Computational Studies on 6-Pyruvoyl Tetrahydropterin Synthase (6-PTPS) of Plasmodium falciparum.

6-Pyruvoyl tetrahydropterin synthase (6-PTPS) is a lyase involved in the synthesis of tetrahydrobiopterin. In Plasmodium species where dihydroneopterin aldolase (DHNA) is absent, it acts in the folate biosynthetic pathway necessary for the growth and survival of the parasite. The 6-pyruvoyl tetrahydropterin synthase of Plasmodium falciparum (PfPTPS) has been identified as a potential antimalarial drug target. This study identified potential inhibitors of PfPTPS using molecular docking techniques. Molecular docking and virtual screening of 62 compounds including the control to the deposited Protein Data Bank (PDB) structure was carried out using AutoDock Vina in PyRx. Five of the compounds, N,N-dimethyl-N'-[4-oxo-6-(2,2,5-trimethyl-1,3-dioxolan-4-yl)-3H-pteridin-2-yl]methanimidamide (140296439), 2-amino-6-[(1R)-3-cyclohexyl-1-hydroxypropyl]-3H-pteridin-4-one (140296495), 2-(2,3-dihydroxypropyl)-8,9-dihydro-6H-pyrimido[2,1-b]pteridine-7,11-dione (144380406), 2-(dimethylamino)-6-[(2,2-dimethyl-1,3-dioxolan-4-yl)-hydroxymethyl]-3H-pteridin-4-one (135573878), and [1-acetyloxy-1-(2-methyl-4-oxo-3H-pteridin-6-yl)propan-2-yl] acetate (136075207), showed better binding affinity than the control ligand, biopterin (135449517), and were selected and screened. Three conformers of 140296439 with the binding energy of -7.2, -7.1, and -7.0 kcal/mol along with 140296495 were better than the control at -5.7 kcal/mol. In silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies predicted good pharmacokinetic properties of all the compounds while reporting a high risk of irritant toxicity in 140296439 and 144380406. The study highlights the five compounds, 140296439, 140296495, 144380406, 135573878 and 136075207, as potential inhibitors of PfPTPS and possible compounds for antimalarial drug development.

Influence of age and education on breast cancer awareness and knowledge among women in South Western Nigeria.

The rising incidence of breast cancer (BC) in sub-Saharan Africa is aggravated by poor prognosis. Health education and several screening methods, including breast self-examination (BSE), clinical breast-examination (CBE) and mammography, have been advanced to achieve early detection and reduction in its mortality rate. This study evaluated the level of awareness and knowledge of BC and BSE amongst female students and staff of six educational institutions in Ota, Southwest Nigeria. The participants, consisting of 917 (80.79%) students and 218 (19.21%) staff, aged between 13 and 60 years, were selected using a stratified random sampling technique and categorized into age groups [adolescents (13-19 years), young adults (21-40 years) and middle-aged adults (41-60 years)] and levels of education. Data was collected via questionnaires and analysed using Epi-info software and SPSS version 20. Frequencies, percentages, regression and correlation co-efficient were calculated and used to determine the levels of association between age groups and levels of education. Mean age of the participants was 21 ± 1.7 years; over 75% were adolescents. BC and BSE awareness was 94.80% and 65.11% respectively, with 7 (0.62%) having BC. The major sources of BC and BSE information were television, health workers and internet. The average BC knowledge score of the participants was 4.06 (40.57%); it was highest among young adults, 4.31 (43.07%), and least among the adolescents, 3.88 (38.78%). The same trend was observed for BSE practice among the age groups. There was a direct relationship between BC knowledge and levels of education; the postgraduates had the highest BC knowledge score of 4.49 (44.89%) while the secondary students had the least score of 3.82 (38.12%). Similar trend was observed for BSE practice and the levels of education. Paucity of BSE knowledge largely accounted for the low BSE practice among the adolescents and secondary students. The huge gap in BC knowledge and BSE practice underscores the need for a structured health education and screening programmes in Nigerian schools to enhance prevention and early detection of BC and other ailments. BSE is free, easy to perform, and able to detect BC at earlier stage. The practice should be encouraged alongside mammography to reduce the burden and mortality rate of BC in Nigeria.

Phytochemical, Antioxidant and Mitochondrial Permeability Transition Studies on Fruit-Skin Ethanol Extract of Annona muricata.

Uncontrolled cell proliferation hallmarks cancer and most cancer cells have developed multiple resistance to the drugs employed for their treatment. The study examined the phytochemical and antioxidant properties of the fruit-skin ethanol extract of Annona muricata Linn. (ESA) and its effect on rat liver mitochondrial membrane permeability transition (MMPT). Qualitative phytochemical study and antioxidant assays were carried out following established protocols while the opening of the MMPT pore in the presence of varying concentrations of the extract was assayed spectrophotometrically under succinate-energized conditions. Calcium chloride (CaCl2) and spermine were used to trigger and inhibit pore opening respectively. Cytochrome c release was assayed for using ELISA kit. Terpenoids, steroids, phenols among other phytochemicals were found present in ESA and the extract showed very low antioxidant properties at the tested concentrations based on the diphenyl-1-picryhydrazyl (DPPH) radical scavenging activity assay. Lipid peroxidation was induced in a concentration-dependent manner on both the cytosolic and mitochondrial hepatocyte fractions in vitro. In the absence of CaCl2 0.84 mg/mL concentration of ESA induced MMPT pore opening by 129% while the extracts showed no inhibitory activity in its presence. The induction fold corresponded with the concentrations of cytochrome c released. The fruit-skin ethanol extract of Annona muricata at certain concentrations may possibly contain bioactive compounds that induce apoptosis.

The interplay of post-translational modification and gene therapy.

Several proteins interact either to activate or repress the expression of other genes during transcription. Based on the impact of these activities, the proteins can be classified into readers, modifier writers, and modifier erasers depending on whether histone marks are read, added, or removed, respectively, from a specific amino acid. Transcription is controlled by dynamic epigenetic marks with serious health implications in certain complex diseases, whose understanding may be useful in gene therapy. This work highlights traditional and current advances in post-translational modifications with relevance to gene therapy delivery. We report that enhanced understanding of epigenetic machinery provides clues to functional implication of certain genes/gene products and may facilitate transition toward revision of our clinical treatment procedure with effective fortification of gene therapy delivery.