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ID PMID Title PublicationDate abstract
30060740 Combination of NF-kB targeted siRNA and methotrexate in a hybrid nanocarrier towards the e 2018 Jul 30 BACKGROUND: The transcription factor NF-kB plays an important role in the pathogenesis of rheumatoid arthritis (RA). Effective treatment of RA is hindered due to the lack of specificity of small molecules in the inflamed joints. In this study, we aimed to develop a unique hybrid-nanoparticles system comprised of calcium phosphate/liposome to deliver NF-kB-targeted siRNA and methotrexate (MTX) to diseased site. RESULTS: We have successfully demonstrated that the combination of siRNA and MTX in a calcium phosphate/liposome-based hybrid nanocarrier could effectively treat the RA. We have showed that folate receptor-targeted nanocarrier system significantly suppression the arthritis progression in mice model. Substantial accumulation of F-siRML was observed in LPS-activated macrophages. These kind of activated macrophages are generally present in the RA and osteoarthritis and folate-targeted nanoparticle enables the effective accumulation of therapeutics in the diseased site. The combinational nanoparticles effectively blocked the NF-kB signaling pathways and reduced the expression of pro-inflammatory cytokines. Furthermore, siRML and F-siRML did not show any decrease in the lymphocyte count indicating that it can avoid the adverse effect of MTX. CONCLUSION: Therefore, siRML and F-siRML provides unique benefits of excellent therapeutic efficacy with excellent safety profile in the arthritic mice and could be an promising approach in the treatment of rheumatoid arthritis.
29696565 Emerging role of semaphorin-3A in autoimmune diseases. 2018 Jun Autoimmune diseases (ADs) are featured by the body's immune responses being directed against its own tissues, resulting in prolonged inflammation and subsequent tissue damage. Currently, the exact pathogenesis of ADs remains not fully elucidated. Semaphorin-3A (Sema3A), a secreted member of semaphorin family, is a potent immunoregulator during all immune response stages. Sema3A has wide expression, such as in bone, connective tissue, kidney, neurons, and cartilage. Sema3A can downregulate ADs by suppressing the over-activity of both T-cell and B-cell autoimmunity. Moreover, Sema3A shows the ability to enhance T-cell and B-cell regulatory properties that control ADs, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and systemic sclerosis. However, it can also induce ADs when overexpressed. Together, these data strongly suggest that Sema3A plays a pivotal role in ADs, and it may be a promising treatment target for these diseases. In the present review, we focus on the immunological functions of Sema3A and summarize recent studies on the involvement of Sema3A in the pathogenesis of ADs; the discoveries obtained from recent findings may translate into novel therapeutic agent for ADs.
30141517 The Expanded Risk Score in Rheumatoid Arthritis (ERS-RA): performance of a disease-specifi 2018 Aug 13 AIMS OF THE STUDY: To assess the performance of the Expanded Risk Score in Rheumatoid Arthritis (ERS-RA), a disease-specific cardiovascular disease (CVD) prediction score, in evaluating the 10-year risk, in comparison with other traditional algorithms in patients with rheumatoid arthritis (RA). METHODS: Consecutive RA patients, aged 40-75 years, without established CVD, were included. We calculated the disease-specific ERS-RA and four traditional CVD prediction scores: the modified Systematic Coronary Risk Evaluation (mSCORE), the Framingham Risk Score using body mass index (FRS BMI), the calculator developed by the American College of Cardiology / American Heart Association in 2013 (ACC/AHA 2013) and the QRISK3. Subjects also underwent ultrasound assessment of the carotid arteries. The presence of a carotid intima-media thickness (CIMT) >0.90 mm or of carotid plaques identified the high-risk patients. RESULTS: Of the 84 patients evaluated, 33 (39.3%), 16 (19.0%), 24 (28.6%), 25 (29.8%) and 33 (39.3%) subjects were defined as having high CVD risk according to ACC/AHA 2013, mSCORE, FRS BMI, QRISK3 and ERS-RA, respectively. Compared with the ultrasound results, all the areas under the receiver operating characteristic curves (AUC-ROC) showed good discrimination properties (0.848 - FRS BMI, 0.816 - mSCORE, 0.828 - ACC/AHA 2013, 0.844 - QRISK3, 0.869 - ESR-RA). Comparison of the AUC-ROCs did not show that discriminative ability for detecting subclinical atherosclerotic damage was improved with ESR-RA. CONCLUSIONS: Using a surrogate marker of subclinical atherosclerotic organ damage as indicator of CVD burden, the newly ERS-RA risk score that incorporates specific aspects of RA performs as well as ACC/AHA 2013, mSCORE, FRS BMI and QRISK3 estimators.
