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Objective:To investigate whether miR-9 plays a role in regulating glycogen synthase kinase-3β (GSK-3β) expression, affecting Wnt/β-catenin pathway activity and the patho-genesis of Osteo-arthritis (OA).Methods:The cartilage tissue of OA patients and normal cartilage tissue after traumatic amputation were collected, and the expressions of miR-9 and GSK-3β were compared. The double luciferase gene reporting test verified whether there was a targeted regulatory relationship between miR-9 and GSK-3β. OA rat model was established and compared with sham group, enzyme-linked immuno sorbent assay (ELISA) was used to detect hydroxyproline (Hyp) content in joint fluid.A kit was used to detect caspase-3 activity, and miR-9 and GSK-3β expression differences were detected in cartilage tissue. The OA model rats were divided into 3 groups: the sham group, the OA+ antagomiR-NC group, the OA + antagomiR-9 group. ELISA was used to detect Hyp content in joint fluid, kit was used to detect caspase-3 activity, and flow cytometry was used to detect cell cartilage tissue. Apoptosis, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to detect the expression of miR-9, GSK-3β, β-catenin and COL2A1. The comparison of mea-surement data between the two groups was conducted by t-test. The comparison of measurement data between multiple groups was conducted by one-way Analysis of Variance (ANOVA) analysis of variance, and then Bon-ferroni method was used for comparison between the two groups. P<0.05 was considered as statistically sign-ificant. Results:The miR-9 expression of cartilage tissue were (1.09±0.25) in the control group, and (2.86±0.25) in the OA group ( t=24.30, P<0.01). The GSK-3 β mRNA expression of cartilage tissue was (0.99±0.11) in the control group, and (0.53±0.10) in the OA group ( t=15.40, P<0.01). There was a targeted regulatory relationship between miR-9 and GSK-3β. The miR-9 expression of cartilage tissue was (1.00±0.21) in the sham group, and (2.61±0.36) in the OA group (t=9.462, P<0.01). The GSK-3 β mRNA expression of cartilage tissue was (1.00±0.18) in the sham group, and (0.52±0.09) in the OA group ( t=5.842, P <0.01). The Hyp content of joint fluid was (10±3) ng/ml in the sham group, and (50±8) ng/ml in the OA group ( t=11.015, P<0.01). The Caspase-3 activity of cartilage tissue was (1.00±0.19) in the sham group, and (2.43±0.36) in the OA group ( t=8.605, P<0.01). The miR-9 expression of cartilage tissue was (2.86±0.31) in the OA+antagomir NC group, and (1.67±0.19) in the OA + antagomir-9 group ( F=105.2, P<0.01). The GSK-3β mRNA expression of cartilage tissue was (0.41±0.09) in the OA antagomir NC group, and (0.81±0.09) in the OA + antagomir-9 group ( F=49.32, P<0.01). The Hyp content of joint fluid was (52.3±6.8) ng/ml in the OA + antagomir NC group, and (30.3±3.4) ng/ml in the OA + antagomir-9 group ( F=119.7, P<0.01). The caspase-3 activity of cartilage tissue was (2.22±0.23) in the OA + antagomir NC group, and (1.43±0.14) in the OA+ antagomir NC group ( F=72.55, P<0.01). Compared with OA + antagomir NC group, the expression of β-Catenin protein in the OA + miran-tagomir-9 group wasdecreased, the expression of GSK-3 β and COL2A1 protein wasincreased, and cell apo-ptosis wasdecreased. Conclusion:The increased expression of miR-9 plays a role in reducing the expression of GSK-3β, enhancing the activity of Wnt/β-catenin pathway, promoting the degradation, destruction of cartilage matrix and the pathogenesis of OA. Inhibition of miR-9 expression can reduce the protective effect of OA.
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Objective To examine the expression of miR-210,miR-155 and miR-34a in the peripheral blood of patients with systemic lupus erythematosus (SLE) and to analyze their clinical significance.Methods One hundred and teenty-six SLE patients were divided into the stable group (n=35),mild active group (n=49),medium and severe active group (n =42) based on systemic lupus erythematosus disease activity index (SLEDAI) score.Meanwhile,40 subjects for healthy check-up were selected as controls.The clinical data of patients were collected.Complete blood count,liver and kidney function and immunological indexes were tested in patients and the lupus activity index was assessed.The expression level of miR-210,miR-155 and miR-34a were determined by real-time polymerase chain reaction.Furthermore,the correlation between their levels and clinical parameters such as erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),SLEDAI score,were analyzed.The expression levels of miR-210,miR-155 and miR-34a in each group were compared by one-way analysis of variance (ANOVA).Correlation analysis was performed by non parametric Spearman test.The difference was statistically significant if P＜0.05.The diagnostic value of SLE was evaluated by the subjects characteristic (ROC) curve.Results The levels of miR-210 and miR-155 were no significantly differencet between the stable group (0.017±0.012);(0.150±0.101) and the control group (0.015±0.010);(0.071±0.034),but they were increased in mild active group (0.502±0.166);(1.521±1.138),medium and severe active group(1.237±0.584),(13.589±9.827) (F=124.321,70.065,P＜0.05).The average expression level of miR-34a in the control group,the stable group,the mild active group and the moderate and severe active group were (0.005±0.003),(0.249±0.137),(2.981±1.762) and (9.625±5.873) respectively,and showed a trend of increase in turn (F=75.688,P＜0.05).The expression level of miR-210,miR-155 and miR-34a was not significantly different between the LN group and the non LN group (P＞0.05).The R values of miR-210,miR-155,miR-34a and each index were IgG (0.347;0.518;0.482);IgA (0.463;0.635;0.379);IgM (0.287;0.392;0.336),ESR(0.317;0.428;0.369),C3(0.243;0.429;0.381),C4(0.317;0.513;0.429),ANA titer (0.462;0.594;0.527),Anti-ds-DNA antibodies (0.391;0.586;0.483),SLEDAI scores (-0.412;-0.558;-0.493),and there were significant correlations (P＜0.05).In patients with SLE,there was no significant correlation between hormone therapy alone or hormone plus immunosuppressive therapy (P＞0.05).The sensitivity and specificity of miR-210,miR-155,miR-34a in combination for the diagnosis of SLE reached 75.7％ and 72.3％,respectively.Conclusion The levels of miR-210,miR-155 and miR-34a in combination may be used as bio-markers for the diagnosis of SLE.
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Objective To evaluate the clinical efficiency of febuxostat on hyperuricemia and hyperlipidemia,provide evidences for the option of clinical treatment.Methods From Mar.2015 to Mar.2016,80 patients with hyperuricemia and hyperlipidemia were enrolled to this study,and they were randomly divided into observation group and control group by random number table,each group with 40 cases.The observation group received 40 mg of fenbuterol tablets once a day.The control group received 100 mg allopurinol tablets three times a day.The levels of serum uric acid,lipids,endothelium-soluble intercellular adhesion molecule-1 (sICAM-1) and endothelium (ET-1) were measured at the baseline,12 weeks after treatment and 24 weeks after treatment.Meanwhile,the liver and kidney function damage and adverse reactions were recorded.Results After treatment,the levels of uric acid,blood lipid,sICAM-1 and ET-1 were decreased in two groups,and there was significant difference between them (P＜0.05).The adverse effects of the two groups were transient.The incidence of liver or kidney damage,side effect of drug in observation group was lower than that in the control group,and there was no significant difference between the two groups (P＞0.05),except the incidence of rash.Conclusion Febuxostat intervention in treatment of patients with hyperuricemia and hyperlipidemia is safe and efficient.