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ID PMID Title PublicationDate abstract
31095464 Eccentric training enhances the αB-crystallin binding to the myofibrils and prevents skel 2019 Jul 1 Patients with rheumatoid arthritis (RA) frequently suffer from muscle weakness. We examined whether eccentric training prevents skeletal muscle weakness in adjuvant-induced arthritis (AIA) rat, a widely used animal model for RA. AIA was induced in the knees of Wistar rats by injection of complete Freund's adjuvant. To induce eccentric contractions (ECCs), neuromuscular electrical stimulation (45 V) was applied to the plantar flexor muscles simultaneously with forced dorsiflexion of the ankle joint (0-40°) and was given every 6 s. ECC exercise was applied every other day for a total of 11 sessions and consisted of 4 sets of 5 contractions. There was a significant reduction in in vitro maximum Ca(2+)-activated force in skinned fibers in gastrocnemius muscle from AIA rats. These changes were associated with reduced expression levels of contractile proteins (i.e., myosin and actin), increased levels of inflammation redox stress-related biomarkers (i.e., TNF-α, malondialdehyde-protein adducts, NADPH oxidase 2, and neuronal nitric oxide synthase), and autolyzed active calpain-1 in AIA muscles. ECC training markedly enhanced the steady-state levels of αB-crystallin, a small heat shock protein, and its binding to the myofibrils and prevented the AIA-induced myofibrillar dysfunction, reduction in contractile proteins, and inflammation-oxidative stress insults. Our findings demonstrate that ECC training preserves myofibrillar function without muscle damage in AIA rats, which is at least partially attributable to the protective effect of αB-crystallin on the myofibrils against oxidative stress-mediated protein degeneration. Thus ECC training can be a safe and effective intervention, counteracting the loss of muscle strength in RA patients. NEW & NOTEWORTHY Eccentric contractions (ECCs) are regarded as an effective way to increase muscle strength. No studies, however, assess safety and effectiveness of ECC training on muscle weakness associated with rheumatoid arthritis. Here, we used adjuvant-induced arthritis (AIA) rats to demonstrate that ECC training prevents intrinsic contractile dysfunction without muscle damage in AIA rats, which may be attributed to the protective effect of αB-crystallin on the myofibrils against inflammation-oxidative stress insults.
32185353 Objective measurement of sedentary time and physical activity in people with rheumatoid ar 2019 Jun BACKGROUND: The accurate measurement of sedentary time and physical activity in Rheumatoid Arthritis (RA) is critical to identify important health consequences and determinants of these behaviours in this patient group. However, objective methods have not been well-validated for measurement of sedentary time and physical activity in RA. AIMS: Specific objectives are to: 1) validate the ActiGraph GT3X+ accelerometer and activPAL3(μTM) against indirect calorimetry and direct observation respectively, and define RA-specific accelerometer cut-points, for measurement of sedentary time and physical activity in RA; 2) validate the RA-specific sedentary time accelerometer cut-points against the activPAL3(μTM); 3) compare sedentary time and physical activity estimates in RA, using RA-specific vs. widely-used non-RA accelerometer cut-points. METHODS: Objective 1: People with RA will wear an ActiGraph GT3X+, activPAL3(μTM), heart rate monitor and indirect calorimeter, whilst being video-recorded undertaking 11 activities representative of sedentary behaviour, and light and moderate intensity physical activity. Objectives 2 and 3: People with RA will wear an ActiGraph GT3X+ and activPAL3(μTM) for 7 days to measure free-living sedentary time and physical activity. DISCUSSION: This will be the first study to define RA-specific accelerometer cut-points, and represents the first validation of the ActiGraph accelerometer and activPAL(TM), for measurement of sedentary time and physical activity in RA. Findings will inform future RA studies employing these devices, ensuring more valid assessment of sedentary time and physical activity in this patient group.
