Anopheles gambiae Trehalase Inhibitors for Malaria Vector Control: A Molecular Docking and Molecular Dynamics Study.

Trehalase inhibitors are considered safe alternatives for insecticides and fungicides. However, there are no studies testing these compounds on Anopheles gambiae, a major vector of human malaria. This study predicted the three-dimensional structure of Anopheles gambiae trehalase (AgTre) and identified potential inhibitors using molecular docking and molecular dynamics methods. Robetta server, C-I-TASSER, and I-TASSER were used to predict the protein structure, while the structural assessment was carried out using SWISS-MODEL, ERRAT, and VERIFY3D. Molecular docking and screening of 3022 compounds was carried out using AutoDock Vina in PyRx, and MD simulation was carried out using NAMD. The Robetta model outperformed all other models and was used for docking and simulation studies. After a post-screening analysis and ADMET studies, uniflorine, 67837201, 10406567, and Compound 2 were considered the best hits with binding energies of -6.9, -8.9, -9, and -8.4 kcal/mol, respectively, better than validamycin A standard (-5.4 kcal/mol). These four compounds were predicted to have no eco-toxicity, Brenk, or PAINS alerts. Similarly, they were predicted to be non-mutagenic, carcinogenic, or hepatoxic. 67837201, 10406567, and Compound 2 showed excellent stability during simulation. The study highlights uniflorine, 67837201, 10406567, and Compound 2 as good inhibitors of AgTre and possible compounds for malaria vector control.

Structural Transformation and Creativity Induced by Biological Agents during Fermentation of Edible Nuts from Terminalia catappa.

Terminalia catappa L. (tropical almond) is a nutritious fruit found mainly in the tropics. This study is aimed to establish the naturally biotransformed molecules and identify the probiotic agents facilitating the fermentation. The aqueous extracts from both the unfermented and fermented T. catappa nuts were subjected to gas chromatography/mass spectrometry (GC/MS) analysis. Syringol (6.03%), glutamine (1.71%), methyl laurate (1.79%), methyl palmitate (1.53%), palmitic acid (5.20%), palmitoleic acid (2.80%), and methyl oleate (2.97%) were detected in the unfermented nuts of the T. catappa. Additionally, two of these natural compounds (palmitic acid (4.19%) and palmitoleic acid (1.48%)) survived the fermentation process to emerge in the fermented seeds. The other natural compounds were biotransformed into 2,3-butanediol (1.81%), butyric acid (16.20%), propane-1,3-diol (19.66%), neoheptanol (2.89%), 2-piperidinone (6.63%), palmitoleic acid (1.18%), formamide, n-(p-hydroxyphenethyl)- (2.80%), and cis-vaccenic acid (1.69%) that newly emerged in the fermented seeds. The phytochemical compounds are likely carbon sources for the organisms facilitating the biotransformed molecules and product production. Four (4) potential probiotic bacteria strains, namely, Probt B1a, Probt B2a, Probt B4a, and Probt B4b, were isolated from the fermented nut. Enterococcus faecum, and Enterococcus faecalis were the organisms identified as driving the fermentation of the seeds. All strains were gram-positive, catalase-negative, and non-hemolytic, which suggests their harmless nature. N-(p-hydroxyphenethyl)-) was associated with fermentation for the first time, and neoheptanol was discovered as the main alcoholic molecule formed during the fermentation of the seeds. This fermentation is a handy tool for bio-transforming compounds in raw food sources into compounds with nutritious and therapeutic potentials.

Fermentation Enhanced Biotransformation of Compounds in the Kernel of Chrysophyllum albidum.

