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ID PMID Title PublicationDate abstract
31879201 Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital 2021 Jun OBJECTIVE: To assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients. METHODS: Retrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included. RESULTS: 320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures). CONCLUSION: The annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.
33745959 Activation of the Nrf2/HO-1 signaling pathway by dimethyl fumarate ameliorates complete Fr 2021 May 15 The nuclear factor erythroid 2-related factor (Nrf2) signaling pathway has recently emerged as a novel therapeutic target in treating various diseases. Therefore, the present study aimed to assess the protective role of the Nrf2 activator, dimethyl fumarate (DMF) in the complete Freund's adjuvant (CFA)- induced arthritis model. DMF (25, 50, and 100 mg/kg) and dexamethasone (2 mg/kg) were orally administered for 14 days. Pain-related tests, paw volume, and arthritic scores were measured weekly. Serum TNF-α, IL-1β, cyclic citrullinated peptide (CCP), C-reactive protein (CRP), and rheumatoid factor (RF) levels were estimated. Nitrite, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), catalase (CAT), and myeloperoxidase (MPO) levels were also evaluated. NF-κB, Nrf2, HO-1, and COX-2 levels were estimated in the joint tissue. DMF treatment exerted anti-arthritic activity by enhancing the nociceptive threshold, improving arthritis scores, and reducing paw edema. Also, DMF suppressed changes in oxidative stress markers and inflammatory mediators and enhanced Nrf2 and HO-1 levels in CFA-injected rats. These findings indicate that the anti-arthritic activity of DMF may be mediated by the activation of the Nrf2/HO-1 pathway, which reduced oxidative damage and inflammation.
32252574 (64)Cu-ATSM and (99m)Tc(CO)(3)-DCM20 potential in the early detection of rheumatoid arthri 2021 Mar OBJECTIVES: Molecular imaging constitutes a promising technique for the early detection of rheumatoid arthritis (RA). Macrophages and hypoxia play significant roles in inflamed synovium. In the present study, we evaluated the efficacy of radiopharmaceuticals that target macrophage mannose receptors ((99m)Tc-labeled mannosylated dextran or (99m)Tc(CO)(3)-DCM20) and hypoxia (copper(II) diacetyl-di(N(4)-methylthiosemicarbazone) or Cu-ATSM) for the early detection of RA in collagen-induced arthritis (CIA) mice models. METHODS: CIA model was developed in DBA/1 mice, and the clinical score for arthritis was visually assessed on a regular basis. Two biodistribution studies were performed in a paired-labeled format using 2-deoxy-2-(18)F-fluoro-D-glucose ((18)F-FDG) as a reference: (1) (99m)Tc(CO)(3)-DCM20 with (18)F-FDG and (2) (67)Cu-ATSM with (18)F-FDG. RESULTS: The accumulation levels of (99m)Tc(CO)(3)-DCM20 and (67)Cu-ATSM in forepaws, hindpaws, and knee joints of CIA mice were significantly higher than that of control mice. In contrast, (18)F-FDG uptake in hindpaws and knee joints showed no significant difference between CIA and control mice. The radioactivity levels of (99m)Tc(CO)(3)-DCM20 and (67)Cu-ATSM were significantly correlated with the clinical scores for the paws. CONCLUSION: These results suggest the potential usefulness of (99m)Tc(CO)(3)-DCM20 and radiolabeled Cu-ATSM for the imaging and early detection of RA.
33717866 Management of inflammatory temporomandibular joint collapse in children. 2021 Apr Juvenile idiopathic arthritis is the most common pediatric rheumatologic condition.( Abramowicz et al., 2016 Jul) 2 The etiology and pathogenesis have not been fully elucidated; a combination of environmental and certain immunogenic factors is suspected. This review will provide current knowledge and concepts of diagnosis and management of children with JIA and TMJ arthritis.
