Radioactivity and dose assessment of naturally occurring radionuclides in terrestrial environments and foodstuffs: a review of Bahi district, Tanzania.

In this review, the online searchable research articles were scrutinized for the data presented in line with radioactivity and dose estimates from both terrestrial environments and foodstuffs from Bahi district and other parts of Tanzania. The data on natural gamma ray dose rates from Bahi localities were observed with variations among researchers. The observed ranges of radioactivity concentrations (Bq kg-1) in soil were 226Ra (28.5-57.4), 232Th (38.1-521.3), and 40K (562.9-665.0). Deep closed water wells with installed pumps from Ilindi and Bahi Mission reported radioactivity concentration of 238U 3.08 Bq L-1 and Ilindi swamps reported radioactivity concentrations of 226Ra 15.35 Bq L-1, whereas radioactivity concentrations of 238U in cereals were within the annual tolerable limits of 0.001-0.02 Bq kg-1. The quantity and accessibility of published studies, as well as the diversity of the data, point to the necessity for additional studies to be carried out in order to obtain comprehensive baseline data.

Ensemble-based virtual screening of African natural products to target human thymidylate synthase.

Human thymidylate synthase (hTS) is a validated drug target for chemotherapy. A virtual screening experiment was used to prioritize a list of compounds from African Natural Products Databases docked against the orthosteric binding pocket of hTS. Consensus scores of binding affinities from ensemble-based virtual screening, hydrated docking and MM-PBSA calculations ranked compounds NEA4433 and NEA4434 as the best candidates owing to binding affinity scores in the picomolar order, their excellent ADMET profiles and the good stability of the protein-ligand complexes formed. The current study demonstrates the role of water in small molecule binding to hTS in mediating protein-ligand interactions. Similarly, the robust ensemble docking (relaxed scheme complex) ranked NEA4433 and NEA4434 as the best candidates. Furthermore, the best candidates prioritized were shown to strongly interact with the same residues that interacted with hTS substrate and cofactor.

Finding alternatives to 5-fluorouracil: application of ensemble-based virtual screening for drug repositioning against human thymidylate synthase.

5-fluorouracil and analogs are used in the treatment of many solid tumours. However, there are many cases of resistance and high toxicity associated with 5-fluorouracil chemotherapy. Repurposing FDA drugs against human thymidylate synthase revealed a number of FDA drugs that have a potential to be further developed for the treatment of various cancers for which 5-fluorouracil and analogs have been used for chemotherapy. Four FDA drugs prioritized for further validation included Erismodegib, Irinotecan, Conivaptan and Ergotamine. The role of water in mediating drug interactions and its contribution to the total binding energy was also shown. MM-PBSA calculations revealed that the binding affinity was the lowest for the hTS-Ergotamine complex (-66.702 ± 1.807 kJ/mol) suggesting moderate inhibition despite a large energetic contribution from van der Waal interactions (-190.889 ± 1.027 kJ/mol).Communicated by Ramaswamy H. Sarma.

Targeting human thymidylate synthase: Ensemble-based virtual screening for drug repositioning and the role of water.

A drug repositioning computational approach was carried to search inhibitors for human thymidylate synthase. An ensemble-based virtual screening of FDA-approved drugs showed the drugs Imatinib, Lumacaftor and Naldemedine to be likely candidates for repurposing. The role of water in the drug-receptor interactions was revealed by the application of an extended AutoDock scoring function that included the water forcefield. The binding affinity scores when hydrated ligands were docked were improved in the drugs considered. Further binding free energy calculations based on the Molecular Mechanics Poisson-Boltzmann Surface Area method revealed that Imatinib, Lumacaftor and Naldemedine scored -130.7 ± 28.1, -210.6 ± 29.9 and -238.0 ± 25.4 kJ/mol, respectively, showing good binding affinity for the candidates considered. Overall, the analysis of the molecular dynamics trajectory of the receptor-drug complexes revealed stable structures for Imatinib, Lumacaftor and Naldemedine, for the entire simulation time.

