Interferences of cannabinoid agonists
and antagonists with synaptic transmission in the cortex may explain the cognitive and memory deficits elicited by these drugs. Neuropsychopharmacology (2012) 37, 1104-1114; doi:10.1038/npp.2011.262; published online 2 November 2011″
“Hepatic stellate cells (HSCs) represent the main fibrogenic cell type accumulating extracellular matrix in the liver. Recent data suggest that hepatitis C virus (HCV) core protein may directly activate HSCs. Therefore, we examined the influence of recombinant HCV core protein on human HSCs. Primary human HSCs and the human HSC line LX-2 were stimulated with recombinant VX-809 in vivo HCV proteins core and envelope 2 protein. Expression of procollagen type I alpha-1, alpha-smooth muscle actin, cysteine-and glycine-rich protein 2, glial fibrillary acidic protein, tissue growth factor beta 1, matrix metalloproteinases 2 (MMP2) and 13, tissue inhibitor of metalloproteinases 1 and 2 was investigated by real-time PCR. Intracellular signaling pathways of ERK1/2, p38 and, jun-amino-terminal
kinase (JNK) were analyzed by western blot analysis. Recombinant HCV core protein induced upregulation of procollagen type I alpha-1, alpha-smooth muscle actin, MMP 2 and 13, tissue inhibitor of metalloproteinases 1 and 2, tissue growth factor beta 1, cysteine-and glycine-rich protein 2, and glial fibrillary acidic protein mRNA expression, whereas HCV envelope 2 protein did not exert any significant effect. Blocking of toll-like Selonsertib datasheet receptor 2 (TLR2) with a neutralizing antibody prevented mRNA upregulation by HCV core protein confirming that the TLR2 pathway was involved. Furthermore, western blot analysis revealed HCV-induced phosphorylation of the TLR2-dependent signaling molecules ERK1/2, p38 and JNK mitogen-activated kinases. Our in vitro results demonstrate a direct effect of HCV core protein on activation of HSCs toward a profibrogenic OSBPL9 state, which is mediated via the TLR2 pathway. Manipulating the TLR2 pathway may thus provide
a new approach for antifibrotic therapies in HCV infection. Laboratory Investigation (2011) 91, 1375-1382; doi: 10.1038/labinvest. 2011.78; published online 2 May 2011″
“The analytical performance of MALDI-MS is highly influenced by sample preparation and the choice of matrix. Here we present an improved MALDI-MS sample preparation method for peptide mass mapping and peptide analysis, based on the use of the 2,5-dihydroxybenzoic acid matrix and prestructured sample supports, termed: matrix layer (ML). This sample preparation is easy to use and results in a rapid automated MALDI-MS and MS/MS with high quality spectra acquisition. The between-spot variation was investigated using standard peptides and statistical treatment of data confirmed the improvement gained with the ML method.