34345282 Expression profiling of genes in rheumatoid fibroblast-like synoviocytes regulated by Fas 2021 Sep Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in synovial tissues. Hyperplasia of synovial tissues leads to the formation of pannus that invades the joint cartilage and bone, resulting in joint destruction. Fas ligand (FasL), which is a member of the tumor necrosis factor superfamily, contributes to the pathogenesis of autoimmune diseases, including RA. The current study attempted to identify genes whose expressions in rheumatoid fibroblast-like synoviocytes (RA-FLS) were regulated by FasL, using cDNA microarray. A total of four individual lines of primary cultured RA-FLS were incubated either with recombinant human FasL protein or PBS as an unstimulated control for 12 h. Gene expression was detected using a microarray assay. The results revealed the expression profiles of genes in RA-FLS regulated by Fas and investigated the functions of the genes that were regulated. Among the genes in this profile, the mRNA expression changes of the following genes were indicated to be of note using RT-qPCR: Dual specificity phosphatase 6, epiregulin, interleukin 11, angiopoietin-like 7, protein inhibitor of activated STAT 2 and growth differentiation factor 5. These genes may affect the pathogenesis of RA by affecting apoptosis, proliferation, cytokine production, cytokine-induced inflammation, intracellular signaling, angiogenesis, bone destruction and chondrogenesis. To the best of our knowledge, the current study is the first study to reveal the expression profile of genes in RA-FLS regulated by FasL. The data demonstrated that FasL may regulate the expression of a number of key molecules in RA-FLS, thus affecting RA pathogenesis. Further studies of the genes detected may improve the understanding of RA pathogenesis and provide novel treatment targets for RA.
34790122 Risk of Adverse Events After Anti-TNF Treatment for Inflammatory Rheumatological Disease. 2021 Background: Adalimumab, golimumab, infliximab, certolizumab, and etanercept are five anti-tumor necrosis factor (anti-TNF) medicines that have been approved for use in rheumatology. Apart from their well-established therapeutic usefulness, -it is unclear to what extent -they are linked to an increased risk of various side effects. The present meta-analysis was carried out to assess the risk of infection and other side effects after anti-TNF- α for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Methods: We searched PubMed, Cinahl (via Ebsco), Scopus, and Web of Sciences databases for trials comparing anti-TNF medications to placebo or no therapy in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis from August 2006 to August 2020. A total of 23 articles were used for meta-analysis. The Cochrane Collaboration's risk of bias tool was used to assess the methodological quality of the included studies. In addition, a random-effects model was used to calculate the pooled odds ratio, and Forest plots were constructed to determine the risk of infections and cancer following the use of anti-TNF treatment. Results: Treatment with anti-TNFα agents resulted in an increase in the risk of serious infections (OR: 1.72, 95% CI: 1.56-1.90, p < 0.00001) and an increase in cancer risk (OR: 1.36, 95% CI: 1.20-1.53, p < 0.00001) whereas the risk of developing tuberculosis was not significantly different with anti-TNFα agents versus those without treatment with anti-TNFα agents (OR: 2.55, 95% CI: 0.40-16.23, p = 0.32) although the number of studies is limited to make a definitive conclusion. The risk of bias of the included studies was unclear to high across most domains, and there was evidence of publication bias for most outcomes. Conclusion: The present meta-analysis suggests an increased risk of infectious adverse events, including overall adverse events and cancer following anti-TNFα treatment, whereas the risk of tuberculosis was not significantly different. Although anti-TNF agents have shown promise to treat inflammatory conditions, their use should be balanced by the risk-benefit ratio as suggested by the meta-analysis.
33932778 Synoviolin is not a pathogenic factor for auto-inflammatory diseases. 2021 Jun 18 Auto-inflammatory syndromes are rare diseases characterized by arthritis and joint destruction, symptoms similar to but distinct from rheumatoid arthritis (RA). Therapeutic targets have not been well characterized for auto-inflammatory syndromes, although the E3 ligase Synoviolin was previously shown to be a novel therapeutic target for RA. Here, we show that Synoviolin loss has little impact on a model of auto-inflammatory diseases. We previously established such a model, the hIL-1 cTg mouse, in which IL-1 signaling was constitutively activated, and animals exhibit symptoms recapitulating auto-inflammatory syndromes such as major joint dominant arthritis. Here, we crossed hIL-1 cTg with Synoviolin flox'd mice to yield hIL-1 cTg/Synoviolin cKO mice. Synoviolin gene expression was ablated in adult hIL-1 cTg/Synoviolin cKO mice by injection of pIpC to activate Mx1 promoter-driven Cre recombinase. However, symptoms seen in hIL-1 cTg mice such as arthritis and joint destruction were not alleviated by targeting Synoviolin, ruling out Synoviolin as a therapeutic target for auto-inflammatory disease. Our results indicate that although similar, RA and auto-inflammatory diseases are different diseases, and treatment strategies should differ accordingly.