31333734 Role of optical coherence tomography in the early detection of macular thinning in rheumat 2019 BACKGROUND: Chloroquine and hydroxychloroquine are drugs that are primarily used for the treatment of malaria and are also recommended for treating connective tissue disorders, autoimmune diseases, and some dermatological and inflammatory diseases. Treatment with these drugs has potential risk for the development of retinopathy, clinically characterized by bilateral pigment changes in the macula, as one serious ocular complication. The aim of this research was to evaluate the parafoveal and perifoveal macular retinal thickness, as central foveal thickness in adult patients with rheumatoid arthritis (RA) on chloroquine therapy using optical coherence tomography (OCT). MATERIALS AND METHODS: In this cross-sectional study, 56 RA patients (56 eyes) were included and examined. All patients were treated with chloroquine (tablets resochin or delagil) at a dose of 250 mg/day without treatment with steroids and other immunosuppressive drugs. Patients were divided into two groups, namely, Group I patients - no visible changes in the macula (26 patients) and Group II patients- with visible changes in the macula (30 patients). The central fovea thickness and parafoveal and perifoveal retinal thickness in all quadrants were measured by OCT and compared in both groups. RESULTS: There are a significantly higher number of eyes without thinning of the macula in Group I patients than in Group II (P < 0.001) patients. There are a higher number of patients with recorded parafoveal thinning in Group II patients, especially in the inferior, nasal, and temporal sectors, respectively (P < 0.05). CONCLUSION: Maculopathy is the main side effect of chloroquine therapy in RA patients that can be detected by OCT in the early stages of the macular involvement.
31110572 Values and Correlations between C-Reactive Protein and Apolipoprotein B after Treatment wi 2019 Apr 30 BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). Lipid changes related to inflammation have been described in RA. Methotrexate (MTX) treatment is effective in controlling inflammation and decreasing the CRP (C-reactive protein) values. AIM: To examine the disease activity, CRP and Apo B values in the detection of new patients with active and untreated RA, and impact of MTX therapy on their levels after 6 months and one year of treatment, and the correlation between their values in this period. METHODS: 80 patients with active and newly discovered RA patients who meet the American Rheumatology Association (ARA) 1987 revised criteria were treated with disease-modifying anti-inflammatory drugs (DMARDs) according to the protocol for treatment. RESULTS: After a year of therapy RA patients achieved significant decrease in the DAS28 (disease activity score) (p < 0.01 and p < 0.001), and CRP values (p < 0.001). Levels of Apo B values at the 12 months were nonsignificantly higher compared to the results obtained at the beginning of the study (p < 0.001). After 6 and 12 months there was a weak nonsignificant negative correlation about the values of CRP and Apo B at baseline and after 12 months (r = -0.15 and r = -0.12 p > 0.05). CONCLUSION: Use of MTX therapy at RA patients had a reduced effect on disease activity and inflammation, but the nonsignificance effect on the values of Apo B lipoproteins.
30805417 Patient Satisfaction Following Total Knee Arthroplasty: Comparison of Short-Term Results i 2019 Jan BACKGROUND: Due to the obvious differences in the natural course of rheumatoid arthritis (RA) and osteoarthritis (OA), different functional outcomes might be expected after Total Knee Arthroplasty (TKA) in these distinct patients. Although several studies have reported the objective outcome of TKA in RA and OA patients, few studies have compared post-operative patient-satisfaction levels. METHODS: In this clinical cohort study 171 patients (RA: n=33, OA: n=138) who underwent TKA with posterior stabilizing knee prosthesis were included. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Oxford Knee Score (OKS) were used to evaluate and compare patients' satisfaction 6 and 12 months after TKA relative to their preoperative state and to make an assessment between two groups. RESULTS: Both of patient-reported scoring systems showed a statistically significant improvement for OA and RA patients at 6 and 12 months after surgery, relative to their preoperative scores. The results of the OKS and KOOS did not show statistically significant improvement from 6 to 12 months n RA patients. Unlike RA group, OKS and KOOS revealed further improvement between 6 and 12 months for the osteoarthritic patients. CONCLUSION: OA patients had continuous improvement in their satisfaction in the first year after TKA with a gentle upward curve. In contrast, in RA patients, recovery was faster and greater in the first six months after surgery and slowed down in the second six months. Patient-reported outcome scores were not significantly different between two groups at the end of the first year.