29954675 IL-17A - A regulator in acute inflammation: Insights from in vitro, in vivo and in silico 2021 Mar Acute inflammation following sterile injury is both inevitable and necessary to restore homeostasis and promote tissue repair. However, when excessive, inflammation can jeopardize the viability of organs and cause detrimental systemic effects. Identifying key-regulators of the immune cascade induced by surgery is vital to attenuating excessive inflammation and its subsequent effects. In this review, we describe the emerging role of IL-17A as a key-regulator in acute inflammation. The role of IL-17A in chronic disease states, such as rheumatoid arthritis, psoriasis and cancer has been well documented, but its significance in acute inflammation following surgery, sepsis, or traumatic injury has not been well studied. We aim to highlight the role of IL-17A in acute inflammation caused by trauma, liver ischemia, and organ transplantation, as well as in post-operative surgical infections. Further investigation of the roles of this cytokine in acute inflammation may stimulate novel therapies or diagnostic modalities.
30530827 Genetics of rheumatoid arthritis: 2018 status. 2019 Apr Study of the genetics of rheumatoid arthritis (RA) began about four decades ago with the discovery of HLA-DRB1 Since the beginning of this century, a number of non-HLA risk loci have been identified through genome-wide association studies (GWAS). We now know that over 100 loci are associated with RA risk. Because genetic information implies a clear causal relationship to the disease, research into the pathogenesis of RA should be promoted. However, only 20% of GWAS loci contain coding variants, with the remaining variants occurring in non-coding regions, and therefore, the majority of causal genes and causal variants remain to be identified. The use of epigenetic studies, high-resolution mapping of open chromatin, chromosomal conformation technologies and other approaches could identify many of the missing links between genetic risk variants and causal genetic components, thus expanding our understanding of RA genetics.
30472493 The CD25+/CD4+ T cell ratio and levels of CII, CIX and CXI antibodies in serum may serve a 2019 Mar OBJECTIVE: Collagen antibodies in serum are involved in the pathogenesis of Rheumatoid Arthritis (RA). The objective of this study was to identify the subtype of collagen antibodies and T cell subtype distribution in pristane-induced arthritis (PIA) and to clarify their roles in the initiation and maintenance of arthritis. METHODS: Arthritis was induced in Dark Agouti (DA) rats by injection of pristane. The severity was evaluated by macroscopic and microscopic score systems. The alteration of CD25+/CD4+ T cell ratio in rats was detected by flow cytometry. Collagen type II (CII), CIX, or CXI antibody in serum was determined by ELISA. The levels of Nitric oxide (NO) and tartrate-resistant acid phosphatase (TRAP) were measured by kits. RESULTS: The serum levels of CII, CIX, CXI antibodies were significantly increased in RA patients while slightly increased in PIA rats. The ratio of CD25+/CD4+ T cells was significantly higher in RA rats than that in the control group. The serum levels of NO and TRAP in PIA rats and RA patients were higher than that in the control groups, which suggested that the activity of osteoclast was increased in RA. CONCLUSION: The ratio of CD25+/CD4+ T cells plays a pivotal role in the development of PIA. The serum levels of NO and TRAP are inflammatory and osteoclast activity indicators. The serum levels of CII, CIX and CXI antibodies may serve as the clinical diagnostic indicators. These findings are important to our understanding of the pathogenesis of RA, and may provide biomarkers of RA diagnosis and therapeutic targets for the treatment of RA.
