[Effects of different types of interferon on the expression of HCV replication-related microRNA].

OBJECTIVE: To explore the effects of different types of interferon (IFN) on the expression of hepatitis C virus(HCV) replication-related miRNAs in human hepatocytes. METHODS: The levels of miRNAs in Huh7 cells treated with types I (IFN-α, IFN-ß), II (IFN-γ) and III (IFN-λ1) interferons (IFNs) were determined by real-time quantitative polymerase chain reaction (PCR). The levels of various miRNAs were compared among different IFN treatment groups. RESULTS: The expression of miRNA-196, miRNA-296, miRNA-351, miRNA-431 and miRNA-448 in IFN-α, IFN-ß and IFN-λ1 treated groups was higher than that in control group (474.5 ± 57.7, 436.0 ± 37.8, 431.3 ± 43.5 vs 99.5 ± 2.4; 389.5 ± 44.0, 416.3 ± 36.7, 284.8 ± 20.9 vs 99.0 ± 0.8; 453.3 ± 51.1, 473.8 ± 24.0, 522.0 ± 40.3 vs 99.5 ± 2.1; 288.3 ± 44.9, 294.3 ± 29.9, 450.0 ± 29.5 vs 100.5 ± 2.4; 319.0 ± 35.4, 357.0 ± 27.5, 446.5 ± 61.2 vs 99.8 ± 1.0; all P < 0.05). The expression of miRNA-196, miRNA-351 and miRNA-448 in IFN-γ-treated group (271.3 ± 29.6, 140.5 ± 27.5, 177.8 ± 23.4) was higher than that in control group (all P < 0.05). But the expression of miRNA-431 and miRNA-296 had no significant difference between IFN-γ treated group and control group (both P > 0.05). The expression of miRNA-122 at difference concentrations (10, 100, 1 000 U/ml) of IFN-α, IFN-ß, IFN-γ and IFN-λ1 (10, 100, 1 000 ng/ml) was lower than that in control group (49.3 ± 4.9, 32.0 ± 3.7, 24.5 ± 3.7 vs 99.5 ± 2.1; 53.5 ± 1.9, 35.5 ± 2.7, 25.8 ± 4.0 vs 98.8 ± 1.3; 60.8 ± 7.1, 43.8 ± 4.0, 33.5 ± 4.2 vs 99.3 ± 2.6; 50.0 ± 2.9, 35.5 ± 3.3, 22.3 ± 3.8 vs 100.3 ± 1.5; all P < 0.01). CONCLUSIONS: Different types of IFN increase the expression of miRNAs that inhibit HCV replication and decrease the expression of miRNA-122 that supports HCV replication. Thus the regulation of HCV replication-related miRNA expression is a general anti-HCV mechanism by different types of IFN. However, the regulation pattern by type II IFN is different from those by other types of IFNs, implying that type II IFN has different anti-HCV mechanisms from other types of IFN at miRNA level.

The effect of MDR1 C3435T polymorphism on the eradication rate of H. pylori infection in PPI-based triple therapy: A meta-analysis.

BACKGROUND: Several studies have reported that multidrug resistance gene 1 (MDR1) C3435T polymorphism was associated with the rate of Helicobacter pylori (H. pylori) eradication in proton pump inhibitor (PPI)-based triple therapy. However, the conclusions were inconsistent. Therefore, this meta-analysis was conducted to evaluate the impact of MDR1 C3435T polymorphism on H. pylori eradication by PPI-based triple therapy. METHODS: Seven eligible studies published up to August 2016 and including 1019 patients were identified by searching the Chinese Biomedical Literature database, Wan fang, PubMed, and the Web of Science electronic databases. Consequently, a meta-analysis was conducted with STATA software, using summary odds ratios (OR) and a 95% confidence interval (CI). RESULTS: Overall, there was no significant difference between MDR1 C3435T polymorphism and the eradication rate of H. pylori in the entire genetic model, irrespective of the PPI used. Furthermore, in Asian populations, the TT genotype decreased H. pylori eradication (TT vs CT+CC: OR=0.411, 95% CI = 0.280-0.602, P = 0.000). In addition, a significantly low eradication rate was observed in a recessive model, in which either lansoprazole (TT vs CT+CC: OR = 0.305, 95% CI = 0.184-0.504, P = 0.000) or omeprazole (TT vs CT+CC: OR = 0.229, 95% CI = 0.069-0.763, P = 0.016) was taken, in a subanalysis of individual PPIs. In the analyses that were stratified by disease type, no significant difference was observed in the peptic ulcer group and the combined diseases subgroup. CONCLUSION: This meta-analysis indicated that the TT genotype of the MDR1 C3435T polymorphism decreased H. pylori eradication in Asian populations and was also associated with a low cure rate of H. pylori in patients taking lansoprazole- and omeprazole-based triple therapies. However, future studies using larger sample sizes are required.

A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer.

The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80-0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08-1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91-1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82-1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63-1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy.