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ID PMID Title PublicationDate abstract
31894846 MicroRNA-101-3p inhibits fibroblast-like synoviocyte proliferation and inflammation in rhe 2020 Jan 31 OBJECTIVE: Rheumatoid arthritis (RA) is the most frequently occurring inflammatory arthritis. The present study was performed to characterize the role of microRNA-101-3p (miR-101-3p) and prostaglandin-endoperoxide synthase 2 (PTGS2) in inflammation and biological activities of fibroblast-like synoviocytes (FLSs) in RA. METHODS: Initially, miR-101-3p and PTGS2 expression in RA tissues of RA patients and RA rats was detected by qRT-PCR and Western blot analysis. Rat model of type II collagen-induced arthritis (CIA) was adopted to simulate RA, followed by injection of miR-101-3p mimics or siRNA against PTGS2. Next, the apoptosis in synovial tissue and the levels of tumor necrosis factor (TNF)-α, IL-1β and IL-6 were identified. Subsequently, FLSs in RA (RA-FLSs) were isolated, after which in vitro experiments were conducted to analyze cell proliferation, apoptosis, migration and invasion upon treatment of up-regulated miR-101-3p and silenced PTGS2. Furthermore, the relationship of miR-101-3p and PTGS2 was determined by bioinformatics prediction and luciferase activity assay. RESULTS: We identified poorly expressed miR-101-3p and highly expressed PTGS2 in synovial tissues of RA patients and RA rats, which showed reduced synoviocyte apoptosis and enhanced inflammation. In response to miR-101-3p mimics and si-PTGS2, the RA-FLSs were observed with attenuated cell proliferation, migration and invasion, corresponding to promoted apoptosis. Down-regulation of PTGS2 could rescue the effect of inhibited miR-101-3p in synovial injury and phenotypic changes of FLS in RA rats. Notably, miR-101-3p was found to negatively regulate PTGS2. CONCLUSION: Taken together, miR-101-3p reduces the joint swelling and arthritis index in RA rats by down-regulating PTGS2, as evidenced by inhibited FLS proliferation and inflammation.
31783137 Zishen Tongluo formula ameliorates collagen-induced arthritis in mice by modulation of Th1 2020 Mar 25 ETHNOPHARMACOLOGICAL RELEVANCE: Zishen Tongluo formula (ZTF) is simplified from the Qingluo Tongbi formula, which has been applied to treat rheumatoid arthritis (RA) in clinical practices for several decades. Our previous studies have verified the effects of ZTF on arthritis animal models. However, its mechanism of treating RA is not clear. AIM OF THE STUDY: The present study was designed to investigate the effects of ZTF on the Th17/Treg balance in RA mice and the role of the different herb groups with the effect of Zishen yangyin (YY), Huatan quyu (HT), or Qufeng chushi (QF) in ZTF. MATERIALS AND METHODS: A mouse model of collagen-induced arthritis (CIA) was established. The animals were randomly divided into the normal, model, positive drug, YY, QF, HT, and the whole compound (ZTF) groups. After oral administration for one-month, cytokine levels in the plasma and histopathological changes of the joint were measured by ELISA and hematoxylin-eosin staining, respectively. Meanwhile, the balance of Th17/Treg cells in blood, spleen or lymph nodes was detected using flow cytometry and qPCR. RESULTS: ZTF or the different functional groups could improve the joint inflammation, decrease the levels of proinflammatory cytokines, restore the balance of Th17 and Treg cells in CIA mice. However, there were some differences in each functional group: YY mainly promoted the responses of Treg cells while QF inhibited the functions of Th17 cells. Besides, HT regulated both Th17 and Treg cells to keep the immune balance. CONCLUSIONS: ZTF could notably ameliorate CIA mice by restoring the balance of Th17/Treg cells. Each functional group could target Th17 and/or Treg cells to produce synergistic/enhancement effects, and ZTF had a better holistic effect in RA treatment.
