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“Multiple sclerosis (MS) is a demyelinating disorder predominantly affecting young people. Currently, interferon beta (IFN beta) is a common treatment for MS. Despite a large effort in recent years, valid biomarkers with predictive value for clinical JNJ-26481585 clinical trial outcome and response to therapy are lacking. In order to identify predictive biomarkers of response to IFN beta therapy in relapsing-remitting MS patients, we analyzed expression of 526 immune-related genes with the nCounter Analysis System (NanoString Technologies, Seattle, WA, USA) on total

RNA extracted from peripheral blood mononuclear cells of 30 relapsing-remitting MS patients. We used a Wilcoxon signed-rank test to CP456773 find an association between certain gene expression profiles and clinical responses to IFN beta. We compared the expression profile of patients who responded to IFNI?. treatment (n = 16) and non-responsive IFN beta patients (n = 14). The analysis revealed that the expression of eight genes could differentiate between responsive and non-responsive men (p smaller than = 0.005). This differentiation was not evident in women. We analyzed results

from an additional cohort of 47 treated and untreated patients to validate the results and explore whether this eight gene cluster could also predict treatment response. Analysis of the validation cohort demonstrated that three out of the eight genes remained significant in only the treated

men (p smaller than = 0.05). Our findings could be used as a basis for establishing a routine test for objective prediction of IFN beta treatment response in male MS patients. (C) 2015 Larotrectinib Elsevier Ltd. All rights reserved.”
“Park Y, Capobianco S, Gao X, Falck JR, Dellsperger KC, Zhang C. Role of EDHF in type 2 diabetes-induced endothelial dysfunction. Am J Physiol Heart Circ Physiol 295: H1982-H1988, 2008. First published September 12, 2008; doi:10.1152/ajpheart.01261.2007. – Endothelium-derived hyperpolarizing factor (EDHF) plays a crucial role in modulating vasomotor tone, especially in microvessels when nitric oxide-dependent control is compromised such as in diabetes. Epoxyeicosatrienoic acids (EETs), potassium ions (K+), and hydrogen peroxide (H2O2) are proposed as EDHFs. However, the identity (or identities) of EDHF-dependent endothelial dilators has not been clearly elucidated in diabetes. We assessed the mechanisms of EDHF-induced vasodilation in wild-type (WT, normal), db/db (advanced type 2 diabetic) mice, and db/db mice null for TNF (db(TNF-)/db(TNF-)).