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ID PMID Title PublicationDate abstract
29786532 Rice-body formation without rheumatic disease or tuberculosis in a "sausage" ring finger. 2018 May 18 Rice bodies are very unusual lesions, generally encountered in chronic synovitis due to rheumatoid diseases or tuberculosis. A 31-year-old right-handed man presented with a 15-year history of progressively growing "sausage-like" swelling of the 4th finger and palm of his right hand. There was an immovable, painless mass with restriction of the finger's ROM without local or general associated signs. Imaging showed a large non-aggressive mass within the tendon sheath. Complete excision of the mass was performed. Histopathological examination showed synovial villi with rice bodies and central necrosis suggestive of tuberculous synovitis or rheumatoid arthritis (RA). Tests for mycobacterial infections were all negative and there was no argument in favor of a rheumatoid pathology. There is no established standard treatment in a case like ours, which has no origin in tuberculosis or RA. Prolonged follow-up will be needed to confirm absence of recurrence after complete excision.
31949736 High mobility group box protein 1 downregulates acid β-glucosidase 1 in synovial fibrobla 2018 High mobility group box protein 1 (HMGB1) plays an important role in the pathogenesis of rheumatoid arthritis (RA), but the pathogenic mechanisms of HMGB1 in RA and the involvement of the lysosomal enzyme acid β-glucosidase 1 (GBA1) are not fully elucidated. The aim of the present study was to use HMGB1 to treat RA synovial fibroblasts (RASFs) and to examine the changes of transcriptional factors. RASFs were isolated from synovial tissues obtained from five RA patients undergoing synovectomy or joint replacement. RASFs were incubated with 100 ng/mL of HMGB1 for different periods. The changes in transcriptional factors were screened by RNA sequencing (RNA-seq) and results were confirmed by quantitative real-time PCR and western blot. The results showed that the mRNA of >60 genes in RASFs were differentially expressed after HMGB1 treatment. Among them, GBA1 was the most markedly decreased (-3.99 folds, P<0.001). These results were confirmed by qRT-PCR and western blot. The late-stage inflammatory mediator HMGB1 probably exerts its pathogenic role in RA by downregulating GBA1.
31938116 Knockdown of LSD1 ameliorates the severity of rheumatoid arthritis and decreases the funct 2018 Rheumatoid arthritis (RA) is an immune-mediated disease that causes chronic inflammation of the joints and involves CD4+ T cell activation. In RA, CD4+ T cells are the main drivers of disease initiation and the perpetuation of the damaging inflammatory process. In the present study, we investigated the role of Lysine-specific histone demethylase 1 (LSD1) in RA. The frequency of LSD1-positive CD4+ T cells in the synovial fluid (SF) of active RA patients was higher than that of inactive RA patients. In CD4+ T cells isolated from SF of active RA patients, LSD1 downregulation significantly increased cell proliferation, as shown by MTT assay. LSD1 knockdown also significantly increased the production of IFN-γ and IL-17, and increased that of IL-10, as determined by ELISA and qRT-PCR aasay. In CD4+ T cells isolated from SF of inactive RA patients, LSD1 was overexpressed by LSD1 plasmid transfection. As expected, LSD1 overexpression resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-γ, IL-17 and IL-10. LSD1 was downregulated in RA mouse by lenti-vector infection. As expected, LSD1 knockdown in vivo significantly alleviated the disease severity and increased the levels of anti-collagen II antibodies. LSD1 downregulation in the early stage was more effective to ameliorate disease severity. Our data suggested the potential therapeutic role of LSD1 in RA patients.
