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ID PMID Title PublicationDate abstract
33373915 Yishen-tongbi decoction inhibits excessive activation of B cells by activating the FcγRII 2021 Feb Rheumatoid arthritis (RA) is a chronic autoimmune disease. Strong evidence supports that excessive activation of B cells plays a critical role in the pathogenesis of RA. Fc gamma receptor b (FcγRIIb) is the B cell inhibitory receptor and inhibits BCR (B cell receptor) signalling in part by selectively dephosphorylating CD19 which is considered a co-receptor for BCR and is essential for B cell activation. Our previous study demonstrated that a FcγRIIb I232T polymorphism presented a strong genetic link to RA and may lead to the excessive activation of B cells. Therefore, novel therapeutic strategies and drugs that can effectively inhibit the excessive activation of B cells by regulating the FcγRIIb are necessary for the treatment of RA. Therefore, we used Burkitt's lymphoma ST486 human B cells (lacking endogenous FcγRIIb) transfected with the 232Thr loss-of-function mutant to construct a FcγRIIb mutant cell line (ST486), and we demonstrated that YSTB treatment not only reduced proliferation and promoted apoptosis in ST486 cells but also did so in a dose-dependent manner. Furthermore, the intracellular Ca(2+) flux of ST486 cells was decreased after treatment with YSTB, inhibiting the excessive activation of ST486 cells, and these effects correlated with the CD19/FcγRIIb-Lyn-SHP-1 pathways. Our data showed that YSTB treatment inhibited the expression of phosphorylated CD19 and upregulated the protein expression of FcγRIIb, Lyn, and SHP-1. Additionally, the CIA model was established to explore the anti-inflammatory and inhibitory effects of YSTB on bone destruction, and we found that YSTB decreased the paw oedema and arthritis index (AI) in CIA rats. It is worth mentioning that YSTB clearly decreased the AI earlier than methotrexate (MTX) (day 10 vs 16). Moreover, synovial hyperplasia, inflammatory cell infiltration and cartilage surface erosion in CIA rats were noticeably reduced after treatment with YSTB as evidenced by histopathological examination. Finally, we found that YSTB treatment suppressed bone erosion and joint space score (JNS) in CIA rats as evidenced by radiographic assessment. In summary, these data suggest that YSTB has great therapeutic potential for RA treatment.
32420568 Cedrol attenuates collagen-induced arthritis in mice and modulates the inflammatory respon 2020 May 1 Ginger has been used as a flavoring agent and traditional medicine for a long time in Asian countries. Pharmacological studies showed that it has antiemetic, anti-inflammatory and analgesic effects, which is attributed to its chemical constituents. The aim of the present study is to investigate the anti-rheumatoid arthritis properties of cedrol (CE) found in ginger. In an in vivo anti-RA study, CE remarkably alleviated the paw swelling and arthritis score in CE-treated CIA mice compared with the model group. The neutrophil count and the productions of TNF-α and IL-1β were inhibited, and the expressions of Rankl, Cox-1 and Cox-2 were down-regulated at the mRNA level. Radiologic evaluation, histopathological analysis and immunohistochemistry indicated that CE ameliorated inflammatory cell infiltration, synovial hyperplasia, and bone and cartilage damage, and exhibited an immunotherapeutic effect. The MTT assay demonstrated that CE (10(-10)-10(-5) M) had no cytotoxicity on fibroblast-like synoviocytes (FLSs), and exhibited an inhibitory effect on the proliferation of LPS-induced FLSs at concentrations of 10(-6) M and 10(-5) M. Mechanism research showed that the suppressed expressions of pivotal inflammatory mediators including COX-1 and COX-2 subsequently reduced the production of PGE(2), thereby causing the secretions of pro-inflammatory cytokines, ultimately attenuating the progression of inflammation. Meanwhile, the reduction in the mRNA levels of Mmp-13 and Mcp-1 responsible for osteoclastogenesis resistance was detected. This illustrated that CE showed anti-rheumatoid arthritis properties via blocking the phosphorylation of ERK/MAPK and p65/NF-κB signaling pathways in LPS-activated FLSs. The current research suggested that CE is an important functional component in ginger, which may be a promising candidate drug for RA therapy.
