Association of low-density lipoprotein receptor genotypes with hepatitis C viral load.

Several data suggest that low-density lipoprotein receptor (LDLR) is a co-receptor for hepatitis C virus (HCV). Soluble LDLR can inhibit HCV infectivity; greater plasma low-density lipoprotein levels are associated with treatment success; LDLR genotypes have a synergistic impact on the likelihood of achieving SVR with Peg-IFN plus RBV, as well as on viral kinetics after starting treatment. The objective of this study was to assess the impact of genetic polymorphisms in genes related to cholesterol synthesis and transport pathways on pre-treatment plasma HCV viral load (VL).

Thiol redox sensitivity of two key enzymes of heme biosynthesis and pentose phosphate pathways: uroporphyrinogen decarboxylase and transketolase.

Uroporphyrinogen decarboxylase (Hem12p) and transketolase (Tkl1p) are key mediators of two critical processes within the cell, heme biosynthesis, and the nonoxidative part of the pentose phosphate pathway (PPP). The redox properties of both Hem12p and Tkl1p from Saccharomyces cerevisiae were investigated using proteomic techniques (SRM and label-free quantification) and biochemical assays in cell extracts and in vitro with recombinant proteins. The in vivo analysis revealed an increase in oxidized Cys-peptides in the absence of Grx2p, and also after treatment with H2O2 in the case of Tkl1p, without corresponding changes in total protein, demonstrating a true redox response.

Omega 3 fatty acids and inborn errors of metabolism.

A number of studies are investigating the role of n-3 polyunsaturated fatty acids in children with metabolic inborn errors, while the effects on visual and brain development in premature infants and neonates are well known. However, their function incertain chronic neurological, inflammatory and metabolic disorders is still under study. Standards should be established to help identify the need of docosahexaenoic acid supplementation in conditions requiring a restricted diet resulting in an altered metabolism system, and find scientific evidence on the effects of such supplementation.

Nuclear translocation of β-catenin during mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype.

Wnt/β-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/β-catenin activation during human mesenchymal stem cells differentiation into hepatocytes.

Association between the IL28B genotype and hepatitis C viral kinetics in the early days of treatment with pegylated interferon plus ribavirin in HIV/HCV co-infected patients with genotype 1 or 4.

Objectives: To evaluate the effect of the interleukin 28B (IL-28B) genotype on hepatitis C virus (HCV) viral kinetics in the first 4 weeks from start of treatment with pegylated interferon plus ribavirin (PEG-IFN/RBV) in HIV/HCV co-infected patients.

Methods: HIV/HCV co-infected patients naive to PEG-IFN/RBV treatment were enrolled in a prospective study. HCV RNA plasma viral loads were measured at baseline and at weeks 1, 2 and 4 after commencement of treatment.

Twelve week post-treatment follow-up predicts sustained virological response to pegylated interferon and ribavirin therapy in HIV/hepatitis C virus co-infected patients.

Objectives: The aim of this study was to evaluate whether the assessment of hepatitis C virus (HCV) RNA serum at 12 weeks after the end of treatment (W12) was as informative as after 24 weeks (W24) for determining sustained virological response (SVR) in HIV/HCV co-infected patients who received a combination of pegylated interferon (PEG-INF) plus ribavirin (PEG-INF/RBV) and had a virological response at the end of treatment.

Methods: Treatment-naive HIV/HCV patients were included in this prospective study if they had completed a full course of therapy with PEG-INF/RBV, had an undetectable serum HCV RNA at the end of treatment and complied with the W12 and W24 schedule for determining HCV RNA. HCV RNA levels were measured using a quantitative PCR assay (detection limit = 15 IU/mL).

Biosynthetic and iron metabolism is regulated by thiol proteome changes dependent on glutaredoxin-2 and mitochondrial peroxiredoxin-1 in Saccharomyces cerevisiae.

Redoxins are involved in maintenance of thiol redox homeostasis, but their exact sites of action are only partly known. We have applied a combined redox proteomics and transcriptomics experimental strategy to discover specific functions of two interacting redoxins: dually localized glutaredoxin 2 (Grx2p) and mitochondrial peroxiredoxin 1 (Prx1p). We have identified 139 proteins showing differential postranslational thiol redox modifications when the cells do not express Grx2p, Prx1p, or both and have mapped the precise cysteines involved in each case.