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Glutathione is the major intracellular redox buffer in the liver and is critical for hepatic detoxification of xenobiotics and other environmental toxins. Hepatic glutathione is also a major systemic store for other organs and thus impacts on pathologies such as Alzheimer's disease, Sickle Cell Anaemia and chronic diseases associated with aging. Glutathione levels are determined in part by the availability of cysteine, generated from homocysteine through the transsulfuration pathway. The partitioning of homocysteine between remethylation and transsulfuration pathways is known to be subject to redox-dependent regulation, but the underlying mechanisms are not known. An association between plasma Hcy and a single nucleotide polymorphism within the NADPH oxidase 4 locus led us to investigate the involvement of this reactive oxygen species- generating enzyme in homocysteine metabolism. Here we demonstrate that NADPH oxidase 4 ablation in mice results in increased flux of homocysteine through the betaine-dependent remethylation pathway to methionine, catalysed by betaine-homocysteine-methyltransferase within the liver. As a consequence NADPH oxidase 4-null mice display significantly lowered plasma homocysteine and the flux of homocysteine through the transsulfuration pathway is reduced, resulting in lower hepatic cysteine and glutathione levels. Mice deficient in NADPH oxidase 4 had markedly increased susceptibility to acetaminophen-induced hepatic injury which could be corrected by administration of N-acetyl cysteine. We thus conclude that under physiological conditions, NADPH oxidase 4-derived reactive oxygen species is a regulator of the partitioning of the metabolic flux of homocysteine, which impacts upon hepatic cysteine and glutathione levels and thereby upon defence against environmental toxins. [ABSTRACT FROM AUTHOR]

Nut shell carbon (NSC)¿nanotitanium dioxide (TiO2) composites were prepared by sol¿gel method. Photocatalytic activity on degradation of dye Rhodamine B was studied. X-ray diffraction, field emission scanning electron microscopy, Brunauer¿Emmett¿Teller surface area, pore size distribution, ultraviolet¿vis light absorption spectrum, and photoluminescence spectrum were carried out to characterize the composite catalyst. The results indicated that the photocatalytic activity of NSC¿nano-TiO2 composites was much higher than P25 (Degussa). NSC could greatly absorb the organic substance and oxygen of solution because of its large surface area. [Copyright &y& Elsevier]

Background and aims Acute ischemia is associated with myocardial endothelial damage and microvessel formation, resulting in leakage of plasma albumin into the myocardial extravascular space. In this study, we tested whether an albumin-binding intravascular contrast agent (gadofosveset) allows for improved quantification of myocardial permeability compared to the conventional extracellular contrast agent Gd-DTPA using late gadolinium enhancement (LGE) and T1 mapping in vivo . Methods MI was induced in C57BL/6 mice (n = 6) and cardiac magnetic resonance imaging (CMR) was performed at 3, 10 and 21 days post-MI using Gd-DTPA and 24 h later using gadofosveset. Functional, LGE and T1 mapping protocols were performed 45 min post-injection of the contrast agent. Results LGE images showed that both contrast agents provided similar measurements of infarct area at all time points following MI. Importantly, the myocardial R 1 measurements after administration of gadofosveset were higher in the acute phase-day 3 (R1 [s −1 ] = 6.29 ± 0.29) compared to the maturation phase-days 10 and 21 (R1 [s −1 ] = 4.76 ± 0.30 and 4.48 ± 0.14), suggesting that the uptake of this agent could be used to stage myocardial remodeling. No differences in myocardial R1 were observed after administration of Gd-DTPA at different time points post-MI (R1 [s −1 ] = 3d: 3.77 ± 0.37; 10d: 2.74 ± 0.06; 21d: 3.35 ± 0.26). The MRI results were validated by ex vivo histology that showed albumin leakage in the myocardium in the acute phase and microvessel formation at later stages. Conclusions We demonstrate the merits of an albumin-binding contrast agent for monitoring changes in myocardial permeability between acute ischemia and chronic post-MI myocardial remodeling. [ABSTRACT FROM AUTHOR]

Abstract: Omic techniques have become key tools in the development of systems biology. As the holistic approaches underlying the practice of traditional Chinese medicine (TCM) and new tendencies in Western medicine towards personalised medicine require in-depth knowledge of mechanisms of action and active compounds, the use of omic techniques is crucial for understanding and interpretation of TCM development, especially in view of its expansion in Western countries. In this short review, omic applications in TCM research are reviewed which has allowed some speculation regarding future perspectives for these approaches in TCM modernisation and standardisation. Guidelines for good practice for the application of omics in TCM research are also proposed. [Copyright &y& Elsevier]

Background/Aims: Chronic infection with the hepatitis B virus (HBV) is strongly associated with the development of hepatocellular carcinoma but the mechanism by which this occurs is unknown. Numerous studies have focused on the HBV X protein showing that it activates signal transduction pathways while few have investigated these changes in HBV-replicating hepatocytes. Methods: We utilized the recombinant adenovirus system to deliver a replication competent HBV genome into Huh7 and primary marmoset hepatocytes (PMH) to examine the effects of active viral replication on the regulation of Ras-ERK signal transduction and related pathways. Results: Huh7 cells and PMHs replicating HBV demonstrated significant upregulation in phosphorylated ERK, Akt, c-myc together with increased p53, cyclin B1 and p21cip1 expression and cell cycle progression to G2 phase in the absence of increased cell proliferation. Phosphorylation of the key cell survival kinase, Akt, was significantly increased, resulting in increased serine phosphorylation of the downstream target, GSK3-β. Conclusions: These results demonstrated simultaneous activation of the MAP Kinase and Akt pathways in HBV-replicating hepatocytes that resulted in dysregulation in the control of cell cycle progression and which help explain the early pathogenic mechanisms that underlie malignant transformation associated with chronic hepatitis B infection. [Copyright &y& Elsevier]