33195306 Joint Destruction Is Associated With All Types of Cardiovascular Events in French Rheumato 2020 Objective: Rheumatoid arthritis (RA) leads not only to joint destruction but also to systemic manifestations, with an increased incidence of cardiovascular events (CVE). Many studies have shown a link between RA severity and CV risk, but the duration of follow-up remains often insufficient to allow a conclusion. The CVE definition was generally reduced to myocardial infarction and stroke, and few studies were conducted in non-Anglo-Saxon countries with low CV incidence. This study aimed to assess the relationship between joint destruction and the occurrence of different types of CVE in a large cohort of French RA patients with a long-term follow-up. Methods: This historical cohort study included 571 RA patients followed between 1992 and 2012 in Lyon, France. The primary endpoint was the first occurrence of a CVE. Logistic regressions were used to identify factors associated with CVE occurrence. Cox proportional hazard models were performed as a separate analysis to take advantage of the long-term follow-up. Results: During a mean follow-up of 16.1 years, 30.3% of patients experienced a CVE, mostly acute arterial events. Joint destruction was associated with an increased risk of CVE [odds ratio = 3.72; 95% confidence interval (CI), 1.09-15.35; p = 0.047] among non-smoker RA patients. A survival analysis revealed that joint destruction was associated with a shorter time to onset of the first CVE only among non-smokers (hazard ratio = 3.44; 95% CI, 1.07-11.04; p = 0.038). Conclusion: Joint destruction is associated with CVE occurrence in RA patients from a population with a lower incidence of CV disease. This study suggests that RA patients, especially those with destruction, merit the institution of precise guidelines to manage this CV risk, and trials are required to evaluate them.
31643570 Penicillamine. 2012 Penicillamine is chelating agent used to decrease copper stores in Wilson disease, which also has immunomodulatory activity in rheumatic diseases such as rheumatoid arthritis, scleroderma and systemic lupus erythematosus. Penicillamine is capable of causing hypersensitivity reactions, some of which are accompanied by liver injury which is typically cholestatic.
33152484 COVID-19 in French patients with chronic inflammatory rheumatic diseases: Clinical feature 2021 Jan OBJECTIVE: To explore how patients with chronic inflammatory rheumatic diseases (CIRDs) coped with their disease during the COVID-19 pandemic and to identify possible predictive factors of SARS-CoV-2 infection in this population. METHODS: Patients followed in a single rheumatology department in France or registered on the Spondy+ platform, a secure e-health platform for spondyloarthritis patients, were invited to complete a questionnaire focused on their experiences around COVID19 symptoms, testing and medications access during the lockdown period. Descriptive statistics were used to report questionnaire's results. Factors associated with COVID-19 or with treatment discontinuation were assessed by logistic regression. RESULTS: We obtained 655 answers from the 2,081 contacted patients: 474 with spondyloarthritis, 129 with rheumatoid arthritis and 52 with psoriatic arthritis. The population was predominantly female (61.8%) with a mean age of 51.0±13.4 years. Incidence of COVID-19 was 6.9% (95%CI: 5.1-9.2%), including 12 confirmed and 33 highly suspicious cases. No death was observed and five patients needed to be hospitalized. Factors independently associated with an increased risk of infection were SARS-CoV-2 exposure, younger age and non-smoking. More than 30% of the patients suspended or decreased the dosage of one of their drugs during the lockdown period. This was followed in 63.4% of them by increased disease activity. Modifications were mostly motivated by fear of contagion (79.3%). CONCLUSION: We did not observe any increase of incidence or severity of COVID-19 in patients suffering of the 3 most common CIRDs. This survey also adds evidence of the safety of anti-rheumatic drugs use regarding COVID-19.
32322976 [Mesenchymal stem cell treatment in autoimmune diseases]. 2020 Jun Mesenchymal stromal or stem cells (MSC) possess strong immunomodulatory properties. Due to their impressive potential to differentiate into various cell types they are capable of inducing mechanisms of tissue repair. Experimental data have demonstrated impaired MSC function in several rheumatic diseases in vitro; however, the relevance of these phenomena for the pathogenesis of rheumatic disorders has not been convincingly demonstrated. Nevertheless, allogeneic MSC transplantation (MSCT), and possibly autologous MSCT as well, could prove to be an interesting instrument for the treatment of autoimmune rheumatic diseases. The first clinical trials have demonstrated positive effects in systemic lupus erythematosus, systemic sclerosis and Sjogren's syndrome; however, questions regarding the long-term benefits and safety as well as the best source, the optimal cultivation technique and the most effective way of application of MSC are still unanswered.
