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ID PMID Title PublicationDate abstract
31984519 Immunometabolism in the development of rheumatoid arthritis. 2020 Mar In rheumatoid arthritis (RA), breakdown of self-tolerance and onset of clinical disease are separated in time and space, supporting a multi-hit model in which emergence of autoreactive T cells is a pinnacle pathogenic event. Determining factors in T cell differentiation and survival include antigen recognition, but also the metabolic machinery that provides energy and biosynthetic molecules for cell building. Studies in patients with RA have yielded a disease-specific metabolic signature, which enables naive CD4 T cells to differentiate into pro-inflammatory helper T cells that are prone to invade into tissue and elicit inflammation through immunogenic cell death. A typifying property of RA CD4 T cells is the shunting of glucose away from glycolytic breakdown and mitochondrial processing toward the pentose phosphate pathway, favoring anabolic over catabolic reactions. Key defects have been localized to the mitochondria and the lysosome; including instability of mitochondrial DNA due to the lack of the DNA repair nuclease MRE11A and inefficient lysosomal tethering of AMPK due to deficiency of N-myristoyltransferase 1 (NMT1). The molecular taxonomy of the metabolically reprogrammed RA T cells includes glycolytic enzymes (glucose-6-phosphate dehydrogenase, phosphofructokinase), DNA repair molecules (MRE11A, ATM), regulators of protein trafficking (NMT1), and the membrane adapter protein TSK5. As the mechanisms determining abnormal T cell behavior in RA are unraveled, opportunities will emerge to interject autoimmune T cells by targeting their metabolic checkpoints.
33308005 Bail-out extracorporeal membrane oxygenation for hydroxychloroquine intoxication: a warnin 2021 Apr This case report describes an intentional intoxication with 18 g of hydroxychloroquine (HCQ) presenting with unconsciousness, ventricular dysrhythmias, cardiogenic shock and pulmonary oedema. Initial treatment consisted of sodium bicarbonate, lipid emulsion, diazepam and norepinephrine. Because of persistent cardiogenic shock veno-arterial extracorporeal membrane oxygenation (V-A ECMO) was successfully used as a bridge to recovery. This case underscores the possible side effects of HCQ and the importance of considering ECMO in cardiogenic shock caused by HCQ intoxication which may occur also in patients with coronavirus disease 2019 (COVID-19) based on the currently frequent use of such a compound.
32059458 Predicting the Risk of Ischemic Stroke among Patients with Rheumatoid Arthritis Using a Si 2020 Feb 12 BACKGROUND AND OBJECTIVES: The aim of this retrospective cohort study was to develop a new score (RA-CHADSV) (rheumatoid arthritis - congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack/thromboembolism, and vascular disease), modified from the CHA(2)DS(2)-VASc score (congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, stroke/transient ischemic attack (doubled), vascular disease, age 65-74 years, and female), in predicting the risk of ischemic stroke in rheumatoid arthritis (RA) patients without atrial fibrillation (AF). MATERIALS AND METHODS: Using the Taiwan's National Health Insurance Research Database, 592 patients with RA diagnosed between 2000 and 2002 were identified and followed until first occurrence of ischemic stroke or the last available date in the database. Incidence rate ratios (IRR) of ischemic stroke for the CHA(2)DS(2)-VASc score were calculated using Poisson regression models. A new prediction score RA-CHADSV was developed using multiple logistic regression analysis with bootstrap validation. RESULTS: The area under the receiver operating characteristic curve of the newly developed RA-CHADSV score and the CHA(2)DS(2)-VASc score were 0.73 (95% confidence interval (CI) 0.64-0.82) and 0.70 (95% CI 0.61-0.79), respectively. The RA-CHADSV score was significantly associated with a higher ischemic stroke incidence in the patients who scored ≥1 (adjusted IRR 7.39, p < 0.001). CONCLUSIONS: A simplified RA-CHADSV score, with comparable efficiency as the CHA(2)DS(2)-VASc score, but easier to use clinically was developed for predicting the risk of ischemic stroke among non-AF RA patients.