32398023 Type 1 interferonopathy presenting as juvenile idiopathic arthritis with interstitial lung 2020 May 12 BACKGROUND: STING-associated vasculopathy with onset in infancy (SAVI) is a type 1 interferonopathy manifesting as a pulmonary and vascular syndrome resulting from gain-of-function mutations in TMEM173, the gene encoding STING. Familial reports in the literature are sparse. CASE PRESENTATION: We report a case series of SAVI in a three generation kindred, with a phenotype of interstitial lung disease (ILD) and rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA). Current and historical medical records were reviewed for clinical and laboratory information. Whole blood from cases 1 and 2, plus stored appendicectomy tissue from case 3, underwent DNA sequencing of the TMEM173 gene. Peripheral blood RNA was obtained from cases 1 and 2 for functional assessment of the TMEM173 mutation. DNA sequencing identified the same heterozygous TMEM173 mutation (c.463G > A; p.Val155Met) in all three cases, consistent with a diagnosis of the autosomal dominant condition SAVI. Functional assessment of this mutation identified a prominent interferon signature which was confirmed on repeat testing. CONCLUSIONS: SAVI presented in this family as ILD with early onset juvenile rheumatoid arthritis. This condition should be considered in all rheumatoid arthritis patients with early-onset ILD and in all JIA patients with ILD.
32724691 Joint-Preserving Surgery for Hyperextension Deformity of the Hallux Interphalangeal Joint 2020 Interphalangeal hyperextension is one of the major hallux deformities in patients with rheumatoid arthritis; however, there is yet no established surgical method for this deformity. We here present the case of a 69-year-old female patient with rheumatoid arthritis who developed hallux interphalangeal hyperextension and painful callosity on the plantar hallux accompanied by limited dorsiflexion at the metatarsophalangeal joint. Lateral weight-bearing radiograph of the foot revealed misalignment of the medial column and hallux, including a collapsed medial arch, elevated first metatarsal, plantar flexion and deviation of the proximal phalanx, and hyperextension of the distal phalanx. The foot was successfully treated and became symptom-free with opening wedge osteotomy of the medial cuneiform, plantar and proximal translation of the metatarsal head, and tenotomy of the extensor hallucis longus. This case suggests that reconstruction of the sagittal alignment of the medial column and hallux through a combination of osteotomy and soft tissue intervention could be an optional treatment for interphalangeal hyperextension.
33268706 JTE-952 Suppresses Bone Destruction in Collagen-Induced Arthritis in Mice by Inhibiting Co 2020 Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and structural destruction of the joints. Bone damage occurs in an early stage after onset and osteoclast activation plays a substantial role in its progression. Colony stimulating factor 1 receptor (CSF1R) is a receptor protein tyrosine kinase specifically expressed in monocytic-lineage cells such as macrophages and osteoclasts. Here, we investigated the effect of JTE-952, a novel CSF1R tyrosine kinase inhibitor, on osteoclast formation in vitro and on bone destruction in a mouse model of collagen-induced arthritis. JTE-952 completely inhibited osteoclast differentiation from human monocytes, with an IC(50) of 2.8 nmol/L, and reduced osteoclast formation from the synovial cells of RA patients. Detectable levels of colony stimulating factor 1 (CSF1), a ligand of CSF1R, were observed in the synovial tissues of the arthritis model, similar to those observed in the pathology of human RA. JTE-952 significantly suppressed increases in the bone destruction score, the number of tartrate-resistant-acid-phosphatase-positive cells, and the severity of arthritis in the model mice. We also examined the efficacy of JTE-952 combined with methotrexate. This combination therapy more effectively reduced the severity of bone destruction and arthritis than monotherapy with either agent alone. In summary, JTE-952 potently inhibited human osteoclast formation in vitro and suppressed bone destruction in an experimental arthritis model, especially when combined with methotrexate. These results indicate that JTE-952 should strongly inhibit bone destruction and joint inflammation in RA patients and effectively prevent the progression of the structural destruction of joints.