Potential of natural phenolic antioxidant compounds from Bersama abyssinica (Meliathacea) for treatment of chronic diseases.

Chronic diseases including cardiovascular, diabetes and cancer persist for a long time in the course of treatment affecting health and are currently the cause of many deaths. In most cases, the treatment of chronic infectious diseases especially Tuberculosis relies on conventional drugs which are currently becoming fruitless due to drug resistance and unpredicted complications in course of treatment. However, herbal medicines have for a long time been used in prevention and treatment of chronic diseases including asthma and heart diseases in Africa. In this study, we extracted metabolites and screened for active compounds with potential free radical scavenging and pharmacological activities from Bersama abyssinica, the plant commonly used in traditional medicine in Tanzania. B. abyssinica root, stembark and leaf were air dried, sequentially extracted in various solvents including petroleum ether, dichloromethane, ethylacetate and methanol to yield extracts and fractions. The extracts and fractions were tested for the presence of several metabolites and antioxidant activity. The analysis of chemical compounds from resultant extracts was done by GC-MS for non-polar factions and LC-MS/MC for moderate polar extracts.High amount of phenolic acid, flavonoids and tannin were identified in ethylacetate fraction compared to ethanol, dichloromethane and petroleum ether. The GC-MS analysis of petroleum ether extract of B. abyssinica stem back yielded twelve (12) compounds with varying composition. The most abundant compounds were 2-Butenoic acid, 3-methyl-, ethyl ester comprising 33.8%, n-Hexadecanoic acid comprising 16.7% and Ethanolpentamethyl- yielded in 16.7%.The LC-MS/MS analysis of Ethyl acetate fractions yielded 20 compounds including; Mangiferin and Isoquercitin were abundant in leaves, stembark and roots. Lastly, ethyl vanillate was identified in both roots and leaves whereas Quercitrin and 7,8-Dimethoxycoumarin were found in stembark and root.These findings indicated that B. abyssinica is rich in phenolic compounds ranging from phenolic acids, flavonoids and coumarin that possess high antioxidant and pharmacological properties potential for treatment of chronic diseases.

Development of a Natural Product Rich in Bioavailable Omega-3 DHA from Locally Available Ingredients for Prevention of Nutrition Related Mental Illnesses.

Objectives: Poor mental health remains a serious public concern worldwide. The most vulnerable individuals are children and adolescents in developing countries. Nutritional deficiency of long-chain omega-3 fatty acids, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have long been recognized as a major contributing factor for mental health illnesses. Provision of ready-to-use natural product rich in preformed Omega-3 DHA and EPA could address this problem. However, most commonly used products are expensive and contain less or no preformed Omega-3 DHA and EPA, making them less suitable for prevention of mental illnesses in resource-poor countries. The main objective of this study was to develop a natural product rich in preformed Omega-3 DHA and EPA from locally available ingredients.Methods: Linear programing (LP) was used to formulate a natural product rich in preformed Omega-3 DHA and other essential nutrients using locally available ingredients other than fish and dairy products. Laboratory analysis was then performed to validate the nutritional value of the LP-formulation using standard analytical methods. The relative difference between the LP tool calculated values, and the laboratory-analyzed values were calculated. Sensory testing was also done to evaluate consumer acceptance of the final product.Results: Optimal formulation contained about 220 mg of preformed Omega-3 DHA + EPA, enough to meet the RDI for children aged 2-10 years. The LP analysis further showed that the cost of the developed product is USD 0.15/100 g, which is 50% lower than that of Plumpy'nut. Laboratory analysis revealed similar results as that of LP at P = 0.05.Conclusions: These findings indicate that ready-to-use natural food rich in preformed DHA and EPA can be developed from locally available ingredients.