30641795 Hypertriglyceridaemic waist is associated with hyperuricaemia and metabolic syndrome in rh 2019 Jan BACKGROUND: /Aim: The hypertriglyceridaemic waist (HTGW) phenotype has been described and suggested in general population as a cardiovascular risk marker. The aim of the present study was to evaluate the HTGW phenotype as a marker related to HUC and MetS in rheumatoid arthritis (RA). MATERIALS AND METHODS: This was a cross-sectional study was designed in 250 RA Mexicans patients. The HTGW phenotype was defined as elevated waist circumference and elevated triglyceride concentration. Logistic regression analysis was used to evaluate the association between the HTGW phenotype, HUC and MetS in its traditional NCEP/ATPIII versions and modified (HTGWm and MetSm). RESULTS: The prevalence of HTGW and HTGWm it was 20.4% and 32%, respectively. All patients with HTGW presented MetS (P < 0.001), and in a multivariate model, the HTGW phenotype was the marker most closely related to HUC in comparison to components of MetS. CONCLUSION: The HTGW may represent a marker for screening of cardiometabolic risk in RA patients, so in clinical practice can be implemented as a low-cost marker in the evaluation of the patient regardless of clinical characteristics of disease.
30154675 Sarilumab: patient-reported outcomes in rheumatoid arthritis. 2018 In the last few decades, strategies for the management of rheumatoid arthritis (RA) have been increasingly oriented toward more comprehensive control of the disease, taking into account even RA extra-articular manifestations, comorbidities, and the patient's perception about the disease. The need for improving the shared decision-making process suggested by European League Against Rheumatism recommendations is leading to an increasing interest in the role of patient-reported outcomes (PROs) beside the usual more objective criteria for defining clinical response based on disease-activity composite indices. Measurement of such PROs as pain or fatigue may be significantly influenced by mood disorders often complicating RA, the pathogenesis of which is deeply interconnected with phlogistic processes mediated by proinflammatory cytokines. IL6 is a pleiotropic mediator involved in neuroendocrine and neuropsychological processes, besides its well known effects on immune, cardiovascular, and metabolic systems. Therefore, there is a growing body of evidence about the efficacy of IL6 blockade in PRO improvement in RA patients. Sarilumab is a monoclonal antibody binding both soluble and membrane-bound IL6Rα, inhibiting the IL6-mediated signaling pathway with favorable efficacy and safety profile. This review analyzes the importance of PROs in strategies for the management of RA and the pathogenic mechanisms linking IL6 with the patient's perception of the disease. Moreover, the main findings from sarilumab randomized controlled trials are summarized in detail, emphasizing the potential role of this IL6 blocker in the holistic treatment of RA.
30087677 DICER1: A Key Player in Rheumatoid Arthritis, at the Crossroads of Cellular Stress, Innate 2018 Loss-of-function or knockout mouse models have established a fundamental role for the RNAse III enzyme DICER1 in development and tissue morphogenesis and/or homeostasis. These functions are currently assumed to result mainly from the DICER1-dependent biogenesis of microRNAs which exhibit important gene expression regulatory properties. However, non-canonical DICER1 functions have recently emerged. These include interaction with the DNA damage response (DDR) pathway and the processing of cytotoxic non-coding RNAs, suggesting that DICER1 might also participate in the regulation of major cellular processes through miRNA-independent mechanisms. Recent findings indicated that reduced Dicer1 expression, which correlates with worsened symptoms in mouse models of joint inflammation, is also noted in fibroblast-like synoviocytes (FLS) harvested from rheumatoid arthritis (RA) patients, as opposed to FLS cultured from biopsies of osteoarthritic patients. In addition, low DICER1 levels are associated with the establishment of cellular stress and its associated responses, such as cellular senescence. Senescent and/or stressed cells are associated with an inflammatory secretome (cytokines and chemokines), as well as with "find-me" and "eat-me" signals which will attract and activate the innate immune compartment (NK cells, macrophages, and neutrophils) to be eliminated. Failure of this immunosurveillance mechanism and improper restauration of homeostasis could lead to the establishment of a systemic and chronic inflammatory state. In this review, we suggest that reduced DICER1 expression contributes to a vicious cycle during which accumulating inflammation and premature senescence, combined to inadequate innate immunity responses, creates the appropriate conditions for the initiation and/or progression of autoimmune-autoinflammatory diseases, such as RA.