32373270 Rheumatoid Meningitis: Clinical Characteristics, Diagnostic Evaluation, and Treatment. 2020 Apr BACKGROUND AND PURPOSE: Due to the potential for high mortality and neurologic complications of rheumatoid meningitis (RM), awaiting biopsy confirmation may delay vital treatment intervention. Our aim was to describe the clinical presentations of RM in our population and determine whether meningeal biopsy impacted diagnosis, treatment, and outcomes. METHODS: A retrospective chart review was completed for patients at Mayo Clinic with a diagnosis of RM within the last 28 years. Those with identified alternative inflammatory, infectious, or neoplastic causes of pachymeningitis or leptomeningitis were excluded. RESULTS: Fourteen patients meeting inclusion/exclusion criteria were identified. All patients were positive for rheumatoid factor or cyclic citrullinated peptide. All patients had magnetic resonance imaging abnormalities characterized by pachymeningeal and/or leptomeningeal enhancement. Of the 10 patients who underwent biopsy, nonspecific findings were seen in 74%. All patients except one were treated with corticosteroids with subsequent symptomatic improvement. Radiographic improvement or resolution was seen in 10 (83%) of 12. Patients improved with corticosteroid treatment, including those who were diagnosed with RM on clinical basis without undergoing a biopsy as well. CONCLUSIONS: This retrospective review displays the myriad of clinical presentations of RM. It also suggests that with appropriate exclusion of infectious, neoplastic, and other autoimmune etiologies, biopsy may not be necessary to initiate treatment.
32005417 Toward better outcomes in Sjögren's syndrome: The promise of a stratified medicine approa 2020 Feb Sjögren's syndrome is a systemic autoimmune disease defined by its targeted inflammation of the salivary and lacrimal glands, resulting in dry mouth and eyes in the majority and persistent or recurrent salivary gland enlargement in a minority of those affected. Involvement of major organs, an increased risk of lymphoma, and autoantibodies against ubiquitous cellular ribonucleoproteins define some of its systemic features. Those affected have a high symptom burden and the development of disease-modifying therapies is thus an urgent need. A stratified medicine approach offers promise as a means of targeting specific therapies to patients for whom the mechanism of action is most relevant. Implementation of this approach will require an understanding of the pathophysiological processes underlying different patient subsets, and then identifying or developing a drug that targets this pathway. Such therapies would be most effective if implemented early in the disease course before the advent of adverse outcomes or glandular damage. This review will provide a disease overview followed by an analysis of the feasibility of a stratified medicine approach, focusing on the disease heterogeneity, predictors of disease progression and adverse outcomes, and recent advances in the development of relevant outcome measures and new therapies.
33376617 Rheumatoid Arthritis and Autoimmune Hemolytic Anemia as First Manifestation of Rhupus. 2020 "Rhupus" syndrome is a rare condition that describes the coexistence of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which prevalence among patients with SLE varies from 0.01% to 9.7%. There are few reported cases of the association between autoimmune hemolytic anemia and rheumatoid arthritis with systemic lupus erythematosus (rhupus). We report a rare case of rhupus in a 29-year-old woman, associated with autoimmune hemolytic anemia.
32775622 Low-dose Methotrexate Toxicity in the Setting of Vancomycin-induced Acute Kidney Injury. 2020 Methotrexate is a disease-modifying anti rheumatic drug (DMARD) that is often used in low dosages as the first line drug for rheumatoid arthritis patients. The chemotherapeutic agent works by inhibiting dihydrofolate reductase, and the primary route of clearance of the drug is via the kidneys. Kidney injury may delay this clearance and lead to toxic level accumulation of the drug- toxicity presenting as diarrhea, vomiting, mucositis, rash, transaminitis and myelosuppression. Antibiotics such as vancomycin may induce acute kidney injury (AKI) through various mechanisms include damage to the renal tubular epithelial cells. In this report, we describe a case in which an elderly female suffered AKI secondary to vancomycin induced nephrotoxicity. The AKI subsequently led to methotrexate accumulation and toxicity presenting as bleeding mouth ulcers, transaminitis and pancytopenia. The condition was managed with leucovorin rescue therapy and sodium bicarbonate to enhance methotrexate excretion. Renally dosing methotrexate in patients on other nephrotoxic drugs, and monitoring creatinine clearance are methods for preventing such a toxicity.
