Abnormality of intestinal cholesterol absorption in ApcMin/+ mice with colon cancer cachexia.

Colorectal cancer syndrome has been one of the greatest concerns in the world, particularly in developed countries. Several epidemiological studies have shown that dyslipidemia may be associated with the progression of intestinal cachexia, but there is little research on the function of the small intestine, which is involved in blood lipid metabolism, in dyslipidemia. In the present study, we aimed to explore the function of intestinal cholesterol absorption in the ApcMin/+ mouse model using an intestinal lipid absorption test. We found that both triglyceride (TG) and total cholesterol (TC) uptake were inhibited in the intestine of ApcMin/+ mice with age and the intestinal peroxisome proliferator-activated receptor α (PPARα) downregulated the processes of ß-oxidation, oxidative stress response, and cholesterol absorption in APC-deficient mice. In addition, reduced expression levels of farnesoid X receptor (FXR) and apical sodium-dependent bile acid transporter (ASBT) indicated that bile acid metabolism might be associated with intestinal cholesterol absorption in ApcMin/+ mice. Thus, our data suggested that the intestine plays an essential role in cholesterol uptake and that bile acid metabolism seems to cause a decrease in intestinal cholesterol uptake in ApcMin/+ mice.

Cirtical role for Salmonella effector SopB in regulating inflammasome activation.

OBJECTIVE: Salmonella is known to evolve many mechanisms to avoid or delay inflammasome activation which remain largely unknown. In this study, we investigated whether the SopB protein critical to bacteria virulence capacity was an effector that involved in the regulation of inflammasome activation. METHODS: BMDMs from NLRC4-, NLRP3-, caspase-1/-11-, IFI16- and AIM2-deficient mice were pretreated with LPS, and subsequently stimulated with a series of SopB-related strains of Salmonella, inflammasome induced cell death, IL-1ß secretion, cleaved caspase-1 production and ASC speckle formation were detected. RESULTS: We found that SopB could inhibit host IL-1ß secretion, caspase-1 activation and inflammasome induced cell death using a series of SopB-related strains of Salmonella; however the reduction of IL-1ß secretion was not dependent on sensor that contain PYD domain, such as NLRP3, AIM2 or IFI16, but dependent on NLRC4. Notably, SopB specifically prevented ASC oligomerization and the enzymatic activity of SopB was responsible for the inflammasome inhibition. Furthermore, inhibition of Akt signaling induced enhanced inflammasome activation. CONCLUSIONS: These results revealed a novel role in inhibition of NLRC4 inflammasome for Salmonella effector SopB.

Characterization of the structural and molecular defects in fibres and follicles of the Merino felting lustre mutant.

The felting lustre (FL) mutation found in Merino sheep results in a fleece that has a lustrous appearance and readily felts. This phenotype was described 50 years ago to result from the mutation of a single gene, but the molecular and cellular changes in the wool are not well understood. In this study, follicle and fibre material of FL mutant (n = 3) and normal control (n = 5) Merino ewes was compared using histological analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), real-time polymerase chain reaction (qPCR) and electron microscopy [scanning electron microscopy (SEM) and transmission electron microscopy (TEM)]. Histological examination suggested that follicle structure in FL mutants is essentially normal, while SDS-PAGE analysis found that some low molecular weight keratin-associated proteins (KAP) were present at much lower levels in FL wool. Examination of transcript prevalence revealed that the KAP6.1, KAP7 and KAP8 genes in FL mutant follicles are downregulated, while the KAP2.12 and KAP4.2 genes are upregulated. TEM analysis indicated that there is only one type of cortical cell, the paracortical cell, in the fibre of FL mutants, while there are paracortical and orthocortical cells in fibres of normal Merino sheep. In contrast, SEM suggested the surface topography of FL wool fibres is normal. The evidence presented here strongly suggests that the properties of FL wool can be ascribed, at least in part, to the lower content of high glycine/tyrosine proteins and the reduction in orthocortical cells in mutant wool fibres.