Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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29992108 | Anti-rheumatoid activity of ethanolic extract of Sesamum indicum seed extract in Freund's | 2018 Jul | Sesamum indicum, one of the first recorded plants used for its seeds, is reported to have analgesic, antioxidant, anticancer, anti-obesity as well as hepato and nephro protective activities. The current study evaluated the effects of two doses (400 and 800 mg/kg) of ethanolic extract of S. indicum seeds in Freund's complete adjuvant induced arthritis in rats in comparison with diclofenac and methotrexate by the changes produced in body weight, body temperature, paw volume and spontaneous activity, hemoglobin, erythrocyte sedimentation rate, total white blood cells, red blood cells, Interleukin-6 and Tumor necrosis factor-α as well as joint changes in X-ray and histological changes in joint tissue. Unlike the untreated group, the groups treated with S. indicum showed significant decrease in paw volume, body weight, white blood cell count, erythrocyte sedimentation rate, Interleukin-6 and Tumor necrosis factor-α and an increase in body weight, spontaneous activity, hemoglobin level, and red blood cell count. Histopathological examination showed gross reduction in synovial inflammation and cartilage damage. X-ray revealed significant improvement in joint space. The effect of ethanolic extract of S. indicum was found to be equivalent to methotrexate and greater than diclofenac. | |
29664689 | Interleukin-34 Aggravates the Severity of Arthritis in Collagen-Induced Arthritis Mice by | 2018 May | To explore the immunological mechanisms underlying the effect of exogenous interleukin-34 (IL-34) on collagen-induced arthritis (CIA) in mouse. We established a CIA mouse model and injected exogenous recombination mouse IL-34 (rmIL-34) intraperitoneally. The articular index (AI) was measured according to the amount of erythema, swelling, or joint rigidity. The concentrations of TNF-α, IL-17, and IL-6 in CIA mice sera were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of TNF-α, IL-17, and IL-6 in CIA synovial tissue were detected by reverse transcription PCR. The CIA mice dosed with rmIL-34 exhibited increased AI. Neutralization of endogenous IL-17 with anti-IL-17 antibody reduced the effect of IL-34. TNF-α, IL-17, and IL-6 levels in serum in IL-34-treated CIA mice were increased compared to those in CIA mice. IL-34 increased the expression of TNF-α and IL-17 mRNA in synovial tissues of CIA mice, but the gene expression of IL-6 was not affected. The effects of IL-34 on TNF-α, IL-17, and IL-6 expression were abolished by anti-IL-17 antibody. In conclusion, IL-34 acts as a proinflammatory factor, aggravating the severity of arthritis in CIA mice by inducing the production of IL-17. | |
29853728 | The impact of nutrition and generally available products such as nicotine and alcohol on r | 2018 | Nutrition habits and diet may influence disease development and course. There are no specific recommendations related to rheumatic diseases for a diet that would facilitate treatment. However, some research results suggest that various nutrients may affect the health of patients, especially in the case of inflammatory rheumatic disease such as rheumatoid arthritis (RA). Scientists have been trying to find a relation between inflammatory rheumatic diseases and diet but have never come up with any firm conclusions that would help in determining the model of a diet for such patients. Nevertheless, there are some consistent results that refer to the influence of nutritional behaviours on symptoms of RA. The article presents a review of the research showing that certain nutrients may be beneficial for the course of disease among some RA patients. | |
29505093 | Disease-Drug Interactions in Inflammatory States via Effects on CYP-Mediated Drug Clearanc | 2018 Jul | The human inflammatory response can result in the alteration of drug clearance through effects on drug-metabolizing enzymes or drug transporters. In this article, clinical examples are reviewed of how diseases with moderate to severe inflammation can decrease cytochrome P450 (CYP)-mediated drug clearance and alter plasma protein binding. Also examined is how albumin, α-1-acid glycoprotein, drug fraction unbound in plasma, CYP content, and oral clearance can change dynamically with time in response to inflammation. | |
29318966 | Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystand | 2018 | Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD. | |