32185565 Clinical Immunogenicity Risk Assessment Strategy for a Low Risk Monoclonal Antibody. 2020 Mar 17 This article provides a theoretical case-study risk assessment report for a low-risk monoclonal antibody (mAb) therapeutic. In terms of risk, there are considerations around risks to safety, but also risks regarding effects on pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Much of the discussion in this document is around the risk of immunogenicity incidence. A higher incidence of immunogenicity would necessitate a detailed review of the PK, efficacy and safety in anti-drug antibody (ADA) positive and ADA negative subjects, in order to evaluate potential effects. The publication is intended to provide a framework of some the current thought processes around assessing immunogenicity risk and for building strategies to mitigate those risks. For this example, we have created a hypothetical antibody, ABC-123, targeting a membrane protein on antigen presenting cells, for the treatment of rheumatoid arthritis (RA). This hypothetical antibody therapeutic is provided as an example for the purposes of risk assessment for a low risk molecule, although any application of similar approach would be case by case.
33138147 Development of Monitoring System for Assessing Rheumatoid Arthritis within 5 Minutes Using 2020 Oct 29 Rheumatoid arthritis (RA) disease activity fluctuates over time. The disease activity score 28 (DAS28(ESR)) is a widely used and validated scoring system for assessing RA activity; however, it requires time and expertise. This study aimed to develop a new molecular assay capable of rapidly and objectively assessing RA activity. We used a rapid immuno-assay system (FRENDâ„¢) to measure soluble CD14 (sCD14) levels, which reflect the DAS28(ESR). SCD14 concentrations in urine and serum of RA patients were measured, and RA activity and responses to anti-rheumatic drugs were examined at baseline and after 6 months. FRENDâ„¢ quantified sCD14 levels in a drop of serum and urine accurately and within 5 min. Serum sCD14 concentrations and its changes correlated well with disease activity and treatment responses, and the results were comparable to C-reactive protein. The new composite indices, including the DAS28(CD14) and simplified DAS(CD14), better detected RA activity than a single sCD14 value and correlated strongly with the DAS28(ESR). These indices exhibited excellent diagnostic performance for discriminating a good response 6 months after treatment. We developed a new system for assessing RA activity and therapeutic outcome within 5 min. CD14-based composite indices may have utility for accurate and frequent monitoring of RA status.
32427126 Improved anti-arthritic activity of ginger extract, a traditional medicine, using novel dr 2020 May 19 BACKGROUND: Ginger and castor oil, both are used in traditional medicine to treat arthritis, the latter is also commonly used as a vehicle in these systems of medicine. The study was designed to prepare a nanostructured lipid carrier (NLC) of ginger extract using castor oil as a novel liquid lipid and evaluate its safety and efficacy in rheumatoid arthritis in experimental animals. METHODS: Ginger extract was standardized using High performance liquid chromatography (HPLC). The optimized NLC formulation was characterized and its therapeutic efficacy was evaluated in Chronic Freund's adjuvant (CFA) induced arthritis in experimental animals. RESULTS: Ginger extract contained 38.76 ± 3.01%w/w of 6-gingerol. The optimized NLC formulation showed a particle size of around 205 nm, a zeta potential of -33.7 and %entrapment efficiency of 76.59 ± 0.83%. Reduction in primary inflammation was significantly higher with NLC when compared with ginger extract and castor oil alone (p<0.001). The formulation also improved hyperalgesia in rats. CONCLUSION: Castor oil can be used as a novel lipid in the preparation of NLC. The NLC effectively enhanced the therapeutic value of poorly bioavailable ginger extract.
