Repression of liver cirrhosis achieved by inhibitory effect of miR-454 on hepatic stellate cells activation and proliferation via Wnt10a.

As is known, hepatic stellate cells (HSCs) activation contributes to liver cirrhosis. This study aims to find out the acting mechanisms of miR-454 inhibiting the activation and proliferation of hepatic stellate cells. The expression of Col1A1, α-smooth muscle actin (α-SMA) and Wnt10a were determined by western blot, and the miR-454 level was determined by quantitative real-time PCR in this study. We took two objects as experiment subjects, one was liver cirrhosis rats, and the other was transforming growth factor (TGF)-ß1-stimulated HSC-T6 cells. After activated with TGF-ß1 and transfected with microRNA-454 mimic, separately or successively, the changes on the Col1A1 and α-SMA expression, HSC proliferation, miR-454 level and Wnt10a expression were examined in HSC-T6 cells, respectively. Interaction between miR-454 and Wnt10a was evaluated with dual luciferase reporter assay. MiR-454 expression was down-regulated in tissues of liver cirrhosis rats. TGF-ß1 caused the down-regulation of the miR-454 in HSC-T6 cells. MiR-454 inhibited the activation and proliferation of HSC-T6 cells. Wnt10a had a targeting relationship with miR-454. TGF-ß1 promoted HSC-T6 activation and proliferation via down-regulating miR-454 expression, which further up-regulated Wnt10a expression. MiR-454 mimic inhibited cirrhosis progression in liver cirrhosis rats. MiR-454 can inhibit the activation and proliferation of HSCs via suppressing the expression of Wnt10a, to restrain liver cirrhosis.

Feasibility of triphasic CT with a modified two-point Patlak plot to determine spit kidney glomerular filtration rate in clinical practice.

PURPOSE: To investigate whether triphasic CT with a simplified Patlak plot can be used in clinical practice for the estimate of split kidney glomerular filtration rate (SKGFR). MATERIALS AND METHODS: The animal experiment included 15 rabbits that underwent 40 dynamic contrast-enhanced CT scans of the kidneys with 1.5 s time interval. Patlak-derived SKGFR was obtained using standard forty-point, two-point (unenhanced phase, arterial phase t α, and portovenous phase t ß), and a modified two-point (MTP) (unenhanced, t α, t ß, and a virtual t τ [t τ = (t α + t ß)/2]) image data, respectively. The MTP-Patlak plot approach was then validated in 13 patients who underwent a triphasic renal contrast-enhanced CT examination. SKGFR measured by 99mTc-DTPA clearance was as a standard reference. RESULTS: MTP-Patlak significantly reduced input function errors than two-point Patlak (21.1 ± 16.2 % vs 30.8 ± 15.2 %, p < 0.01) and showed good concordance with standard Patlak for measurement of SKGFR in animal experiment (1.20 ± 0.38 mL/g/min vs 1.51 ± 0.43 mL/g/min; linear correlation coefficient r = 0.87, p < 0.001). Human study showed that mean SKGFR was 45.7 mL/min (range, 26.5-86.2 mL/min) obtained from 99mTc-DTPA, and 38.2 mL/min (range, 18.6-79.3 mL/min) obtained from triphasic CT using MTP-Patlak plot. Linear correlation between the two methods was r = 0.75 (p < 0.01). The mean difference between SKGFRs as determined with the two methods was 7.4 ± 9.0 mL/min. CONCLUSION: The MTP-Patlak approach, featured with simplicity, is feasible in a clinically indicated CT examination for the evaluation of split renal function.