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ID PMID Title PublicationDate abstract
31902241 Identifying the differentially expressed microRNAs in autoimmunity: A systemic review and 2020 May The evidence indicates that microRNAs (miRNAs) can regulate gene expression and play an important role in the pathogenesis of autoimmune diseases, yet studies on expression profiles of miRNAs are still inconclusive. Our objective is to identify miRNAs that demonstrate enduring differential expression on autoimmune diseases. A systemic review and meta-analysis were performed by analysing the expression profile of miRNAs in several types of autoimmune disease, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type-1 diabetes (T1D). Several most significant differentially expressed miRNAs were identified and showed significant deregulation in autoimmune diseases. The most compelling results for SLE were with miR-21, miR-148a, miR-223, miR-125b in blood and miR-26a in kidney samples, for RA, miR-21, miR-24, miR-26a, miR-155 and miR-223 in blood, and for T1D, miR-148a, miR-181a in blood and miR-21, miR-155 in urine samples. Interestingly, some of miRNAs were differentially expressed in more than one autoimmune disease, such as miR-21, miR-26a, miR-155, miR-148a, miR-223. These miRNAs are commonly associated with the immune response and increases in the activity of the immune system and inflammation in specific organs such as skin, joint, lung, and kidney. These miRNAs can potentially be not only good biomarkers for the prediction, diagnosis, but also therapeutic targets in autoimmune diseases.
33912221 Intravenous injection of autologous bone marrow-derived mesenchymal stem cells on the gene 2020 BACKGROUND: Rheumatoid arthritis (RA) is the most prevalent autoimmune disease, in which CCL2 and CCL5 are critically involved. The objective was to evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells (MSCs) on the foregoing chemokines in RA patients. MATERIALS AND METHODS: Thirteen RA patients were evaluated in terms of clinical manifestations, paraclinical factors, gene expression, and plasma levels of CCL2 and CCL5 prior to treatment and 1 and 6 months after intervention. Real-time-polymerase chain reaction and enzyme-linked immunosorbent assay were employed to assess the gene expression and plasma levels of CCL2 and CCL5 at different time points after MSC therapy. Statistical analysis was performed by SPSS 16 and Prism 7. RESULTS: The CCL2 gene expression had statistically significantly increased (P = 0.034), and its plasma level had insignificantly reduced after 1 month. Furthermore, the gene expression and plasma level of CCL5 had statistically significantly decreased (P = 0.032, P < 0.001). The CCL5 gene expression had statistically significantly increased after 6 months (P = 0.001) and its plasma level had insignificantly reduced. CONCLUSION: The most significant inhibitory effects of MSC therapy on the gene expression and plasma level of CCL5 were observed at the end of 1 month. The differences between the gene expression and protein levels during the treatment might be related to microRNA effects or the insufficient number of MSC injection.
33381695 Associations between cytokine gene polymorphisms and rheumatoid arthritis in Turkish popul 2020 OBJECTIVE: Various cytokine polymorphisms have been associated with genetic risk factors predisposing to Rheumatoid Arthritis (RA) in different populations. To predict the clinical outcome as well as response to therapy in RA, studies aimed to describe genetic markers. The present study aims to search for polymorphisms of 13 cytokine coding genes in the Eastern Black Sea Region of Turkey. METHODS: DNAs of 49 patients and 96 healthy bone marrow and kidney donors were isolated from peripheral blood samples. Genotyping was performed using the Heidelberg Cytokine Typing Tray kit. PCR products were visualized on an agarose gel, and results were analyzed using the interpretation scheme provided with the kit. Arlequin 3.5 software was used for statistical analysis. RESULTS: No positive association was found between allele frequencies and the disease. However, a negative association was found for the IL-A -889 C allele (p=0.02, OR=0.533, Wald's 95% CI=0.318-0.893). IL-12 -1188 CC (p=0.01, OR=3.667, Wald's 95% CI=1.246-10.786), IL-4 -1098 GT (p=0.02, OR=2.405, Wald's 95% CI=1.129-5.125) genotypes were found positively associated with the RA, while IL-4 -590 CT (p=0.02, OR=0.422, Wald's 95% CI=0.201-0.886) was found negatively associated with the disease. In addition, IL-6 GG haplotype was found positively associated with the RA (p=0.02, OR=1.880, Wald's 95% CI=1.086-3.254). CONCLUSION: Our findings suggest that some polymorphisms of the IL-1A, IL-2, IL-4, IL-6 and IL-12 could be responsible for the susceptibility or protective to RA in our study population. Multi-centered and large numbers of subjects containing studies that search for cytokine polymorphisms will gather more information regarding the susceptibility to RA of Turkish patients.