29963294 Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis 2018 Periodontitis, rheumatoid arthritis (RA), atherosclerosis (AS), and Alzheimer's disease (AD) are examples of complex human diseases with chronic inflammatory components in their etiologies. The initial trigger of inflammation that progresses to these diseases remains unresolved. Porphyromonas gingivalis is unique in its ability to secrete the P. gingivalis-derived peptidyl arginine deiminase (PPAD) and consequently offers a plausible and exclusive link to these diseases through enzymatic conversion of arginine to citrulline. Citrullination is a post-translational enzymatic modification of arginine residues in proteins formed as part of normal physiological processes. However, PPAD has the potential to modify self (bacterial) and host proteins by deimination of arginine amino acid residues, preferentially at the C-terminus. Migration of P. gingivalis and/or its secreted PPAD into the bloodstream opens up the possibility that this enzyme will citrullinate proteins at disparate body sites. Citrullination is associated with the pathogenesis of multifactorial diseases such as RA and AD, which have an elusive external perpetrator as they show epidemiological associations with periodontitis. Therefore, PPAD deserves some prominence as an external antigen, in at least, a subset of RA and AD cases, with as yet unidentified, immune/genetic vulnerabilities.
29769765 Comparison of serum tumor necrosis factor-α levels in rheumatoid arthritis individuals wi 2018 Mar BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is indicated to play a major function in chronic inflammatory disorders. OBJECTIVE: To assess and compare the cytokine level (TNF-α) in the serum of chronic periodontitis (CP), rheumatoid arthritis (RA), RA with CP, and healthy volunteers. MATERIALS AND METHODS: This original research was carried out on 80 participants, divided into Group-I 20 RA patients, Group-II 20 CP patients, Group III 20 RA with CP (RA + CP), and Group IV 20 healthy volunteers. Clinical periodontal and rheumatological parameters were assessed in all the four groups. Blood serum samples have been collected from all individuals and investigated for levels of TNF-α by mean of enzyme-linked immunosorbent assay. RESULTS: TNF-α level were remarkably elevated in the RA+CP group (30.5±2.2) followed by RA group (17.9 ± 3.6), and CP group (11.9 ± 0.96) when compared with the controls (5.5 ± 3.3). The results showed a statistical significance of P < 0.001. Correlation was not observed on comparision of clinical periodontal parameters and Rheumatological parameters with TNF-α levels. CONCLUSION: The outcome of this present research revealed the presence of higher levels of TNF-α in individuals with RA with CP in our samples.
29503820 Tools for the Assessment of Comorbidity Burden in Rheumatoid Arthritis. 2018 INTRODUCTION: Comorbidities influence the prognosis, clinical outcomes, disease activity, and treatment response in rheumatoid arthritis (RA). RA patients have a high-comorbidity burden necessitating their study. Comorbidity indices are used to measure comorbidities and to study their impacts on different outcomes. A large number of such indices are used in clinical research. Some indices have been specifically developed in RA patients. AIM: This review aims to provide an overview of generic and specific comorbidity indices commonly used in RA research. METHODS: We performed a critical literature review of comorbidity indices in RA using the PubMed database. RESULTS/DISCUSSION: This non-systematic literature review provides an overview of generic and specific comorbidity indices commonly used in RA studies. Some of the older but commonly used comorbidity indices like the Charlson comorbidity index and the Elixhauser comorbidity measure were primarily developed to estimate mortality risk from comorbid diseases. They were not specifically developed for RA patients but have been widely used in rheumatology comorbidity measurement. Of the many comorbidity indices available, only the rheumatic disease comorbidity index (RDCI) and the multimorbidity index have been specifically developed in RA patients. The functional comorbidity index was developed to look at functional disability and has been used in RA patients considering that morbidity is more important than mortality in such patients. While there is limited data comparing these indices, available evidence seems to favor the use of RDCI as it predicts mortality, hospitalization, disability, and healthcare utilization. The choice of the index, however, depends on several factors such as the population under study, outcome of interest, and sources of data. More research is needed to study the RA-specific comorbidity measures to make evidence-based recommendations for the choice of a comorbidity measure.