30424593 | Late Subaxial Lesion after Overcorrected Occipitocervical Reconstruction in Patients with | 2019 Apr | STUDY DESIGN: Retrospective case-control study, level 4. PURPOSE: To clarify the risk factors for late subaxial lesion after occipitocervical (O-C) reconstruction. We examined cases requiring fusion-segment-extended (FE) reconstruction in addition to/after O-C reconstruction. OVERVIEW OF LITERATURE: Patients with rheumatoid arthritis (RA) frequently require O-C reconstruction surgery for cranio-cervical lesions. Acceptable outcomes are achieved via indirect decompression using cervical pedicle screws and occipital plate-rod systems. However, late subaxial lesions may develop occasionally following O-C reconstruction. METHODS: O-C reconstruction using cervical pedicle screws and occipital plate-rod systems was performed between 1994 and 2007 in 113 patients with RA. Occipito-atlanto-axial (O-C2) reconstruction was performed for 89 patients, and occipito-subaxial cervical (O-under C2) reconstruction was performed for 24 patients. We reviewed the cases of patients requiring FE reconstruction (fusion extended group, FEG) and 26 consecutive patients who did not require FE reconstruction after a follow-up of >5 years (non-fusion extended group, NEG) as controls. RESULTS: FE reconstructions were performed for nine patients at an average of 45 months (range, 24-180 months) after O-C reconstruction. Of the 89 patients, three (3%) underwent FE reconstruction in cases of O-C2 reconstruction. Of the 24 patients, five (21%) underwent FE reconstruction in cases of O-under C2 reconstruction (p=0.003, Fisher exact test). Age, sex, RA type, and neurological impairment stage were not significantly different between FEG and NEG. O-under C2 reconstruction, larger correction angle (4° per number of unfixed segment), and O-C7 angle change after O-C reconstruction were the risk factors for late subaxial lesions on radiographic assessment. CONCLUSIONS: Overcorrection of angle at fusion segments requiring O-C7 angle change was a risk factor for late subaxial lesion in patients with RA with fragile bones and joints. Correction should be limited, considering the residual mobility of the cervical unfixed segments. | |
30370468 | Real-World Tocilizumab Use in Patients with Rheumatoid Arthritis in Canada: 12-Month Resul | 2018 Dec | INTRODUCTION: This study was conducted to observe patterns of use of the interleukin-6 receptor-alpha inhibitor tocilizumab in routine clinical practice in patients with rheumatoid arthritis (RA). METHODS: This was a 12-month noninterventional, observational study in adult patients with RA who initiated tocilizumab in routine practice in Canada according to the local product monograph. The primary end point was the proportion of patients receiving tocilizumab at 6 months. Secondary end points were treatment patterns, effectiveness, and safety of tocilizumab over 12 months. RESULTS: Of 200 patients who initiated tocilizumab (91.0% at 8 mg/kg), 67 (33.5%) received tocilizumab monotherapy and 133 (66.5%) received tocilizumab combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Kaplan-Meier analysis estimated that 85% (95% CI 74-92%) of monotherapy and 89% (95% CI 82-93%) of combination therapy patients continued to receive tocilizumab at 6 months (log-rank p = 0.0888). During the observation period, 12 (17.9%) monotherapy and 27 (20.3%) combination therapy patients withdrew from the study. At month 12, 58.5% in the monotherapy group and 59.3% in the combination therapy group achieved Disease Activity Score at 28 joints remission (≤ 2.6), 25.6% and 24.7% achieved Simplified Disease Activity Index remission (≤ 3.3), and 18.2% and 22.3% achieved Clinical Disease Activity Index remission (≤ 2.8), respectively. Rates of serious adverse events and serious infections were found in 29.6/100 patient-years (PY) and 3.1/100 PY, respectively, for monotherapy and 19.2/100 PY and 4.8/100 PY, respectively, for combination therapy. CONCLUSIONS: Patients initiating tocilizumab in routine practice had comparable effectiveness and safety outcomes regardless of whether they received tocilizumab as monotherapy or as combination therapy with csDMARDs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01613378 FUNDING: F. Hoffmann-La Roche (Roche) Canada. | |