Antimicrobial activities of Tephrosia vogelii against selected pathogenic fungi and bacteria strains.

Candida albicans and Cryptococcus neoformans are dangerous pathogens causing fungal diseases. C. albicans and C. neoformans developed resistance to fungicides such as fluconazole. Similarly, pathogenic bacteria Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Salmonella typhi have become resistant to antibiotcs such as methicillin. Thus, searching for alternative antimicrobial agents is inevitable. Tephrosia vogelii used traditionally for management of fungal and bacterial diseases is potential source of antimicrobial agents. It is in this vein that, antimicrobial activities of leaf and root extracts of T. vogelii were evaluated against C. albicans (ATCC 90028), C. neoformans (clinical isolate), S. aureus (ATCC25923), E. coli (ATCC29953), K. pneumoniae (ATCC 700603) and S. typhi (NCTC 8385). A two-fold serial dilution method using the sterilised 96 wells of polystyrene microlitre plates used to determine the minimum inhibitory concentration (MIC) of extracts. Hexane and dichloromethane extracts exhibited the lowest activity against fungi strains with MICs >10 mg/mL. Root and leaf methanolic extracts exhibited activity at MICs of 5 and 1.25 mg/mL, respectively, against both tested fungi. Dichloromethane and methanolic extracts exhibited antibacterial activity with MICs ranging from 2.5 - 10 mg/mL and 0.625 - 5 mg/mL, respectively. Antimicrobial activities of the extracts of T. vogelii revealed potentiality of bioactives against fungal and bacterial diseases.

Effects of Nanoparticles of Metal Oxides on the Survival of the Entomopathogenic Nematode: Steinernema carpocapsae.

Nanoparticles (NPs) are technological engineered materials with unique physical and chemical properties, and dimension of less than 100 nm. Nanotechnology has developed at a rapid pace, resulting into tremendous wide application that has resulted into concerns and ecotoxicological consequences. The antimicrobial potentials of the nanoparticles have been extensively studied, however, little has been done on the allied health and environmental toxicity assessments. Thus, the current work evaluated the toxicity effects of the ZnO, TiO2 and Fe3O4 NPs on the survival of the entomopathogenic nematodes (Steinernema carpocapsae), as well as their growth inhibition effects on the nematode symbiotic bacteria (Xenorhabdus nematophila). The metal oxides NPs were characterized by scanning electron microscope and transmission electron microscope. Their toxicity effects were evaluated at various concentrations with the consideration of the media on the toxicity influence. All metal oxides had less influence on the survival of the entomopathogenic nematode and growth of the nematode symbiotic bacterial partner in a concentration dependant manner NPs. The observed toxicity was in the order of Fe3O4 < TiO2 < ZnO NPs respectively, with no significant difference between the NPs. The less toxic effect of the NPs noted may be associated with the ability of entomopathogenic nematodes and their bacterial partner to tolerate toxicants. Nonetheless, other toxicity parameter of NPs on the beneficial nematodes needs to be evaluated for consideration of the compatibility potential of the nematodes and NPs for pest management.

Influence of Metal Oxides Nanoparticles on Pathogenicity of Steinernema carpocapsae Nematodes Against Lepidopteran Galleria mellonella.