29467860 Roles of microRNA-539 and osteopontin in rheumatoid arthritis. 2018 Mar The present study aimed to investigate the role and mechanism of microRNA-539 (miR-539) in rheumatoid arthritis (RA). A total of 68 RA patients and 46 osteoarthritis patients were enrolled into the current study. Peripheral blood and joint fluid were collected prior to treatment. Reverse transcription-quantitative polymerase chain reaction was performed to detect osteopontin (OPN) mRNA and miR-539 expression levels, while ELISA and western blot analysis were applied to detect OPN protein expression. In addition, bioinformatics analysis predicted that miR-539 directly targeted OPN, while dual-luciferase assay was used to validate this finding. Furthermore, agomiR-539 transfection and OPN knockdown by siRNA were conducted in MH7A cells, and MTT assay was used to detect MH7A cell proliferation. The results indicated that OPN was significantly increased in the blood and joint fluid of RA patients, while miR-539 expression was significantly decreased in the two types of specimens (P<0.05). Subsequent to silencing OPN by siRNA, the proliferation of MH7A cells was decreased (P<0.05). Following upregulation of miR-539, OPN expression was significantly decreased and cell proliferation was inhibited. Dual-luciferase assay revealed that miR-539 regulated OPN expression through complementary binding to 3'-untranslated region. OPN was also significantly increased in the blood and joint fluid of RA patients, which may be associated with the downregulation of miR-539. Thus, miR-539 may promote the development and progression of RA through regulating OPN.
29470832 Real-World Treatment Patterns for Golimumab and Concomitant Medications in Japanese Rheuma 2018 Jun INTRODUCTION: The aim of this study was to investigate real-world treatment patterns for use of golimumab and concomitant medications in Japanese patients with rheumatoid arthritis. METHODS: This study was a post hoc retrospective analysis from post-marketing surveillance data on 2350 Japanese patients with moderate/severe rheumatoid arthritis who received golimumab for 24 weeks. The study population was divided based on initiation treatment or dose adjustment patterns with golimumab, methotrexate, or oral glucocorticoids. RESULTS: Logistic regression analysis revealed that the baseline factors associated with administration of golimumab (100 mg) were higher body weight, failure of prior biological therapy (bio-failure), no previous methotrexate use, and respiratory disease, while previous methotrexate use and absence of renal impairment or respiratory disease were associated with concomitant methotrexate therapy, and previous glucocorticoid use was associated with concomitant glucocorticoid therapy. The following associations were identified with regard to dose adjustment during treatment: bio-failure, no previous methotrexate use, previous csDMARDs use, presence of respiratory disease, allergy history, and higher CRP for golimumab dose escalation; shorter disease duration, previous GC, and no previous methotrexate use for methotrexate dose escalation; no prior biological therapy and renal impairment for methotrexate dose reduction; no previous GC use for glucocorticoid dose escalation; and absence of Steinbrocker's stage II/III/IV, absence of Steinbrocker's class II, no bio-failure, and no previous csDMARDs use for glucocorticoid dose reduction. CONCLUSIONS: This study revealed that various baseline factors were associated with initiation of treatment and dose adjustment of golimumab, methotrexate, or oral glucocorticoids, reflecting both the treatment strategies of physicians for improving RA symptoms and/or reducing adverse events. FUNDING: Janssen Pharmaceutical K.K. and Mitsubishi Tanabe Pharma Corporation.