30337953 | Optimization of fermentation conditions for an Escherichia coli strain engineered using th | 2018 | BACKGROUND: Fermentation condition optimization and nutrients screening are of equal importance for efficient production of plasmid DNA vaccines. This directly affects the downstream purification and final quality and yield of plasmid DNA vaccines. The present study aimed to optimize the fermentation conditions for high-throughput production of therapeutic DNA vaccine pcDNA-CCOL2A1 by engineered Escherichia coli DH5α, using the response surface method (RSM). RESULTS: We hypothesized that optimized fermentation conditions significantly increase the yield of pcDNA-CCOL2A1 therapeutic DNA vaccine, a novel DNA vaccine for treating rheumatoid arthritis (RA). Single-factor analysis was performed to evaluate the optimal basal culture medium from LB, 2 × YT, TB, M9 (Glycerol) and M9 (Glucose), respectively. Thereafter, the Plackett-Burman design (PBD) was used to ascertain the three most significant factors affecting the vaccine yields, followed by the paths of steepest ascent to move to the nearest region of maximum response. Initial screening through the PBD revealed that the most key factors were peptone, mannitol, and inoculum concentration. Subsequent use of RSM was further optimized for the production of therapeutic DNA vaccine pcDNA-CCOL2A1 through Box-Behnken design (BBD). The final optimized fermentation conditions were as follows: peptone, 25.86 g/L; mannitol, 8.08 g/L; inoculum concentration, OD = 0.36. Using this statistical experimental design, the yield of therapeutic DNA vaccine pcDNA-CCOL2A1 markedly increased from 223.37 mg/L to339.32 mg/L under optimal conditions, and a 51.9% increase was observed compared with the original medium. CONCLUSIONS: The present results provide a basis for further production of high-quality and high-yield therapeutic DNA vaccine pcDNA-CCOL2A1 in pilot-scale and even industrial-scale. | |
29732036 | Effect of long-term low dose prednisolone administration on bone mineral density: Relating | 2018 Spring | BACKGROUND: Long-term treatment of rheumatoid arthritis (RA) with prednisolone (PRED) is associated with bone mineral density (BMD) loss. This study aimed to determine the status of BMD in non-compliant women who used PRED alone for RA. METHODS: Non-adherent RA taking < 7.5 mg daily PRED without DMARDs for > 6 months, and RA patients taking methotrexate +PRED (RA control) were compared with age-matched non-RA controls. BMD was measured by dual energy x-ray absorptiometry (DXA) method and osteoporosis (OP) was diagnosed by WHO criteria. Influence of PRED on RA bone mass, and the risk of OP in RA was assessed by comparing PRED users RA and RA control,versus non-RA controls. RESULTS: Sixty-four PRED user RA, 39 RA controls and 111 non RA-controls, with respective mean (±SD) age of 52±11; 8, 51±11; and 52±7.5 years (P=0.91) were studied. Median duration of treatment in PRED users and RA control was 2.5 and 4 years, respectively. BMD g/cm(2) at the femoral neck (FN-BMD) and lumber spine (LS-BMD) in PRED users and RA control was significantly lower than non-RA control (P=0.001). The prevalence of OP at either FN or LS in both RA groups was significantly higher than controls (P=0.001). In PRED users, the risk of OP increased by OR=4.9, P=0.001) and in RA controls by OR=1.7 (P=0.20). The risk of OP in PRED user RA was 2.89 times (P=0.014) greater than RA controls. CONCLUSIONS: These findings indicate significantly lower BMD, and higher prevalence of osteoporosis in non-compliant women with RA taking low-dose PRED alone for a median period of 2.5 years, as compared with patients taking standard treatment comprising methotrexate +PRED. | |
29581736 | miR-143-3p regulates cell proliferation and apoptosis by targeting IGF1R and IGFBP5 and re | 2018 Apr | It has been demonstrated that the deregulation of microRNAs (miRNAs) affects the development of rheumatoid arthritis (RA). The primary objective of the current study was to determine the role of miR-143-3p in the progression of RA. The expression of miR-143-3p in synovium taken from patients with RA was assessed by reverse transcription-quantitative polymerase chain reaction. The expression of miR-143-3p was higher in synovium tissues of RA than that of osteoarthritis (OA). The decreased expression of miR-143-3p suppressed cell proliferation and promoted apoptosis in vitro. In addition, inhibition of miR-143-3p decreased levels of inflammatory cytokines, as determined by an enzyme-linked immunosorbent assay. IGF1R and IGFBP5 were found to be the target genes of miR-143-3p, and it was demonstrated that miR-143-3p regulated the proliferation and apoptosis of MH7A cells by targeting IGF1R and IGFBP5. Furthermore, TNF-α treatment stimulated the Ras/p38 mitogen activated protein kinase (MAPK) signaling pathway, whereas miR-143-3p inhibition suppressed it. The results of the current study indicate that miR-143-3p may regulate cell proliferation and apoptosis by targeting IGF1R and IGFBP5 expression and regulating the Ras/p38 MAPK signaling pathways. Therefore, miR-143-3p may be a novel therapeutic target in RA. | |