34712530 Causes of the Failure of Biological Therapy at a Tertiary Center: A Cross-Sectional Retros 2021 Sep Introduction Rheumatoid arthritis (RA) is one of the most commonly encountered autoimmune diseases. Treatment generally includes disease-modifying anti-rheumatic drugs (DMARDs) and/or biological therapy. However, a significant proportion of the patients do not respond to treatment either as a (primary failure) or lose efficacy over time (secondary failure). Several factors are assumed to influence these conditions. Objectives To estimate the prevalence of failure of biological therapy in patients with RA and its causes. Methods A total of 335 RA patients who were diagnosed at a tertiary center in Jeddah, Saudi Arabia, and had a failure after receiving biological therapy were included in this study. Several variables were considered; patient's socio-demographic data, comorbid conditions, types of biological therapy, the duration of using biological therapy in months, number of biological therapies, allergic reactions, disease activity, and treatment duration. Results Overall the prevalence of failure to biological therapy was 58%; 77% primary failure and 23% secondary failure. Patients with negative rheumatoid factor (RF) (p=0.006), using low-dose steroids, and with a longer disease duration had a significant failure of biological therapy (p=0.023). Conclusion A high percentage of RA patients had a failure of biological therapy. A multicentric trial is recommended to look for additional factors.
34646840 Real-Life Retention Rates and Reasons for Switching of Biological DMARDs in Rheumatoid Art 2021 Aims: To determine real-life biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) retention rates in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), explore reasons for switching and to compare results to previously published data. Methods: Time-to-event analysis for mean treatment duration (estimated as the Restricted Mean Survival Time), b/tsDMARD failure, and b/tsDMARDs switching was performed for 230 patients (n = 147 RA, 46 PsA, 37 AS) who commenced their first b/tsDMARD between 2008 and 2018. Patients were managed in a dedicated "biologics" clinic in a tertiary hospital; the choice of b/tsDMARD was clinician driven based on medical factors and patient preferences. The effect of covariates on switching risk was analysed by a conditional risk-set Cox proportional-hazards model. Treatment retention data was compared to a historical analysis (2002-2008). Results: The proportions remaining on treatment (retention) were similar, throughout follow-up, for the first, second and third b/tsDMARDs across all patients (p = 0.46). When compared to RA patients, the risk of b/tsDMARD failure was halved in PsA patients [Hazard Ratio (HR) = 0.50], but no different in AS patients (HR = 1.0). The respective restricted mean (95%CI) treatment durations, estimated at 5 years of follow-up, were 3.1 (2.9, 3.4), 4.1 (3.7, 4.6), and 3.3 (2.8, 3.9) years, for RA, PsA, and AS, respectively. Age, gender, disease duration, smoking status and the use of concomitant csDMARDS were not associated with the risk of bDMARD failure. The most common reasons for switching in the first and subsequent years were secondary (n = 62) and primary (n = 35) failure. Comparison with historical data indicated no substantive differences in switching of the first biologic for RA and PsA. Conclusion: Similar retention rates of the second and third compared to the first b/tsDMARD in RA, PsA, and AS support a strategy of differential b/tsDMARDs use informed by patient presentation. Despite greater availability of b/tsDMARDs with differing mechanisms of action, retention rates of the first b/tsDMARD remain similar to previous years.
34661415 NMR-Based Metabolomics Revealed the Underlying Inflammatory Pathology in Reactive Arthriti 2021 Nov 5 Reactive arthritis (ReA) is an aseptic synovitis condition that often develops 2-4 weeks after a distant (extra-articular) infection with Chlamydia, Salmonella, Shigella, Campylobacter, and Yersinia species. The metabolic changes in the synovial fluid (SF) may serve as indicative markers to both improve the diagnostic accuracy and understand the underlying inflammatory pathology of ReA. With this aim, the metabolic profiles of SF collected from ReA (n = 58) and non-ReA, i.e., rheumatoid arthritis (RA, n = 21) and osteoarthritis (OA, n = 20) patients, respectively, were measured using NMR spectroscopy and compared using orthogonal partial least-squares discriminant analysis (OPLS-DA). The discriminatory metabolic features were further evaluated for their diagnostic potential using the receiver operating characteristic (ROC) curve analysis. Compared to RA, two (alanine and carnitine), and compared to OA, six (NAG, glutamate, glycerol, isoleucine, alanine, and glucose) metabolic features were identified as diagnostic biomarkers. We further demonstrated the impact of ReA synovitis condition on the serum metabolic profiles through performing a correlation analysis. The Pearson rank coefficient (r) was estimated for 38 metabolites (profiled in both SF and serum samples obtained in pair from ReA patients) and was found significantly positive for 71% of the metabolites (r ranging from 0.17 to 0.87).