28598775 Rheumatologists' guideline adherence in rheumatoid arthritis: a randomised controlled stud 2018 Jan OBJECTIVES: To assess the effects of education, feedback and a computerised decision support system (CDSS) versus education and feedback alone on rheumatologists' rheumatoid arthritis (RA) guideline adherence. METHODS: A single-centre, randomised controlled pilot study was performed among clinicians (rheumatologists, residents and physician assistants; n=20) working at the study centre, with a 1:1 randomisation of included clinicians. A standardized sum score (SSS) on guideline adherence was used as the primary outcome (patient level). The SSS was calculated from 13 dichotomous indicators on quality of RA monitoring, treatment and follow-up. The randomised controlled design was combined with a before-after design in the control group to assess the effect education and feedback alone. RESULTS: Twenty clinicians (mean age 44.3±10.9 years; 55% female) and 990 patients (mean age 62 ± 13 years; 69% female; 72% rheumatoid factor and/or anti-CCP positive) were included. Addition of CDSS to education and feedback did not result in significant better quality of RA care than education and feedback alone (SSS difference 0.02; 95%-CI -0.04 to 0.08; p=0.60). However, before/after comparison showed that education and feedback alone resulted in a significant increase in the SSS from 0.58 to 0.64 (difference 0.06; 95%-CI 0.02 to 0.11; p<0.01). CONCLUSIONS: Our results suggest that CDSS did not have added value with regard to guideline adherence, whereas education and feedback can lead to a small but significant improvement of guideline adherence.
29768427 Differential effects of TNF-α and IL-1β on the control of metal metabolism and cadmium-i 2018 OBJECTIVE: Interleukin-1-beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) are both monocyte-derived cytokines. Both cytokines have been previously described to exert a role in rheumatoid arthritis (RA) pathogenesis synergizing with other pro-inflammatory mediators, such as interleukin-17 (IL-17) on target cells, for the perpetuation of the inflammatory response (e.g. IL-6 production). In the context of experimental RA, Cd addition has an anti-proliferative and anti-inflammatory effect when associated to IL-17/TNF-α stimulation, due to its accumulation in synoviocytes. The aim of this work was to evaluate if IL-1β interaction with IL-17 also contributes to metal-import mechanisms and its effects on cell viability and inflammation. METHODS: IL-17 and IL-1β were added to synoviocyte cultures with or without exogenous Cd addition (0.1 ppm, 0.89 μM). IL-6 production, Cd import kinetics, gene expression of ZIP-8 importer and metallothioneins (MTs) and cell viability were evaluated by ELISA, inductively-coupled mass spectrometry (ICP-MS), q-RT-PCR and viability assays (neutral red and annexin V) respectively. RESULTS: IL-17 and IL-1β acted in synergy on synoviocytes to induce IL-6 production similarly to the IL-17/TNF-α combination. Metal import was lower with IL17/ IL-1β in comparison to IL-17/TNF-α exposed-synoviocytes, as the expression of ZIP-8 and MT-1F was less induced. Monocyte and PBMCs exposure to Cd resulted in a reduced production of IL-1β and an increased production of TNF-α and this result was confirmed in co-cultures of synoviocytes and PBMCs. The IL-17/IL-1β combination with Cd slightly reduced cell viability in comparison to the IL-17/TNF-α combination and resulted in a strong induction of IL-6 production. CONCLUSION: IL-17/TNF-α combination but not IL-17/IL-1β combination mainly drives the accumulation of Cd in synoviocytes and its effects on cell viability and inflammation.