32851374 Serum C-Reactive Protein/Albumin Ratio in Rheumatoid Arthritis and its Relationship With D 2020 Jun OBJECTIVES: This study aims to evaluate the relationship between C-reactive protein (CRP)/albumin ratio (CAR) and disease activity, quality of life (QoL), and physical function in rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 121 RA patients (22 males, 99 females; mean age 57.6±11.2 years; range, 32 to 85 years) applying to Ankara University School of Medicine Rheumatology Outpatient Clinic between January 2019 and February 2019 were included in this cross-sectional study. The inclusion criteria were fulfilling the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria, being over 18 years and accepting to participate in the study. Demographic and clinical parameters including serum erythrocyte sedimentation rate (ESR), CRP and albumin levels were recorded. Disease activity was measured using Disease Activity Score 28 (DAS28)-ESR. General health, fatigue, and pain were questioned by means of a 100 mm visual analog scale (VAS). The QoL was assessed with the Rheumatoid Arthritis Quality of Life (RAQoL) Questionnaire. The functional status was determined using the Health Assessment Questionnaire (HAQ). RESULTS: Rheumatoid factor (RF) was positive in 56.2% of the patients. The median ESR was 19.0 mm/hour [interquartile range (IQR): 19.5] and median CRP was 5.6 (IQR: 9) mg/L. The median CAR was 1.3 (IQR: 2.1) and median DAS 28-ESR was 3.6 (IQR: 1.5). There was a significant but weak correlation between CAR and DAS28-ESR [p<0.001, Spearman's correlation coefficient (rs)=0.327]. Moreover, CAR was positively correlated with ESR, CRP, and VAS physician's global assessment (p<0.001, rs=0.497; p<0.001, rs=0.987, p<0.001, rs=0.401, respectively). However, no correlation was observed between CAR, HAQ, and RAQoL. In the RF positive group, there was a significant but weak correlation between CAR and RF titers (p=0.016, rs=0.292). CONCLUSION: We observed a positive but weak correlation between CAR and DAS28-ESR, ESR, and the RF titer. Further studies are warranted to investigate the role of CAR in RA.
32604884 Systemic Manifestations and Complications in Patients with Rheumatoid Arthritis. 2020 Jun 26 Rheumatoid arthritis (RA) is a systemic autoimmune disease with symmetrical peripheral polyarthritis, predominantly involving the small joints [...].
33293243 Development and feasibility of 4 checklists for the evaluation of comorbidity in patients 2020 Dec 5 OBJECTIVE: To develop and assess the feasibility in daily practice of four comorbidity checklists, for common use in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: A multidisciplinary panel of experts on comorbidity was established. Data from the GECOAR, GECOAX and GECOAP projects were analysed and a narrative literature review in Medline on RA, axSpA and PsA comorbidity was performed in order to select the most relevant and common comorbidities across the three diseases. With these results and those obtained from a focus group of patients, in a nominal group meeting, the experts generated preliminary checklists. These were afterwards modified by an external evaluation by two associations, a patients' association and an association of health professionals related to rheumatology. As a result, the final checklists were generated. A cross-sectional study was conducted to test the feasibility of three of the checklists in daily practice, in which eight health professionals evaluated the checklists in five patients with RA, five with axSpA and five with SpA. RESULTS: Four comorbidity checklists were designed, three for health professionals (one to assess current comorbidity, one on prevention/health promotion and one with the referral criteria to other health professionals), and another for patients. The feasibility study showed them to be simple, clear, and useful for use in routine clinical practice. CONCLUSIONS: The use of specific and common checklists for patients with RA, axSpA and PsA is feasible and might contribute favorably to their prognosis as well as in daily practice.