34455977 Cardiovascular disease risk calculators to reflect the subclinical atherosclerosis of coro 2021 Aug 30 BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death in patients with rheumatoid arthritis (RA). Coronary artery calcium (CAC) score quantifies the severity of atherosclerosis. We estimated CVD risk using several methods and compared these with the CAC score to identify the most suitable CVD risk calculator in RA patients. METHODS: We recruited RA patients, and the 10-year CVD risk was assessed using various tools, viz. Framingham risk score, Systemic Coronary Risk Evaluation (SCORE), Atherosclerotic Cardiovascular Disease (ASCVD) risk estimator plus, QRISK3, Expanded Risk Score in Rheumatoid Arthritis (ERS-RA), and Reynolds risk score. Computed tomography was used to determine the CAC score of each patient. Correlation analysis and linear regression analysis between the CAC score and CVD risk score was performed. RESULTS: In total, 54 RA patients were enrolled. ERS-RA showed the highest correlation coefficient (r = 0.430, P = 0.001). In multivariate linear regression analysis, ERS-RA (β = 10.01, 95% confidence interval 3.78-16.23) showed a positive association with the CAC score in RA patients. CONCLUSIONS: The ERS-RA method was highly correlated with the CAC score in RA patients. Therefore, the application of the ERS-RA method may be suitable for predicting subclinical atherosclerosis and CVD risk in RA patients.
34526896 Integrated Phytochemical Analysis Based on UPLC-MS/MS and Network Pharmacology Approaches 2021 Odontites vulgaris Moench has the effect of clearing away heat, detoxification, dispelling wind, and clearing dampness. In this study, the potential anti-inflammatory compounds of O. vulgaris were investigated using ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) combined with the network pharmacology approach and further confirmed on an LPS-activated RAW 264.7 macrophage model. Monomer compounds were prepared from the active fraction using modern advanced separation and purification methods. UPLC-Q-Exactive HRMS was used to identify the chemical compounds in the active fractions of O. vulgaris. D-mannitol, geniposidic acid, salidroside, shanzhiside methyl ester, eleutheroside B, geniposide, 7,8-dihydroxycoumarin, gardoside methyl ester, arenarioside, vanillic acid, p-hydroxy-cinnamic acid, melampyroside, syringaresinol, tricin, and diosmetin were isolated from O. vulgaris for the first time. A compound database of O. vulgaris was established based on the existing literature to predict the mechanism of O. vulgaris in the treatment of rheumatoid arthritis. The results suggest that the PI3K-Akt pathway mediates O. vulgaris and deserves more attention in the treatment of RA. Finally, the anti-rheumatoid arthritis effects of the four target compounds were validated with the decreased levels of NO, TNF-α, IL-6 and IL-1β in RAW 264.7 macrophage cells treated with LPS. The present study explored the potential targets and signaling pathways of O. vulgaris in the treatment of RA, which may help to illustrate the mechanisms involved in the action of O. vulgaris and may provide a better understanding of the relationship between O. vulgaris and RA. This study provides novel insights into the development of new drugs and utilization of Mongolian traditional Chinese medicine resources.