29882689 Mid-term clinical outcome of constrained condylar knee prosthesis for patients with rheuma 2019 Jul Objectives: This study retrospectively investigated the mid-term outcome of Legacy constrained condylar knee (LCCK) prosthesis in patients with rheumatoid arthritis (RA) having severe varus/valgus deformity, instability, and/or bone loss. Methods: Between January 2000 and December 2015, LCCK prostheses had been performed in 32 knees of 25 patients with RA, and 23 knees of 17 patients of the postoperative follow-up minimum 2 years were analyzed in this study (Primary: 14 knees, Revision: 9 knees). The average of follow-up duration was 6.9 ± 2.7 years, all were female, and the average of age and RA duration at the surgery was 59.0 ± 9.5 years and 26.6 ± 13.5 years, respectively. Clinical result was analyzed by Knee Society Score (KSS) knee and function at preoperative time and final visit. Imaging outcome was investigated by femoral tibial angle (FTA), four component alignment angles, and radiolucent line at pre-/postoperative time. Results: KSS knee/function scores and radiographic FTAs were improved after operation. Radiolucent lines around components were seen in 17 knees (73.9%), of which only one knee (4.3%) has shown aseptic loosening. The seven-year Kaplan-Meier survivorship analysis resulted in 91.7%. Conclusion: LCCK prosthesis in RA patients was achieved to the excellent mid-term clinical and radiographic result.
29465348 Increased circulating CD14brightCD16+ intermediate monocytes are regulated by TNF-α and I 2018 Jul OBJECTIVES: Although circulating CD14brightCD16+ monocyte subsets are increased in inflammatory disease, the pathogenesis of the increase in the inflammatory condition of the cells is still unclear and the relationship to cytokines is unknown particularly in rheumatoid arthritis (RA). The purpose of this study was to investigate the influence anti-cytokine treatment has on CD14brightCD16+ monocytes in patients with RA. METHODS: Thirty-two RA patients and 14 healthy volunteers (HV) were enrolled in this study. All the patients had never been treated with methotrexate (MTX) or biological agents. Peripheral blood samples and clinical information of the patients were obtained at the time of 0, 12 and 24 weeks of treatment. Peripheral blood samples were also obtained from the HV. The expression levels of CD14 and CD16 on monocytes were measured by flow cytometry (FCM). RESULTS: Eight patients received anti-interleukin (IL)-6 receptor antibody, tocilizumab (TCZ) treatment alone, 12 patients received anti-tumour necrosis factor (TNF)-α antibody, adalimumab (ADA) with MTX treatment and the others received only MTX treatment. FCM analysis revealed that the proportion of CD14brightCD16+ monocytes significantly increased in patients at baseline compared with HV. The proportion of CD14brightCD16+ monocytes significantly decreased after TCZ, and ADA with MTX treatment. The proportion of intermediate monocytes was significantly and positively correlated with disease activity and it improved in accordance with the proportion of CD14brightCD16+ monocytes after inhibition of signal transduction of inflammatory cytokines. CONCLUSIONS: We showed that the population of CD14brightCD16+ monocytes significantly decreased with the change of disease activity by key cytokines, IL-6 or TNF-α signal blockade in RA. This result indicates that the proportion of those monocytes is important for reflecting disease activity in RA.
29452839 Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(M 2018 May 1 A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib's core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo test through oral administration. Compound 6 showed improved selectivity for JAK1 compared to that of tofacitinib (IC(50) 11, 2.4 × 10(2), 2.8 × 10(3), and 1.1 × 10(2) nM for JAK1, JAK2, JAK3, and TYK2, respectively). In CIA and AIA model tests, compound 6 exhibited similar efficacy to tofacitinib citrate.
30332708 [Predictors of Ambulatory Medical Care Utilization by the Elderly with Osteoarthritis, Rhe 2019 Nov BACKGROUND: Since chronic musculoskeletal disorders (MD) cause considerable costs for the German health care system, service providers and policy makers need information on the use of the different health care services. On the basis of Andersen's behavioral model, the article provides predictors of ambulatory medical care utilization in the fields of general medicine, orthopaedics and physiotherapy relevant to chronic MD in the 65- to 79-year-old population affected by arthritis, rheumatoid arthritis or osteoporosis in Germany. METHODS: Based on data of the first wave of the German Health Interview and Examination Survey for Adults (DEGS1) relationships between ambulatory medical care utilization and explanatory variables were analysed using models for count data. RESULTS: An increased use of general medicine is associated with individual disease factors (considerable health restriction: incidence rate ratio (IRR) 1.64 (1.18-2.27); joint pain: IRR 1.38 (1.06-1.79)). An increased use of orthopaedics is associated with an increased use of general medicine (IRR 1.05 (1.01-1.10)) and an increased use of physiotherapy is determined by structural as well as individual factors (eastern Germany (including Berlin): IRR 0.66 (0.47-0.93); considerable health restriction: IRR 1.84 (1.09-3.12); increased use of orthopaedics: IRR 1.07 (1.01-1.14). CONCLUSION: As expected, individual disease factors play an important part in explaining the use of health care services. Concurrently, the absence of comorbidity reveals a previously unidentified predictor of a decreased use of general medicine by those with chronic MD.