29479473 | Response to baricitinib therapy in patients with rheumatoid arthritis with inadequate resp | 2018 | OBJECTIVE: We analysed the effects of baseline characteristics on the safety and efficacy of baricitinib in patients with rheumatoid arthritis (RA) with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) from two phase III trials. METHODS: In RA-BEAM (NCT01710358), patients with inadequate response to methotrexate were randomised to placebo, baricitinib 4 mg or adalimumab 40 mg. RA-BUILD (NCT01721057) patients had inadequate response to ≥1 csDMARDs and were randomised to either placebo or once-daily baricitinib (2 or 4 mg). Both study populations were naïve to biologic DMARDs (bDMARDs). Primary end point for both studies was American College of Rheumatology 20% improvement (ACR20) response at week 12. Pooled data from the two trials were analysed post hoc based on select subgroups defined by age, previous csDMARD use, baseline RA disease activity, etc, with assessment of clinical and safety outcomes at week 12 and radiographic outcomes at week 24 for the baricitinib 4 mg and placebo-treated patients. RESULTS: Efficacy was observed with baricitinib 4 mg treatment irrespective of patient demographics and baseline disease characteristics. ORs primarily favoured baricitinib over placebo in the ACR20 response. In other outcomes such as Disease Activity Score for 28 joints based on high-sensitivity C reactive protein levels, Simplified Disease Activity Index score ≤11 and radiographic progression, baricitinib 4 mg showed better responses than placebo regardless of baseline characteristics. Safety events were more common in patients over 65 years, but similar between baricitinib 4 mg and placebo patients. CONCLUSION: Baseline characteristics did not substantially affect clinical response to baricitinib 4 mg in patients with RA with inadequate response to csDMARDs. | |
29359131 | Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during an | 2017 | Symptoms of rheumatoid arthritis (RA) improve during pregnancy, a phenomenon that was found to be associated with N-glycosylation changes of immunoglobulin G. Recent advances in high-throughput glycosylation analysis allow the assessment of the N-glycome of human sera as well. The aim of this study was to identify new protein N-glycosylation properties that associate with changes in RA disease activity during and after pregnancy. A longitudinal cohort of serum samples was collected during 285 pregnancies (32 control individuals and 253 RA patients). Per individual one sample was collected before conception, three during pregnancy, and three after delivery. Released serum protein N-glycans were measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) after employing chemical modification of the sialic acids to allow discrimination of sialic acid linkage isomers. Serum protein N-glycosylation showed strongly modified during pregnancy, with similar changes visible in control individuals and RA pregnancies. Namely, a decrease in bisection and an increase in galactosylation in diantennary glycans were found, as well as an increase in tri- and tetraantennary species and α2,3-linked sialylation thereof. The change in RA disease activity [DAS28(3)-CRP] proved negatively associated with the galactosylation of diantennary N-glycans, and positively with the sialylation of triantennary fucosylated species (A3FGS). While the protein source of the novel finding A3FGS is thus far unknown, its further study may improve our understanding of the etiology of RA disease severity. | |
