negatively correlated with GC exposure. No significant associations were observed between age or sex and objective measures of deep sleep. Conclusions: Among patients with RA, GC exposure was associated with poorer sleep continuity and reduced deep sleep despite comparable disease activity. Given the small sample size of this exploratory single-center study, these findings should be interpreted cautiously. Larger longitudinal studies using objective sleep measures are warranted to confirm these associations. Full article

C-C motif chemokine ligand 2 (CCL2) interacts with cytokines, adipokines, miRNAs, and multiple synovial cell populations. Experimental studies indicate that these interactions can form a CCL2-associated inflammatory amplification network across cell types. In cellular and animal models, increased CCL2 is associated with monocyte recruitment, synovial fibroblast activation, osteoclast-related bone remodelling, and vascular responses. Therapeutic strategies targeting the CCL2-centered inflammatory network include antagonists of the CCL2/CCR2 axis, natural products, synthetic compounds, conventional antirheumatic drugs, and emerging delivery-based approaches. Notably, direct CCL2/CCR2 inhibition has shown biological activity in experimental models but has not produced consistent clinical benefit in established rheumatoid arthritis (RA). Although these findings do not establish CCL2 as a dominant causal driver of RA, human observational studies suggest that circulating CCL2 may complement established markers in preclinical RA risk assessment, disease activity and remission classification, estimation of treatment response, and evaluation of RA-related complications such as interstitial lung disease. Of note, no validated concentration cut-off or standardized assay currently supports its routine clinical use. This review examines the CCL2-related inflammatory network in RA and evaluates its cellular mechanisms, therapeutic implications, and potential clinical applications. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects mainly peripheral joints because of inflammation of the synovial membrane. Current treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, although effective, are associated with high costs and several adverse effects. In this context, natural products have emerged as promising alternatives because of their potential therapeutic effects and lower toxicity. The objective of this review was to identify and evaluate natural substances with potential applications in RA treatment on the basis of studies published between 2015 and 2020. A literature search was conducted in SciELO, PubMed, and Google Scholar using the keywords “rheumatoid arthritis”, “treatment”, “toxicity”, and “natural products”. Additionally, we applied in silico methods to predict pharmacokinetic and toxicological parameters using ADMET Predictor^® (Simulation Plus) and compared the results with those of commercial drugs such as diclofenac, ibuprofen, and naproxen. Target fishing (reverse docking) was also performed to identify possible molecular targets related to RA. Seven natural compounds were identified, mostly evaluated through in vivo studies. Among them, paeoniflorin, quercetin, resveratrol, and celastrol are in clinical phases and present potential as RA treatments. In silico analysis highlighted curcumin, tetramethylpyrazine, and resveratrol as the most promising candidates, with ADMET profiles comparable or superior to those of current NSAIDs. In conclusion, natural products represent viable alternatives for RA therapy. However, further studies are essential to better understand their safety, pharmacokinetics, and drug interactions to ensure their clinical applicability. Full article

Objective: Genetic factors contribute to physical activity (PA) and sedentary behavior (SB), two complex behavioral traits. They may be associated with musculoskeletal and inflammatory diseases. However, the relationships of domain-specific PA and SB traits with osteoporosis (OS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA) remain unclear. A two-sample Mendelian randomization (MR) analysis assessed potential bidirectional associations between these behavioral traits and the three diseases. Methods: GWAS summary statistics were used to examine five domain-specific PA traits, three SB traits, and OS, RA, and PsA. Primary causal estimates were obtained using the inverse-variance weighted (IVW) method. Complementary analyses used MR-Egger regression, the weighted median method, and the weighted mode method. Sensitivity analyses were performed using Cochran’s Q test, the MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Multiple testing was addressed using false discovery rate (FDR) correction. Results: In the forward MR analyses, genetically predicted liability to Light DIY was associated with lower odds of PsA after FDR correction (OR = 0.006, 95% CI = 0.0002–0.236, FDR-adjusted p = 0.018). Genetically predicted longer television viewing was linked to increased odds of PsA (OR = 2.205, 95% CI = 1.089–4.463, FDR-adjusted p = 0.028) and RA (OR = 1.006, 95% CI = 1.002–1.010, FDR-adjusted p = 0.004). Walking for pleasure showed a nominal inverse association with PsA, and computer use showed a nominal inverse association with RA. Neither association remained significant after FDR correction. No evidence of associations with the broad self-reported OS diagnosis was observed. Reverse MR analyses showed lower odds of Walking for pleasure (OR = 0.662, 95% CI = 0.484–0.906, FDR-adjusted p = 0.013) and Other exercises (OR = 0.651, 95% CI = 0.490–0.864, FDR-adjusted p = 0.006) for genetic liability to RA. RA liability was also associated with longer television viewing time (β = 0.708, 95% CI = 0.251–1.165, FDR-adjusted p = 0.006). No reverse associations were observed for PsA. Conclusions: This bidirectional MR study identified several potential genetically predicted associations of domain-specific PA and SB traits with PsA and RA. The findings for television viewing and RA may suggest a potential bidirectional association. However, the results should be considered hypothesis-generating. These findings require independent replication and further validation before causal or clinical conclusions can be drawn. Full article