32974365 Effect of Vitamin D Supplementation on Bone Mineral Density in Rheumatoid Arthritis Patien 2020 Objectives: To assess the effect of vitamin D supplementation on bone mineral density (BMD) in rheumatoid arthritis (RA) patients with osteoporosis and determine whether supplementation of more than 800 IU/day, which is the currently recommended dose, is beneficial. Methods: RA patients with osteoporosis who received bisphosphonate were included. Patients were classified into four groups according to the dose of vitamin D supplementation (0, 400, 800, and ≥1,000 IU/day). Multivariable linear regression models were performed to evaluate the effect of each dose of vitamin D supplementation on 1-year% change of BMD. Results: In total, 187 RA patients with osteoporosis were included. In the multivariate model adjusted for potential confounders, patients receiving vitamin D supplementation had a significantly higher increase in 1-year % change in lumbar spine BMD (400 IU/day: β = 2.51 [95% CI: 0.04-4.99], 800 IU/day: β = 2.90 [95% CI: 0.47-5.33], and ≥1,000 IU/day: β = 6.01 [95% CI: 3.71-8.32]) and femoral neck BMD (400 IU/day: β = 3.88 [95% CI: 1.83-5.94], 800 IU/day: β =4.30 [95% CI: 2.25-6.35], and ≥1,000 IU/day: β = 6.79 [95% CI: 4.87-8.71]) than those not receiving the supplementation. Notably, the ≥1,000-IU/day group had a significantly higher increase in 1-year % change in lumbar spine BMD (β = 3.11 [95% CI: 0.86-5.37]) and femoral neck BMD (β = 2.50 [95% CI: 0.63-4.36]) than the 800-IU/day group. Conclusion: In RA patients with osteoporosis receiving bisphosphonates, vitamin D supplementation was associated with a higher increase in BMD. This effect was higher in the vitamin D supplementation dose of ≥1,000 IU/day than in 800 IU/day.
32905201 JAK/STAT pathway in pathology of rheumatoid arthritis (Review). 2020 Oct Rheumatoid arthritis (RA) is classified as an inflammatory, chronic autoimmune and disabling disease based on the intricate interplay between environmental and genetic factors. With a prevalence ranging from 0.3 to 1%, RA is the most prevalent inflammatory joint disease observed in adults. Disruption of immune tolerance becomes evident when abnormal stimulation of the innate and adaptive immune system occurs. This cascade of events causes persistent joint inflammation, proliferative synovitis and, ultimately, damage of the underlying cartilage as well as the subchondral bone, leading to permanent joint destruction, deformity and subsequent loss of function. With cytokines being the key to a multitude of biological processes, including inflammation, hematopoiesis and overall immune response, one must inevitably look at the main pathways through which a significant number of those molecules exert their function. Janus kinase/signal transducers and activators of transcription (JAK/STATs) represent one such pathway and, recently, JAK inhibitors (JAKinibs) have shown promise in the treatment of several inflammatory diseases, including RA. This narrative review focuses on the intricate signaling pathways involved as well as on the clinical aspects and safety profiles of JAKinibs approved for the treatment of RA.
32801959 A Computerized Assessment of Verbal and Visuospatial Memory (Dys)functions in Patients wit 2020 PURPOSE: Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease associated with various degrees of impairment across different cognitive domains. We aimed to provide a detailed computerized investigation of verbal and visuospatial short-term and working memory (dys)functions in RA patients, assessing both accuracy and response speed, while relating them to age, disease-related activity, affective problems, psychomotor speed and other clinical parameters. PATIENTS AND METHODS: The study included 29 RA patients (mean age 50.6 ± 12.3 years, 79% female) and 30 controls (matched according to age, gender and education), assessed with short-term and working memory tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Automated Working Memory Assessment (AWMA). RESULTS: RA patients were significantly slower on the basic processing speed test (Motor Screening Test, p =0.003). Their short-term information storage (verbal and visuospatial) was comparable to controls, yet this similar accuracy came at the expense of a longer response time to retain information correctly (on spatial span, p = 0.04). On tasks with higher executive demands, both visuospatial and verbal working memory were compromised, as RA patients took longer (p = 0.004) and had a higher number of total errors (p = 0.02) when conducting a strategic memory-guided search (Spatial Working Memory), and had a significantly lower verbal working memory span on the backwards digit recall test (p = 0.02). CONCLUSION: The findings of this study emphasize the usefulness of performing computerized tests to detect subtle signs of cognitive impairment and of intact performance, which can inform memory training protocols for this vulnerable population.
