Homology modeling of human BAP1 and analysis of its binding properties through molecular docking and molecular dynamics simulation.

BRCA1-associated protein 1 (BAP1) is a nuclear-localized Ubiquitin C-terminal hydrolase (UCH) that functions as a tumour suppressor, and although BAP1 has been linked to cancer, the molecular mechanism by which BAP1 regulates cancer and its crystal structure have not been elucidated. In this study, computational approaches were used to identify the protein model of BAP1 and its potential inhibitors. The structure of the BAP1 model was constructed through homology modeling and the generated BAP1 model was observed to exhibit good quality protein model as the distribution of its amino acids in the Ramachandran's plot corresponded to 87.7% in the most favoured regions. Docking and simulating of the ubiquitin on the BAP1 model structure revealed the rearrangement of F228, F50, and H169 residues of the BAP1 and switching of BAP1's conformation into a productive state. Our screening results of potential BAP1 inhibitors against the FDA approved drugs shortlisted two potential inhibitors, which are FDA1065 and FDA755. We then performed molecular dynamics simulations and Molecular mechanics Poisson-Boltzmann surface area (MMPBSA) analysis on both inhibitors and found that only the BAP1-FDA755 formed a stable complex and the FDA755 ligand remained its position inside the active site of the BAP1 with a total binding energy of (-51.77 ± 3.49 kcal/mol). We speculate that the presence of methyl group in FDA755 play an important role in stabilizing the BAP1-FDA755 complex.Communicated by Ramaswamy H. Sarma.

Annatto (Bixa orellana) δ-TCT Supplementation Protection against Embryonic Malformations through Alterations in PI3K/Akt-Cyclin D1 Pathway.

Protective action by annatto-derived delta-tocotrienol (δ-TCT) and soy-derived alpha-tocopherol (α-TOC) through the regulation of the PI3K/Akt-cyclin D1 pathway against nicotine-induced DNA damage is the focus of the present study. Nicotine, which has been widely reported to have numerous adverse effects on the reproductive system, was used as a reproductive toxicant. 48 female balb/c mice (6⁻8 weeks) (23⁻25 g) were randomly divided into eight groups (Grp.1⁻Grp.8; n = 6) and treated with either nicotine or/and annatto δ-TCT/soy α-TOC for seven consecutive days. On Day 8, the females were superovulated and mated before euthanization for embryo collection (46 h post-coitum). Fifty 2-cell embryos from each group were used in gene expression analysis using Affymetrix QuantiGene Plex2.0 assay. Findings indicated that nicotine (Grp.2) significantly decreased (p < 0.05) the number of produced 2-cell embryos compared to the control (Grp.1). Intervention with mixed annatto δ-TCT (Grp.3) and pure annatto δ-TCT (Grp.4) significantly increased the number of produced 2-cell embryos by 127% and 79%, respectively compared to Grp.2, but these were lower than Grp.1. Concurrent treatment with soy α-TOC (Grp.5) decreased embryo production by 7%. Supplementations with δ-TCT and α-TOC alone (Grp.6-Grp.8) significantly increased (p < 0.05) the number of produced 2-cell embryos by 50%, 36%, and 41%, respectively, compared to control (Grp.1). These results were found to be associated with alterations in the PI3K/Akt-Cyclin D1 genes expressions, indicating the inhibitory effects of annatto δ-TCT and soy α-TOC against nicotinic embryonic damage. To our knowledge, this is the first attempt in studying the benefits of annatto δ-TCT on murine preimplantation 2-cell embryos.

Pubertal anabolic androgenic steroid exposure in male rats affects levels of gonadal steroids, mating frequency, and pregnancy outcome.