30911211 | Surgical Treatment of Tenosynovitis of Extensor Tendons of Fourth Compartment of Wrist in | 2019 Apr | Purpose Proliferative tenosynovitis of the extensor tendons is a very common painful wrist condition that can occur both in presence and absence of rheumatoid arthritis (RA). This study aims to evaluate a series of patients without RA, having extensor tendon tenosynovitis, its pathology, and results of surgical treatment. Materials and Methods A consecutive series of 10 patients without RA, having tenosynovitis of fourth extensor compartment were treated surgically and evaluated in the study. All patients were operated upon by a single surgeon, and intraoperative specimens were sent for histopathologic evaluation by a single pathologist. The functional outcome of the patients was evaluated by comparing the post- and preoperative wrist extension. Results All patients presented with painful mass over dorsum of the wrist, overlying the fourth extensor compartment. On clinical examination, there was severe limitation of active wrist extension with extended fingers and improvement in wrist extension on flexing the fingers. All patients had significant improvement in wrist extension after surgery. The histopathologic examination of the intraoperative samples revealed similar findings of tenosynovitis in all cases, which was different than that seen in RA. Conclusion This study reveals a distinct tenosynovitis in a group of patients without RA resembling traumatic tenosynovitis on histopathologic examination. Radiologic and intraoperative findings reveal presence of nodular mass in the affected tendon due to proliferative tenosynovitis, which blocks effective proximal excursion of the tendon, leading to decreased wrist extension. This study shows that surgical treatment in the form of tenosynovectomy gives excellent relief to these patients. Type of Study This is a Level IV, therapeutic study. | |
30701884 | Atherosclerosis: perspectives of anti-inflammatory therapy. | 2018 May 11 | According to modern ideas, chronic low-grade inflammation, which development is associated with uncontrolled activation of both innate and adaptive immunity, plays a fundamental role in all stages of the atherosclerotic process. The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease - rheumatoid arthritis. In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1β (IL-1β), which plays an important role in the development of many acute and chronic immunosuppressive diseases. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1β canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications. The results of CÐNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative anti-inflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications. | |
30197693 | Evaluation of Effect of Low-Dose Methotrexate on Osseointegration of Implants: A Biomechan | 2018 | BACKGROUND: Methotrexate (MTX) is an immunosuppressive drug, widely used in inflammatory disturbances including rheumatoid arthritis. However, there is no consensus regarding the effect of MTX on implant osseointegration. OBJECTIVE: The purpose of this experimental study was to investigate the effect of low dose MTX on Bone-Implant Contact (BIC) of dogs. METHODS: Six mandibular premolar teeth (bilateral) of 8 mature dogs were extracted. After 3 months of healing, 6 implants (bone level, resorbable blast media surface) were inserted into the mandible of each dog (3 in each side). Dogs were randomly divided into a study group (receiving 2.5 mg/week MTX orally, 3 times per week for 4 weeks) and a control group each containing 4 dogs. In the 1(st) week, postoperative BIC was evaluated in 4 dogs, two from each group. In the 4(th) week, reverse torque and BIC were evaluated in the remaining 4 dogs. Data were analyzed with two-way ANOVA test for 95% confidence interval. RESULTS: The reverse torque test of the 4(th) week, showed a satisfying osseointegration. Histopathologic evaluation revealed that the BIC was significantly higher in the control group in comparison to the MTX group in the 1(st) and 4(th) week. In addition, the BIC of both groups were significantly increased in the 4(th) week in comparison to the 1(st) week in both groups. CONCLUSION: MTX has the potential to interfere with osseointegration process. | |
