Efficacy and safety of leflunomide treatment in Takayasu arteritis: Case series from the East China cohort.

OBJECTIVE: To evaluate the efficacy and safety of leflunomide (LEF) as induction treatment in a series of Takayasu arteritis (TA) patients based on a Chinese cohort. METHOD: Fifty-six patients from the East China TA cohort treated with LEF for at least 3 months were enrolled in this study, including the naïve LEF treatment patients (n = 41) and the cyclophosphamide (CYC)-resistant LEF treatment patients (n = 15). Data in clinical features, NIH score and angiography were collected. Response to treatment was assessed by rates of complete remission (CR) and partial remission (PR) and response rate (RR) after 6 and 12 months of treatment. RESULTS: The total CR rate and RR were 67.86% and 83.93% after 6 months, and 55.36% and 69.64% after 12 months, respectively. ESR and CRP levels and NIH scores decreased significantly after 12 months of LEF treatment (P < 0.05). Patients of CYC-resistant switched to LEF and reached the CR of 60.00% (9/15) and RR of 86.67% (13/15) after 6 months, and 73.33% (11/15) and 80.00% (12/15) after 12 months, respectively, with decrease in NIH scores (all P < 0.05). After following up for 14.44 ± 6.86 months, 48 patients (85.71%) continued LEF treatment with good tolerance. One patient died from progression of TA after 2 months, 2 patients relapsed, and 3 patients with side effects were switched to other immunosuppressive agents. CONCLUSIONS: LEF led to a quick induction and sustained remission of TA, especially in refractory cases, and therefore, should be considered as an alternative treatment for TA.

MicroRNA-192 suppresses cell proliferation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes by downregulating caveolin 1.

Fibroblast-like synoviocytes (FLSs) play an important role in the pathogenesis of rheumatoid arthritis (RA). This study was conducted to explore the role of microRNA (miR)-192 in the regulation of the biology of RA-FLSs. The expression of miR-192 in RA and healthy synovial tissues was measured. The effects of overexpression of miR-192 on RA-FLS proliferation and apoptosis were investigated. Luciferase reporter assay and Western blot analysis were performed to identify direct target genes of miR-192. RA synovial tissues had significantly lower levels of miR-192 than healthy controls (P = 0.004). Moreover, miR-192 levels were 2.9-fold lower in RA-FLSs relative to normal human FLSs (P < 0.05). Ectopic expression of miR-192 significantly inhibited the proliferation and caused a cell cycle arrest at the G0/G1 phase in RA-FLSs. Moreover, miR-192 overexpression triggered apoptosis, which was accompanied by an increase in caspase-3 activity and Bax/Bcl-2 ratio. Caveolin 1 (CAV1) was identified to be a direct target of miR-192. Overexpression of miR-192 led to a reduction of endogenous CAV1 in RA-FLSs. Silencing of CAV1 significantly decreased cell proliferation and promoted apoptosis in RA-FLSs. Rescue experiments with a miR-192-resistant variant of CAV1 showed that enforced expression of CAV1 restored cell proliferation and attenuated apoptosis in miR-192-overexpressing RA-FLSs. In conclusion, miR-192 is downregulated in RA synovial tissues and restoration of its expression elicits growth-suppressive effects on RA-FLSs by targeting CAV1. The miR-192/CAV1 pathway may represent a novel target for prevention and treatment of RA.

Effect of pterostilbene on glioma cells and related mechanisms.

Neuroglioma is the most common primary malignant tumor in neurosurgery. Due to unfavorable life quality of patients, the treatment of glioma is a major challenge in clinics. The search for effect treatment drugs thus benefits patient prognosis. As one derivative of resveratrol, pterostilbene has a wide spectrum of pharmaceutical functions, especially with the anti-tumor effects. This study thus investigated the effect of pterostilbene on neuroglioma and related mechanisms. U87 glioma cell line was divided into control, normal culture and different dosages of pterostilbene groups, which received 5 mM or 10 mM pterostilbene for 48 h. MTT assay was used to detect U87 cell proliferation, while invasion assay was employed to test the effect of pterostilbene on cell invasion, followed by flow cytometry assay for analyzing U87 cell apoptosis. Real-time PCR was used to test mRNA expression of Bcl-2 and Bax in glioma cells under the effect of pterostilbene, while Western blotting was used to detect alternation of Bcl-2 and Bax protein levels. Pterostilbene significantly inhibited proliferation and invasion abilities of glioma cells compared to those in control group (P<0.05). It can also enhance cell apoptosis, decrease mRNA and protein of Bcl-2 expression, and increase mRNA and protein expressions of Bax (P<0.05 compared to control group) in a dose-dependent manner. Pterostilbene can facilitate apoptosis of glioma cells, and inhibit their proliferation and invasion via mediating apoptotic/anti-apoptotic homeostasis.