92 research outputs found
Microwave Gaseous Discharges
Contains reports on three research projects.United States Atomic Energy Commission (Contract AT (30-1) 1842
Ire1 alpha/xbp1 axis sustains primary effusion lymphoma cell survival by promoting cytokine release and stat3 activation
Primary Effusion Lymphoma (PEL) is a highly aggressive B cell lymphoma associated with Kaposi’s Sarcoma-associated Herpesvirus (KSHV). It is characterized by a high level of basal Endoplasmic Reticulum (ER) stress, Unfolded Protein Response (UPR) activation and constitutive phosphorylation of oncogenic pathways such as the Signal Transducer and activator of Transcription (STAT3). In this study, we found that the inositol requiring kinase (IRE) 1alpha/X-box binding protein (XBP1) axis of UPR plays a key role in the survival of PEL cells, while double stranded RNA-activated protein kinase-like ER kinase (PERK) and activating transcription factor (ATF) 6 slightly influence it, in correlation with the capacity of the IRE1alpha/XBP1 axis to induce the release of interleukin (IL)-6, IL-10 and Vascular-Endothelial Growth Factor (VEGF). Moreover, we found that IRE1alpha/XBP1 inhibition reduced STAT3 Tyr705 phosphorylation and induced a pro-survival autophagy in PEL cells. In conclusion, this study suggests that targeting the IRE1alpha/XBP1 axis represents a promising strategy against PEL cells and that the cytotoxic effect of this treatment may be potentiated by autophagy inhibition
Microwave Gaseous Discharges
Contains research objectives and reports on five research projects
Cardiovascular Risk Factors Associated With the Metabolically Healthy Obese (MHO) Phenotype Compared to the Metabolically Unhealthy Obese (MUO) Phenotype in Children
Background: In pediatric age the prevalence of obesity is high. Obese children who do not have other risk factors than excess weight have been defined as \u201cmetabolically healthy obese\u201d (MHO).
Aim: The aim of this study is to evaluate, in a population of obese children, the prevalence of the MHO and \u201cmetabolically unhealthy obese\u201d (MUO) phenotype. Furthermore, we evaluated the distribution of Uric Acid, HOMA index and Waist-Height ratio (W-Hr) in the MHO and MUO sub-groups and the impact of these non-traditional risk factors on the probability to be MUO.
Methods: In 1201 obese children and adolescents [54% males, age (\ub1SD) 11.9 (\ub13.0) years] weight, height, waist circumference, systolic (SBP) and diastolic (DBP) blood pressure, pubertal status, glucose, insulin, HDL cholesterol, triglycerides and Uric Acid serum values were assessed. MUO phenotype was defined as the presence of at least one of the following risk factors: SBP or DBP 65 90th percentile, glycaemia 65 100 mg/dl, HDL cholesterol <40 mg/dl, triglycerides 65100 mg/dl (children <10 years) or 65130 mg/dl (children 6510 years). A multivariate logistic regression analysis was used to estimate the association between MUO phenotype and non-traditional cardiovascular risk factors.
Results: The prevalence of the MUO status was high (61%). MUO subjects were more often male, older and pubertal (p < 0.001). The levels of the three non-traditional risk factors were significantly higher in MUO children compared to MHO children (p < 0.001) and all of them were independent predictors of the fact of being MUO [OR 1.41 (95% CI 1.24\u20131.69); 1.15 (95% CI 1.06\u20131.23) and 1.03 (95% CI1.01\u20131.05) for Uric Acid, HOMA index and W-Hr, respectively]. About 15% of MHO subjects had serum Uric Acid, HOMA index and W-Hr values within the highest quartile of the study population.
Conclusion: The prevalence of MUO subjects in a large pediatric population is high and serum Uric Acid, HOMA index and W-Hr values are independent predictors of the probability of being MUO. A non-negligible percentage of subjects MHO has high values of all three non-traditional risk factors
Elevated blood pressure, cardiometabolic risk and target organ damage in youth with overweight and obesity
Background and aim: To compare cardiometabolic risk profile and preclinical signs of target organ damage in youth with normal and elevated blood pressure (BP), according to the American Academy of Pediatrics (AAP) guidelines. Methods and results: This cross-sectional multicenter study included 2739 youth (5-17 year-old; 170 normal-weight, 610 overweight and 1959 with obesity) defined non hypertensive by the AAP guidelines. Anthropometric, biochemical and liver ultrasound data were available in the whole population; carotid artery ultrasound and echocardiographic assessments were available respectively in 427 and 264 youth. Elevated BP was defined as BP 65 90th to <95th percentile for age, gender and height in children or BP 65 120/80 to <130/80 in adolescents. The overall prevalence of elevated BP was 18.3%, and significantly increased from normal-weight to obese youth. Young people with elevated BP showed higher levels of body mass index (BMI), insulin resistance and a higher prevalence of liver steatosis (45% vs 36%, p < 0.0001) than normotensive youth, whilst they did not differ for the other cardiometabolic risk factors, neither for carotid intima media thickness or left ventricular mass. Compared with normotensive youth, individuals with elevated BP had an odds ratio (95%Cl) of 3.60 (2.00\u20136.46) for overweight/obesity, 1.46 (1.19\u20131.78) for insulin-resistance and 1.45 (1.19\u20131.77) for liver steatosis, controlling for centers, age and prepubertal stage. The odds for insulin resistance and liver steatosis persisted elevated after correction for BMI-SDS. Conclusion: Compared to normotensive youth, elevated BP is associated with increased BMI, insulin resistance and liver steatosis, without significant target organ damage
Protein Kinase A Regulatory Subunits in Human Adipose Tissue: Decreased R2B Expression and Activity in Adipocytes From Obese Subjects
OBJECTIVE—In human adipocytes, the cAMP-dependent pathway mediates signals originating from β-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e., lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B regulatory isoform is the most expressed in mouse adipose tissue, where it protects against diet-induced obesity and fatty liver development. The aim of the study was to investigate possible differences in R2B expression, PKA activity, and lipolysis in adipose tissues from obese and nonobese subjects
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