29853534 Decreased MiR-128-3p alleviates the progression of rheumatoid arthritis by up-regulating t 2018 Aug 31 Background: Rheumatoid arthritis (RA) is a inflammatory disease that characterized with the destruction of synovial joint, which could induce disability. Inflammatory response mediated the RA. It has been reported that MiR-128-3p is significantly increased in RA, while the potential role was still unclear.Methods: T cells in peripheral blood mononuclear cell (PBMC) were isolated from the peripheral blood from people of RA and normal person were used. Real-time PCR was performed to detect the expression of MiR-128-3p, while the protein expression of tumor necrosis factor-α-induced protein 3 (TNFAIP3) was determined using Western blot. The levels of IL-6 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA). The expression of CD69 and CD25 was detected using flow cytometry. The RA mouse model was constructed for verification of the role of MiR-128-3p.Results: The expression of MiR-128-3p was significantly increased, while TNFAIP3 was decreased, the levels of IL-6 and IL-17 were also increased in the T cells of RA patients. Down-regulated MiR-128-3p significantly suppressed the expression of p-IkBα and CD69, and CD25in T cells. MiR-128-3p targets TNFAIP3 to regulate its expression. MiR-128-3p knockdown significantly suppressed the activity of nuclear factor κB (NF-κB) and T cells by up-regulating TNFAIP3, while cells co-transfected with si-TNFAIP3 abolished the effects of MiR-128-3p knockdown. The in vivo experiments verified the potential role of MiR-128-3p on RA.Conclusion: Down-regulated MiR-128-3p significantly suppressed the inflammation response of RA through suppressing the activity of NF-κB pathway, which was mediated by TNFAIP3.
30132352 Combined treatment with omalizumab and etanercept in a patient with chronic spontaneous ur 2019 Jun We present a case report of a 64-year old female patient with rheumatoid arthritis and chronic spontaneous urticaria. She was treated with a combination of etanercept and omalizumab with good results and no adverse effects. In selected patients with severe inflammatory disease activity it is worth considering combined biologic therapy. However, treatment should be closely monitored as short-term and long-term side effects are not properly elucidated.
29522194 Neutralization of CD40 ligand costimulation promotes bone formation and accretion of verte 2018 Jun 1 OBJECTIVE: Immunosuppressive biologics are used in the management of RA and additional immunomodulators are under investigation including modulators of the CD40/CD40 ligand (CD40L) costimulation pathway. Tampering with immune function can have unanticipated skeletal consequences due to disruption of the immuno-skeletal interface, a nexus of shared cells and cytokine effectors serving discrete functions in both immune and skeletal systems. In this study, we examined the effect of MR1, a CD40L neutralizing antibody, on physiological bone remodelling in healthy mice. METHODS: Female C57BL6 mice were treated with MR1 and BMD was quantified by dual energy X-ray absorptiometry and indices of trabecular bone structure were quantified by micro-CT. Serum biochemical markers were used to evaluate bone turnover and formation indices by histomorphometry. RESULTS: Unexpectedly, MR1 stimulated significant accretion of BMD and trabecular bone mass in the spine, but not in long bones. Surprisingly, bone accretion was accompanied by a significant increase in bone formation, rather than suppression of bone resorption. Mechanistically, MR1-induced bone accrual was associated with increased Treg development and elevated production of cytotoxic T lymphocyte antigen 4, a costimulation inhibitor that promotes T cell anergy and CD8+ T cell expression of the bone anabolic ligand Wnt-10b. CONCLUSION: Our studies reveal an unexpected bone anabolic activity of pharmacological CD40L suppression. Therapeutic targeting of the CD40L pathway may indeed have unforeseen consequences for the skeleton, but may also constitute a novel strategy to promote bone formation to ameliorate osteoporotic bone loss and reduce fracture risk in the axial skeleton.