32447218 Evaluation of Encapsulated Eugenol by Chitosan Nanoparticles on the aggressive model of rh 2020 Aug Chitosan Nanoparticles Eugenol recognizes as a potent antioxidant that can use the first therapeutic chemical to treat rheumatoid arthritis (RA) instead of Methotrexate. The purpose of this study was to investigate the effects of Chitosan Nanoparticles Eugenol as a potent Nano-herbal agent in the healing process of experimental neonatal RA compared to Methotrexate. The neonatal Wistar rats induced rheumatoid arthritis in both genders were divided into sham, control, the treatment receiving Methotrexate, and the second treatment receiving encapsulated Eugenol by Chitosan Nanoparticles groups. Afterward, Malondialdehyde, for assessment of lipid peroxidation as an oxidative stress biomarker by assay kit, FOXO3 protein as an antioxidant up-regulating by western blotting and expression of the TGF-β and CCL2/MCP-1 genes by real-time PCR evaluation, supported by a cartilage histopathology analysis. Based on these results, Methotrexate and Eugenol encapsulated by Chitosan Nanoparticles, a significant decrease is observed in the serum level of MDA and FOXO3 protein expression in comparison to the control group. Additionally, Nanoparticle herbal agent and Methotrexate has a decreasing effect on the expression of TGF-β and MCP-1 genes and a significant positive correlation was observed between MCP-1 and TGF-β. Inflammation, synovial hyperplasia, and pannus formation were extreme in the Collagen Induced Arthritis rats. It can be concluded that Encapsulated Eugenol by Chitosan Nanoparticles and Methotrexate, probably by dint of their immunomodulatory, anti-inflammatory, and antioxidant potential has a protective effect against RA. Nano Eugenol is capable of delivering promising lines results to treat autoimmune diseases such as RA can also be suggested.
32662409 BENEFIT: real-world effectiveness of SB4 after transition from reference etanercept in rhe 2021 Mar OBJECTIVES: The objective of this non-interventional study was to evaluate the effectiveness and safety of the etanercept biosimilar SB4 (BenepaliTM) following transition from reference etanercept in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). METHODS: Data were collected from clinical records of adult patients with stable RA or axSpA, in France, Germany, Italy and Spain. Key outcomes included the change from transition to 3 and 6 months in Disease Activity Score 28 (DAS28) for RA or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axSpA. RESULTS: In total, 358 patients with RA and 199 patients with axSpA were enrolled. The mean individual change in disease score from transition was -0.02 (95% confidence interval [CI] -0.11, 0.08) at 3 months and 0.01 (95% CI -0.09, 0.11) at 6 months for DAS28, and -0.01 (95% CI -0.24, 0.21) at 3 months and -0.11 (95% CI -0.31, 0.10) at 6 months for BASDAI. In the RA cohort, 19 (5.3%) and 5 patients (1.4%) reported adverse events and serious adverse events (SAEs), respectively. In the axSpA cohort, 12 (6.0%) and 2 patients (1.0%) reported adverse events and SAEs, respectively. One SAE of pneumonia (RA cohort) was considered to be related to SB4 administration. At 6 months post-transition, the SB4 retention rate was 90.8% (95% CI 87.2%, 93.4%) in the RA cohort and 92.4% (95% CI 87.5%, 95.4%) in the axSpA cohort. CONCLUSIONS: Transition from reference etanercept to SB4 is effective and safe in patients with stable RA and axSpA.
31854294 Association between malignancy and methotrexate and biological disease-modifying antirheum 2020 Mar OBJECTIVE: This study was aimed at investigating the risk of malignancies in rheumatoid arthritis patients treated with methotrexate (MTX), and whether the addition of biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignancies in patients receiving MTX therapy, by using data from a spontaneous adverse reaction database. MATERIALS: Patient data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2015 were analyzed. METHODS: A data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignancies in patients receiving MTX therapy. RESULTS: MTX showed significant associations with all malignancies except liver cancer. bDMARDs showed significant associations with stomach cancer, colorectal cancer, prostate cancer, ovarian cancer, malignant melanoma, and lung cancer. In addition, bDMARD use increased the risk of breast, ovarian, and lung cancers in rheumatoid arthritis patients receiving MTX therapy. CONCLUSION: MTX use was significantly associated with various malignancies. Moreover, concomitant use of bDMARDs further increased the risk of breast, ovarian, and lung cancers in MTX-treated patients with rheumatoid arthritis.