30697252 Efficacy and safety of various anti-rheumatic treatments for patients with rheumatoid arth 2019 Jan INTRODUCTION: Biologics and traditional disease-modifying anti-rheumatic drugs (DMARDs) are generally used in treating patients with rheumatoid arthritis (RA). Previous studies have presented abundant data and information about the efficacy of such treatments, but the results were incomplete and inconclusive. This network meta-analysis was conducted to compare and assess the efficacy and safety of 15 therapies employing biologics and DMARDs for RA patients. MATERIAL AND METHODS: Six outcomes (American College of Rheumatology 20% response rate (ACR20), ACR50, ACR70, remission, adverse events (AEs) and serious adverse events (SAEs)) were used to evaluate the efficacy and safety of different treatments. The node-splitting method was used to assess the inconsistency, and the rank probabilities of the therapies were estimated by surface under the cumulative ranking curve. Besides, Jadad scale was used to evaluate the methodological quality of eligible studies. RESULTS: A total of 67 randomized controlled trials with 20,898 patients met the inclusion criteria. Most of the therapies presented better performance than conventional DMARDs (cDMARDs) and placebo in ACR20, ACR50 and ACR70. Conversely, the safety of cDMARDs and placebo seemed to be superior in AEs and SAEs. Also, tocilizumab (TCZ) and TCZ + methotrexate (MTX) showed better remission in pain compared to other treatments. Overall, certolizumab pegol (CZP) + MTX and TCZ + MTX had higher probability than the other treatments in efficacy outcomes. CONCLUSIONS: We recommend CZP + MTX as the optimal drug therapy because it has the highest ranking in efficacy outcomes and relatively low risk of adverse events. TCZ + MTX is recommended as an alternative. Abatacept (ABT) and cDMARDs are not recommended due to their low efficacy.
32010888 Reliability and Validity of the Turkish Version of the ABILHAND Questionnaire in Rheumatoi 2019 Dec OBJECTIVES: This study aims to assess the reliability and validity of the Turkish version of the ABILHAND questionnaire in individuals with rheumatoid arthritis (RA) [ABILHAND-RA (TR)] using the Rasch analysis. MATERIALS AND METHODS: A total 90 individuals (15 males, 75 females; mean age 51.8±10.9 years; range, 20 to 65 years) diagnosed as RA according to the criteria of the American College of Rheumatology were included. The ABILHAND-RA (TR) was used to determine manual ability, while disease activity was evaluated by the use of Disease Activity Score 28 (DAS28). Jamar hand dynamometer and pinch-meter were used to examine grip and pinch strength of the participants. Nine Hole Peg Test (NHPT) and Duruoz Hand Index (DHI) measured hand disability level. Nottingham Health Profile (NHP) was used to assess quality of life. ABILHAND-RA (TR) results were analyzed using the Rasch analysis method. RESULTS: Item 20 was excluded from the 27-item ABILHAND-RA (TR) as 96% of the individuals rated this item as "easy". The new set of 18 items (7 subtests and 11 items) were found to sustain item invariance and fit to the Rasch model. Significant relationships were found between ABILHAND-RA (TR) and DAS28, bilateral grip strength, NHPT dominant side results, DHI, and NHP. CONCLUSION: Turkish version of the ABILHAND-RA was found to be clinically valid, reliable, and sensitive enough to be used in clinical evaluations, rehabilitation interventions, and for progression follow-up in individuals with RA.