32110458 PL-7 Antisynthetase Syndrome in Association with Sjögren's, Systemic Lupus Erythematosus, 2020 We present a rare case of PL-7 antisynthetase syndrome (ASS) in association with Sjögren's, systemic lupus erythematosus (SLE), and seropositive rheumatoid arthritis (RA). Initially, the patient was diagnosed with Sjögren's followed by Sjögren's/SLE overlap and then Sjögren's/SLE/RA overlap. She was eventually diagnosed with Sjögren's/SLE/RA overlap with PL-7 ASS with interstitial lung disease (ILD). ILD was discovered after complaints of pleuritic chest pain with subsequent workup with coronary computed tomography (CT) revealing pulmonary fibrosis. This case demonstrates the ambiguity with which symptoms of ASS can present; given the high respiratory morbidity and mortality of ASS especially in non-Jo-1 patients, those who present with Raynaud's, myositis, or joint pain, whether together or in isolation, should be assessed for presence of additional features of ASS and potentially undergo testing for ASS antibodies if appropriate.
32850035 Ultrasonography in Early Rheumatoid Arthritis of Hand and Wrist Joints: Comparison with Ma 2020 Sep BACKGROUND: The aim of the study was to evaluate the use of ultrasonography (USG) including power Doppler in detecting hand and wrist joint changes in early rheumatoid arthritis (RA) and to compare USG findings with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Thirty-four patients diagnosed as RA by 2010 ACR/EULAR criteria; with the onset of symptoms within last one year, were included in the study after institute ethical clearance and informed consent to undergo USG and contrast-enhanced MRI of the dominant affected hand. Second to fifth metacarpophalangeal (MCP) joints, second to fifth proximal interphalangeal (PIP) joints and wrist joints (total nine joints) were evaluated for synovitis, erosions along with tenosynovitis. USG and MRI features were compared; agreement on the two imaging modalities as well as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of ultrasonography compared to MRI (gold standard) was calculated. RESULTS: One hundred thirty-six MCP, 136 PIP and 34 wrist joints (total 306 joints) and 136 flexor tendons were evaluated. The sensitivity, specificity, PPV, NPV and diagnostic accuracy of USG for diagnosing synovitis was 78.6%, 91.1%, 86.1%, 85.8%, 86.3%; for erosions 67.2%, 97.5%, 84.8%, 90.5%, 91.5%; for tenosynovitis 86.5%, 100%, 100%, 92.3% and 94.8% respectively. The overall agreement between USG and MRI for detection of synovitis was achieved in 83% joints and for erosions in 89.5% joints. CONCLUSION: In early RA, USG was nearly as effective in diagnosing features of joint and tendon sheath involvement, with relatively better performance of USG for tenosynovitis. The performance of USG in diagnosing erosions was limited likely due to difficult access of three-dimensional joint structure.
32612711 Doubtful swelling on clinical examination reflects synovitis in rheumatoid arthritis. 2020 AIMS: The aim of this study was to evaluate the implication of doubtful joint swelling on clinical examination with respect to objective markers of synovitis by ultrasound (US) in patients with rheumatoid arthritis (RA). METHODS: Two independent observers performed a modified 28 swollen joint assessment (28SJC), in which joints could be graded as either definitely swollen, non-swollen, or doubtfully swollen. Two examiners blinded to clinical information performed US assessment of the hands. We performed descriptive statistics and models to analyse the links between clinical assessment and objective markers of inflammation. RESULTS: A total of 1204 joints were evaluated in 43 RA patients; 93% (40/43) of patients had ⩾1 joint with doubtful swelling (range: 0-4/patient). Inter-reader reliability for the modified 28SJC was good (0.74). Generally, both grey scale (GS) and power Doppler (PD) discriminated across not swollen, doubtful, and swollen joints. GS signals discriminated better than PD between doubtful swelling and no swelling [odds ratio (OR) for GS: 5.2; 95% confidence interval (CI) 1.2-23.3 versus OR for PD 1.7; 95% CI 0.2-13.0], whereas PD discriminated better than GS between swelling and doubtful swelling (OR for PD: 28.7; 95% CI 3.6-228.2 versus GS: 1.7; 95% CI 0.3-8.4). Joint osteophytes did not increase the degree of doubtfulness. CONCLUSION: Clinical doubt in the assessment of joint swelling constitutes an intermediate state between unequivocal swelling and the lack thereof also regarding the objectively quantified level of inflammation. In order to increase sensitivity for joint inflammation, the historical clinical approach of considering doubtful swelling the absence of swelling should be revisited to interpret clinical doubtfulness as an indication of swelling.