33098626 Low dose IL-2 suppress osteoclastogenesis in collagen-induced arthritis via JNK dependent 2020 Dec BACKGROUND: Rheumatoid arthritis (RA) is one of the most common chronic immune joint diseases, mainly involving blood vessels and small joints. The complex pathogenesis of RA greatly increases the difficulty of treatment. At present, the common hormone and immunosuppressive therapy are not effective, while low-dose interleukin-2 (IL-2) recently has been found to possess some advantages for immunotherapy. However, its related signal pathway remains to be elucidated. METHODS: We fabricated the model of arthritis in mice, and then low-dose IL-2 was injected at a fixed time point to observe the changes of related vascular and organ pathology, inflammatory factors, and signal pathway proteins, which were verified by statistical analysis. RESULTS: Low dose IL-2 can reduce the severity of vascular and bone lesions in collagen-induced arthritis immune model, and inhibit osteoclast formation in vitro by phosphorylation of nuclear factor-κB (NF-κB), which inhibits the receptor activator of NF-κB ligand effect through c-Jun N-terminal kinase (JNK) pathway, and its immunotherapeutic effect depends on the activation of JNK. CONCLUSION: It is the first time for us to prove that low dose IL-2 can inhibit osteoclast formation in collagen-induced arthritis through the JNK dependent pathway, which will provide the angle and theoretical basis for future immunotherapy of IL-2.
32232740 Methotrexate Discontinuation and Dose Decreases After Therapy With Tocilizumab: Results Fr 2020 Jun INTRODUCTION: Similar outcomes have been observed between patients with rheumatoid arthritis (RA) responding to tocilizumab (TCZ) with methotrexate (MTX) who discontinued vs. continued MTX and between patients receiving MTX who added TCZ vs. switched to TCZ monotherapy. This study examined MTX discontinuation and dose decreases in patients with RA initiating TCZ in a real-world setting. METHODS: TCZ-naïve patients enrolled in the Corrona RA registry who initiated TCZ in combination with MTX and had a 6-month follow-up visit without TCZ discontinuation were included. Patients were grouped by MTX dose at the time of TCZ initiation (≤ 10 mg, > 10 to ≤ 15 mg, > 15 to ≤ 20 mg, > 20 mg). The primary outcome was the proportion of patients with changes in MTX use at 6 months, with a secondary analysis at 12 months. Changes in disease activity [Clinical Disease Activity Index (CDAI)] and patient-reported outcomes (PROs) at 6 and 12 months were summarized descriptively. RESULTS: Of 444 included patients, 82.7% were female and 83.7% white, with mean (SD) disease duration of 11.6 (9.3) years, baseline CDAI score of 24.0 (15.4), and baseline MTX dose of 17.7 (5.8) mg. At 6 months, 139 patients (31.3%) discontinued or decreased their MTX dose. All MTX dose groups and patients who discontinued, decreased, maintained, or increased their MTX dose displayed improvements in CDAI scores and PROs at 6 months. Similar patterns and results were observed at 12 months. CONCLUSIONS: A considerable proportion of patients initiating TCZ discontinued or decreased their MTX dose after TCZ initiation. Improvements in disease activity and functionality were observed in patients who decreased or stopped MTX. This real-world study confirmed prior observations that discontinuing or decreasing MTX may be a treatment strategy for patients initiating TCZ combination therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01402661.
33052698 Optimization and Development of Methotrexate- and Resveratrol-Loaded Nanoemulsion Formulat 2020 Nov/Dec Methotrexate (MTX) is the first line of choice for the management of rheumatoid arthritis (RA) and has been reported for its low bioavailability and side effects. Combination therapy has been widely investigated to overcome bioavailability issues and to reduce adverse effects associated with monotherapy. Various phytoconstituents such as resveratrol (RSV) and curcumin have been found to possess potent anti-inflammatory activity via downregulating the signaling of cytokines (interleukin [IL]-1, IL-6, and tumor necrosis factor alpha) and nuclear factor kappa B signaling. The prime objective of this study was to develop transdermal gel containing MTX-RSV loaded nanoemulsions (NEs) to overcome bioavailability issues and adverse effects of RA monotherapy. The NEs optimized by using Box-Behnken Design were incorporated within gel, and an in vitro skin permeation study performed on rat skin by using vertical Franz diffusion cells exhibited controlled drug release up to 48 h. Subsequently, anti-inflammatory and potential anti-arthritic activities of the combination in nanocarrier were assessed in rats and showed 78.76 ± 4.16% inhibition in inflammation and better anti-arthritic effects. Consequently, integration of dual delivery with nanotechnology can hopefully produce successful therapeutic options for rheumatic diseases.