Entomopathogenic nematodes (EPNs) have been cited as a safe and effective method for pest management. Their virulence against lepidopterans and other foliar pest has been demonstrated in the laboratory, but achieving field efficacy is challenged with environmental conditions such as desiccation and ultraviolet radiations. Nanoparticles (NPs) as UV-blocking agents have been reported to provide an alternative approach to enhance the EPNs efficacy. We screened the effect of ZnO, TiO2 and Fe3O4 NPs on survival and pathogenicity of EPNs, and determined whether the nanoparticles could provide protection to the EPNs at low concentrations when applied in direct sunlight. All nanoparticles had less influence on the survival of infective juveniles and did not deprive their pathogenic properties following prolonged exposure. The survival rate of nematodes decreased with increased concentrations, with no measurable difference between NPs. Moreover, the survival rate of nematodes exposed to UV radiation in different formulation decreased significantly with the increase in exposure time (p < 0.001). On the other side when EPNs in nanoparticles formulations were exposed to sunlight, their efficacy significantly improved by protecting nematodes from ultraviolet radiation when compared to the water-based formulation. Pathogenic efficacy after exposure to sunlight was in the order of ZnO > TiO2 > Fe3O4 > H2O, indicating the compatibility of nematodes and NPs, and the benefit of different NPs in EPNs formulations. General nanoparticles are novel ingredients that provide suitable protection of EPNs for management of foliar pests. However, the EPNs nanoparticles formulation under a specific agricultural system and climatic condition need to be established.

Larvicidal activity of Hypoestes forskaolii (Vahl) R. Br root extracts against Anopheles gambiae Giless.s, Aedes aegypti L, and Culex quinquefasciatus Say.

Aim: This study aimed to evaluate larvicidal activity of Hypoestes forskaolii R. Br root extract against 3rd instar Anopheles gambiae, Aedes aegypti, and Culex quinquefasciatus. Methods: A protocol developed by the World Health Organization was adopted, with minor modification using chloroform and methanol extracts with concentrations ranging from 25-750 µg/mL. Results: The H. forskaolii chloroform extract exhibited very high larvicidal activity after 72 hours of exposure, with LC50 2.0322, 3.8989, 6.0004 µg/mL against A. gambiae, A. aegypti, and C. quinquefasciatus, respectively. Conclusion: The larvicidal activity of H. forskaolii is reported for the first time in this paper. The effectiveness of H. forskaolii chloroform extract warrants further research to develop botanical mosquito repellants from this source.

Molecular identification of Salmonella Typhimurium from village chickens based on invA and spvC genes.

AIM: This study aimed to identify Salmonella enterica serovars by polymerase chain reaction (PCR) based on virulence genes invasion A (invA) and Salmonella plasmid virulence C (spvC). MATERIALS AND METHODS: DNA extraction of eight bacteria isolates was done using the PowerSoil® DNA Isolation Kit. The amplification of invA and spvC genes was done using conventional PCR. The positive PCR products were purified using the GeneJET Purification Kit and then sequenced using ABI 3730 XL automated genetic analyzer. The sequences obtained were compared for similarities with other Salmonella serovars deposited on the NCBI GenBank using BLASTN. RESULTS: Four out of eight samples were amplified by primers FS139/RS141 that target invA gene with products of about 284 bp, and three out of four of the same invA positive samples were also amplified by primers FSPV-1/RSPV-2 targeting spvC with a product of about 571 bp. One sample was not amplified by primers FSPV-1/RSPV-2 as it lacked virulence plasmid. Analysis of sequences indicated 100% homology with closely related serovars of S. enterica subspecies enterica serovar Typhimurium. CONCLUSION: Salmonella Typhimurium that contained invA and spvC genes are pathogenic and virulent strains.

Antimalarial activity of Cucumis metuliferus and Lippia kituiensis against Plasmodium berghei infection in mice.