32509015 Differential long non-coding RNA expression profiles in the peripheral blood and CD4(+) T 2020 Jul The human transcriptome is primarily composed of long non-coding RNAs (lncRNAs), which are key regulatory molecules of multiple biological processes. In the present study, the expression profiles of lncRNAs in the peripheral blood and CD4(+) T cells of patients with active rheumatoid arthritis (RA) were determined. Based on the expression profiles, 493 lncRNAs and 374 mRNAs were identified to be differentially expressed in the peripheral blood of active RA patients and healthy donors. Further verification of lncRNAs was performed using reverse transcription-quantitative (RT-q) PCR analysis of peripheral blood from 5 healthy donors and 5 patients with active RA and 14 additional differentially expressed genes were identified. CD4(+) T cells in peripheral blood from 12 patients with active RA and 8 healthy donors were isolated using magnetic beads and qPCR was used to assess differentially expressed lncRNAs. The results suggested that 7 lncRNAs were upregulated and 2 were downregulated. The results indicated that these 9 lncRNAs may be involved in the pathogenesis of RA. An increased ratio of Th17: T-regulatory (Treg) cells was also observed. It may be hypothesized that LncRNAs serve important roles in the differentiation of CD4(+) T cells. Receiver operating characteristic curve analysis suggested that these 9 lncRNAs are of potential clinical diagnostic value for RA. Pearson correlation analysis indicated that the correlation coefficient between Ensembl transcript (ENST)00000569543 and complement C4 was 0.623 (P<0.05), and that between ENST00000420096 and anti-cyclic citrullinated peptide antibody or disease activity evaluation score, the correlation coefficient was 0.662 and 0.605, respectively (P<0.05 for each). In conclusion, the results of the present study suggest a possible role of lncRNAs in the differentiation of CD4(+) T cells and the pathogenesis of RA, as well as the potential value as diagnostic biomarkers for active RA.
32425683 Joint remodeling outcome of serum levels of Dickkopf-1 (DKK1), cartilage oligomeric matrix 2020 INTRODUCTION: Rheumatoid arthritis (RA) is the most widespread chronic inflammatory rheumatic disease over the world. It is characterized by chronic proliferation of synovium, cartilage destruction, and periarticular erosion/bone loss. We investigated the serum levels of the C-telopeptide of type II collagen (CTX-II), Dickkopf-1 (DKK1), and cartilage oligomeric matrix protein (COMP) in relationship to the disease activity. MATERIAL AND METHODS: Serum COMP, CTX-II, and DKK1 levels were measured in 63 RA patients and 50 person age and gender matched as a healthy controls by ELISA test. Disease activity score (DAS) were calculated. RESULTS: The mean level of and COMP and CTX-II were significantly higher in patients with RA than in healthy controls (5.71 ±7.04 vs. 2.70 ±1.31 ng/ml, and 0.45 ±0.27 vs. 0.23 ±0.16 ng/ml, respectively; p < 0.001). Also, DKK1 serum levels were significantly higher in patients with RA than in healthy controls (6970.68 ±7566.68 vs. 3276.96 ±1306.77 pg/m; p < 0.001). There was a positive significant correlation between DKK1 and swollen joint (r = 0.42, p < 0.001). There were no significant differences in the number of patients, gender, the duration of RA disease, DAS, and RF. Sensitivity was 58.7% and specificity was 85.7% at a cut-off point (> 3.6 ng/ml) for serum COMP in RA patients, while, sensitivity was 100% and specificity was 52.4% at a cut-off point (> 0.15 ng/ml) for serum CTX-II and sensitivity was 68.3% and specificity was 95.2 % at a cut-off point (> 4876 pg/ml) for serum DKK1. CONCLUSIONS: Measurement of some serological biomarkers such as CTX-II, COMP, and DKK1 that reflect bone and cartilage destruction in RA patients could be used to indicate disease activity and early joint affection.