35110179 Combination of denosumab and biologic DMARDs in inflammatory muscle-skeletal diseases and 2021 Oct OBJECTIVE: Osteoporosis (OP) can complicate the course of rheumatic musculoskeletal diseases (RMDs) and connective tissue diseases (CTDs). Denosumab, a monoclonal antibody against RANK-L, showed beneficial effect in rheumatoid arthritis in inhibiting radiographic progression and erosive burden. We tested the efficacy, safety, and persistence on the treatment of the combination of biologic disease-modifying antirheumatic drugs (bDMARDs)/denosumab versus bDMARD in patients with RMD and CTD. METHODS: This is a retrospective evaluation of a single center, including patients with RMD/CTD (including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic sclerosis, and overlap syndromes) treatment with bDMARD/denosumab, compared to age, gender, disease, bDMARD, and conventional synthetic disease-modifying antirheumatic drugs-matched controls. RESULTS: Twenty-eight bDMARD/denosumab patients and 49 bDMARD patients were eligible. Despite a statistically significant difference during the first-year efficacy (due to the different baseline timepoint), there was no difference in the efficacy profile in the second year of treatment and in the safety profile (including local, systemic, and serious adverse events). Moreover, no statistically significant difference in the persistence of bDMARD treatment over 2 years of evaluation was found. The combination of bDMARD and denosumab was not an independent predictor of disease flare or bDMARD treatment withdrawal. CONCLUSION: The combination of bDMARD and denosumab does not alter the efficacy and the safety profile of the bDMARD in patients with RMD/CTD. Future studies verifying the radiological disease inhibition could support denosumab use in RMD/CTD other than rheumatoid arthritis, when complicated by OP.
33344167 Hepatocyte growth factor overexpression promotes osteoclastogenesis and exacerbates bone l 2021 Mar BACKGROUND: Hepatocyte growth factor (HGF) is a multifunctional growth factor that promotes various biological processes. However, the effect of HGF on bone metabolism in rheumatoid arthritis (RA) remains unknown. Here, we investigated the role of HGF in regulating osteoclastogenesis and bone resorption in RA. METHODS: The expression of HGF in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of HGF on osteoclastogenesis was analysed by osteoclastogenesis and bone resorption assays. The effect of HGF inhibition was evaluated in a CIA mice model. The mechanism of HGF in regulating osteoclastogenesis and bone resorption was explored by a series of in vitro studies. RESULTS: HGF was overexpressed in CIA and RA. HGF stimulated osteoclastogenesis in vitro. SU11274, a selective small molecule blocker of c-Met, impeded the effect of HGF on osteoclastogenesis and bone resorption. HGF regulated osteoclastogenesis by JNK and AKT-GSK-3β-NFATc1 signallings. SU11274 protected CIA mice from pathological bone loss. CONCLUSIONS: These data strongly suggest that the highly expressed HGF in the joint tissues contributes to bone loss in RA. Inhibition of HGF/c-Met could effectively alleviate pathological bone loss and inflammatory symptoms in CIA mice. HGF/c-Met may be used as a new target for the treatment of bone loss in RA.
34895887 Relationship between polyautoimmunity and sarcopenic obesity in rheumatoid arthritis patie 2021 Dec 8 OBJECTIVE: Sarcopenia is a major cause of morbidity in rheumatoid arthritis patients. Our purpose was to determine whether polyautoimmunity is associated with sarcopenia and alterations in whole body composition in patients with rheumatoid arthritis (RA). METHODS: We performed a cross-sectional observational study of a series of cases of RA. All patients were recruited consecutively from a rheumatology clinic. Body composition by dual-energy x-ray absorptiometry (DEXA) was assessed. The variables of interest were polyautoimmunity (RA associated with other autoimmune diseases), sarcopenia, fat mass, and body mass index (BMI). Other variables included were clinical-analytical and inflammatory cytokines and adipokines. The relationship between sarcopenic obesity and the presence of polyautoimmunity was studied using multivariate analysis. RESULTS: Of the 94 patients with RA included in the study, 15 (16%) had polyautoimmunity. A total of 23 patients with RA (24.5%) had sarcopenia, which was more prevalent in patients with polyautoimmunity than in patients without polyautoimmunity (46.7% vs 20.3%; p = .029). Sarcopenia was not associated with body fat content (p = .870) or with BMI (p = .998). The multivariate analysis showed the factors associated with polyautoimmunity in RA to be sarcopenia (odds ratio [95% CI], 4.80 [1.49-13.95]), BMI (1.18 [1.04-1.35]), and resistin (1.249 [1.01-1.53]). CONCLUSION: Sarcopenia and obesity were more prevalent in patients with RA and polyautoimmunity. Resistin values were also higher in this group than in patients with RA without polyautoimmunity.