BACKGROUND: The search for new antimalarial drugs has become progressively urgent due to plasmodial resistance to most of the commercially available antimalarial drugs. As part of this effort, the study evaluated the antimalarial activity of Cucumis metuliferus and Lippia kituiensis, which are traditionally used in Tanzania for the treatment of malaria. MATERIALS AND METHODS: In vivo antimalarial activity was assessed using the 4-day suppressive antimalarial assay. Mice were infected by injecting via tail vein 1×107 erythrocytes infected by Plasmodium berghei ANKA. Extracts were administered orally; chloroquine (10 mg/kg/day) and dimethyl sulfoxide (5 mL/kg/day) were used as positive and negative controls, respectively. The level of parasitemia, survival time, packed cell volume (PCV) and variation in body weight of mice were used to determine the antimalarial activity of the extract. RESULTS: The ethyl acetate, methanolic and chloroform extracts of C. metuliferus and L. kituiensis significantly (p<0.05) inhibited parasitemia in a dose-dependent manner and prevented loss of body weight at the dose levels of 600 mg/kg and 1500 mg/kg, respectively. In addition, the extracts prolonged the mean survival time of P. berghei-infected mice compared to the non-treated control. The plant extracts did not show reduction of PCV except at the low dose of 300 mg/kg. The highest suppression was recorded at the dose level of 1,500 mg/kg. At this dose, C. metuliferus in chloroform, methanolic and ethyl acetate extracts had percentage suppression of 98.55%, 88.89% and 84.39%, respectively, whereas L. kituiensis in ethyl acetate, chloroform and methanolic extracts exhibited suppression of the pathogens of 95.19%, 93.88% and 74.83%, respectively. CONCLUSION: It is worth reporting that the two plants induced suppression which is equivalent to that induced by chloroquine (C. metuliferus chloroform and L. Kituiensis ethyl acetate). The two plants have been demonstrated to be potential sources of antimalarial templates.

Chemical Composition of Ethanolic Extracts of Some Wild Mushrooms from Tanzania and Their Medicinal Potentials.

The ethanolic extracts of 5 edible and inedible wild mushrooms collected from the Southern Highlands of Tanzania were characterized by gas chromatography-mass spectrometry. A total of 75 chemical compounds were obtained, mainly fatty acids, carotenoids, alkaloids, phenols, terpernes, steroids, pyranoside, saccharides, and amino acids. Chemical compounds were identified from the ethanolic extract of Russula cellulata, R. kivuensis, Lactarius densifolius, L. gymnocarpoides, and Lactarius sp. In addition, mass spectra of 4 major groups of compounds were also determined. This study confirms the presence of some important bioactive compounds, such as essential fatty acids (oleic and linoleic), amino acids, and carotenoids. The reported chemical profiles give an insight into the use of wild mushrooms as a potential source of bioactive compounds for nutraceuticals and pharmaceuticals.

New furanoditerpenoids from Croton jatrophoides.

Four furanoditerpenoids were isolated from roots of Croton jatrophoides (Euphorbiaceae) collected in Tanzania. In addition to the known compounds penduliflaworosin and teucvin (mallotucin A), a new teucvin isomer, which was named isoteucvin, and a furanoditerpenoid with a new skeleton, for which the name jatrophoidin was adopted, were isolated. Their structures were elucidated by spectroscopic methods such as ESI-MS and NMR, including (1)H-, (13)C-, and two-dimensional NMR. The crystal structures of isoteucvin and jatrophoidin were solved using single-crystal X-ray diffraction, by which we also established the absolute configuration of jatrophoidin. The refined crystal structure of isoteucvin has the same (absolute) configuration as jatrophoidin, although the X-ray diffraction data of isoteucvin were not conclusive with respect to the absolute configuration.

Antimicrobial and radical scavenging flavonoids from the stem wood of Erythrina latissima.

From the stem wood of Erythrina latissima, two isoflavones and a flavanone were isolated and characterized as 7,3'-dihydroxy-4'-methoxy-5'-(gamma,gamma-dimethylallyl)isoflavone (erylatissin A), 7,3'-dihydroxy-6'',6''-dimethyl-4'',5''-dehydropyrano [2'',3'': 4',5']isoflavone (erylatissin B), (-)-7,3'-dihydroxy-4'-methoxy-5'-(gamma,gamma-dimethylallyl)flavanone (erylatissin C), respectively, in addition to 10 known flavonoids. Structures of these compounds were determined on the basis of their spectroscopic data. These compounds showed antimicrobial activity against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Candida mycoderma. The isolated compounds also exhibited weak radical scavenging properties towards DPPH radical.