29358919 | The Calcium-Induced Regulation in the Molecular and Transcriptional Circuitry of Human Inf | 2017 | Rheumatoid arthritis synovial fibroblasts (RASFs) are fundamental effector cells in RA driving the joint inflammation and deformities. Celastrol is a natural compound that exhibits a potent anti-arthritic effect promoting endoplasmic reticulum (ER) stress mediated by intracellular calcium (Ca(2+)) mobilization. Ca(2+) is a second messenger regulating a variety of cellular processes. We hypothesized that the compound, celastrol, affecting cytosolic Ca(2+) mobilization could serve as a novel strategy to combat RA. To address this issue, celastrol was used as a molecular tool to assay the inflammatory gene expression profile regulated by Ca(2+). We confirmed that celastrol treatment mobilized cytosolic Ca(2+) in patient-derived RASFs. It was found that 23 genes out of 370 were manipulated by Ca(2+) mobilization using an inflammatory and autoimmunity PCR array following independent quantitative PCR validation. Most of the identified genes were downregulated and categorized into five groups corresponding to their cellular responses participating in RA pathogenesis. Accordingly, a signaling network map demonstrating the possible molecular circuitry connecting the functions of the products of these genes was generated based on literature review. In addition, a bioinformatics analysis revealed that celastrol-induced Ca(2+) mobilization gene expression profile showed a novel mode of action compared with three FDA-approved rheumatic drugs (methotrexate, rituximab and tocilizumab). To the best of our knowledge, this is a pioneer work charting the Ca(2+) signaling network on the regulation of RA-associated inflammatory gene expression. | |
30072998 | Apremilast Ameliorates Experimental Arthritis via Suppression of Th1 and Th17 Cells and En | 2018 | Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor suppressing immune and inflammatory responses. We assessed the anti-inflammatory effects of Apremilast in type II collagen (CII)-induced arthritis (CIA) mouse model. To determine whether Apremilast can ameliorate arthritis onset in this model, Apremilast was given orally at day 14 after CII immunization. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti-mouse CII antibody levels were measured by enzyme-linked immunosorbent assay, and Th17, Th1 cells, and CD4(+)Foxp3(+) regulatory T (Treg) cells were assessed by flow cytometry in the lymph nodes. Human cartilage and rheumatoid arthritis (RA) synovial fibroblasts (RASFs) implantation in the severe combined immunodeficiency mouse model of RA were used to study the role of Apremilast in the suppression of RASF-mediated cartilage destruction in vivo. Compared with untreated and vehicle control groups, we found that Apremilast therapy delayed arthritis onset and reduced arthritis scores in the CIA model. Total serum IgG, IgG1, IgG2a, and IgG2b were all decreased in the Apremilast treatment groups. Moreover, Apremilast markedly prevented the development of bone erosions in CIA mice by CT analysis. Furthermore, in the Apremilast treated group, the frequency of Th17 cells and Th1 cells was significantly decreased while Treg cells' frequency was significantly increased. The high dose of Apremilast (25 mg/kg) was superior to low dose (5 mg/kg) in treating CIA. Apremilast treatment reduced the migratory ability of RASFs and their destructive effect on cartilage. Compared with the model group, Apremilast treatment significantly reduced the RASFs invasion cartilage scores in both primary implant and contralateral implant models. Our data suggest that Apremilast is effective in treating autoimmune arthritis and preventing the bone erosion in the CIA model, implicating its therapeutic potential in patients with RA. | |
30622734 | Effects of exercise and physical activity promotion: meta-analysis informing the 2018 EULA | 2018 | OBJECTIVE: To evaluate the effectiveness of exercise and physical activity (PA) promotion on cardiovascular fitness, muscle strength, flexibility, neuromotor performance (eg, balance) and daily PA in people with rheumatoid arthritis (RA), spondyloarthritis (SpA) and hip/knee osteoarthritis (HOA/KOA). METHODS: systematic review (SR) and meta-analysis (MA) were performed searching the databases PubMed/Medline, CENTRAL, Embase, Web of Science, Emcare and PsycInfo until April 2017. We included randomised controlled trials (RCTs) in adults (≥18 years) with RA, SpA and HOA/KOA, investigating the effects of exercise or PA promotion according to the public health PA recommendations by the American College of Sports Medicine. The time point of interest was the first assessment after the intervention period. If suitable, data were pooled in a MA using a random-effects model presented as standardised mean difference (SMD). RESULTS: The SR included 63 RCTs, of which 49 (3909 people with RA/SpA/HOA/KOA) were included in the MA. Moderate effects were found of aerobic exercises and resistance training on cardiovascular fitness (SMD 0.56 (95% CI 0.38 to 0.75)) and muscle strength (SMD 0.54 (95% CI 0.35 to 0.72)), respectively, but no effect of combined strength/aerobic/flexibility exercises on flexibility (SMD 0.12 (95% CI -0.16 to 0.41)). PA promotion interventions produced a small increase in PA behaviour (SMD 0.21 (95% CI 0.03 to 0.38)). CONCLUSION: Exercises and PA promotion according to public health recommendations for PA improved cardiovascular fitness, muscle strength and PA behaviour, with moderate effect sizes in people with SpA, RA and HOA/KOA. TRIAL REGISTRATION NUMBER: CRD42017082131. | |