33554027 Effusive-constrictive cholesterol pericarditis: a case report. 2021 Jan BACKGROUND: Cholesterol pericarditis (CP) remains a rare pericardial disease characterized by chronic pericardial effusions with high cholesterol concentrations with or without the formation of cholesterol crystals. Effusions are often large and can cause ventricular compression and subsequent pericardial adhesion formation. CP can be idiopathic but has associations with rheumatoid arthritis (RA), tuberculosis and hypothyroidism. CASE SUMMARY: We present a case of a 72-year-old male with a background of seropositive RA with a finding of an incidental pericardial effusion on computed tomography thorax abdomen and pelvis. Transthoracic echocardiogram demonstrated a large effusion with echocardiographic features of tamponade. On review, he was breathless with a raised venous pressure, bilateral ankle oedema, and pulsus paradoxus was present. Pericardial drainage was performed with fluid analysis demonstrating a cholesterol concentration of 8.3 mmol/L and numerous cholesterol crystal formation. Interval imaging demonstrated recurrence of the effusion with pericardial thickening and progressive constriction. He remained asymptomatic and underwent a successful pericardial window. At present, he is under close clinical outpatient surveillance with symptoms guiding a future pericardiectomy if warranted. DISCUSSION: CP can present as an emergent situation with signs and symptoms of acute heart failure with prompt pericardiocentesis required in cases of clinical tamponade. However, the disease course is often one of chronicity with relapsing large effusions that tend to recur following drainage, with the development of pericardial constriction necessitating pericardiectomy for definitive management.
32044247 The microbiome in autoimmune rheumatic disease. 2020 Feb Microbial contributions to the immunopathogenesis of autoimmune rheumatic diseases have been studied since the advent of germ theory in the 19th century. With the exception of Group A Streptococcus in rheumatic fever, early studies failed to establish causal relationships between specific pathobionts and rheumatic disease. Today, systemic autoimmune diseases are thought to result from a complex interplay of environmental factors, individual genetic risk, and stochastic events. Interactions of microbiota and the immune system have been shown to promote and sustain chronic inflammation and autoimmunity. In mechanistic studies, microbe-immune cell interactions have been implicated in the initiation of autoimmune rheumatic diseases, e.g., through the posttranslational modification of autoantigens in rheumatoid arthritis or through neutrophil cell death and cross-reactivity with commensal orthologs in systemic lupus erythematosus. In parallel, modern molecular techniques have catalyzed the study of the microbiome in systemic autoimmune diseases. Here, I review current insights gained into the skin, oral, gut, lung, and vascular microbiome in connective tissue diseases and vasculitis. Mechanism relevant to the development and propagation of autoimmunity will be discussed whenever explored. While studies on autoimmune rheumatic disease have almost invariably shown abnormal microbiome structure (dysbiosis), substantial variability in microbial composition between studies makes generalization difficult. Moreover, an etiopathogenic role of specific pathobionts cannot be inferred by association alone. Integrating descriptive studies of microbial communities with hypothesis-driven research informed by immunopathogenesis will be important in elucidating targetable mechanisms in preclinical and established rheumatic disease.
