Effect of interferon-alpha-based antiviral therapy on hepatitis C virus-associated glomerulonephritis: a meta-analysis.

BACKGROUND: Hepatitis C virus (HCV) is associated with various glomerulopathies, in which HCV is responsible not only for the onset of glomerulopathy but also for its progressive loss of kidney function. The effect of antiviral treatment on the glomerular lesions and subsequent course of kidney disease remains controversial. Therefore, we performed a systematic analysis of the available evidence on the effect of interferon (IFN)-α-based therapy on HCV-associated chronic kidney disease. METHODS: A meta-analysis was performed of controlled and uncontrolled clinical studies related to IFNα-based antiviral therapy and its impact on kidney function in HCV-associated glomerulonephritis. Improvement of proteinuria and serum creatinine levels after antiviral therapy was taken as the end points of interest. Data from eligible studies selected according to protocols were analysed using Review Manager 5.0. RESULTS: Eleven clinical trials involving 225 patients were included in our meta-analysis. At the end of antiviral therapy, the summary estimate of the mean decrease in proteinuria was 2.71 g/24 h [95% confidence interval (CI) 1.38-4.04, P < 0.0001], P-value for heterogeneity 0.05 (I(2) = 53%). The pooled decrease in mean serum creatinine levels was 0.23 mg/dL (95% CI 0.02-0.44, P = 0.03), P-value for heterogeneity 0.30 (I(2) = 17%). Comparison of non-sustained virological response (SVR) to SVR groups demonstrated a mean difference of proteinuria decrease in the SVR group of 1.04 g/24 h (95% CI 0.20-1.89, P = 0.02), P-value for heterogeneity 0.21 (I(2) = 36%) and of serum creatinine decrease of 0.05 mg/dL (95% CI -0.33 to 0.43, P = 0.80), P-value for heterogeneity 0.70 (I(2) = 0%). CONCLUSION: Antiviral therapy based on IFNα can significantly decrease proteinuria and stabilize serum creatitine, and therefore, should be undertaken in patients with HCV-associated glomerulonephritis. The improvement in protein excretion is greater in those who achieve HCV RNA clearance, a finding in line with a causal role for HCV in glomerulonephritis.

[Effect of KLF6 and its splice variant KLF6V on proliferation and differentiation of human hepatocellular carcinoma HepG2 cells].

OBJECTIVE: To investigate the roles of Kruppel-like factor 6 (KLF6) and its splice variant KLF6V on suppressing growth and inducing differentiation of human hepatocellular carcinoma hepG2 cells. METHOD: KLF6V cDNA was amplificated by RT-PCR from human hepatocellular carcinoma (HCC) tissue and then sequenced. The recombinant vectors expressing KLF6 variant (KLF6V) were constructed using molecular clone technology based on established plasmid pcDNA3.1A(-)/wtKLF6. KLF6V or KLF6-transfected HepG2 cells were established after being screened with G418. Growth activity of HepG2/KLF6 or HepG2/KLF6V cells was detected by in vitro MTT assay. Expression of p21WAF1 or cyclin D1 protein was detected by Western blot, and expressions of AFP or ALB protein were measured by radioimmunoassay. RESULTS: A novel alternatively spliced transcript of the human KLF6 gene was found and its sequencing revealed that the variant form of KLF6 lacked 126nt and its encoded protein products had a deletion of 42 aa near the COOH-terminal amino acid in comparison with full-length KLF6. Although KLF6 alternative splicing was present in both normal and cancerous tissues, expression of the KLF6 splice variants seemed to be up-regulated in HCCs tissues. The isoform of KLF6 proteins antagonized the ability of wild-type KLF6 to up-regulate p21 expression or down-regulate cyclin D1 expression and suppress HepG2 cell proliferation. KLF6 gene increased albumin production and decreased alpha fetoprotein production of the cells. CONCLUSION: The isoform of KLF6 protein, present in HCC tissue, antagonizes the ability of wild-type KLF6 to suppress cell proliferation and induce cellular differentiation.

[Soil water resource use limit in semi-arid loess hilly area].

Taking Caragana korshinskii as test object, and by using neutron probe, a long term observation was conducted on the soil water and plant growth during the process of vegetation restoration in semi-arid loess hilly area. The results showed that after seeding on waste land, the capability of plant community in conserving soil and water was promoted with time, with the depth of roots to absorb and use soil water increased and the soil water content reduced. Then, the dried soil layer appeared, and its deepness and thickness increased with increasing plant age. Therefore, the plant use of soil water had a limit, soil water resource use limit, i.e., the soil water storage when the deepness of dried soil layer was equal to the largest depth that rain could recharge. In the C. korshinskii woodland in semi-arid loess hilly area, the soil water resource use limit in 0-290 cm layer was 249.4 mm. When the soil water storage in woodland was close or equal to the soil water resource use limit, effective measures should be taken to decrease soil evapotranspiration or increase soil water supply to ensure the sustainable water use of plant roots.