30546311 | Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Me | 2018 | Objective: Analysis of the relationship between single nucleotide polymorphisms (SNPs) and outcomes of methotrexate (MTX) therapy for rheumatoid arthritis (RA) in China. Materials and Methods: TYMS 28 bp VNTR (rs34743033), MTHFR [677C>T (rs1801133) and 1298A>C (rs1801131)], ATIC 347C>G (rs2372536), MTR A2756G (rs1805087), and MTRR 66A>G (rs1801394) enzyme proteins may be related to the outcomes of MTX therapy, according to our previous meta-analysis. A total of 162 patients with RA were included in our study. SNPs were evaluated using polymerase chain reaction (PCR). Disease Activity Score 28 (DAS28) was used to evaluate the clinical response, and adverse drug reactions (ADRs) were collected after physical examinations of the patients. Results: The MTHFR 677C>T gene showed a relationship with the ADRs of MTX in the Recessive model [TT vs. (CC+CT)] (p = 0.04, OR = 2.20, 95% CI: 1.01, 4.77). In the Codominant model [CT vs. (CC+TT)], the MTHFR 677C>T gene also showed a trend of association with ADRs (p = 0.08, OR = 0.52, 95% CI: 0.25, 1.08). No significant difference was found between TYMS, MTHFR, ATIC, MTR, and MTRR gene polymorphisms and the RA response or ADRs related to MTX in our study. Conclusion: Our results showed that the MTHFR [677C>T (rs1801133)] TT genotype is associated with ADRs to MTX in Chinese RA patients. Other SNPs, including TYMS 28bp VNTR (rs34743033), MTHFR [677C>T (rs1801133) and 1298A>C (rs1801131)], ATIC 347C>G (rs2372536), MTR A2756G (rs1805087), and MTRR 66A>G (rs1801394) gene polymorphisms, were not associated with MTX treatment outcomes. Further studies are required to validate these findings. | |
30524277 | Real World Experience of Disease Activity in Patients With Rheumatoid Arthritis and Respon | 2018 | The current study investigate the disease activity and effectiveness of treatment in patients with RA on biological disease modifying antirheumatic drugs (bDMARDs) in combination with a conventional synthetic DMARD (csDMARD) and determine whether or not the benefits of different therapies were sustained over a follow up period of 1 year. 124 patients were selected with a mean age 55.26 ± 13, 18SD years, meeting the 1987 ACR and /or ACR/ EULAR (2010) classification criteria for Rheumatoid arthritis (RA). Patients were arranged according to treatment regimens: Tocilizumab (TCL) - 30 patients, Certolizumab (CZP) - 16, Golimumab (GOL) - 22, Etanercept (ETN) 20, Adalimumab (ADA) 20, Rituximab (RTX) - 16. Disease activities was the primary concern. Independent joint assessor evaluated 28 joints on baseline, 6th and 12th month's thereafter. C-reactive protein (CRP) was used to measure the inflammatory process. DAS28-CRP, clinical disease activity index (CDAI) and simplified disease activity index (SDAI) were calculated. On baseline all of the patients' groups had severe disease activity (mean DAS28-CRP > 5.2, mean CDAI > 22, mean SDAI > 26. It was noted that, during the 6th month follow-up period all of the treatment groups significantly decreased DAS28-CRP, CDAI, SDAI and reach moderate disease activity. After 6th and 12th months of treatment all of the groups on bDMARDs had significantly lower disease activity. The GOL group reach remission only according to DAS28-CRP: 2.49 ± 0.76, and low disease activity as measured by CDAI: 6.78 ± 4.51 and SDAI 7.80 ± 5.67. The other 5 groups after 12 months reach the level of low disease activity according to the three activity parameters: DAS28-CRP (TCL 3.07 ± 0.73, CZP 3.06 ± 0.65, ETN 2.85 ± 0.55, ADA 3.15 ± 0.82, RTX 2.90 ± 0.70), CDAI (TCL 9.80 ± 4.91, CZP - 9.33 ± 4.22, ETN 7.97 ± 3.80, ADA 10.00 ± 5.25, RTX 7.48 ± 2.99) and SDAI (TCL 10.45 ± 5.14, CZP 9.94 ± 4.43, ETN 9.03 ± 4.25, ADA 10.50 ± 5.61, RTX 8.08 ± 3.24). The therapy with different bDMARDs added to a csDMARD led to very similar results - a minimal disease activity and a state of remission in the GOL treatment group only as per DAS28-CRP. |