34688134 IgD promotes pannus formation by activating Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in 2021 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation, synovial hyperplasia, cartilage degeneration, bone erosion, and pannus. Immunoglobulin D (IgD) plays an important role in autoimmune diseases although the content of it in vivo is low. Increased concentrations of anti-IgD autoantibodies have been detected in many RA patients. IgD-Fc-Ig fusion protein is constructed by connecting human IgD Fc domain and IgG1 Fc domain, which specifically block the IgD/ IgDR pathway and regulate the function of cells expressing IgDR to treat RA. The expression levels of Wnt5A and Frizzled 5 are higher in RA synovial tissue specimens. The complex of Wnt5A-Fzd5-LRP5/6-CTHRC1 promotes the expression of hypoxia inducible factor-1α by activating nuclear factor kappa-B (NF-κB), leading to high expression of VEGF and participating in angiogenesis. VEGF is the strongest angiogenic factor found so far. Here, we aimed to explore whether IgD participates in synovitis by binding to IgDR and regulating the activation of Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in fibroblast synovial cells (FLSs), whether IgD-Fc-Ig fusion protein inhibits VEGF production in FLS of CIA and explore mechanism. We found that IgDR is expressed on MH7A and FLS. IgD promotes VEGF expression by activating Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in MH7A and FLS. After activation of Fzd5 with Wnt5A, IgD-Fc-Ig reduced VEGF-A level in the culture supernatant of MH7A stimulation by IgD. The expressions of CTHRC1, Fzd5, p-P65 and VEGF in MH7A and FLSs were down-regulated after IgD-Fc-Ig treatment. IgD-Fc-Ig suppressed the combination of CTHRC1 and Fzd5 as well. By using the animal model, we demonstrated that IgD-Fc-Ig suppress ankle CTHRC1 and Fzd5 production resulted in inhibition of index of joint inflammation of CIA rats, which were consistent with vitro results. Conclusively, IgD-Fc-Ig inhibits IgD and Wnt5A-induced angiogenesis and joint inflammation by suppressing the combination of CTHRC1 and Fzd5. Our results show that IgD-Fc-Ig exerts its suppressive effect on IgD and Wnt5A by Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway.
35264827 Surgical Solution for Total Carpectomy due to Destructive Wrist Pan-Osteomyelitis Using a 2022 Jan Osteomyelitis of the hand is rare, even more so in the carpal bones. Patients with rheumatoid arthritis (RA) have a higher infection rate overall, and up to a 14-fold increase in the incidence of septic arthritis of the hand. The destruction of immunologic barriers, such as cartilage and joint capsules, as well as the use of immunosuppressive medications will have an impact on the higher incidence of articular infections and osteomyelitis in these patients. Infection in these cases is often overlooked because of the similarity of presentation to an acute event of RA. When osteomyelitis is present, rapid and aggressive treatment should be given. Surgical debridement, lavage, and excision of necrotic bone is the best choice, followed by cemented antibiotic impregnated spacer to resolve the acute scenario. Vascularized bone grafts (VBG) can then be used for a definitive solution, as these have great biologic properties that increase the possibility of a good outcome. We hereby present a report of a wrist arthrodesis, using a free medial femoral condyle VBG for the treatment of destructive osteomyelitis of the carpal bones in a female patient with RA.
33466905 In Vivo Fluorescence Imaging of Passive Inflammation Site Accumulation of Liposomes via In 2021 Jan 14 Nanocarriers such as liposomes have been attracting attention as novel therapeutic methods for inflammatory autoimmune diseases such as rheumatoid arthritis and ulcerative colitis. The physicochemical properties of intravenously administered nanomedicines enable them to target inflamed tissues passively. However, few studies have attempted to determine the influences of nanoparticle surface characteristics on inflammation site accumulation. Here, we aimed to study the effects of polyethylene glycol (PEG) modification and surface charge on liposome ability to accumulate in inflammatory sites and be uptake by macrophages. Four different liposome samples with different PEG modification and surface charge were prepared. Liposome accumulation in the inflammation sites of arthritis and ulcerative colitis model mice was evaluated by using in vivo imaging. There was greater PEG-modified than unmodified liposome accumulation at all inflammation sites. There was greater anionic than cationic liposome accumulation at all inflammation sites. The order in which inflammation site accumulation was confirmed was PEG-anionic > PEG-cationic > anionic > cationic. PEG-anionic liposomes had ~2.5× higher fluorescence intensity than PEG-cationic liposomes, and the PEG-liposomes had ~2× higher fluorescence intensity than non-PEG liposomes. All liposomes have not accumulated at the inflammation sites in healthy mice. Furthermore, cationic liposomes were taken up to ~10× greater extent by RAW264.7 murine macrophages. Thus, PEG-cationic liposomes that have the ability to accumulate in inflammatory sites via intravenous administration and to be taken up by macrophages could be useful.