31707603 Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors a 2019 Nov 9 INTRODUCTION: No published studies exist comparing the effectiveness of tofacitinib with other advanced therapies for the treatment of rheumatoid arthritis (RA) in real-world clinical practice. Here, we report differences in effectiveness of tofacitinib compared with standard of care, tumor necrosis factor inhibitors (TNFi), with or without concomitant methotrexate (MTX), using US Corrona registry data. METHODS: This observational cohort study included RA patients receiving tofacitinib (from 6 November 2012; N = 558) or TNFi (from 1 November 2001; N = 8014) with or without MTX until 31 July 2016. Efficacy outcomes at 6 months included modified American College of Rheumatology 20% responses, Clinical Disease Activity Index (CDAI) and Pain. Outcomes were compared between patients receiving TNFi and tofacitinib with or without MTX and by line of therapy. Outcomes within therapy lines were compared using propensity-score matching; between-group differences were estimated using mixed-effects regression models. RESULTS: Patients receiving tofacitinib had longer RA duration and a greater proportion had previously received biologics than those receiving TNFi; other baseline characteristics were comparable. In patients receiving second- and third-line TNFi therapy, CDAI low disease activity/remission response rates were significantly better with concomitant MTX. Too few patients received tofacitinib as second line for meaningful assessment. No significant differences were observed in outcomes between tofacitinib as monotherapy and tofacitinib with concomitant MTX. CONCLUSIONS: In clinical practice, TNFi efficacy is improved with concomitant MTX in the second and third line. In the third/fourth line, patients are likely to achieve similar efficacy with tofacitinib monotherapy, or TNFi or tofacitinib in combination with MTX. FUNDING: Pfizer Inc.
31628617 Changes in Opioid Utilization Following Tumor Necrosis Factor Inhibitor Initiation in Pati 2019 Dec INTRODUCTION: Pain control is one of the most important aspects of rheumatoid arthritis (RA) management from the patient's perspective. Newer generations of RA treatment including tumor necrosis factor inhibitor (TNFi) have the potential to alleviate pain and thus reduce opioid utilization. However, patterns of opioid utilization before and after TNFi initiation have not been well characterized. This study aims to examine multiple measures of change in opioid utilization after the initiation of TNFi. METHODS: Patients aged ≥ 18 years with RA and 24 months continuous enrollment between January 2007 and December 2015 who newly initiated a TNFi in IQVIA™ Health Plan Claims Data were included in our study. Opioid utilization at baseline and during follow-up were identified and compared. RESULTS: Of 2330 patients with RA that were included in the study, 38.8% of patients used opioids in both baseline and follow-up periods. From pre-index to post-index, the proportion of patients receiving any opioid decreased from 54.0 to 51.0%. In addition, the proportion of those who received ≥ 50 mg median daily MED decreased from 12.6 to 10.6% during pre-post periods. CONCLUSIONS: This real-world study of commercially insured patients with RA suggests that opioid use among these patients is prevalent. There was a small decrease in overall opioid utilization after TNFi initiation.
31544843 Specificity of Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis. 2019 Jun 7 Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. The majority of individuals with RA are positive for the disease-specific anti-citrullinated protein antibodies (ACPAs). These antibodies are primarily of cross-reactive nature, hence, the true autoantigen to ACPA remains unidentified. In this study, we analyzed the reactivity of RA sera to several post-translationally modified epitopes, in order to further characterize the specific nature of ACPAs by immunoassays. Substituting citrulline with other amino acids, e.g., D-citrulline, homo-citrulline and methyl-arginine illustrated that ACPAs are utmost specific for citrullinated targets. Collectively, these findings support that ACPAs and citrullinated targets are specific for RA, making citrulline-containing peptide targets the most effective assays for detection of ACPAs.
31031533 A Longitudinal Study of the 28 Joints of Disease Activity Score by Ultrasonographical Exam 2019 Jan BACKGROUND: The damaging effect of rheumatoid arthritis (RA) on cartilage, bone, ligaments, and tendons has raised the importance of the disease activity and severity assessment to enable therapeutic decisions and to evaluate disease outcome. AIM: The aim is to compare the clinical examination of the Disease Activity Score (DAS)-28 with the musculoskeletal ultrasonography (US) examination in RA patients. Moreover, finding if we can use ultrasonographical results as a tool for predicting subsequent radiological damage. PATIENTS AND METHODS: It is a longitudinal study included 60 adult RA patients. Patients were under assessment at baseline, 6 months, and 12 months from the recruitment time. Twenty-eight joints of DAS were assessed for tenderness and swelling. US gray scale (GS) and US power Doppler (PD) score also was done at each visit. RESULTS: DAS-28, with its parameters, is positively and highly significantly correlated to synovitis severity both by US GS and US-PD score along the study follow-up visits. There was highly significant difference between the number of 28 swollen and tender joints by clinical examination with both US GS and US-PD. Linear regression analysis to predict the number of swollen and tender joints after 12 months showed significance between US PD with swollen and tender joints' numbers. The correlation was positive and significant between Larsen score at 12 months with GS US and PD US assessment, but linear regression analysis was only significant for Larsen score with only GS US. CONCLUSION: GS US and PD is a sensitive and reliable noninvasive method complementary to standard clinical assessment and could be a tool for predicting subsequent joints' damage.
