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Rheumatoid arthritis (RA) is a chronic inflammatory, autoimmune disease that gradually affects the synovial membrane and joints. Many intrinsic and/or extrinsic factors are crucial in making RA pathology challenging throughout the disease. Substantial enzymatic or non-enzymatic modification of proteins driving inflammation has gained a lot of interest in recent years. Endogenously modified glycated protein influences disease development linked with AGEs/non-AGEs and is reported as a disease marker. In this review, we summarized current knowledge of the differential abundance of glycated proteins by compiling and analyzing a variety of AGE and non-AGE ligands that bind with RAGE to activate multi-faceted inflammatory and oxidative stress pathways that are pathobiologically associated with RA-fibroblast-like synoviocytes (RA-FLS). It is critical to comprehend the connection between oxidative stress and inflammation generation, mediated by glycated protein, which may bind to the receptor RAGE, activate downstream pathways, and impart immunogenicity in RA. It is worth noting that AGEs and non-AGEs ligands play a variety of functions, and their functionality is likely to be more reliant on pathogenic states and severity that may serve as biomarkers for RA. Screening and monitoring of these differentially glycated proteins, as well as their stability in circulation, in combination with established pre-clinical characteristics, may aid or predict the onset of RA., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory disease of the synovium that affects the movable joints. It develops due to the infiltration and invasion of the synovial joints by immune cells. Metabolism is anabolic or catabolic chemical reactions occurring in a cell. The biochemical pathways in synovial and immune cells are altered affecting the downstream metabolite formation. Changes in the metabolite levels alter signaling cascades which further intensify the disease. Despite current knowledge of metabolomics, there remain certain features that need to be elucidated to correlate the differential metabolite levels with RA., Recent Findings: Metabolite profiling can be used to find altered patterns of metabolites in RA. Glucose, lipid, amino acid, and estrogen metabolism are the key pathways that are altered and contribute to the aggravation of RA. The altered metabolic pathways involved in different cells in RA results in complex interactions between metabolites and biomacromolecules; thus, it generates autoantigens. Moreover, understanding the correlation between differential metabolites and disease severity might help reveal potential new biomarkers and therapeutic targets for RA pathogenesis. So, considering the multi-faceted role of altered metabolites in the pathogenesis of RA, metabolic pathways of different cells are needed to be studied for a better understanding of their functions in the disease and thus, improving the present therapeutic strategies.

Objective: To evaluate the clinical therapeutic effects and safety on rheumatoid arthritis (RA) treated with acupuncture at the points detected with thermosensitive moxibustion in Zhuang medicine combined with western medication., Methods: A total of 168 RA patients in compliance with the inclusive criteria were collected and randomized into an observation group and a control group, 84 cases in each one. In the control group, in reference to the updated guideline of new drugs by the European League Against Rheumatism (EULAR) in 2013, the medication scheme was formulated for oral administration, methotrexate tablet 7.5 mg, once a week; salazosulfapyridine enteric-coated tablets, 100 mg, twice a day; hydroxychloroquine sulfate tablets, 20 mg, twice a day; and meloxicam tablets, 15 mg, once a day. In the observation group, besides the treatment as the control group, the acupuncture therapy at the points detected with thermosensitive moxibustion in Zhuang medicine was given. The mild moxibustion was applied near to the affected joint with the moxa material of Zhuang herbal medicine to detect the sensitization points. Afterwards, the acupuncture technique of Zhuang medicine was given on those points, without any manipulation applied. The needles were retained for 30 min, once daily. The treatment for 2 weeks was as one course, continuously for 2 courses. The indexes were observed before and after treatment in the two groups including gripping power, the time of morning stiffness, the swollen joint count 28 (SJC 28), the tender joint count 28 (TJC 28), the disease activity score 28 (DAS 28), the score of patient global assessment of disease activity (PtGA) and the score of provider global assessment of disease activity (PhGA), as well as rheumatoid factors (RF), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anti-cyclic peptide containing citrulline (A-CCP). The clinical therapeutic effects were evaluated in the two groups., Results: After 4-week treatment, a total of 163 patients accomplished the clinical trial, 81 cases in the observation group and 82 cases in the control group. The results of gripping power, the time of morning stiffness, SJC 28, TJC 28, PtGA, PhGA, DAS 28, RF, CRP, ESR and A-CCP were all improved as compared with those before treatment (all P <0.05). In 4 weeks of treatment, the results of gripping power, the time of morning stiffness, SJC 28, TJC 28, PtGA, PhGA, DAS 28, as well as CRP and ESR in the observation group were better than those in the control group (all P <0.05). The results of RF and A-CCP were not different significantly between the two groups (both P >0.05). The total effective rate was 85.19% (69/81) in the observation group, higher than 70.73% (58/82) in the control group ( P <0.05)., Conclusion: The acupuncture therapy at the points detected with thermosensitive moxibustion in Zhuang medicine achieves the satisfactory clinical effects with few adverse effects.