A Systematic Review and Network Meta-Analysis about the Efficacy and Safety of Tripterygium wilfordii Hook F in Rheumatoid Arthritis.

Objective: This study aims to evaluate the efficacy of various conventional synthetic DMARDs, including Tripterygium wilfordii Hook F (TwHF) for treating rheumatoid arthritis (RA) by network meta-analysis. Methods: We retrieved the related literature from online databases and supplemented it by using a manual retrieval method. Data was extracted from the literature and analyzed with STATA software. Results: A total of 21 trials (5,039 participants) were identified. Assessment of ACR20 response found that TwHF combined with methotrexate (MTX) had the greatest probability for being the best treatment option among the treatments involved, while TwHF used singly was second only to TwHF combined with MTX. Assessment of ACR50 response found that TwHF combined with MTX ranked second in all treatment options after cyclosporine A (CsA) combined with leflunomide (LEF) and TwHF alone, followed by TwHF combined with MTX. Assessment of ACR70 response found that CsA combined with LEF ranked first, TwHF combined with LEF ranked second, TwHF combined with MTX ranked third, and TwHF used singly ranked fourth. In the safety analysis, TwHF had the least probability of adverse event occurrence, followed by TwHF combined with MTX, which ranked first and second, respectively. Conclusion: Compared with the current csDMARDs for treating RA, the efficacy of TwHF was clear, and TwHF combined with MTX performed well under various endpoints. In the future, large, rigorous, and high-quality RCTs are still needed to confirm the benefits of TwHF therapy on RA.

[Effect of Silencing SET Gene on Acute Promyelocytic Leukemia NB4-R1 Cells].

OBJECTIVE: To investigate the effect of silencing SET gene on the biological characteristics of acute promyelocytic leukemia NB4-R1 cells. METHODS: The expression vector of pGCSIL containing SET-shRNA were transfected into 293T cells by using other packaging plasmids. The supernatant of the 293T cells was harvested for lentivirus. The SET-shRNA lentiviral vector was transfected into acute promyelocytic leukemia NB4-R1 cells and a stably transfected cell line was established. Real-time quantitative PCR and Western blot were used to assay the silencing efficiency on SET gene and the expression of PP2A. The cell cycle distribution was tested by flow cytometry. RESULTS: The expression of SET in experimental group statistically decreased as compared with that of the control group. The expression of PP2A was obviously raised at the level of mRNA and protein. The percentage of NB4-R1 cells in G0/G1 phase significantly increased, while the percentage of cells in S phase significantly decreased. CONCLUSION: The silencing gene in acute promyelocytic leukemia NB4-R1 cells using SET-shRNA lentiviral vector can increase the expression of PP2A and interfere of the cell cycle in NB4-R1 cells. This study has laid a experimental base for targed therapy of patients with acute promyelocytic leukemia.

[Apoptosis of retinoic acid-resistant APL NB4-R1 cells induced by As4S4 and its molecular mechanism].

OBJECTIVE: This study was to investigate the apoptosis-inducing effect of As(4)S(4) on the retinoic acid-resistant acute promyelocytic leukemia (APL) NB4-R1 cells and its potential mechanisms. METHODS: The leukemia cell line NB4-R1 was cultured in vitro and divided into control group and treatment group. The apoptosis rate and cell cycle were detected by flow cytometry. The apoptotic DNA fragments were analyzed by agarose gel electrophoresis. The changes of BCL-2, BAX and Caspase-3 were determined by Western blot. RESULTS: After NB4-R1 cells were treated with As(4)S(4)(25 µmol/L) for 0 h, 24 h, 48 h, the percentage of early apoptotic cells was obviously raised from 0% to 24.49% and 47.41%, the percentage of late apoptotic cells were elevated from 0.08% to 14.72% and 20.70%. Compared with control group, the DNA degradation revealed a characteristic DNA ladder during agarose gel electrophoresis after treatment for 24 h. The drug significantly induced an accumulation of the S phase cell population from 31.85% of the untreated cells to 42.53% and 55.12% treated with the different time whereas the NB4-R1 cells in G0/G1 phase decreased from 57.30% to 37.56% and 28.51%. As(4)S(4) could decrease the expression of BCL-2 and increase the level of BAX. Pro-caspase-3 could be cleaved into small active fragments under the apoptotic stimulation. CONCLUSION: As(4)S(4) can efficiently induce NB4-R1 cell apoptosis, which may be related with the down-regulation of BCL-2 and the up-regulation of BAX, as well as the activation of Caspase-3.

[Effect of realgar on induction of apoptosis in DLBCL cell line SU-DHL-4 and its possible mechanisms].

This study was aimed to explore the effect of realgar (As4S4) on growth inhibition and apoptosis induction of DLBCL cell line SU-DHL-4 and its mechanisms. The inhibitory effect of realgar on the cell growth were detected by MTT method. The morphological changes of SU-DHL-4 were observed by transmission electron microscopy (TEM). The apoptosis of SU-DHL-4 cells treated with realgar were detected by flow cytometry with Annexin V-FITC/PI double staining and DNA agarose gel electrophoresis. The cell cycle was examined by flow cytometry with PI staining. The expressions of apoptosis-related proteins (BCL-2 , Caspase-3,BAX) were detected by Western blot. The results showed that the realgar at the concentration of 20, 40, 80 µmol/L all could inhibit the proliferation of SU-DHL-4 (P < 0.05), and in a certain time and concentration range, the inhibition rate was enhanced in a time and dose dependent manner(r = 0.982). Flow cytometric test results showed that realgar could induce SU-DHL-4 cell apoptosis after treating for 48 hours, and the apoptosis rate increased with the increasing of drug concentration (P < 0.05). After treating SU-DHL-4 cells with Realgar for 48 h, the cell cycle was blocked in the S phase (P < 0.05). TEM results revealed that when treated with realgar for 48 h, the typically apoptosis morphology-apoptotic bodies were observed in all drug-treated group, furthermore, some necrotic cells in the 80 µmol/L group were observed. After intervened by realgar for 48 h, the DNA Ladder pattern was seen according to agarose gel electrophoresis. Western blot showed that the expression of Bcl-2 protein was down-regulated while the expressions of BAX and Caspase-3 protein were up-regulated when treating SU-DHL-4 cells with realgar for 48 h. It is concluded that realgar can inhibit cell growth and induce cell apoptosis, which may be related with up-regulation of Caspase-3 and BAX expression and down-regulation the of BCL-2 expression.