31776092 Bone marrow-derived mesenchymal stem cells-secreted exosomal microRNA-192-5p delays inflam 2020 Jan BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease closely correlated to synovial tissue inflammation. Exosomes are known to transfer microRNAs (miRNAs) between cells and have been validated as the vehicles for delivery of therapeutic molecules. AIM AND SCOPE: The current study was set to examine the functional values of bone marrow-derived mesenchymal stem cells (BMSCs)-secreted exosomal miR-192-5p (exo-miR-192-5p) on inflammation in RA. METHODS: Following the screening of differentially expressed genes in RA and miRNA-mRNA target prediction, BMSCs were infected with lentivirus expressing miR-192-5p to obtain miR-192-5p-overexpressed exosomes. To study the effect of exo-miR-192-5p on the expression of ras-related C3 botulinum toxin substrate 2 (RAC2), collagen-induced arthritis (CIA) rat models were established, and the clinical and histopathological changes were evaluated in the rats injected with exosomes. Subsequently, the expression patterns of pro-inflammatory factors were determined by ELISA. RESULTS: miR-192-5p was found to be down-regulated, while RAC2 was up-regulated in RA samples. Bioinformatics prediction revealed that the up-regulated RAC2 in RA may be regulated by miR-192-5p, which was further confirmed by dual luciferase reporter gene assay. The clinical arthritic scores, joint destruction, and inflammatory response were reduced after the injection of exosomes in rats with CIA targeting RAC2, and the treatment efficacy was even better with miR-192-5p-overexpressed exosomes. CONCLUSION: Our study established that the BMSCs-secreted exosomal miR-192-5p can delay the event of the inflammatory response in RA and may represent a possible therapeutic strategy for the treatment of RA.
31526593 Definition and construct validation of clinically relevant cutoffs on the Flare Assessment 2020 Apr OBJECTIVE: The Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire was devised for the detection of flares in patients with RA. We aimed to define construct validity and cut-off(s) for the FLARE-RA questionnaire. METHODS: This cross-sectional study included adult patients with prevalent RA (2010 ACR/EULAR criteria) attending outpatient rheumatology clinics in France (n = 138), Denmark (n = 253), USA (n = 75), and Argentina (n = 105). Flare occurrence over the past 3 months was assessed with the FLARE-RA questionnaire scoring from 0 (no flare) to 10 (maximum flare). The cut-offs for the FLARE-RA score were defined using the following anchor items obtained at the same encounter: (1) Patient report of flare; (2) DAS28-CRP > 3.2; (3) Change of anti-rheumatic treatment, based on the area under the receiver operating characteristic curve (AUC) and distance to (0,1). RESULTS: Four hundred seventy four patients with RA duration ≥2 years (mean age 58.6 years, 74.9% female) were included in the main analysis. The discrimination for the FLARE-RA cut-offs was acceptable-to-excellent: AUC for the global FLARE-RA score ranged from 0.71 to 0.92. The cut-offs for the FLARE-RA score were lower using "patient report of flare" than DAS28-CRP and "change of anti-rheumatic treatment". Proposed FLARE-RA cut-offs for clinical detection and change of anti-rheumatic treatment are 2 and 5, respectively, for patients with RA duration 2-5 years, and 2 and 3.5, respectively, for patients with RA duration >5 years. CONCLUSIONS: Proposed FLARE-RA cut-offs have acceptable discriminative capacity across the tested anchor items and are expected to aid in early recognition and timely management of RA flares.
33080909 Modestly Elevated Serum Procalcitonin Levels in Patients with Rheumatoid Arthritis Free of 2020 Oct 17 Background and objectives: To investigate the serum procalcitonin (PCT) levels among patients with rheumatoid arthritis (RA) without active infection compared with healthy controls and to understand the relationship of PCT with RA disease activity, and treatment received by patients. Materials and Methods: Patients aged 20 years and above with clinician-confirmed diagnosis of RA and healthy volunteers were included during regular outpatient visits, and those with active infection symptoms and signs were excluded. RA disease activity was measured using the Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (DAS28-ESR). Medications received by the patients were also recorded. Results: A total of 623 patients with RA and 87 healthy subjects were recruited in this study. The mean PCT were significantly higher in patients with RA (6.90 ± 11.81 × 10(-3) ng/mL) compared with healthy controls (1.70 ± 6.12 × 10(-3) ng/mL) (p < 0.001) and the difference remained statistically significant after adjusting for age and sex. In addition, multiple linear regression analysis showed that a lower rank-transformed PCT serum level was significantly correlated with the use of biologics (p = 0.017) and a high DAS28-ESR score (p = 0.028) in patients with RA. Conclusion: Patients with RA have a significantly higher serum PCT levels compared with healthy controls. The use of biologics and an active RA disease activity were associated with a lower level of PCT in patients with RA. Further investigation is required to determine the optimal cutoff value of PCT among patients with RA and its association with disease activity and biologic usage.