Chrysophyllum albidum Linn (African star apple) is a fruit with extensive nutritional and medicinal benefits. The fruit and kernel in the seed are both edible. Strains of lactic acid bacteria (LAB) were isolated from fermented seeds and assessed for probiotic characteristics. The extracts in both the unfermented and the fermented aqueous extracts from the kernels obtained from the seeds of C. albidum were subjected to analysis using the gas chromatography/mass spectrometry (GC-MS) method. This analysis identified the bioactive compounds present as possible substrate(s) for the associated organisms inducing the fermentation and the resultant biotransformed products formed. Three potential probiotic LAB strains identified as Lactococcus raffinolactis (ProbtA1), Lactococcus lactis (ProbtA2a), and Pediococcus pentosaceus (ProbtA2b) were isolated from the fermented C. albidum seeds. All strains were non hemolytic, which indicated their safety, Probt (A1, A2a, and A2b) grew in an acidic environment (pH 3.5) during the 48-h incubation time, and all three strains grew in 1% bile, and exhibited good hydrophobicity and auto-aggregation properties. Mucin binding proteins was not detected in any strain, and bile salt hydrolase was detected in all the strains. l-lactic acid (28.57%), norharman (5.07%), formyl 7E-hexadecenoate (1.73%), and indole (1.51%) were the four major constituents of the fermented kernel of the C. albidum, while 2,5-dimethylpyrazine (C1, 1.27%), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (C2, 2.90%), indole (C3, 1.31%), norharman (C4, 3.01%), and methyl petroselinate (C5, 4.33%) were the five major constituents of the unfermented kernels. The isolated LAB are safe for consumption. The fermenting process metabolized C1, C2, and C5, which are possible starter cultures for the growth of probiotics. Fermentation is an essential tool for bioengineering molecules in foods into safe and health beneficial products.

Anti-inflammatory Mechanism of Ruzu Bitters on Diet-Induced Nonalcoholic Fatty Liver Disease in Male Wistar Rats.

Nonalcoholic fatty liver disease (NAFLD) has become notorious globally. Increasingly emerging evidence shows that NAFLD is strongly associated with inflammation, with proinflammatory cytokines such as interleukin-2 (IL-2), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) playing a vital role in its progression. In this work, an attempt was made to verify the anti-inflammatory activity of Ruzu herbal bitters (RHB), an antiobesity medicinal concoction, on NAFLD induced by a high-fat diet (HFD) in albino Wistar rats. Twenty-five (25) rats were divided into five groups as follows: Group 1, the normal control, was maintained on standard rat chow and received normal saline (1 ml/kg body weight (BW)/day) for twelve weeks. The other groups were maintained on HFD for twelve weeks. Thereafter, groups 2-5 were treated with pioglitazone (4 mg/kg BW/day), RHB (0.6 ml/kg BW/day), normal saline (1 ml/kg BW/day), and fenofibrate (10 mg/kg BW/day), respectively. The animals were sacrificed after the experimental period. Biochemical indicators of oxidative stress and inflammation were assayed in the liver according to standard methods. The histological features of the liver were also compared to assess liver damage. RHB significantly (p < 0.05) reduced body weight and liver index, inhibited oxidative stress, boosted antioxidant enzymes by increasing the activity and level of SOD and GSH, reduced proinflammatory markers (IL-2, IL-6, TNF-α), and reversed histological alterations induced by NAFLD in rat liver. In conclusion, the anti-inflammatory activity of RHB in the prevention of NAFLD in rats has been confirmed.

Estimate of the incidence of bladder cancer in Africa: A systematic review and Bayesian meta-analysis.

