The authors of this article leave the reader with no doubt. Susceptibility to PSC is largely determined by DRβ-37, with some help from DRβ-86 and maybe DRβ-71 and DRβ-74. However, they also suggest that this is not the whole story. There are differences between published series. The reasons for this are complex and are recognized

by the authors.7 When considering studies performed between 1992 and 2011, we are not comparing like with like. There have been major advances learn more in the methods used, which explains some but not all of the variation reported. It is true to say earlier studies were limited. However, even the present study made assumptions, particularly with regard to the potential role of paralogous DRB genes, and there are exclusions (HLA-DQB1 for example). Also, there is still some dispute over the secondary association with risk haplotype 2,3 which does not exist in the Scandinavian patients, but is present in the United Kingdom and has a significant effect on analysis of the PD-0332991 price UK series.5, 6 Finally, we have the ancestral 8.1 haplotype to consider

(risk haplotype 1). HLA 8.1 raises two points for consideration. First, the patient population presented has a very large number of 8.1 homozygotes, much larger than would be expected, and it does not appear to be due to population homogeneity. Second, recent genome-wide association studies1 indicate a strong role for the HLA class I region in PSC, and earlier association studies suggested roles for HLA-C,18HLA-B,19 and MICA (MHC class I polypeptide-related sequence A).19, 20 Considering the involvement of these genes in activation of lymphocytes that are common in the liver, such as natural killer cells, natural killer T cells, and γδ T cells, any future studies of HLA will need to considered this region if we are to fully Silibinin unravel the immunopathology of PSC. This article marks a major step forward

in PSC. Although there is still much work to be done, it presents a good model, particularly if it can be used to evaluate any future experimental studies of antigen presentation in this disease, as the authors suggest. “
“Metabolic changes are common features of many cancer cells and are frequently associated with the clinical outcome of patients with various cancers, including hepatocellular carcinoma (HCC). Thus, aberrant metabolic pathways in cancer cells are attractive targets for cancer therapy. However, our understanding of cancer-specific regulatory mechanisms of cell metabolism is still very limited. We found that Tat-activating regulatory DNA-binding protein (TARDBP) is a novel regulator of glycolysis in HCC cells. TARDBP regulates expression of the platelet isoform of phosphofructokinase (PFKP), the rate-limiting enzyme of glycolysis that catalyzes the irreversible conversion of fructose-6-phosphate to fructose-1,6-bisphosphate.