Low molecular weight compounds from mushrooms as potential Bcl-2 inhibitors: docking and virtual screening studies

Mushrooms have the ability to promote apoptosis in tumor cell lines, but the mechanism of action is not quite well understood. Inhibition of the interaction between Bcl-2 and pro-apoptotic proteins could be an important step that leads to apoptosis. Therefore, the discovery of compounds with the ability to inhibit Bcl-2 is an ongoing research topic in drug discovery. In this study, we started by analyzing Bcl-2 experimental structures that are currently available in Protein Data Bank database. After analysis of the more relevant Bcl-2 structures, 4 were finally selected. An analysis of the best docking methodology was then performed using a cross-docking and re-docking approach while testing 2 docking softwares: AutoDock 4 and AutoDock Vina. Autodock4 provided the best docking results and was selected to perform a virtual screening study applied to a dataset of 40 Low Molecular Weight (LMW) compounds present in mushrooms, using the selected Bcl-2 structures as target. Results suggest that steroid are the more promising family, among the analyzed compounds, and may have the ability to interact with Bcl-2 and this way promoting tumor apoptosis. The steroids that presented lowest estimated binding energy (ΔG) were: Ganodermanondiol, Cerevisterol, Ganoderic Acid X and Lucidenic Lactone; with estimated ΔG values between -8,45 and -8,23 Kcal/mol. A detailed analysis of the docked conformation of these 4 top ranked LMW compounds was also performed and illustrates a plausible interaction between the 4 top raked steroids and Bcl-2, thus substantiating the accuracy of the predicted docked poses. Therefore, tumoral apoptosis promoted by mushroom might be related to Bcl-2 inhibition mediated by steroid family of compounds.

Body image perception in adolescents and concern with weight

In a holistic conception of health, youth health is moderated by their self image and the perception that adolescents have of themselves is conditioned by social and cultural pressure, and low selfesteem is often observed, possibly caused by the way they perceive their own body, having as a consequence, an health proile with morbidities. Recognize the level of youth heath assessing Body Image perception and their concern with weight. It is a descriptive, quantitative and transversal study. Based on a sampling error lower than 5% and a conidence level of 95%, the study was carried out on a sample of 600 adolescents aged between 12 and 18. A self-ad-ministered questionnaire validated for adolescents was conducted by Di Pietro (2002). The sample is composed of 44% male and 56% female adolescents, with an age mean of 15.54. 61.2% of the boys and 83.6% of the girls stated to be concerned with their weight. The main reasons given for this concern were health associated with aesthetics (29.1% of boys and 38.5% of girls). The results show that 12.8% of boys and 23.5% of girls are dissatisied with their body image. The study revealed that the variable gender is statistically moderating in relation to the variables: body image perception and concern with weight: female adolescents show a higher dissatisfaction with their body image (0.003) and a bigger concern with weight (0.000). The results point out towards the need for assessment/ intervention in this population as body image represents a paramount issue in adolescence, with the body image self-perception being strongly associated with the biopsychosocial maturing process, which interferes with their level of health and personal and social development.