29303021 Therapeutic effect of acetazolamide, an aquaporin 1 inhibitor, on adjuvant-induced arthrit 2018 Apr OBJECTIVES: Previous studies have shown that aquaporin 1 (AQP1) is up-regulated in synovium and cartilage of rheumatoid arthritis (RA) patients and that AQP1 may be involved in joint swelling and synovial inflammation. This study was aimed to investigate the potential therapeutic effect of acetazolamide (AZ, an AQP1 inhibitor) on rat adjuvant-induced arthritis (AIA) and explore its related mechanisms. MATERIALS AND METHODS: Rat AIA was induced by complete Freund's adjuvant. The effect of AZ on rat AIA was evaluated by secondary hind paw swelling, arthritis index, TNF-α and IL-1β serum levels and histological examination of ankle joint. Proteoglycans expression and mRNA levels of type-II collagen (COII) and aggrecan in cartilage were measured by alcian blue staining and real-time PCR, respectively. The protein levels of AQP1, IκBα, phospho-IκBα (p-IκBα), NF-κB p65 and phospho-NF-κB p65 (p-NF-κB p65) in synovial tissues were detected by western blot. RESULTS: AZ treatment could inhibit secondary hind paw swelling and arthritis index, reduce serum levels of TNF-α and IL-1β, and ameliorate pathological changes of ankle joint in AIA rats. AZ increased proteoglycans production and mRNA levels of COII and aggrecan in cartilage tissues. Moreover, AZ decreased AQP1 protein level and suppressed the activation of NF-κB pathway in synovium, indicated by inhibiting the degradation and phosphorylation of IκBα and reducing p-NF-κB p65 protein level. CONCLUSIONS: AZ as an AQP1 inhibitor has a powerful therapeutic effect on rat AIA via inhibiting NF-κB activation, suggesting AQP1 inhibition might be of potential clinical interest in RA treatment.
29722610 Cinnamon Consumption Improves Clinical Symptoms and Inflammatory Markers in Women With Rhe 2018 May 3 OBJECTIVE: This study evaluated the effect of cinnamon on disease activity, serum levels of some inflammatory markers, and cardiovascular risk factors in women with rheumatoid arthritis (RA). METHODS: In this randomized double-blind clinical trial, 36 women with RA were randomly divided to 2 groups, receiving 4 capsules of either 500 mg cinnamon powder or placebo daily for 8 weeks. Fasting blood sugar (FBS), lipid profile, liver enzymes, serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), erythrocyte sedimentation rate (ESR), blood pressure, and clinical symptoms were determined at baseline and end of the week 8. RESULTS: At the end of the study, there was a significant decrease of serum levels of CRP (p < 0.001) and TNF-α (p < 0.001) in the cinnamon group as compared to the placebo group. Diastolic blood pressure was also significantly lower in the intervention group compared with the control group (p = 0.017). Compared with placebo, cinnamon intake significantly reduced the Disease Activity Score (DAS-28) (p < 0.001), Visual Analogue Scale (VAS) (p < 0.001), and tender (TJC) (p < 0.001) and swollen joints (SJC) (p < 0.001) counts. No significant changes were observed for FBS, lipid profile, liver enzymes, or ESR. CONCLUSION: Cinnamon supplementation can be a safe and potential adjunct treatment to improve inflammation and clinical symptoms in patients with RA.
29951877 The Influence of LPS-Induced Maternal Inflammation on Postnatal Collagen-Induced Arthritis 2018 Oct Maternal health and nutritional status influence offspring health and the diseases that may develop in them. The effects of maternal inflammation on offspring from the perspective of the inflammatory response and immune changes are not fully understood. We hypothesized that maternal inflammation modulates immune and metabolic functions, affecting the pathophysiology of inflammatory diseases in offspring. This study investigated whether maternal inflammation affects the onset of collagen-induced arthritis (CIA), a murine model of human rheumatoid arthritis. Female DBA/1J mice received a single intraperitoneal injection of lipopolysaccharide (LPS) 5 days before conception. Male offspring of LPS-treated dams were placed in the maternal LPS group (MLG). To induce CIA, type II collagen (CII) was emulsified with Freund's complete adjuvant and injected twice into each mouse, at 13 and 16 weeks. The offspring were sacrificed at 26 weeks to analyze immunological and metabolic parameters. The degree of joint swelling at an early stage of CIA was lower in the MLG than in the control group. From histological analysis, the severity of joint destruction (severity of arthritis score) and CII-specific IgG titer were significantly lower in the MLG. However, at 26 weeks, serum interleukin (IL)-6 levels, an index of CIA disease activity, were significantly higher in the MLG. Moreover, serum leptin levels were lower in the MLG, and a negative correlation between leptin and serum IL-6 was observed. In conclusion, maternal inflammation does not merely suppress inflammation; it may delay CIA in offspring. The analysis of inflammatory cytokines and leptin concentrations at 26 weeks suggests that the pathophysiology of arthritis was worsening. This study also suggests that maternal inflammation modulates postnatal inflammatory response patterns in offspring.