34849618 Chondroprotective effects of CDK4/6 inhibition via enhanced ubiquitin-dependent degradatio 2021 Nov 25 OBJECTIVE: Targeting synovial fibroblasts (SF) using a cyclin-dependent kinase (CDK) 4/6 inhibitor (CDKI) could be a potent therapy for rheumatoid arthritis (RA) via inhibition of proliferation and MMP-3 production. This study was designed to elucidate the mechanism of chondroprotective effects on SFs by CDK 4/6 inhibition. METHODS: CDK4/6 activity was inhibited using CDKI treatment or enhanced by adenoviral gene transduction. Chondroprotective effects were evaluated using a collagen induced arthritis model (CIA). Gene and protein expression were evaluated with quantitative PCR, ELISA, and Western blotting. The binding of nuclear extracts to DNA was assessed with an electrophoresis mobility shift assay. RNA-Seq was performed to identify gene sets affected by CDKI treatment. RESULTS: CDKI attenuated cartilage destruction and MMP-3 production in CIA. In RASFs, CDKI impaired the binding of AP-1 components to DNA and inhibited the production of MMP-1 and MMP-3, which contain the AP-1 binding sequence in their promoter. CDK4/6 protected JUN from proteasome-dependent degradation by inhibiting ubiquitination. The RNA-Seq analysis identified CDKI-sensitive inflammatory genes, which were associated with the pathway of RA-associated genes, cytokine-cytokine receptor interaction, and IL-17 signalling. Notably, the AP-1 motif was enriched in these genes. CONCLUSION: The mechanism of chondroprotective effects by CDK4/6 inhibition was achieved by the attenuation of AP-1 transcriptional activity via the impaired stability of JUN. Since the pharmacologic inhibition of CDK4/6 has been established as tolerable in cancer treatment, it could also be beneficial in patients with RA due to its chondroprotective and anti-inflammatory effects.
33711984 Validating potent anti-inflammatory and anti-rheumatoid properties of Drynaria quercifolia 2021 Mar 12 BACKGROUND: The fronds of Drynaria quercifolia have traditionally been used in rheumatic pain management. The goal of the present study was to validate the potent anti-inflammatory and anti-rheumatoid properties of the methanolic-extract of its rhizome using in vitro, in vivo and in silico strategies. METHODS: The plant was collected and the methanolic extract was prepared from its rhizome. Protein denaturation test, hypotonicity and heat-induced haemolysis assays were performed in vitro. The in vivo anti-rheumatoid potential was assessed in Freund's complete adjuvant (FCA)-induced Wistar rat model through inflammatory paw-edema, haematological, biochemical, radiological and histopathological measurements. Moreover, metabolites of methanolic extract were screened by gas chromatography-mass spectrometry (GC-MS) and 3D molecular structures of active components were utilized for in silico docking study using AutoDock. RESULTS: In vitro results evinced a significant (p < 0.05) anti-inflammatory activity of the rhizome methanolic extract in a dose-linear response. Further, Drynaria quercifolia rhizome methanolic extract (DME) significantly ameliorated rheumatoid arthritis as indicated by the inhibition of arthritic paw-edema (in millimeter) in the rat rheumatoid arthritis models in both the low (57.71 ± 0.99, p < 0.01) and high dose groups (54.45 ± 1.30, p < 0.001) when compared to arthritic control. Treatment with DME also normalized the haematological (RBC, WBC, platelet counts and hemoglobin contents) and biochemical parameters (total protein, albumin, creatinine and ceruloplasmin) significantly (p < 0.05), which were further supported by histopathological and radiological analyses. Furthermore, GC-MS analysis of DME demonstrated the presence of 47 phytochemical compounds. Compounds like Squalene, Gamma Tocopherol, n-Hexadecanoic acid showed potent inhibition of cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL-6) in the docking analysis. CONCLUSION: Results from in vivo and in vitro studies indicated that DME possesses a potent anti-inflammatory and anti-arthritic activity. In silico studies delineated the emergent potent inhibitory effects of several bio-active components on the target inflammatory markers (COX-2, TNF-α and IL-6).