30666791 Comparative study on serum-induced arthritis in the temporomandibular and limb joint of mi 2019 Apr INTRODUCTION: The subject of the present study was a systematic comparative analysis of the rheumatoid arthritis (RA)-induced pathomechanisms in the temporomandibular joint with those of the limb joints using the serum-induced arthritis K/BxN model. METHODS: In 18 BALB/c mice the induction of RA was performed according to the Kouskoff method. Another healthy cohort served as controls (n = 12). Joint swelling of the paws was measured using a micrometer. Functional data were obtained analyzing locomotion. Three-dimensional examination of the temporomandibular joint was performed with micro-computed tomography imaging, followed by histological evaluation of the extremity joints and the temporomandibular joint. Additionally, immunohistochemical investigations were carried out to evaluate inflammatory and immunological changes. RESULTS: Measurement of joint swelling showed a significant increase in the diameter of the paws, as well as a decrease in locomotor activity compared to control animals and the time before arthritis induction. Histological and immunohistochemical investigations showed clear signs of inflammation in the extremity joints. In contrast, no histological or immunohistochemical indications of an inflammatory process were detectable in the temporomandibular joint. In addition, the three-dimensional analysis by micro-computed tomography of the temporomandibular joints did not show any obvious morphological changes. CONCLUSION: For the first time, using the K/BxN model we could demonstrate that, due to its anatomical and mechanical conditions, the temporomandibular joint seems to be less susceptible to the initiation of RA compared to limb joints. Therefore, additional investigations are needed on other arthritis models as well, in order to further improve our understanding of the pathogenesis and defense mechanisms of the disease.
30007486 Guideline recommended treatment to targets of cardiovascular risk is inadequate in patient 2019 Jan 1 OBJECTIVES: Patients with inflammatory joint diseases (IJD) have an increased risk of cardiovascular disease (CVD). Our goal was to examine indications for, and use of, lipid-lowering therapy (LLT) and antihypertensive treatment (AntiHT) in patients with IJD. Furthermore, to investigate the frequency of low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) goal attainment among IJD patients. METHODS: The cohort was derived from the NOrwegian Collaboration on Atherosclerosis in patients with Rheumatic joint diseases (NOCAR). Indications for AntiHT were: systolic/diastolic BP ≥ 140/90 mm Hg, self-reported hypertension or AntiHT. CVD risk was estimated by the systematic coronary risk evaluation (SCORE) algorithm. LDL-c goals were <2.6 mmol/L in case of diabetes, total cholesterol > 8 mmol/L or a SCORE estimate ≥ 5%, and <1.8 mmol/L for those with established CVD or SCORE ≥ 10%. Comparisons across IJD entities were performed using age and sex adjusted logistic regression. RESULTS: In total, 2277 patients (rheumatoid arthritis: 1376, axial spondyloarthritis: 474, psoriatic arthritis: 427) were included. LLT and AntiHT were indicated in 36.1% and 52.6% of the patients, of whom 37.6% and 47.0% were untreated, respectively. LDL-c and BP targets were obtained in 26.2% and 26.3%, respectively. Guideline recommended treatment and/or corresponding treatment targets were not initiated or obtained in approximately 50%. Rheumatoid arthritis patients were particularly likely to be undertreated with LLT, whereas hypertension undertreatment was most common in psoriatic arthritis. CONCLUSIONS: Inadequate CVD prevention encompasses all the three major IJD entities. The unmet need for CVD preventive measures is not only prevalent in RA, but exists across all the major IJD entities.