32635645 Notch-1 Signaling Modulates Macrophage Polarization and Immune Defense against Mycobacteri 2020 Jul 5 Despite the extensive research on Notch signaling involvement in inflammation, its specific role in macrophage response in autoimmune disease and defense mechanisms against bacterial infection, such as Mycobacterium avium paratuberculosis (MAP), remains unknown. In this study, we investigated the molecular role of Notch-1 signaling in the macrophage response during MAP infection. In particular, we measured the in vitro effect of MAP on Notch-1 signaling and downstream influence on interleukin (IL)-6 and myeloid cell leukemia sequence-1 (MCL-1) and consequent cellular apoptosis, MAP viability, and macrophage polarization. Overall, the data show significant upregulation in Notch-1, IL-6, and MCL-1 in MAP-infected macrophages, parallel with a decrease in apoptosis and elevated pro-inflammatory response in these infected cells. On the contrary, blocking Notch signaling with γ-secretase inhibitor (DAPT) decreased MAP survival and burden, increased apoptosis, and diminished the pro-inflammatory response. In particular, the treatment of infected macrophages with DAPT shifted macrophage polarization toward M2 anti-inflammatory phenotypic response. The outcome of this study clearly demonstrates the critical role of Notch signaling in macrophage response during infection. We conclude that MAP infection in macrophages activates Notch-1 signaling and downstream influence on IL-6 which hijack MCL-1 dependent inhibition of apoptosis leading to its chronic persistence, and further inflammation. This study supports Notch-1 signaling as a therapeutic target to combat infection in autoimmune diseases such as Crohn's disease and Rheumatoid Arthritis.
33758817 Obesity and Remission Rates in Japanese Patients With Rheumatoid Arthritis Requiring Anti- 2020 Dec OBJECTIVES: This study aims to determine if obesity is a risk factor for a poor response to anti-tumor necrosis factor alpha (anti-TNFα) therapy in Japanese patients with rheumatoid arthritis (RA) using the appropriate body mass index (BMI) cut-off points for Asian populations. PATIENTS AND METHODS: This retrospective cohort study evaluated 382 outpatients with RA (98 males, 284 females; mean age 54.2 years; range, 18 to 84 years) who had received anti-TNFα therapy between May 2009 and July 2017. Patients were classified according to BMI at baseline as follows: <18.5 kg/m(2) (underweight), 18.5-23.0 kg/m(2) (normal weight), 23.0-27.5 kg/m(2) (overweight), and ≥27.5 kg/m(2) (obese). The response variable was defined as Simplified Disease Activity Index (SDAI) remission after 12 months. We estimated odds ratios (ORs) and their 95% confidence intervals (CIs) for poor response to the therapy. RESULTS: After 87 patients were excluded, 183 (62.0%) of 295 had reached remission at the 12-month follow-up. Compared with normal-weight patients, the multivariate OR for poor response of obese patients was 2.2 (95% CI: 0.5-9.4). Adjusting for the baseline SDAI score, the corresponding OR was 1.8 (0.4-7.6). CONCLUSION: We found no statistically significant association between obesity and poor response to anti-TNFα therapy in Japanese patients with RA. Because this may partly be due to the limited statistical power of our study, further research is warranted to examine the possible effect modification across countries.
33456537 Network analysis and transcriptome profiling in peripheral blood mononuclear cells of pati 2021 Feb The present study aimed to investigate the differential expression of long non-coding RNAs (lncRNAs) in rheumatoid arthritis (RA). High-throughput gene sequencing technology was used to detect the expression of lncRNA and mRNA in three patients with RA (RA group) and normal controls (NC group). A Bioinformatics analysis was used to assess the effects of differentially expressed mRNAs on signaling pathways and biological functions. The selected dysregulated lncRNAs were verified by reverse transcription-quantitative (RT-q)PCR in the peripheral blood mononuclear cells (PBMCs) of patients with RA and age- and sex-matched controls. A correlation analysis was used to analyze the relationship between lncRNAs and clinical indexes. From the lncRNA sequencing data, significantly differentially expressed lncRNAs between the RA and NC groups were identified by a fold change ≥2 and P<0.05. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the differentially expressed mRNAs were mainly involved in organelle composition, intracellular regulation, signaling pathways, cancer, virus and inflammation. A total of four of these lncRNAs were confirmed by RT-qPCR to be significantly differentially expressed (LINC00304, MIR503HG, LINC01504 and FAM95B1). Through the correlation analysis, it was confirmed that there was a strong correlation between these lncRNAs and clinical laboratory indicators and indexes such as course of disease, arthrocele and joint tenderness. Overall, the present results suggested that the expression levels of LINC00304, MIR503HG, LINC01504 and FAM95B1 in PBMCs from patients with RA may serve as potential biomarkers for RA diagnosis, influencing the occurrence and progress of RA.