29643053 A Novel Mobile App and Population Management System to Manage Rheumatoid Arthritis Flares: 2018 Apr 11 BACKGROUND: Rheumatoid arthritis flares have a profound effect on patients, causing pain and disability. However, flares often occur between regularly scheduled health care provider visits and are, therefore, difficult to monitor and manage. We sought to develop a mobile phone app combined with a population management system to help track RA flares between visits. OBJECTIVE: The objective of this study is to implement the mobile app plus the population management system to monitor rheumatoid arthritis disease activity between scheduled health care provider visits over a period of 6 months. METHODS: This is a randomized controlled trial that lasts for 6 months for each participant. We aim to recruit 190 patients, randomized 50:50 to the intervention group versus the control group. The intervention group will be assigned the mobile app and be prompted to answer daily questionnaires sent to their mobile devices. Both groups will be assigned a population manager, who will communicate with the participants via telephone at 6 weeks and 18 weeks. The population manager will also communicate with the participants in the intervention group if their responses indicate a sustained increase in rheumatoid arthritis disease activity. To assess patient satisfaction, the primary outcomes will be scores on the Treatment Satisfaction Questionnaire for Medication as well as the Perceived Efficacy in Patient-Physician Interactions questionnaire at 6 months. To determine the effect of the mobile app on rheumatoid arthritis disease activity, the primary outcome will be the Clinical Disease Activity Index at 6 months. RESULTS: The trial started in November 2016, and an estimated 2.5 years will be necessary to complete the study. Study results are expected to be published by the end of 2019. CONCLUSIONS: The completion of this study will provide important data regarding the following: (1) the assessment of validated outcome measures to assess rheumatoid arthritis disease activity with a mobile app between routinely scheduled health care provider visits, (2) patient engagement in monitoring their condition, and (3) communication between patients and health care providers through the population management system. TRIAL REGISTRATION: ClinicalTrials.gov NCT02822521, http://clinicaltrials.gov/ct2/show/NCT02822521 (Archived by WebCite at http://www.webcitation.org/6xed3kGPd).
29359662 Inflammatory Arthritis and Heart Disease. 2018 BACKGROUND: The term inflammatory joint disease (IJD) includes a group of chronic conditions, particularly rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA), with predominant joint involvement and increased risk of cardiovascular (CV) complications and premature mortality. OBJECTIVE: The study aims to review of the most relevant CV manifestations from clinical point of view associated with IJD. METHODS: To update the current knowledge on CV manifestations in patients with IJD, we review the most relevant literature studies published in English (PubMed database) from January 2007 to February 2017. RESULTS: Ischemic heart disease and congestive heart failure are the most relevant complications and those causing higher mortality. Pericarditis and myocarditis may be seen in patients with RA, especially in flares of disease, although they are often asymptomatic. Left ventricular diastolic ventricular dysfunction is an increasing recognized problem. Arrhythmias and cardiac conduction disturbances may be observed in patients with IJD. Chronic inflammation and fibrosis of the cardiac conduction system may be responsible for these complications. Noninvasive diagnostic tools including cardiac magnetic resonance imaging and echocardiography have improved considerably our understanding of the cardiovascular disease in IJD. CONCLUSION: Cardiac manifestations in IJD are frequent and they are the leading cause of an increased morbimortality in IJD. Clinicians would be aware of that, given that early diagnosis of these complications may reduce the frequency of CV events and improve survival of patients with IJD.