30020997 Healthcare resource utilization and costs among patients with rheumatoid arthritis on biol 2018 OBJECTIVES: This nationwide population-based study aimed at evaluating healthcare resource utilization and direct medical costs among rheumatoid arthritis (RA) patients receiving biologic therapies in Taiwan. DESIGN AND SETTING: A retrospective cohort of 2,425 RA patients who had received first-line tumor necrosis factor (TNF)-α antagonist treatment for at least 6 months (the baseline period) between 2007 and 2011 was identified from the National Health Insurance Research Database in Taiwan. OUTCOME MEASURES: Healthcare resource utilization and direct medical costs of those patients were analyzed and compared 1 year before the index date and during the 1-year follow-up. RESULTS: Analytical results demonstrated that 87.7% of RA patients received the same TNF-α antagonist during the 1-year follow-up, 2.4% of the patients switched to another TNF-α antagonist after the baseline period, 7.1% of the study cohort received a second-line biologic agent, while the remaining patients discontinued use of any TNF-α antagonist. Compared to 1 year before the index date, there were significant reductions in emergency room visits and hospitalization days for RA patients treated with the same TNF-α antagonist during the 1-year follow-up. However, there was an increase of outpatient visits among those patients. For those RA patients who switched to another TNF-α antagonist or received a second-line biologic agent, they consumed more healthcare resources. Furthermore, the corresponding medication costs went up markedly during the 1-year follow-up, but nearly all total direct medical costs (biologics excluded) were significantly reduced across the study cohort. Lastly, male patients incurred slightly higher medical costs than their counterparts, albeit in a statistically insignificant fashion. CONCLUSIONS: This investigation revealed that RA patients treated with biologics utilized fewer emergency room visits and shorter hospitalization days, but incurred higher costs. In summary, this study provides meaningful information on healthcare resource utilization and medical costs of RA patients for healthcare providers and policymakers.
30406861 JAK Inhibitors in Rheumatology: Implications for Paediatric Syndromes? 2018 Nov 8 PURPOSE OF REVIEW: Given the recent increase in the profile and use of Janus kinase inhibitors (JAKinibs) in adult patients with rheumatic diseases, we aimed to review the current evidence accruing for use in paediatric rheumatology patients. RECENT FINDINGS: Significant advances have been made in the management of rheumatic diseases in the past two decades. The introduction of biologic agents in both adults and children has provided significant improvements to patient outcomes and led to better quality of life. Moreover, responses to similar agents allude to common effector pathways operating across juvenile and adult synovitis especially. However, inefficacy and intolerance of these agents leads to a subset of children with limited treatment options. Since 2012, Janus kinase (JAK) inhibitors (JAKinibs), a novel group of oral small molecule inhibitors, have demonstrated their efficacy in several forms of adult inflammatory arthritis, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). There are hopes that these successes will be transferable to the paediatric population. In the following review, we discuss the development and progress of JAKinibs in this regard.
30132861 Exosome-encapsulated miR-6089 regulates inflammatory response via targeting TLR4. 2019 Feb Exosome-encapsulated microRNAs (miRNAs) have been identified as potential biomarkers in autoimmune diseases. However, little is known about the role of exosome-delivered miRNAs in rheumatoid arthritis (RA). In this study, we investigated the profile of specific exosomal miRNAs by microarray analysis of serum exosomes from three patients with RA and three healthy controls. Quantitative real-time PCR (qRT-PCR) was performed to validate the aberrantly expressed exosomal miRNAs. A total of 20 exosome-encapsulated miRNAs were identified to be differently expressed in the serum of patients with RA compared with controls. Interestingly, we found that exosome-encapsulated miR-6089 was significantly decreased after validation by qRT-PCR in serum exosomes from 76 patients with RA and 20 controls. Besides, miR-6089 could inhibit lipopolysaccharide (LPS)-induced cell proliferation and activation of macrophage-like THP-1 cells. TLR4 was a direct target for miR-6089. MiR-6089 regulated the generation of IL-6, IL-29, and TNF-α by targetedly controlling TLR4 signaling. In conclusion, exosome-encapsulated miR-6089 regulates LPS/TLR4-mediated inflammatory response, which may serve as a novel, promising biomarker in RA.