31530199 Gadolinium-conjugated CB86: a novel TSPO-targeting MRI contrast agent for imaging of rheum 2020 Apr TSPO is up-regulated in activated macrophages, and serves as an attractive target for macrophages molecular imaging and therapy. MRI may be an ideal technique in the clinical management of RA due to its excellent spatial resolution. In the present study, a novel TSPO-targeting MRI contrast agent was developed by conjugating a novel TSPO ligand CB86 with gadolinium chelate to visualise inflamed regions in RA mice model. A novel TSPO ligand CB86 was linked to DTPAA, followed by chelation with gadolinium to obtain MRI targeted contrast agent CB86-DTPA-Gd. CB86-DTPA-Gd was characterised by MRI relaxivity, cell cytotoxicity, cell specificity and in vitro stability analysis. The distribution and MRI intensity was evaluated in RA rat model. Synthesis of CB86-DTPA-Gd was completed successfully with MRI relaxivity of 11.05/mM/sec (9.4 T, 25 °C). CB86-DTPA-Gd exhibited a good stability in human serum, high RAW264.7 cells specificity and no cytotoxicity in RAW264.7 cells. The biodistribution and MRI studies showed that the accumulation and signal intensity of CB86-DTPA-Gd in the right RA ankles was higher and stronger than those of Gd‑DTPA. This study demonstrates that CB86-DTPA-Gd can identify phagocytic active macrophages in the synovial joints, and has potential as a promising targeting MRI contrast agent for imaging of peripheral inflammation.
33356304 Proteomic Data Analysis for Differential Profiling of the Autoimmune Diseases SLE, RA, SS, 2021 Feb 5 Early and correct diagnosis of inflammatory rheumatic diseases (IRD) poses a clinical challenge due to the multifaceted nature of symptoms, which also may change over time. The aim of this study was to perform protein expression profiling of four systemic IRDs, systemic lupus erythematosus (SLE), ANCA-associated systemic vasculitis (SV), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), and healthy controls to identify candidate biomarker signatures for differential classification. A total of 316 serum samples collected from patients with SLE, RA, SS, or SV and from healthy controls were analyzed using 394-plex recombinant antibody microarrays. Differential protein expression profiling was examined using Wilcoxon signed rank test, and condensed biomarker panels were identified using advanced bioinformatics and state-of-the art classification algorithms to pinpoint signatures reflecting each disease (raw data set available at https://figshare.com/s/3bd3848a28ef6e7ae9a9.). In this study, we were able to classify the included individual IRDs with high accuracy, as demonstrated by the ROC area under the curve (ROC AUC) values ranging between 0.96 and 0.80. In addition, the groups of IRDs could be separated from healthy controls at an ROC AUC value of 0.94. Disease-specific candidate biomarker signatures and general autoimmune signature were identified, including several deregulated analytes. This study supports the rationale of using multiplexed affinity-based technologies to reflect the biological complexity of autoimmune diseases. A multiplexed approach for decoding multifactorial complex diseases, such as autoimmune diseases, will play a significant role for future diagnostic purposes, essential to prevent severe organ- and tissue-related damage.
33191426 A biopolymer-based and inflammation-responsive nanodrug for rheumatoid arthritis treatment 2020 Nov 26 Rheumatoid arthritis (RA) is a common chronic autoimmune disease associated with progressive disability, systemic complications, and poor prognosis. The improved understanding of the roles of immune signaling pathway inhibitors has shed light on designing new and more effective approaches for RA treatment. In this work, an inflammation-responsive and molecularly targeted drug system has been developed for RA therapy. The drug carrier was synthesized by covalently grafting hydrophobic cholesterol (Chol) molecules onto a hydrophilic chondroitin sulfate (CS) chain via the inflammation-responsive diselenide bonds (SeSe). The resultant amphiphilic polymer CSSeSeChol readily forms nanoparticles (NPs) and encapsulates two kinase inhibitors tofacitinib and SP600125 in aqueous media. Upon administration into the RA mouse model, the nanodrug accumulates in RA lesions and releases the inhibitors for regulating the JAK-STAT and JNK pathways. As a result, the nanodrug exhibits satisfactory efficacy in RA treatment by suppressing the expression of relevant pro-inflammatory cytokines, blocking the activation of osteoclasts and providing protection for cartilage and joints.