32411714 Impact of Rheumatoid Arthritis on Alopecia: A Nationwide Population-Based Cohort Study in 2020 Objectives: Studies on the relationship between rheumatoid arthritis (RA) and alopecia areata (AA) are limited. This study investigated the effect of RA on alopecia areata risk in a nationwide cohort study. Methods: We analyzed 2000-2012 data from the Longitudinal Health Insurance Database in Taiwan. The follow-up period was extended up to the end of 2013. We defined RA as a diagnosis using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 714.0 during at least three outpatient visits or one admission and the use of disease-modifying antirheumatic drugs (DMARDs) for >30 days. The enrollees with AA were identified using the ICD-9-CM code 704.01. We enrolled a comparison cohort comprising participants randomly matched by age and sex, with the same index date as that of the study cohort. Furthermore, we investigated alopecia risk by using Cox proportional-hazards regression models after propensity score matching for sex, age, comorbidities, and medication use. Results: In total, 2,905 patients with RA (74% women, mean age: 51.9 years) and 2,905 controls were followed for 22,276 and 25,732 person-years, respectively. Alopecia risk was 2.64-fold (95% confidence interval = 1.47-4.76) higher in patients with RA than in patients without RA after age, sex, comorbidities, and medication use were adjusted for. In addition, patients with thyroid disease presented considerable alopecia risk. Patients with RA in the younger age group (20-40 years) had the highest alopecia risk. Conclusions: Alopecia risk is significantly higher in patients with RA than in those without RA, particularly in the younger age group (20-40 years). RA assessment should be considered when examining patients with alopecia, especially young adults.
35117622 The utility of histological subtype for predicting survival of lung cancer patients with r 2020 Apr BACKGROUND: This study determined whether the survival of lung cancer (LC) patients with rheumatoid arthritis (RA) is differed by histological subtype. MATERIALS: This observational, retrospective study compared the LC survival rate of 34 RA patients with that of 132 age- and sex-matched patients without RA who received medical care from 2011 to 2016. Survival curves were generated using the Kaplan-Meier method. Cox proportional hazards regression analyses were used to estimate hazard ratios and determine risk factors predicting mortality according to histological subtype, including small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). RESULTS: The predominant histological subtype was adenocarcinoma in both groups, however, a larger proportion of SCLC patients was noted in patients with both LC and RA, compared to those with LC but without RA (26.5% vs. 12.9%, respectively; P=0.0317). LC patients with RA had a significantly lower body mass index (P=0.0488), and a higher proportion of interstitial lung disease (P<0.0001), compared to patients without RA. There was no statistical difference in the distribution of smoking status, stage, or comorbidity index between groups. Overall survival did not differ between LC patients with and without RA. Mortality was significantly worse for RA patients with SCLC than those with NSCLC (P=0.0404), and RA was associated with a 3.26-fold increase in mortality for SCLC patients with versus without RA (P=0.0350; 95% confidence interval: 1.05-9.56). However, RA was not a risk factor for mortality in NSCLC and, even in histological subtypes including lung adenocarcinoma and squamous cell carcinoma. CONCLUSIONS: RA was not associated with a lower overall survival rate for LC patients, irrespective of histological subtype. Because the effects of RA on LC mortality might differ between SCLC and NSCLC patients, future studies should recognize that the histological subtype may affect the outcome.
32180009 Assessment of cervical spine involvement in rheumatoid arthritis patients in the era of bi 2020 Jun Cervical spine involvement may lead to severe complications in rheumatoid arthritis (RA). In the era of modern therapies, atlantoaxial subluxation (AAS) may be rare; however, it may still be detected in asymptomatic patients. The onset of myelopathy can occur at any time. Altogether 49 female RA patients were included. Among them, 15 were methotrexate treated, biologic free, while 34 patients received biologics. The patients had no cervical pain or any neurological symptoms. We assessed the first (C1) and second (C2) cervical vertebrae by 3 T magnetic resonance imaging (MRI). In addition to AAS, we also determined odontoid erosion or periodontal soft tissue thickening. We associated our MRI findings with clinical, laboratory parameters, and hand radiography. We detected anterior AAS and soft tissue thickening in one-quarter, while odontoid erosions in eight (16%) of RA patients. There were no significant differences among the therapeutic subgroups. No posterior or vertical AAS was seen. Anterior AAS was associated with higher degree of inflammation, soft tissue thickening was seen at younger age, while odontoid erosions were associated with van der Heijde-Sharp scores of the hand. None of the patients had any lesions requiring surgery. The presence of cervical involvement in RA patients with 10-11 years of disease duration is still an important and frequent phenomenon. Higher disease activity and erosive disease are associated with atlantoaxial involvement. 3 T MRI is a sensitive method to assess AAS, as well as soft tissue lesions and odontoid erosions.