33437356 LncRNA LOC100912373 modulates PDK1 expression by sponging miR-17-5p to promote the prolife 2020 Rheumatoid arthritis (RA) is a common autoimmune disease and characterized by chronic inflammation, abnormal synovial cell proliferation, and joint swelling and tenderness, and it causes patients substantial pain. To date, the pathogenesis of RA remains unclear, and specific treatment is still lacking in the clinic. Evidence from previous research indicated that the long noncoding RNA (lncRNA) LOC100912373 is a key lncRNA and involved in RA. However, our understanding of the specific mechanism of lncRNA LOC100912373 in RA development and progression is still in its infancy. In this study, fibroblast-like synoviocytes (FLSs) were cultured by enzyme-dispersed and substrate-attached explant methods. The MTT method, flow cytometry and transmission electron microscopy were used to determine the effect of lncRNA LOC100912373 on FLSs. The expression of key genes such as lncRNA LOC100912373, miR-17-5p, PDK1 and AKT in FLSs was detected by RT-qPCR, immunofluorescence and Western blot. The localization of lncRNA LOC100912373 was determined by fluorescence in situ hybridization. The specific targeting relationship between lncRNA LOC100912373 and miR-17-5p/PDK1 was verified by RNA immunoprecipitation and luciferase reporter gene analysis. The results showed that lncRNA LOC100912373 localized in the cytoplasm and was highly expressed in the synovial tissues and FLSs of AA rats. LncRNA LOC100912373 overexpression promoted the proliferation of FLSs. In addition, lncRNA LOC100912373 could bind to miR-17-5p, and the expression of lncRNA LOC100912373 was negatively correlated with miR-17-5p and positively correlated with PDK1/AKT. In conclusion, lncRNA LOC100912373 may upregulate the expression of PDK1 by sponging miR-17-5p, accelerating the phosphorylation of AKT and inducing the proliferation of FLSs, thus promoting the occurrence and development of RA.
33424444 Relation Between Anti-CCP Antibodies and Sharp Score in Rheumatoid Arthritis. 2020 Sep INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic rheumatic disease, very complex, with many different forms, progressive course, with pronounced changes in the joints, still unknown etiology and poorly understood pathology. Assessing of structural change can be done with proposed scores which observe changes on wrist and wrist joints, as a Sharp score. AIM: To examine the correlation between Anti-Citrullinated Protein Antibodies (Anti-CCP) values and Sharp score, and to determine the importance of Sharp score in the progression of RA. METHODS: The study had prospective character and followed patients in the period from January 1, 2017 to December 31, 2017. The study included 40 patients with RA. At the beginning of the follow-up of patients, X-ray of hands and feet were performed. RESULTS: Out of total of 40 patients, 34 or 85% had a follow-up examination after one year. Of these, 14 patients (41.2%) were reported to have complications. The subjects were divided into two groups according to Anti-CCP values. First group included patients with Anti-CCP values <4 and second those who had Anti-CCP> 4. Statistical analysis of the number of patients with complications at first and repeated examination indicated that there were no significant differences and that the sample was consistent between the first and repeated results (p> 0.05). Patients with higher Anti-CCP values also had a higher Sharp score with statistically significant differences during repeated examination (p <0.05). Correlation analysis shows that there was statistically significant (p <0.05) positive correlation with Anti-CCP values, and that an increase in values leads to an increase in the Sharp score (first measurement rho = 0.193, p> 0.05; repeated measurement rho = 0.645, p <0.0001). No statistically significant differences in Sharp score values at the first examination were compared with the repeated examination, but there was a statistically significant difference after one year in patients with complications (X2 = 13,388; p = 0.001), indicating that the Sharp score reflects disease progression. CONCLUSION: Anti-CCP values are also directly correlated with the Sharp score, which should be routine in both initial and repeated examination of a patient with RA. Sharp's score represents a marker of progression as well as of therapeutic modality of RA.
32290218 Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows 2020 Apr 10 Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5-1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10-20% of mortality, with a mean survival of 5-8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.
