ABSTRACT
Background: Inactivation of microRNA-100 (miR-100) is involved in hepatocellular carcinoma (HCC) and miR-100 behaves as a tumor suppressor. To understand miR-100 function in HCC genesis and development in vivo, we developed hepatocyte-specific miR-100 deficient mice. Methods: Mice homozygous for floxed miR-100 allele that carried the Alb-Cre transgene (miR-100flox/floxAlb -Cre+) were developed by mating miR-100flox/flox mice with Alb-Cre+/+mice. The mice tails DNA were genotyped using the primers for LoxP sites and Cre recombinase, respectively. The specific deletion of miR-100 in the livers was verified by quantitative Real-time PCR (qRT-PCR). HE-staining was performed for histology analysis. Liver function was assessed by transaminase activity. The metabolic profiles of the hepatocytes were detected using a Seahorse XFe24 extracellular flux analyzer. The direct targets of miR-100 (such as IGF1R-ß, mTOR and CDC25A) and HCC related protein (SHP-2) were detected by qRT-PCR and Western blot in liver tissues. Results: The resultant homozygous knockout mice with genotype of miR-100flox/flox-Alb-Cre+ showed an 80% decrease in hepatic miR-100 expression. In adult mice, miR-100 knockout has no effect on the liver function and morphology. In aged mice, HE staining showed that miR-100 knockout caused infiltration of inflammatory cells and expansion of hepatocellular nuclei. Consistently, liver function was impaired in miR-100 knockout aged mice as indicated by increased serum AST and ALT levels. The metabolic analysis demonstrated that the miR-100 knockout hepatocytes tend to adopt glycolysis. The expressions of the miR-100 target genes, such as IGF1R-ß, CDC25A and mTOR, were increased. In addition, the known HCC related protein, SHP-2 also was up-regulated in the knockout livers. Conclusions: We successfully generated a miR-100 hepatocyte-specific knock-out mouse model. The malignant transformation related to HCC were observed in aged mice. Therefore, this model is suitable for investigating the mechanism of miR-100 inactivation contributing to HCC genesis in vivo.
ABSTRACT
Noble gas (41)Ar was measured with a 4πß-4πγ coincidence system, in which gamma- and beta-rays were respectively detected with a well-type NaI(Tl) and plastic scintillator (PS) detector. The activity of (41)Ar was determined from an efficiency extrapolation method, in which the beta detector efficiency was varied by electronic discrimination using the software developed under Visual basic. In addition, high resolution gamma spectroscopy with HPGe detector was also used for activity determination of (41)Ar, and the result was satisfactory in agreement with that obtain by the efficiency extrapolation method. This work demonstrated that the activity of (41)Ar can be accurately measured by efficiency extrapolation method.
ABSTRACT
The fission gaseous (138)Xe products play an important role in the research of nuclear-reaction products and radioisotope applications. Therefore, precise data for emission probabilities of gamma-ray from decay of (138)Xe are highly desired. However, a high precision is not achievable with a sufficient accuracy due to the limitations of the usual experimental techniques. In this paper, after the homogeneous sources of (138)Xe-(138)Cs were prepared, the activity of (138)Xe was obtained by the decay relationship between (138)Xe and (138)Cs using a HPGe detector. The full-energy peak efficiencies of gamma-ray for (138)Xe and (138)Cs were accurately calibrated using many activity standard sources and self-absorption was corrected. As a result, the absolute emission probabilities of the 258.4, 434.6 and 1768.3 keV gamma-ray from decay of (138)Xe were determined to be 34.9(10)%, 22.2(6)% and 18.8(5)%, respectively.