32723058 Wrist Arthroplasty to Facilitate Communication in the Hearing Impaired. 2020 Sep Management of wrist arthritis may involve many options, including motion preserving and motion sacrificing procedures. Total wrist arthrodesis is often considered the gold standard for severe wrist arthritis, failing non-operative management. We present the first case to our knowledge of total wrist arthroplasty (TWA) for patient with rheumatoid arthritis who is also deaf, requiring sign language for communication with excellent results.
32737115 Association of the RPA3-UMAD1 locus with interstitial lung diseases complicated with rheum 2020 Oct OBJECTIVES: The genetic background of rheumatoid arthritis-interstitial lung disease (RA-ILD) has been evaluated in Europeans, but little knowledge has been obtained in non-Europeans. This study aimed to elucidate genome-wide risk of RA-ILD in non-Europeans. METHODS: We performed an initial genome-wide association study (GWAS) of RA-ILD in the Japanese population. By conducting the meta-analysis of the three GWAS datasets of the RA cohorts and biobank of Japanese, our study included 358 RA-ILD cases and 4550 RA subjects without ILD. We then conducted the stratified analysis of the effect of the GWAS risk allele in each CT image pattern. RESULTS: We identified one novel RA-ILD risk locus at 7p21 that satisfied the genome-wide significance threshold (rs12702634 at RPA3-UMAD1, OR=2.04, 95% CI 1.59 to 2.60, p=1.5×10(-8)). Subsequent stratified analysis based on the CT image patterns demonstrated that the effect size of the RA-ILD risk allele (rs12702634-C) was large with the UIP pattern (OR=1.86, 95% CI 0.97 to 3.58, p=0.062) and the probable UIP pattern (OR=2.26, 95% CI 1.36 to 3.73, p=0.0015). CONCLUSION: We revealed one novel genetic association with RA-ILD in Japanese. The RA-ILD risk of the identified variant at RPA3-UMAD1 was relatively high in the CT image patterns related to fibrosis. Our study should contribute to elucidation of the complicated aetiology of RA-ILD.
33110080 Blood pro-resolving mediators are linked with synovial pathology and are predictive of DM 2020 Oct 27 Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A(4) and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA.
32704073 Leflunomide monotherapy versus combination therapy with conventional synthetic disease-mod 2020 Jul 23 Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of rheumatoid arthritis. However, there are few reports on the comparison of efficacy between LEF alone and combined with other csDMARDs. Here, the efficacy and safety of LEF monotherapy (88) and combination (361) therapy groups were evaluated. After 3 months, there were no significant differences in 28-joint disease activity score (DAS28), health assessment questionnaire (HAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between the monotherapy and combination groups (all P > 0.05). According to the European League Against Rheumatism (EULAR) response criteria, it was found that the DAS28 response rates were similar in the two groups (P > 0.05). Besides, the two groups presented similar safety profiles. Subgroup analysis found that there was no difference in efficacy among the three combined therapies (LEF + methotrexate (MTX), LEF + hydroxychloroquine (HCQ), and LEF + MTX + HCQ) and LEF monotherapy. Furthermore, when the dose of LEF was less than 40 mg/day, no significant difference in efficacy was observed between low and high doses. Overall, these results indicated that low dose LEF monotherapy was not inferior to the combination therapy.
31441345 Revisit of autoimmunity to glucose-6-phosphate isomerase in experimental and rheumatoid ar 2020 Mar Rheumatoid arthritis (RA) is an inflammatory disorder characterized by synovial inflammation in multiple joints. Autoantibodies (Abs) are the hallmark of RA, and as disease-specific and diagnostic markers, rheumatoid factor and anti-citrullinated protein antibody (ACPA) are produced pre-clinically, but their pathogenic roles in RA remain elusive. In this review, we focus on one of the candidate autoantigens in RA; glucose-6-phosphate isomerase (GPI). The arthritogenic role of GPI has been confirmed in two different mouse models: the K/BxN- and GPI-induced arthritis models. Both anti-GPI Abs and citrullinated-GPI peptide Abs have been detected in human RA. Studies conducted in these rodent models have confirmed that the pathogenesis of arthritis involves the localization of autoantigens not only in the joints but also in the circulation. In this review, we revisit and summarize the arthritogenic relevance of GPI in animal RA models and in human RA, and extend the discussion to joint-specific inflammation.