30809149 Astragalin Suppresses Inflammatory Responses and Bone Destruction in Mice With Collagen-In 2019 Astragalin, as a bioactive flavonoid with anti-inflammatory, antioxidant, and protective properties, provides a potential agent for rheumatoid arthritis (RA). In this study, its therapeutic efficacy and the underlying mechanisms were explored using DBA/1J mice with collagen-induced arthritis (CIA). It was demonstrated that astragalin could significantly attenuate inflammation of CIA mice. The effects were associated with decreased severity of arthritis (based on the arthritis index), joint swelling and reduced bone erosion and destruction. Furthermore, astragalin treatment suppressed the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8), and inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) in chondrocytes and synovial cells of CIA mice. Fibroblast-like synoviocytes derived from RA patients (MH7A cells) were applied to verify these effects. In vitro, astragalin inhibited the expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-13) dose-dependently in TNF-α-induced MH7A cells, with no apparent cytotoxicity. Furthermore, astragalin suppressed the phosphorylation of p38, JNK, and the activation of c-Jun/AP-1 in TNF-α-induced MH7A cells. In conclusion, it has proven that astragalin could attenuate synovial inflammation and joint destruction in RA at least partially by restraining the phosphorylation of MAPKs and the activating of c-Jun/AP-1. Therefore, astragalin can be a potential therapeutic agent for RA.
30677505 Translocation of dead or alive bacteria from mucosa to joints and epiphyseal bone-marrow: 2020 Jan The recent demonstration that DNA from several mucosal bacteria, including Prevotella spp, could be found in numerous tissues (mesenteric lymph nodes, spleen, serum, liver, lung, eye and ankle joints), either in HLA-B27 rats with or without arthritis, or control rats without HLA-B27, could be a revolution in our understanding of spondyloarthritis and close disorders, including rheumatoid arthritis. Indeed, similar translocations of dead or alive bacteria or fungi from mucosa to joints, could contribute to the onset and flares of inflammatory rheumatisms. This state of the art article addresses six questions revived by this finding: 1-How does this bacterial DNA or living bacteria traffic from mucosa to joints? 2-Can some mucosal bacteria remain alive in those tissues, including joints? 3-Could bacteria from the gut microbiota ('self-bacteria') protect the host cells from invasion by more pathogenic bacteria (like dog-shepherds protect from wolves)? 4-Does the composition of the joint or bone marrow microbiota depends on local metabolism, which might differ from gut metabolism? 5-Could bacterial antigens from mucosal microbiota be sufficient to trigger trained immunity of presenting cells in joints, or does such phenomenon (with lasting epigenetic changes of presenting cells) require intra-cellular infection of presenting cells or their ancestors? 6-In which subsets of cells could living bacteria preferentially persist for a long period in the joint area? Transient or dormant infections within bone-marrow mesenchymal stem cells leading to trained immunity of some of their daughter cells in joints or enthesis, lasting after clearance or the invader, is an attractive hypothesis to test.