OBJECTIVES: To quantify the epidemiology of bladder cancer in Africa to guide a targeted public health response and support research initiatives. METHODS: We systematically searched publicly available sources for population-based registry studies reporting the incidence of bladder cancer in Africa between January 1980 and June 2017. Crude incidence rates of bladder cancer were extracted. A Bayesian network meta-analysis model was used to estimate incidence rates. RESULTS: The search returned 1328 studies. A total of 22 studies carried out across 15 African countries met our pre-defined selection criteria. Heterogeneity across studies was high (I2  = 98.9%, P < 0.001). The pooled incidence of bladder cancer in Africa was 7.0 (95% credible interval 5.8-8.3) per 100 000 population in men and 1.8 (95% credible interval 1.2-2.6) per 100 000 in women. The incidence of bladder cancer was consistently higher in North Africa in both sexes. Among men, we estimated a pooled incidence of 10.1 (95% credible interval 7.9-11.9) per 100 000 in North Africa and 5.0 (95% credible interval 3.8-6.6) per 100 000 in sub-Saharan Africa. In women, the pooled incidence was 2.0 (95% credible interval 1.0-3.0) per 100 000 and 1.5 (95% credible interval 0.9-2.0) per 100 000 in North Africa and sub-Saharan Africa, respectively. Incidence rates increased significantly among men from 5.6 (95% credible interval 4.2-7.2) in the 1990s to 8.5 (95% credible interval 6.9-10.1) per 100 000 in 2010. CONCLUSIONS: The present study suggests a growing incidence of bladder cancer in Africa in recent years, particularly among men and in North Africa. This study also highlights the lack of quality data sources and collection of essential clinical and epidemiological data in several African countries, and this hinders public health planning.

Evaluation of the toxicological profile of the leaves and young twigs of Caesalpinia bonduc (Linn) roxb.

Acute and sub-acute toxicological effects of ethanolic extract of the leaves and young twigs of Caesalpinia bonduc were carried out on albino rats. Single extract doses from 2000 to 5000 mg/kg body weight were administered orally and monitored for 14 days in acute study, while extract doses from 200 to 1600 mg/kg body weight were orally administered daily for 28 days in sub-acute study and recovery was assessed 14 days after dosing. Biochemical, haematological and histopathological examinations were carried out. There was no mortality in the experimental animals in all acute treatment doses. However, there were significant alterations in the biomarkers and induced cellular damage to the liver in all acute treatment doses. In the sub-acute toxicity treatment, the assessed biomarkers were unaffected at extract dose of 200 mg/kg body weight compared to control, while significant changes were observed in rats administered with extract doses of 400 mg/kg body weight and above. No significant difference was observed between the tested groups and the recovery groups in the sub-acute toxicity study. In conclusion, the ethanolic extract of C. bonduc could be toxic to selected organs of the rat body in acute and sub-acute treatments.

Correlation between body mass index and waist circumference in nigerian adults: implication as indicators of health status.

BACKGROUND: Anthropometric measures have been widely used for body weight classification in humans. Waist circumference has been advanced as a useful parameter for measuring adiposity. This study evaluated the correlation between body mass index (BMI) and waist circumference and examined their significance as indicators of health status in adults. DESIGN AND METHODS: The subject included 489 healthy adults from Ota, Nigeria, aged between 20 and 75 years, grouped into early adulthood (20-39 years), middle adulthood (40-59 years) and advanced adulthood (60 years and above). Weight, height and abdominal circumference were measured. BMI was calculated as weight kg/height2 (m2) and World Health Organization cut-offs were used to categorize them into normal, underweight, overweight and obese. RESULTS: Abnormal weight categories accounted for 60 % of the subjects (underweight 11 %, overweight 31%, and obese 18%). The waist circumference of overweight and obese categories were significantly (P<0.05) higher than the normal weight category. There was no significant difference between waist circumference of underweight and normal subjects. The correlation coefficient values of BMI with waist circumference (r=0.63), body weight (r=0.76) and height (r=-0.31) were significant (P<0.01) for the total subjects. CONCLUSIONS: The study indicates that waist circumference can serve as a positive indicator of overweight and obesity in the selected communities; however, it may not be used to determine underweight in adults. Regular BMI and waist circumference screening is recommended as an easy and effective means of assessing body weight and in the prevention of weight related diseases in adults. Significance for public healthThis manuscript describes the correlation between body mass index, waist circumference and body weight of two communities in Ota, Ogun State, Nigeria and the use of these anthropometric measures for body weight classification in human populations of the selected communities. This was carried out to evaluate the health status of the indigenes of the two communities for proper health awareness and public health intervention programmes.