Search results for " GAM"
showing 10 items of 2166 documents
Decrease in αβ/γδ T-cell ratio is accompanied by a reduction in high-fat diet-induced weight gain, insulin resistance, and inflammation.
2018
The implication of αβ and γδ T cells in obesity-associated inflammation and insulin resistance (IR) remains uncertain. Mice lacking γδ T cells show either no difference or a decrease in high-fat diet (HFD)-induced IR, whereas partial depletion in γδ T cells does not protect from HFD-induced IR. αβ T-cell deficiency leads to a decrease in white adipose tissue (WAT) inflammation and IR without weight change, but partial depletion of these cells has not been studied. We previously described a mouse model overexpressing peroxisome proliferator-activated receptor β (PPAR-β) specifically in T cells [transgenic (Tg) T-PPAR-β] that exhibits a partial depletion in αβ T cells and no change in γδ T-ce…
Improved electroless platinum contacts on CdZnTe X- and γ-rays detectors
2020
AbstractPlatinum is a promising candidate for the realization of blocking electrical contacts on cadmium-zinc-telluride (CdZnTe or CZT) radiation detectors. However, the poor mechanical adhesion of this metal often shortens the lifetime of the final device. In this work, a simple and effective procedure to obtain robust platinum contacts by electroless deposition is presented. Microscopical analysis revealed the final thickness and composition of the contact layer and its adhesion to the bulk crystal. The blocking nature of the Pt-CdZnTe junction, essential to obtain low noise devices, was confirmed by current–voltage measurements. The planar Pt-CdZnTe-Pt detectors showed good room temperat…
A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival
2016
AbstractMultiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then sel…
Genetically elevated gamma-glutamyltransferase and Alzheimer's disease
2018
Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer's disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer's Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associ…
Anticancer properties of 4-thiazolidinone derivatives depend on peroxisome proliferator-activated receptor gamma (PPARγ)
2017
Peroxisome proliferator-activated receptors (PPARs) play an important role in numerous chronic diseases such as diabetes, obesity, atherosclerosis and cancer, and PPAR modulators are among the approved drugs and drug-candidates for their treatment. The aim of this study was to elucidate the involvement of PPARs in the mechanism of cytotoxic and pro-apoptotic action of novel anticancer 4-thiazolidinone derivatives (Les-2194, Les-3377, Les-3640) and approved 4-thiazolidinones (Rosiglitazone, Pioglitazone) towards the human squamous carcinoma (SCC-15) cell line. Experiments with 4-thiazaolidinone derivatives and PPAR-specific siRNA were conducted and PPARα, PPARβ and PPARγ mRNA expression was …
Impact of elastin-derived VGVAPG peptide on bidirectional interaction between peroxisome proliferator-activated receptor gamma (Pparγ) and beta-galac…
2018
The process of degradation of the elastin-rich extracellular matrix produces elastin-derived peptides (EDPs). Different types of EDPs are detectable in the cerebrospinal fluid in healthy individuals and in patients after ischemic stroke. To date, it has been demonstrated that EDPs can regulate the development of insulin resistance in mice in a peroxisome proliferator-activated receptor gamma (Pparγ)-dependent manner. Therefore, the aim of this study was to investigate the impact of the elastin-derived valine-glycine-valine-alanine-proline-glycine (VGVAPG) peptide on Pparγ and beta-galactosidase (β-Gal) expression in mouse cortical astrocytes in vitro. Primary astrocytes were maintained in D…
Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease
2017
BACKGROUND AND AIMS: Hepatic cholesterol deposition drives inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). The Niemann-Pick type C2 (NPC2) protein plays an important role in regulating intracellular cholesterol trafficking and homeostasis. We hypothesized that intravenous NPC2 supplementation reduces cholesterol accumulation, hepatic inflammation and fibrogenesis in a nutritional NASH rat model.METHODS: Rats were fed a high-fat, high-cholesterol (HFHC) diet for four weeks resulting in moderately severe NASH. Animals were treated with intravenous NPC2 or placebo twice weekly for either the last two weeks or the entire four weeks. End-points were liver/body- and spleen/body…
DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
2019
Background Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. Methods We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring. Results We identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10−7) associated with exposure to maternal smoking in adolesc…
Peroxisome proliferator-activated receptor-γ coactivator-1α mediates neuroprotection against excitotoxic brain injury in transgenic mice: role of mit…
2016
Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator involved in the regulation of mitochondrial biogenesis and cell defense. The functions of PGC-1α in physiology of brain mitochondria are, however, not fully understood. To address this we have studied wild-type and transgenic mice with a two-fold overexpression of PGC-1α in brain neurons. Data showed that the relative number and basal respiration of brain mitochondria were increased in PGC-1α transgenic mice compared with wild-type mitochondria. These changes occurred concomitantly with altered levels of proteins involved in oxidative phosphorylation (OXPHOS) as studied by proteomi…
Elastin-derived peptide VGVAPG affects the proliferation of mouse cortical astrocytes with the involvement of aryl hydrocarbon receptor (Ahr), peroxi…
2019
Abstract During aging and ischemic and hemorrhagic stroke, elastin molecules are degraded and elastin-derived peptides are released into the brain microenvironment. Val-Gly-Val-Ala-Pro-Gly (VGVAPG) is a repeating hexapeptide in the elastin molecule. It is well documented that the peptide sequence binds with high affinity to elastin-binding protein (EBP) located on the cell surface, thereby transducing a molecular signal into the cell. The aim of our study was to investigate whether EBP, aryl hydrocarbon receptor (Ahr), and peroxisome proliferator-activated receptor gamma (Pparγ) are involved in VGVAPG-stimulated proliferation. Primary astrocytes were maintained in DMEM/F12 medium without ph…