31208713 A cross talk between dysbiosis and gut-associated immune system governs the development of 2019 Dec BACKGROUND: Emerging evidence suggests that dysbiosis, imbalanced gut microbial community, might be a key player in the development of various diseases, including inflammatory arthropathies, such as rheumatoid arthritis, spondyloarthritis (mainly, ankylosing spondylitis and psoriatic arthritis), and osteoarthritis. Yet, the underlying mechanisms and corresponding interactions remain poorly understood. METHODS: We conducted a critical and extensive literature review to explore the association between dysbiosis and the development of inflammatory arthropathies. We also reviewed the literature to assess the perspectives that ameliorate inflammatory arthropathies by manipulating the microbiota with probiotics, prebiotics or fecal microbiota transplantation. RESULTS: Some bacterial species (e.g. Prevotella, Citrobacter rodentium, Collinsella aerofaciens, Segmented filamentous bacteria) participate in the creation of the pro-inflammatory immune status, presumably via epitope mimicry, modification of self-antigens, enhanced cell apoptosis mechanisms, and destruction of tight junction proteins and intestinal barrier integrity, all leading to the development and maintainance of inflammatory arthropathies. Whether dysbiosis is an epiphenomenon or is an active driver of these disorders remains unclear, yet, recent observations clearly suggest that dysbiosis precedes and triggers their development implying a causative relationship between dysbiosis and inflammatory arthropathies. The underlying mechanisms include dysbiosis-mediated changes in the functional activity of the intestinal immune cell subsets, such as innate lymphoid cells, mucosa-associated invariant T cells, invariant natural killer T cells, T-follicular helper and T-regulatory cells. In turn, disturbed functionality of the gut-associated immune system is shown to promote the overgrowth of many bacteria, thus establishing a detrimental vicious circle of actively maintaining arthritis. CONCLUSIONS: Analysis of the data described in the review supports the notion that a close, dynamic and tightly regulated cross talk between dysbiosis and the gut-associated immune system governs the development of inflammatory arthropathies.
31333447 Anti-Inflammatory and Anti-Arthritic Efficacies of an Indian Traditional Herbo-Mineral Med 2019 Rheumatoid arthritis (RA) is defined as a chronic autoimmune inflammatory disorder that causes damage to limb joints and progressive injuries to secondary organs. Medical practitioners prescribe Methotrexate (MTX) as standard care medicine for treating RA. However, the long-term application of MTX has shown to have adverse health-related effects. Divya Amvatari Ras (DAR), an Indian Ayurvedic herbo-mineral formulation, has been described in ancient texts to provide relief from RA inflammation associated distress. Therefore, in the present study, we explored the biocompatibility, anti-inflammatory, and anti-arthritic efficacy of DAR using in vivo and in vitro disease models. Using carrageenan (CA)-stimulated Wistar rat paw edema model, we showed a reduction in inflammation-induced paw edema at human equivalent dose of DAR. Anti-rheumatic efficacy of DAR was studied using collagen-antibody cocktail (C-Ab) Induced Arthritis (CAIA) mouse model. The onset of RA in the CAIA mice was determined using parameters such as the increase in arthritis score, and induction of disease associated lesions in the ankle and knee joints, and increase in mechanical and thermal hyperalgesia. Treatment of CAIA animals with a human equivalent dose of DAR significantly reversed the RA-associated pathogenesis. These effects were comparable with the standard of care RA drug, MTX. DAR acted at multiple levels of inflammation associated with RA to reduce progressive pathogenesis. Animal serum biochemistry showed DAR was capable of ameliorating RA induced increase in liver enzyme Alanine Aminotransferase (ALT) and pro-inflammatory cytokine interleukin 6 (IL-6). In the lipopolysaccharide stimulated THP-1 cells, DAR was found to inhibit the release of IL-6, IL-1β, TNF-α, and upstream inflammatory gene regulatory protein, NFκB. The study endorsed the anti-arthritic and anti-inflammatory activity of the Indian Traditional herbo-mineral medicine, DAR. These results also confirm that DAR was highly biocompatible and would show minimal health-related side effects than those associated with standard of care MTX. Taken together, we show that the DAR could be utilized as a promising alternative or complementary therapy for treating rheumatoid arthritis.