29863076 5-Hydroxy-2-methylpyridine Isolated from Cigarette Smoke Condensate Aggravates Collagen-In 2018 The risk of rheumatoid arthritis (RA) is linked to environmental and genetic factors. Cigarette smoking is an established environmental risk factor for the disease that contributes to its development and severity. Previously, we found that cigarette smoke condensate (CSC), both mainstream and sidestream, aggravates collagen type II-induced arthritis (CIA), which was observed following either intraperitoneal inoculation or nasal exposure. In the present study, we aimed to identify the compound in CSC, which aggravates CIA. By sequential fractionation and analysis, extraction with water/ether in different pH values, silica gel column chromatography, TLC, octadecyl silica (ODS) HPLC, GC/MS, and NMR, the active compound was identified as 5-hydroxy-2-methylpyridine (5H2MP). Its isomer 2-hydroxy-3-methylpyridine, but not 3-hydroxy-2-methylpyridine, was also active. 5H2MP was not mutagenic, and did not exhibit aryl hydrocarbon receptor-dependent activity. Our data help clarify the mechanism underlying the pathogenic effects of cigarette smoking on RA.
30564450 Bromodomain protein inhibition: a novel therapeutic strategy in rheumatic diseases. 2018 The reading of acetylation marks on histones by bromodomain (BRD) proteins is a key event in transcriptional activation. Small molecule inhibitors targeting bromodomain and extra-terminal (BET) proteins compete for binding to acetylated histones. They have strong anti-inflammatory properties and exhibit encouraging effects in different cell types in vitro and in animal models resembling rheumatic diseases in vivo. Furthermore, recent studies that focus on BRD proteins beyond BET family members are discussed.
29679855 Rutin and rutin-conjugated gold nanoparticles ameliorate collagen-induced arthritis in rat 2018 Jun Numerous studies have suggested that nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) are important mediators of inflammatory response in human and animal models of arthritis. Besides, oxidative stress markers, nitric oxide (NO) and peroxide (PO) are also major contributors in the pathogenesis of rheumatoid arthritis (RA). Over expression of these inflammatory mediators leads to the extracellular matrix degradation, and excessive cartilage and bone resorption, ultimately leading to the irreversible damage to joints. The aim of the present study was to investigate the anti-arthritic mechanism of bioflavonoids, rutin and rutin-conjugated gold nanoparticles (R-AuNPs) by determining their role in the modulation of NF-κB and iNOS expression in collagen-induced arthritis (CIA) model of rats. Arthritis was induced by the subcutaneous administration of bovine type II collagen. Treatment was started with rutin, indomethacin + rutin (I + R) and R-AuNPs on the day of CIA induction. The severity of arthritis was determined by measuring the arthritic score on alternate days until mean arthritic score of 4 was observed. The NO and PO levels were also analyzed in serum samples. NF-κB and iNOS expression levels were determined in spleen tissue samples by real time RT-PCR and immunohistochemistry. Marked reduction in the arthritic score as well as in the NO and PO levels was observed in the treated groups. A significant downregulation in the NF-κB and iNOS expression levels was also observed in the treatment groups compared to the arthritic control group. Collectively, the findings suggest potential clinical role of rutin and R-AuNPs in the treatment of rheumatoid arthritis.
30701881 Multiple calcifying aponeurotic fibroma: case report and review of the literature. 2018 Apr 19 We describe the first case of diagnosis of generalized calcifying aponeurotic fibroma in 52 year-old man receiving long-term therapy for seronegative rheumatoid arthritis with rheumatoid nodules. The prevalence of lesions (presence of multiple subcutaneous nodules in the aponeuroses and fascia of the head, neck, trunk, upper and lower extremities with massive deposition of calcium salts), and a combination with monoclonal secretion (IgGκ serum, BJκ in the urine), raised inflammation markers, suggest that this case of the disease is unique, so both in domestic and foreign literature contains no description of this unusual course of this type of mesenchymal tumor. We have shown that subcutaneous nodules biopsy followed by morphological and immunohistochemical study is required in the diagnosis of the disease. We have given the literature data on the clinical manifestations, methods of diagnosis and differential diagnosis of this disease with a variety of pathologies, accompanied by the development of multiple calcification.