33180388 T Regulatory Cells in Rheumatoid Arthritis with Reference to Anti-Citrullinated Peptide An 2020 Jan T regulatory cells (Tregs) plays an important role in maintaining self-tolerance and preventing autoimmune diseases by inhibiting proliferation and cytokine production of self-reactive T cells. Controversy was reported regarding the frequency of CD4+CD25+ Tregs in the peripheral circulation of rheumatoid arthritis (RA) patients compared to normal controls. Also, some showed that treatment with TNF-α inhibitor restored the capacity of Tregs. This work aimed to study Tregs in the peripheral blood of RA patients versus control in addition to those on TNF-α inhibitor therapy compared to those who have not received it and to correlate with status of anti-cyclic citrullinated peptide antibody (ACPA). Two groups of RA patients were studied; one on TNF-α inhibitor therapy and the other not. Additionally, age-matched apparently healthy controls were studied. The percentage of CD4+CD25+ T cells in the total lymphocytic cell population was determined by flow cytometry analysis while ACPA concentration was measured by a second-generation peptide-based ELISA. Mean level of Tregs was significantly lower in the studied RA patients compared to the control group. Patients in early disease (0-5 years) had low mean Tregs percentage compared to patients with long duration of disease (> 10 years) (P=0.044). Patients on TNF-α blocker therapy had elevated Tregs percentage relative to patients on methotrexate (MTX) (P=0.022) and other therapies. No effect of gender or age was found on Tregs levels. In RA patients, 85.4% were ACPA seropositive and 65.9% of seropositive patients have concentration of > 100U/ml. The mean Treg percentage was significantly lower in ACPA seronegative group compared to the seropositive group (P=0.013). In conclusion, the studied RA patients have low Treg, and TNF-α blocker therapy increased its number, compared to other therapies.
32151943 Innovated formulation of TCM pangolin scales to develop a nova therapy of rheumatoid arthr 2020 Jun Pangolin scale (PS) is a traditional Chinese medicine (TCM) for treating rheumatic arthritis (RA), and diverse medicinal formulations and therapeutic properties of PS have proved great potential to supplement conventional treatments in integrative medicine-based strategies. However, few studies have investigated how different PS formulations can impact the management of RA. Herein, we developed an innovative formulation of PS processed with vinegar (PSP) and evaluated it by comparing with the traditional decoction of PS (PSD) and non-steroidal anti-inflammatory drug (NASID) (i.e., meloxicam) in a RA Sprague Dawley rat model, which is induced with a complete Freund's adjuvant (CFA). The anti-inflammatory activities were evaluated by paw edema measurement, arthritic score, histopathological examination, pro-inflammatory cytokines (IL-1β and TNF-α) production and the whole blood viscosity. PSP treatments (249.0 mg/kg.bw) from day 14-42 alleviated paw edema (P < 0.001), arthritic index (score 0-1.5) and the inflammatory cell infiltration in the ankle joint, which may be attributed to inhibiting the production of TNF-α (P < 0.01) and IL-1β (P < 0.05) in the serum. Although PSP is with fewer efficacies than meloxicam, it outperformed traditional formulation PSD (830 mg/kg.bw) in all above mentioned metrics. Furthermore, PSP exhibited a unique effect on reducing whole blood viscosity (P < 0.05) unobserved in meloxicam intervention. The present study demonstrates that PSP showed more efficient anti-inflammatory activity than PSD in CFA-induced RA rats, possibly due to the presence of higher levels of active ingredients. Thus, PSP may be a promising therapy for anti-inflammation in RA and can be integrated with conventional treatments, particularly for long-term RA management in an integrative treatment strategy.
32403241 A Herbal Mixture from Propolis, Pomegranate, and Grape Pomace Endowed with Anti-Inflammato 2020 May 11 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by the production of inflammatory factors. In order to overcome the side effects of currently used anti-inflammatory drugs, several attempts have been made to identify natural products capable of relieving RA symptoms. In this work, a herbal preparation consisting of propolis, pomegranate peel, and Aglianico grape pomace (PPP) extracts (4:1:1) was designed and evaluated for its effect on a murine collagen-induced arthritis (CIA) model. Firstly, the chemical contents of four different Italian propolis collected in the Campania region (Italy) were here reported for the first time. LC-MS analyses showed the presence of 38 constituents, identified in all propolis extracts, belonging to flavonoids and phenolic acids classes. The Pietradefusi extract was the richest one and thus was selected to design the PPP preparation for the in vivo assay. Our results highlight the impact of PPP on RA onset and progression. By using in vivo CIA models, the treatment with PPP resulted in a delayed onset of the disease and alleviated the severity of the clinical symptoms. Furthermore, we demonstrated that early PPP treatment was associated with a reduction in serum levels of IL-17, IL-1b, and IL-17-triggering cytokines.