33244703 A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with 2021 Mar INTRODUCTION: Upadacitinib and tofacitinib are Janus kinase inhibitors approved for moderate-to-severe rheumatoid arthritis (RA). In the absence of head-to-head trials comparing their effectiveness, this study assessed the efficacy of upadacitinib 15 mg once-daily monotherapy/combination therapy against tofacitinib 5 mg twice-daily combination therapy among patients with RA using matching-adjusted indirect comparisons (MAICs). METHODS: The first of two MAICs used individual patient data (IPD) from the 14-week SELECT-MONOTHERAPY trial (upadacitinib [n = 217] vs. methotrexate [n = 216]) and published data from the ORAL Standard trial (tofacitinib + methotrexate [n = 204] vs. methotrexate [n = 108]). The second MAIC used IPD from the 26-week SELECT-COMPARE trial (upadacitinib + methotrexate [n = 647] vs. adalimumab + methotrexate [n = 324]) and published data from ORAL Strategy (tofacitinib + methotrexate [n = 376] vs. adalimumab + methotrexate [n = 386]). Data from patients in the upadacitinib trials were re-weighted based on age, sex, race, swollen joint count 66/28, tender joint count 68/28, C-reactive protein (CRP), and patients' global assessments to match the patient characteristics in tofacitinib trials. After matching, ACR20/50/70 and clinical remission (SDAI[CRP] ≤ 3.3, CDAI ≤ 2.8, DAS28-ESR/CRP < 2.6) were compared for upadacitinib vs. tofacitinib + methotrexate at month 3 and upadacitinib + methotrexate vs. tofacitinib + methotrexate at months 3 and 6 using Wald tests. RESULTS: At month 3, upadacitinib monotherapy patients experienced significantly larger improvement in ACR70 compared to tofacitinib + methotrexate (mean difference in difference [DID]: 9.9%; p = 0.019), while upadacitinib + methotrexate was associated with higher ACR50 compared to tofacitinib + methotrexate (DID: 12.9%; p = 0.011). At month 6, upadacitinib + methotrexate patients experienced significantly larger improvement in SDAI/CDAI/DAS28-ESR clinical remission compared to tofacitinib + methotrexate, with DIDs of 9.1% (p = 0.011), 7.5% (p = 0.038), and 11.3% (p = 0.002), respectively. CONCLUSIONS: Compared to tofacitinib combination therapy, treatment with upadacitinib monotherapy and combination therapy were associated with improved outcomes at 3/6 months (monotherapy: ACR70; combination: ACR50, SDAI, CDAI, and DAS28-ESR remission).
33066470 Synthesis, Molecular Docking, and In Vitro Boron Neutron Capture Therapy Assay of Carboran 2020 Oct 14 In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl-n-butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl-n-butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine (1) using potassium carbonate in a solvent of N,N-dimethyl formamide, with 4-methylcarboranyl-n-butyl iodide, (2) forms methylcarboranyl-n-butyl sinomenine (3) in 54.3% yield as a new product. This new compound was characterized by (1)H, (13)C, and (11)B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of 3, along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively.
32982898 Effect of an 8-Week Yoga-Based Lifestyle Intervention on Psycho-Neuro-Immune Axis, Disease 2020 Various external stressors and environmental challenges lead to the provocation of the immune system in autoimmune diseases like Rheumatoid arthritis (RA). The inappropriate immune response further triggers the cascade of inflammatory changes resulting in precipitation of symptoms and hampers quality of life (QOL). The underlying psycho-somatic component of the disease requires a holistic approach to its treatment dimension rather than the use of pharmacotherapy. The applicability of mind-body interventions has become essential in today's fast-paced life. Yoga, a mind-body technique, alters the mind's capacity to facilitate systemic functioning at multiple organ system levels. Hence, we conducted this study to evaluate the impact of 8 weeks of a yoga-based lifestyle intervention (YBLI) on psycho-neuro-immune markers, gene expression patterns, and QOL in RA patients on routine medical therapy. A total of 66 patients were randomized into two groups: yoga group or non-yoga group and were assessed for a panel of inflammatory cytokines (IL-6, IL-17A, TNF-α, and TGF-β), mind-body communicative markers (BDNF, DHEAS, β-endorphin, and sirtuin) and transcript levels of various genes (IL-6, TNF-α, NFKB1, TGF-β, and CTLA4). We assessed disease activity and QOL using the DAS28-ESR and WHOQOL-BREF questionnaire, respectively. Yoga group observed significant improvements in the levels of markers, which influenced the psycho-neuro-immune axis (p < 0.001) with an estimated effect size from small to medium range. In the yoga group, there was a significant reduction in DAS28-ESR (p < 0.001) and improvement seen in the physical health, psychological, social relationships domains (p < 0.001) of QOL, except environmental (p > 0.05). The yoga group showed downregulation of IL-6, TNF-α, and CTLA4 and upregulation of TGF-β. These results suggest that a decrease in disease activity after yoga practice is associated with a significant reduction in inflammatory cytokines, the elevation of mind-body communicative markers, and normalization of various transcript levels, which improved QOL. Thus the adoption of YBLI improves clinical outcome in RA, and decreases systemic inflammation by its beneficial effects on psycho-neuro-immune axis and normalization of dysregulated transcripts. Thus YBLI may be used for RA patients as an adjunctive therapy.
