Sirt2 is a target for the treatment of neurological, metabolic, and age-related diseases including cancer. Here we report a series of Sirt2 inhibitors based on the 1,2,4-oxadiazole scaffold. These compounds are potent Sirt2 inhibitors active at single-digit μM level by using the Sirt2 substrate α-tubulin-acetylLys40 peptide and inactive up to 100 μM against Sirt1, -3, and -5 (deacetylase and desuccinylase activities). Their mechanism of inhibition is uncompetitive toward both the peptide substrate and NAD, and the crystal structure of a 1,2,4-oxadiazole analog in complex with Sirt2 and ADP-ribose reveals its orientation in a still unexplored subcavity useful for further inhibitor development. Tested in leukemia cell lines, 35 and 39 induced apoptosis and/or showed antiproliferative effects at 10 or 25 μM after 48 h. Western blot analyses confirmed the involvement of Sirt2 inhibition for their effects in NB4 and in U937 cells. Our results provide novel Sirt2 inhibitors with a compact scaffold and structural insights for further inhibitor improvement.
The Coronavirus pandemic has impacted the entire school population’s emotions and the disruption of the organization of the school world. In this context it is important to reflect on the role of health promotion at school. The present study aimed at exploring school leaders’ and teachers’ perspectives and experiences about COVID-19 pandemic and its effects in the school and education system. The first objective was to gather the experience of school leaders regarding the change in school organization, with particular attention to organizational and health promotion aspects. The second was to investigate the perception of health promotion and self-efficacy of teachers in primary, middle and high schools. The research was conducted using qualitative (focus groups for the school leaders) and quantitative methods (questionnaires for the teachers). The findings showed new ways of improving wellbeing at school and implementing health promotion through the sharing of good practice between school leaders. The need for time and space to reflect among school leaders on the educational and didactic aspects of school organization also emerged. Teachers showed a low to medium level of self-efficacy regarding the adoption of strategies in line with health promotion; specificities for each grade and level will be discussed.
Lifestyle is a complex and often generic concept that has been used and defined in different ways in scientific research. Currently, there is no single definition of lifestyle, and various fields of knowledge have developed theories and research variables that are also distant from each other. This paper is a narrative review of the literature and an analysis of the concept of lifestyle and its relationship to health. This contribution aims to shed light on the lifestyle construct in health psychology. In particular, the first part of this manuscript reexamines the main definitions of lifestyle in the psychological and sociological fields through three perspectives: internal, external, and temporal. The main components that characterise lifestyle are highlighted. The second part of this paper explores the main concepts of lifestyle in health, underlining their strengths and weaknesses, and proposes an alternative definition of a healthy lifestyle, which integrates the individual dimensions with the social and cycle dimensions of life. In conclusion, a brief indication of a research agenda is presented.
Background: Biofortified yellow cassava has been developed to alleviate vitamin A deficiency. We examined the potential contribution of yellow cassava to total Retinol Activity Equivalent (RAE) intake if replacing white by yellow cassava among pre-school Nigerian children. Methods: Dietary intake was assessed as part of a randomized controlled trial. Preschool children (n=176) were randomly assigned to receive either white cassava (WC) or yellow cassava (YC) for 17 weeks. Dietary intake assessments were conducted during the intervention and one month after, when children had resumed their habitual diet. Differences in RAE intake between groups and time points were compared using a linear mixed model regression analysis. Results: During intervention, median RAE intake was 536 µg/day in the YC group and 301 µg/day in the WC group (p<0.0001). YC contributed ˜40% to total RAE intake. Nine percent of children in the YC versus 29% in the WC groups had RAE intake below the Estimated Average Requirement. After intervention, median RAE intake was 300 µg/day and did not differ between intervention groups (p=0.5). The interaction effect of group and time showed a 37% decrease in RAE intake in the YC group after the intervention (Exp(β) = 0.63 [95% CI 0.56, 0.72]). If WC was replaced by YC after intervention, the potential contribution of YC to total RAE intake was estimated to be ˜32%. Conclusions: Yellow cassava increased total RAE intake and showed a substantially lower inadequacy of intake. It is therefore recommended as a good source of provitamin A in cassava-consuming regions.
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