ABSTRACT
Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
Subject(s)
Animals , Male , Rats , Antirheumatic Agents , Arthritis , Drug Therapy , Urine , Biomarkers , Urine , Collagen Type II , Dose-Response Relationship, Drug , Immunosuppressive Agents , Magnetic Resonance Spectroscopy , Methods , Metabolome , Methotrexate , Proteome , Protons , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Treatment OutcomeABSTRACT
ObjectiveTo study the regulatory effect of Tripterygium wilfprdii polyglycoside (TWP) on the expression of EGFR and ErbB-2 induced arthritis rats.The effect of TWP on arthritis was also explored.MethodsAfter the model of CIA rats were established,the expression of EGFR and ErbB-2 in the synovium and articular cartilage were tested by immunohistochemical stain and real time PCR.ANOVA was used for statistical analysis.ResultsThe protein and mRNA expression of EGFR and ErbB-2 in the synovium (EGFR 0.268±0.059,ErbB-2 0.25±0.04,EGFR mRNA:14.2±0.55,ErbB-2 mRNA 23.46±3.64) and articular cartilage (EGFR 0.193±0.018,ErbB-2 0.217±0.033,EGFR mRNA:4.16±0.50,ErbB-2 mRNA 9.23±0.66) of the model group were significantly higher than those of the control group(P＜0.01).After being treated with TWP and MTX,the protein and mRNA expression of the EGFR and ErbB-2 decreased markedly (P＜0.01).Conclusion EGFR and ErbB-2 may play an important role in the pathogenesis of arthritis development.The molecular mechanism that TWP can treat synovitis and bone destruction of RA is related to the inhibition of EGFR and ErbB-2.
ABSTRACT
Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
ABSTRACT
Three cases of swimming pool granuloma are reported.Case 1:a 40-year-old female presented with a 2-month history of nodules and plaques on the right hand and forearm.She was a tropical fish salesperson but denied trauma history.Skin examination revealed multiple irregularly sized,dark-red nodules and plaques on the joints of right fingers,wrist,and elbow,as well as multiple subcutaneous nodules simulating strings of beads on the right upper limb.Case 2:a 48-year-old female presented with a 2-month history of nodules and plaques on the left hand and forearm.There was a history of trauma due to tropical fish tank and filter cleaning.Physical examination showed multiple deep purple plaques and painless subcutaneous nodules scattered on the left hand,wrist,and upper limb.Case 3:a 39-year-old male presented with a 3-month history of nodules on the fingers of both hands.There was no history of trauma,but he was a tropical aquarist.Skin examination revealed multiple soybean-sized dark-red nodules on the extensor aspect of interphalangeal joints of both hands.Fungal examinations yielded negative results in the 3 cases,while histopathology revealed infectious granuloma with a mixed inflammatory cell infiltrate.All of the cases showed positive results in purified protein derivative (PPD)skin test.Mycobacterium marinum was isolated from the lesional tissue of Case 1 and 2,but not from Case 3.All the patients were diagnosed with swimming pool granuloma,and given anti-atypical mycobacterial therapy including oral rifampin and clarithromycin.The lesions disappeared after 1 to 3 months of treatment,with the treatment course varying from 2 to 5 months.No recurrence was observed during a 3- to 12-month follow-up.