32600980 «Living with Rheumatoid Arthritis» in an Indigenous Qom Population in Argentina. A Quali 2020 Jun 26 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic disease which impacts patients' quality of life. The prevalence of RA in the qom population was 2.4% and represented an aggressive and disabling disease. The study goal was to describe the experience of the indigenous qom community individual suffering from RA, along with their experience with the local health care system in the city of Rosario, Santa Fe, Argentina. METHODS: Qualitative Study using techniques of participant observation and semi-structured interviews; following a guideline developed by a multidisciplinary research group comprising anthropologists, rheumatologists, nurses, and psychologists. A triangulation strategy was implemented for the analysis. RESULTS: A total of 33 interviews were conducted in 29 individuals with RA. The results showed a «normalization» of their symptoms and of their limitations in performing daily tasks. The individual relationships with the local health care system was complex and limited in several aspects (e.g. access to health care, continuity of treatment, complexity of medical care pathway and lack of cultural competence). CONCLUSIONS: RA is a disease that has a negative impact on the daily lives of the qom people living in Rosario. Improving the relationship between this population and the local health care system as well as the implementation of multidisciplinary work should be priorities.
32057667 Effectiveness of intravenous tocilizumab in routine clinical practice in a cohort of Costa 2021 Jun OBJECTIVE: To determine the effectiveness and the incidence of severe adverse events in a cohort of Costa Rican patients with Rheumatoid Arthritis (RA) treated with intravenous (IV) tocilizumab (TCZ). PATIENTS AND METHODS: A retrospective analysis was carried out in 45 patients that were unresponsive to disease-modifying antirheumatic drugs (DMARDs). The study included patients who received IV TCZ every 4 weeks (4mg/kg) along with methotrexate or leflunomide. Effectiveness was measured through the incidence of clinical remission according to a disease activity score - erythrocyte sedimentation rate (DAS28-ESR) less than 2.6. Safety was assessed by the incidence rate of serious adverse events. An univariate and multivariate logistic regression analysis was performed to assess the association of potential variables with the probability of achieving remission during the first 3 months of TCZ therapy. RESULTS: During the 3(rd) month of TCZ therapy, a total of 22 patients (48.9%; 95% Confidence Interval (CI) 34.3-63.5%) achieved remission. The cumulative incidence of patients with remission at month 12 was 75.0% (n=34) (95% CI: 62.3-87.6%). A total of 18 patients (40%; 95% CI: 25.7-54.3%) were switched to a 8mg/kg dose due to the absence of remission. The incidence rate of serious adverse events was .98 per 100 patients/year, all of them due to infectious diseases with no fatal events reported. Only basal DAS28-ESR was associated with the probability of achieving remission at month 3. CONCLUSIONS: IV TCZ (4mg/kg) is an effective and safe treatment for RA patients in a clinical setting in Costa Rica.
31828424 [Pregnancy and rheumatic diseases]. 2020 Feb Inflammatory rheumatic diseases preferentially affect women of childbearing age. Immunological alterations can have positive or negative effects on the maternal disease. Most of these women can have a successful pregnancy with careful medical and obstetric care. Nevertheless, complications are more frequent than in healthy women. Pregnancies should therefore be planned during inactive phases of the disease and patients should be educated in advance about possible maternal and child risks and about treatment options compatible with pregnancy. In pregnancy, individualized and interdisciplinary care can promote a stable course of the disease and reduce the risks for mother and child. Especially with respect to a compatible treatment, detailed information for the patients is necessary for a shared decision making.