31746064 Epigallocatechin 3-gallate attenuates arthritis by regulating Nrf2, HO-1, and cytokine lev 2020 May Epigallocatechin 3-gallate (EGCG) is a polyphenol that has been shown to have antioxidant and anti-inflammatory effects. In this study, collagen-induced arthritis (CIA) model, in Wistar albino rats, was used to elucidate the effect of EGCG on pathogenetic pathways in inflammatory arthritis. The levels of serum TNF-α, IL-17, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx); the expression levels of tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); histopathologically, perisynovial inflammation and cartilage-bone destruction were examined. In the sham group, serum TNF-α, IL-17, and MDA levels increased, while SOD, CAT, GPx levels, and the expressions of Nrf2 and HO-1 decreased. On the other hand, in the EGCG administered groups, serum TNF-α, IL-17, and MDA levels improved, while SOD, CAT, GPx levels and the expressions of Nrf2 and HO-1 increased. Moreover, histopathological analysis has shown that perisynovial inflammation and cartilage-bone destruction decreased in the EGCG administered groups. These results suggest that EGCG has an antiarthritic effect by regulating the oxidative-antioxidant balance and cytokine levels in the CIA model, which is a surrogate experimental model of rheumatoid arthritis.
32116681 Alpha-Glucosidase Inhibitors Alter Gut Microbiota and Ameliorate Collagen-Induced Arthriti 2019 Acarose is an anti-diabetic drug and exhibits anti-arthritic effects. We hypothesized that acarbose influences the gut microbiota to affect the course of arthritis and tested this hypothesis in a collagen-induced arthritis (CIA) murine model. Acarbose in drinking water was administered via gastric gavage started prior to or at the time of CIA induction. Gut microbiota were evaluated with 16S rRNA gene sequencing from fecal pellets collected prior to arthritis induction, during onset of arthritis, and after treatment. Immune response was evaluated by measuring changes in T helper-17 (Th17) and T regulatory (Treg) cells in the spleen and intestine, as well as serum cytokine levels. Before induction of CIA, acarbose significantly reduced the incidence of arthritis and attenuated clinical severity of arthritis. The frequency of Th17 cells was significantly decreased in the intestinal lamina propria in acarbose treated mice. Mice that were treated with acarbose showed significantly increased CD4(+)CD25(+)Foxp3(+) Treg cells with elevation of Helios and CCR6. A remarkable alteration in microbial community was observed in acarbose treated mice. Bacterial diversity and richness in mice with arthritis were significantly lower than those in acarbose treated groups. The frequency of Firmicutes was significantly reduced after arthritis onset but was restored after treatment with acarbose. The frequency of Lactobacillus, Anaeroplasma, Adlercreutzia, RF39 and Corynebacterium was significantly higher in control groups than in acarbose treated, while Oscillospira, Desulfovibrio and Ruminococcus enriched in acarbose treated group. Miglitol, another α-glucosidase inhibitor showed a similar but less potent anti-arthritic effect to that of acarbose. These data demonstrate that acarbose alleviated CIA through regulation of Th17/Treg cells in the intestinal mucosal immunity, which may have resulted from the impact of acarbose on gut microbial community. Inexpensive antidiabetic drugs with an excellent safety profile are potentially useful for managing rheumatoid arthritis.