Background Testosterone, nandrolone, and stanozolol are among the highly consumed anabolic androgenic steroids (AASs). Although the desired effects of AAS are being achieved by the abusers, unfortunately, this leads to numerous physical and physiological side effects. The present study was designed to investigate and determine whether early pubertal exposure to AAS treatment had detrimental effects on blood testosterone and estradiol concentrations, mating behavior, and pregnancy outcome during the pubertal period in male rats. Materials Early pubertal rats (PND41) were given two doses (2.5 mg/kg and 5 mg/kg) each of testosterone, nandrolone, and stanozolol subcutaneously for 6 weeks. Upon completion, three rats with the highest weight were chosen from each group for mating with the females, in a ratio of one male to two females for 10 days. After 10 days, all male rats were sacrificed to obtain the testes for weight recording, and blood samples were collected for testosterone and estradiol quantitation. Pregnant females were housed separately until birth, and the number of offsprings produced was counted. Results The results clearly show a reduction in reproductive hormonal and behavioral parameters between testosterone and nandrolone, and testosterone and stanozolol. Stanozolol administration exhibited suppressing effects in all parameters including testicular weight deterioration, serum testosterone and estradiol reduction, low mating preferences, and declined pregnancy outcome. Conclusions AAS exposure during the onset of puberty results in reproductive detrimental effects, which are postulated to affect the pregnancy rate.

Vitamin E as an Antioxidant in Female Reproductive Health.

Vitamin E was first discovered in 1922 as a substance necessary for reproduction. Following this discovery, vitamin E was extensively studied, and it has become widely known as a powerful lipid-soluble antioxidant. There has been increasing interest in the role of vitamin E as an antioxidant, as it has been discovered to lower body cholesterol levels and act as an anticancer agent. Numerous studies have reported that vitamin E exhibits anti-proliferative, anti-survival, pro-apoptotic, and anti-angiogenic effects in cancer, as well as anti-inflammatory activities. There are various reports on the benefits of vitamin E on health in general. However, despite it being initially discovered as a vitamin necessary for reproduction, to date, studies relating to its effects in this area are lacking. Hence, this paper was written with the intention of providing a review of the known roles of vitamin E as an antioxidant in female reproductive health.

Histological changes in testes of rats treated with testosterone, nandrolone, and stanozolol.

BACKGROUND: Anabolic androgenic steroids (AAS) is being used in medical treatments, but AAS also was identified to have the risks of adverse effects towards patients and consumers health. OBJECTIVE: Present study was conducted to observe the effects of testosterone, nandrolone, and stanozolol (forms of AAS) intake during onset of puberty on the rat testicular histology. MATERIALS AND METHODS: Juvenile male Sprague-Dawley (SD) rats (n=42) were divided into seven groups and were injected subcutaneously with medium dose of polyethylene glycol-200 (PEG-200) (control), testosterone, nandrolone, and stanozolol for six weeks (PND 41-87). The animals were weighed daily and sacrificed on PND 88. Testes were removed, weighed, and prepared for histological assessment and finally specimens were observed under microscope. RESULTS: The results showed an insignificant increase in mean daily body weight with highest and lowest body weight gained was of 177.6±1.69 gr and 140.0±12.26 gr respectively. There was significant decrease in the testes absolute weight (p≤0.01) in all experimental groups except in the nandrolone 2.5 mg/kg/week treated group. Testicular histology of rats treated with AAS also showed slight changes in the uniformity of arrangements of seminiferous tubules. CONCLUSION: Data from present study suggests that AAS have been initiating the adverse effects on testicular normal functions in rats during onset of puberty.

Sexual education in malaysia: accepted or rejected?

BACKGROUND: Introduction to sexual education in schools was suggested by the Malaysian government as one of the effort taken in the aim to reduce the sexual-related social problems among Malaysian teenagers nowadays. This study was proposed in the aim to determine the rate of acceptance among adolescents on the implementation of sexual education in schools. METHODS: This study was conducted using questionnaires distributed to 152 pre-degree students in Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Kampus Puncak Alam, Selangor, Malaysia. Obtained data were statistically analyzed. RESULTS: Almost half (49.3%) of the respondents agreed that sexual education might help to overcome the social illness among school teenagers. Besides, a large number (77.6%) of respondents also agreed that this module should be incorporated with other core subjects compare to the feedback received on the implementation of this module on its own (28.9%). CONCLUSION: These results have provided some insight towards the perception of sexual education among the teenagers. Since most of the respondents agreed with this idea, so it might be a sign that the implementation of sexual education is almost accepted by the adolescents.