31921569 Fluorometric Imaging for Early Diagnosis and Prognosis of Rheumatoid Arthritis. 2020 Jan Early diagnosis and monitoring of disease progress are of significant importance in the effective treatment of rheumatoid arthritis (RA), because the continuing inflammation can lead to irreversible joint damage and systemic complications. However, applying imaging modalities for the prognosis of RA remains challenging, because no tissue-specific guidelines are available to monitor the progressive course of RA. In this study, fluorometric imaging of RA is reported using bioengineered targeted agents of the blood vessel, bone, and cartilage in combination with the customized optical fluorescence imaging system. Separate but simultaneous tissue-specific images of synovitis, cartilage destruction, and bone resorption are obtained from a mouse model of RA, which allows quantification of the prognosis of diseases at each stage. Thus, the fluorometric imaging of RA by using tissue-specific contrast agents plays a key role in the systemic treatment of RA by monitoring structural damage and disease progression.
33693010 The Relationship of Acupuncture Use to the Endometriosis Risk in Females With Rheumatoid A 2020 Objectives: Women affected by rheumatoid arthritis (RA) have a higher risk of endometriosis, an estrogen-dependent, chronic inflammatory disease. Though acupuncture has long been a safe and effective therapy for treating inflammatory conditions, it is unclear whether it could prevent the onset of endometriosis. This study aims to determine the effect of acupuncture on the subsequent risk of endometriosis in female RA patients. Methods: Between 1998 and 2010, female subjects with RA were recruited from a nationwide database (5,736 patients; age ≥20 years). Enrolled patients included 2,407 acupuncture users and 2,407 nonusers randomly selected using propensity scores. The occurrence of endometriosis was recorded through the end of 2012. Cox proportional hazards regression was used to estimate the adjusted hazard ratio (HR) associated with acupuncture use. Results: During the follow-up period, 35 acupuncture users and 94 non-users developed endometriosis, with incidence rates of 2.36 and 4.91 per 1,000 person-years, respectively. Acupuncture use was associated with a 55% lower endometriosis risk (adjusted HR, 0.45; 95% confidence interval, 0.31-0.65). Those who received high intensity acupuncture (≥15 packages) had the greatest benefit. Conclusions: Findings suggest that adding acupuncture to conventional therapy may decrease the subsequent endometriosis risk in female RA patients. Prospective randomized trials are recommended to further clarify whether the association revealed in this study supports a causal link.
32957710 Increased Risk of Temporomandibular Joint Disorder in Patients with Rheumatoid Arthritis: 2020 Sep 17 We evaluated the incidence of temporomandibular disorder (TMD) in patients with rheumatoid arthritis (RA) and examined the association between TMD and RA, through longitudinal follow-up. Population data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015 was used. From 514,866 subjects, 3122 with RA were matched with 12,488 controls in a 1:4 ratio. The crude and adjusted models (for obesity, smoking, alcohol consumption, blood pressure, blood glucose, total cholesterol, and Charlson Comorbidity Index scores) were calculated. Chi-square tests, Kaplan-Meier (KM) analysis, and two-tailed analyses were used for statistical analysis. Stratified Cox proportional hazard models were used to assess the hazard ratios (HR) and 95% confidence intervals (CI) for TMD in the RA group, compared to those in the control group. The adjusted HR for TMD in RA was 2.52 (95% CI = 1.70-3.74), compared to the control group. The results were consistent with the subgroup analyses, according to age and sex, except in men older than 60 years of age. KM analysis showed similar results. Hence, we found that patients with RA have a higher risk of TMD, and should be observed for symptoms of the initial stage of TMD to prevent the risk of aggravation.
