Warnerbendtsen1579

The production of superoxide anions (O



) by the phagocyte NADPH oxidase complex has a crucial role in the destruction of pathogens in innate immunity. Majority of in vitro studies on the functioning of NADPH oxidase indirectly follows the enzymatic reaction by the superoxide reduction of cytochrome c (cyt c). Only few reports mention the alternative approach consisting in measuring the NADPH consumption rate. When using membrane vesicles of human neutrophils, the enzyme specific activity is generally found twice higher by monitoring the NADPH oxidation than by measuring the cyt c reduction. Up to now, the literature provides only little explanations about such discrepancy despite the critical importance to quantify the exact enzyme activity.

We deciphered the reasons of this disparity in studying the role of key parameters, including. cyt c and arachidonic acid concentrations, in conjunction with an ionophore, a detergent and using Clark electrode to measure the O

consumption rates.

Our results show that the O



low permeability of the vesicle membrane as well as secondary reactions (O



and H

O

disproportionations) are strong clues to shed light on this inconsistency.

These results altogether indicate that the cyt c reduction method underestimates the accurate Nox2 activity.

These results altogether indicate that the cyt c reduction method underestimates the accurate Nox2 activity.

Oxysterols, which are derivatives of cholesterol produced by enzymic or non-enzymic pathways, are potent regulators of cellular lipid homeostasis. Sterol homeostasis in the brain is an important area of interest with regards to neurodegenerative conditions like Alzheimer's disease (AD). Brain cells including neurons and astrocytes express sterol transporters belonging to the ABC transporter family of proteins, including ABCA1, ABCG1 and ABCG4, and these transporters are considered of interest as therapeutic targets. Although regulation of ABCA1 and ABCG1 is well established, regulation of ABCG4 is still controversial, in particular whether the transporter is an Liver X receptor (LXR) target. ABCG4 is thought to transport cholesterol, oxysterols and cholesterol synthesis intermediates, and was recently found on the blood brain barrier (BBB), implicated in amyloid-beta export. In this study, we investigate the regulation of ABCG4 by oxysterols, cholesterol-synthesis intermediates and cholesterol itself.

ABC transporter expression was measured in neuroblastoma and gliablastoma cell lines and cells overexpressing ABCG4 in response to synthetic LXR ligands, oxysterols and cholesterol-synthesis intermediates.

In contrast to previous reports, ABCG4 expression was induced by a synthetic LXR ligand in U87-MG astrocytes but not in neuroblastoma and BBB endothelial cell lines. In addition, ABCG4 protein was stabilized by cholesterol as was previously shown for ABCG1. ABCG4 protein was furthermore stabilized by cholesterol-synthesis intermediates, desmosterol, lathosterol and lanosterol.

These results identify new aspects of the post-translational control of ABCG4 that warrant further exploration into the role of this transporter in the maintenance of sterol homeostasis in the brain.

These results identify new aspects of the post-translational control of ABCG4 that warrant further exploration into the role of this transporter in the maintenance of sterol homeostasis in the brain.

To identify predictors of unplanned hospitalization and emergency department (ED) use among head and neck oncology patients.

Peer reviewed publications were identified through a systematic search of MEDLINE, Embase and Cochrane CENTRAL. Studies describing a cohort of HNC patients that detailed predictors of unplanned hospitalization or ED use in risk-adjusted models were eligible for inclusion. ML351 The methodologic quality of included studies was assessed using the Quality In Prognostic Studies (QUIPS) tool and an adapted version of the GRADE framework.

Of the 932 articles identified, 39 studies met our inclusion criteria with 31/39 describing predictors of surgical readmission and 10/39 describing predictors of ED use or unplanned hospitalization during radiation/chemoradiation treatment. Risk factors were classified into either 'patient-related', 'cancer severity' or 'process' factors. In the subset of studies looking at readmission following surgery wound complications (10/14 studies), presence of comorbidity (16/28 studies), low socioeconomic status (8/17 studies), cancer stage (9/14 studies), and prolonged hospital stay (7/18 studies) were the variables most frequently associated with readmission on multivariable analysis. Presence of comorbidity (6/10) and chemotherapy use (4/10) were more frequently associated with ED use and unplanned hospitalization.

Several consistent predictors have been identified across a variety of studies. This work is a critical first step towards the development of readmission and ED prediction models. It also enables meaningful comparison of hospital readmission rates with risk adjustment in HNC patients.

Several consistent predictors have been identified across a variety of studies. This work is a critical first step towards the development of readmission and ED prediction models. It also enables meaningful comparison of hospital readmission rates with risk adjustment in HNC patients.DNA damage plays a crucial role in the transforming potential of the human carcinogen arsenic. The arsenic biotransformation enzyme AS3MT is known to participate in the generation of ROS after arsenic exposure, whereas MTH1 sanitizes oxidized dNTP pools to prevent the incorporation of damaged bases into DNA. In this work, we sought to assess the role of these two enzymes in the genotoxic and carcinogenic effects of arsenic exposure. Thus, mouse embryonic fibroblasts (MEF), transformed by chronic arsenite exposure, were monitored for DNA damage by the comet and the micronucleus assays at different time-of-exposure intervals lasting for 50 weeks. Results indicate that the oxidative and DNA damage of chronically exposed MEF cells increased time-dependently up to the point of transformation. As3mt expression followed a pattern like that of DNA damage, and its forced inhibition by shRNA technology before transformation resulted in a DNA damage decrease. On the other hand, Mth1 mRNA levels increased after the transformation point, and its forced knock-down increased significantly the levels of DNA damage and decreased the aggressiveness of the oncogenic phenotype.