30905278 β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in 2019 Dec CONTEXT: β-Sitosterol (BS), the primary constituent of plants and vegetables, exhibits multiple biological effects. OBJECTIVE: This study explores its effect of immune-regulation on macrophages and its potential for rheumatoid arthritis (RA) therapy. MATERIALS AND METHODS: In vitro, bone marrow-derived macrophages (BMDMs) were treated with 5, 25 and 50 μM BS in the M1 or M2 polarization conditions. In vivo, either i.p. injection with 20 or 50 mg/kg BS every 2 d after boost immunization of collagen-induced arthritis (CIA) or adoptive transfer of 2 × 10(6) BS-treated BMDMs (BS-BMDMs) at the day before CIA were adopted in mice to test the therapeutic effect. IL-10 antibody depletion was used in the period of above treatments to discuss the underlying mechanism. RESULTS: The phenotypes and function of BMDMs showed that 5, 25 and 50 μM BS significantly repressed the M1 polarization and augmented M2 polarization dependent upon concentration. The expression of iNOS, IL-1β, CD86 and MHCII in 25 μM BS-treated M1-polarized BMDMs was reduced by 50.2, 47.1, 87.1 and 31.3%, respectively. In contrast, the expression of arginase-1, IL-10, CD163 and CD206 in 25 μM BS-treated M2-polarized BMDMs was increased by 65.6, 107.4, 23.5 and 51.3%, respectively. In CIA mice, either i.p. injection with BS or adoptive transfer of BS-BMDMs could alleviate the symptoms of ankle swelling (vehicle group: 3.13 ± 0.102 mm; 20 mg/kg BS group: 2.64 ± 0.043 mm; 50 mg/kg BS group: 2.36 ± 0.084 mm; BMDMs group: 3.09 ± 0.174 mm; BS-BMDMs group: 2.43 ± 0.042 mm), reduce the levels of collagen-specific antibodies (IgG and IgG1, but not IgG2c, p < 0.05) and inhibit the production of pro-inflammatory cytokines (p < 0.05). Depletion of IL-10 counteracted the effect of BS treatment (α-IL-10 vs. RatIgG1, p < 0.01 on day 16), highlighting the role of IL-10 in the anti-inflammatory response. CONCLUSIONS: These results suggested that BS could modulate the functions of macrophages and might be a promising agent for RA therapy.
31308804 Panax ginseng: a candidate herbal medicine for autoimmune disease. 2019 Jul Panax ginseng Meyer (P. ginseng; Korean ginseng) is well known for its medicinal properties. It can alleviate pathological symptoms, promote health, and prevent potential diseases via its anti-inflammatory, antioxidant, homeostatic, and other positive effects on biological metabolism. Although many studies have determined effects of P. ginseng on various diseases, such as cardiovascular, neurological, and immunological diseases, little is known about the effect of P. ginseng on autoimmune diseases. Here, we review a few reports about effects of P. ginseng on autoimmune diseases (e.g., multiple sclerosis, Crohn's disease, ulcerative colitis, atopic dermatitis, and rheumatoid arthritis) and suggest the possibility of P. ginseng as a candidate herbal medicine to prevent and treat autoimmune diseases as well as the need to study it.
30585643 CR6-interacting factor 1 controls autoimmune arthritis by regulation of signal transducer 2019 Apr CR6-interacting factor 1 (CRIF1) is a nuclear protein that interacts with other nuclear factors and androgen receptors, and is implicated in the regulation of cell cycle progression and cell growth. In this study, we examined whether CRIF1 exerts an immunoregulatory effect by modulating the differentiation and function of pathogenic T cells. To this end, the role of CRIF1 in rheumatoid arthritis, a systemic autoimmune disease characterized by hyperplasia of synovial tissue and progressive destruction of articular cartilage structure by pathogenic immune cells [such as T helper type 17 (Th17) cells], was investigated. p3XFLAG-CMV-10-CRIF1 was administered to mice with collagen-induced arthritis 8 days after collagen type II immunization and the disease severity and histologic evaluation, and osteoclastogenesis were assessed. CRIF1 over-expression in mice with collagen-induced arthritis attenuated the clinical and histological signs of inflammatory arthritis. Furthermore, over-expression of CRIF1 in mice with arthritis significantly reduced the number of signal transducer and activator of transcription 3-mediated Th17 cells in the spleen as well as osteoclast differentiation from bone marrow cells. To investigate the impact of loss of CRIF1 in T cells, we generated a conditional CRIF1 gene ablation model using CD4-cre transgenic mice and examined the frequency of Th17 cells and regulatory T cells. Deficiency of CRIF1 in CD4(+) cells promoted the production of interleukin-17 and reduced the frequency of regulatory T cells. These results suggest a role for CRIF1 in modulating the activities of Th17 cells and osteoclasts in rheumatoid arthritis.