32182619 Tea Consumption Is Associated with Decreased Disease Activity of Rheumatoid Arthritis in a 2020 INTRODUCTION: The role of tea consumption on rheumatoid arthritis (RA) has been studied in recent years, but no clear conclusion has been drawn as a result of small sample size of the studies or the fact that only in vitro studies have been performed. OBJECTIVES: The aim of this study was to explore the possible association of tea consumption with RA through a large-scale, real-world study. METHODS: A total of 733 RA patients were investigated from June to December, 2016. The disease activity of RA was assessed according to disease activity score 28-erythrocyte sedimentation rate. The amount and types of tea consumption were recorded by on-site self-administered questionnaires. Logistic regression models were applied to analyze the correlation between tea consumption and disease activity, adjusting for demographics, clinical and laboratory factors. RESULTS: There was an inverse association between tea consumption and disease activity in RA patients (OR 0.66, 95% CI 0.46-0.94). Compared with non-tea drinkers, a higher-intake of tea (>750 mL/day) was associated with lower disease activity of RA (OR 0.39, 95% CI 0.19-0.79), but not low-intake (≤750 mL/day; OR 0.83, 95% CI 0.42-1.63). A significant dose-response association was found between the amount of tea consumption and disease activity (p for trend <0.01). Further hierarchical regression analysis showed that such inverse associations were mainly present in female patients (p = 0.004), non-smokers (p = 0.01) or elders (≥60 years; p = 0.01). CONCLUSION: Tea consumption is associated with decreased disease activity of RA, suggesting the potential beneficial effect of tea in the disease.
32792961 Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthr 2020 Rheumatoid arthritis (RA) is a chronic autoimmune disease involving joint and bone damage that is mediated in part by proteases and cytokines produced by synovial macrophages and fibroblast-like synoviocytes (FLS). Although current biological therapeutic strategies for RA have been effective in many cases, new classes of therapeutics are needed. We investigated anti-inflammatory properties of the natural alkaloid tryptanthrin (TRYP) and its synthetic derivative tryptanthrin-6-oxime (TRYP-Ox). Both TRYP and TRYP-Ox inhibited matrix metalloproteinase (MMP)-3 gene expression in interleukin (IL)-1β-stimulated primary human FLS, as well as IL-1β-induced secretion of MMP-1/3 by FLS and synovial SW982 cells and IL-6 by FLS, SW982 cells, human umbilical vein endothelial cells (HUVECs), and monocytic THP-1 cells, although TRYP-Ox was generally more effective and had no cytotoxicity in vitro. Evaluation of the therapeutic potential of TRYP and TRYP-Ox in vivo in murine arthritis models showed that both compounds significantly attenuated the development of collagen-induced arthritis (CIA) and collagen-antibody-induced arthritis (CAIA), with comparable efficacy. Collagen II (CII)-specific antibody levels were similarly reduced in TRYP- and TRYP-Ox-treated CIA mice. TRYP and TRYP-Ox also suppressed proinflammatory cytokine production by lymph node cells from CIA mice, with TRYP-Ox being more effective in inhibiting IL-17A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and receptor activator of nuclear factor-κB ligand (RANKL). Thus, even though TRYP-Ox generally had a better in vitro profile, possibly due to its ability to inhibit c-Jun N-terminal kinase (JNK), both TRYP and TRYP-Ox were equally effective in inhibiting the clinical symptoms and damage associated with RA. Overall, TRYP and/or TRYP-Ox may represent potential new directions for the pursuit of novel treatments for RA.
33353028 Increased Encapsulation Efficiency of Methotrexate in Liposomes for Rheumatoid Arthritis T 2020 Dec 18 Methotrexate (MTX) is a common drug used to treat rheumatoid arthritis. Due to the excessive side effects, encapsulation of MTX in liposomes is considered an effective delivery system, reducing drug toxicity, while maintaining its efficacy. The ethanol injection method is an interesting technique for liposome production, due to its simplicity, fast implementation, and reproducibility. However, this method occasionally requires the extrusion process, to obtain suitable size distribution, and achieve a low level of MTX encapsulation. Here, we develop a novel pre-concentration method, based on the principles of the ethanol injection, using an initial aqueous volume of 20% and 1:1 ratio of organic:aqueous phase (v/v). The liposomes obtained present small values of size and polydispersity index, without the extrusion process, and a higher MTX encapsulation (efficiency higher than 30%), suitable characteristics for in vivo application. The great potential of MTX to interact at the surface of the lipid bilayer was shown by nuclear magnetic resonance (NMR) studies, revealing mutual interactions between the drug and the main phospholipid via hydrogen bonding. In vivo experiments reveal that liposomes encapsulating MTX significantly increase the biological benefit in arthritic mice. This approach shows a significant advance in MTX therapeutic applications.