29717774 Physcion 8‑O‑β‑glucopyranoside extracted from Polygonum cuspidatum exhibits anti†2018 Aug The present study aimed to investigate the anti‑arthritic effect of physcion 8‑O‑β‑glucopyranoside (POGD) and its possible mechanisms. The anti‑proliferative effects of POGD on MH7A cells were detected using a CCK‑8 assay, and the release of pro‑inflammatory cytokines, interleukin (IL)‑1β, IL‑6, IL‑8, IL‑12 and IL‑17A, were determined by ELISA. A type II collagen‑induced arthritis (CIA) rat model was established to evaluate the anti‑arthritic effect of POGD in vivo. The paw volumes, arthritis indices and serum levels of tumor necrosis factor (TNF)‑α, IL‑1β, IL‑6, IL‑8, IL‑17A were determined by ELISA. The mRNA expression levels of matrix metalloproteinase (MMP)‑2, MMP‑3, MMP‑9, vascular endothelial growth factor and cyclooxygenase‑2 were determined by reverse transcription‑quantitative polymerase chain reaction analysis, and the expression levels of transforming growth factor (TGF)‑β1, small mothers against decapentaplegic (Smad)4, Smad7, c‑Jun N‑terminal kinase (JNK), phosphorylated (p‑)JNK, p‑P38, P38, p‑extracellular signal‑regulated kinase (ERK)1/2, ERK1/2, nuclear factor (NF)‑κB p65 in the nucleus (N), cytosolic NF‑κB p65 (C), and inhibitor of NF‑κB (IκB) were determined by western blot analysis. The results indicated that POGD significantly inhibited MH7A cell growth. POGD markedly inhibited paw swelling and the arthritis indices of the CIA rats, and POGD may also inhibit the release of pro‑inflammatory cytokines. Furthermore, POGD downregulated the expression levels of TGF‑β1, Smad4, NF‑κB p65 (N), p38, p‑p38, p‑ERK1/2, JNK, p‑JNK, TGF‑β1, Smad4, p‑JNK, JNK, p‑P38, P38, p‑ERK1/2, ERK1/2 and NF‑κB p65 (N), and upregulated the Smad7, NF‑κB p65 (C) and IκB in TNF‑α induced MH7A cells. In conclusion, the results suggested that POGD is a promising potential anti‑inflammatory drug, and that POGD may decrease the expression of pro‑inflammatory cytokines and mediators via inhibiting the TGF‑β/NF‑κB/mitogen‑activated protein kinase pathways.
29614335 Comparison of efficacy of TNF inhibitors and abatacept in patients with rheumatoid arthrit 2018 Jun The aim of this study was to compare the clinical outcome of patients with rheumatoid arthritis seen in routine clinical practice treated with either TNF inhibitors or abatacept. To overcome potential bias, both propensity score matching and Inverse Probability of Treatment Weighting were used for patient selection. The propensity score matching procedure selected 315 matched pairs of patients who were treated with TNF inhibitors or abatacept. At week 52, SDAI in TNF inhibitors was lower than abatacept. In contrast, analysis of biologics-naive patients using the propensity-score matching (n = 150; in each group) showed comparable clinical efficacy. Consistent results were obtained by the use of Inverse Probability of Treatment Weighting (581 patients treated with TNF inhibitors and 353 patients treated with abatacept). The predictors of response to each treatment were different; abatacept appeared to benefit patients with high baseline RF titers while TNF inhibitors appeared to benefit patients with low baseline HAQ-DI.