In silico pharmacokinetic and therapeutic evaluation of Musa acuminata peels against aluminium chloride-induced hepatotoxicity in adult BALB/c mice.

East Africa (Musa spp.), notably Musa acuminata, "Matooke" a staple and economically important food in the region. Here, 12 selected M. acuminata peels extract (MAPE) bioactive compounds were studied for hepatoprotective potentials in aluminium chloride-induced hepatoxicity in adult BALB/c mice. GC-MS analysis was used to identify active components of MAPE. In silico estimation of the pharmacokinetic, the GCMS-identified compounds' toxicity profile and molecular docking were compared with the standard (Simvastatin) drug. Hepatotoxicity was induced using aluminium-chloride treated with MAPE, followed by biochemical and histopathological examination. Twelve bioactive compounds 2,2-Dichloroacetophenone (72870), Cyclooctasiloxane 18993663), 7-Hydroxy-6,9a-dimethyl-3-methylene-decahydro-azuleno[4,5-b]furan-2,9-dione (534579), all-trans-alpha-Carotene (4369188), Cyclononasiloxane (53438479), 3-Chloro-5-(4-methoxyphenyl)-6,7a-dimethyl-5,6,7,7a-tetrahydro-4H-furo[2,3-c]pyridin-2-one (536708), Pivalic acid (6417), 10,13-Octadecadienoic acid (54284936), Ethyl Linoleate (5282184), Oleic acid (5363269), Tirucallol (101257), Obtusifoliol (65252) were identified by GC-MS. Of these, seven were successfully docked with the target proteins. The compounds possess drug likeness potentials that do not inhibits CYP450 isoforms biotransformation. All the docked compounds were chemoprotective to AMES toxicity, hERGI, hERGII and hepatotoxicity. The animal model reveals MAPE protective effect on liver marker's function while the histological studies show regeneration of the disoriented layers of bile ducts and ameliorate the cellular/histoarchitecture of the hepatic cells induced by AlCl3. The findings indicate that MAPE improved liver functions and ameliorated the hepatic cells' cellular or histoarchitecture induced by AlCl3. Further studies are necessary to elucidate the mechanism action and toxicological evaluation of MAPE's chronic or intermittent use to ascertain its safety in whole organism systems.

Tween-80 enhanced biodegradation of naphthalene by Klebsiella quasipneumoniae.

Accidental spillage of petroleum products and industrial activities result in various hydrocarbons in the environment. While the n-hydrocarbons are readily degraded, the polycyclic aromatic hydrocarbons (PAHs) are recalcitrant to natural degradation, toxic to aquatic life and are responsible for diverse health challenges in terrestrial animals; suggesting the need for faster and more eco-friendly ways of removing PAHs from the environment. In this study, the surfactant tween-80 was used to enhance a bacterium's intrinsic naphthalene biodegradation activity. Eight bacteria isolated from oil-contaminated soils were characterised using morphological and biochemical methods. The most effective strain was identified as Klebsiella quasipneumoniae using 16S rRNA gene analysis. High-Performance Liquid Chromatography (HPLC) analyses showed that the detectable concentration of naphthalene was decreased from 500 to 157.18 µg/mL (67.4%) after 7 d in the absence of tween-80, while 99.4% removal was achieved in 3 d in the presence of tween-80 at 60 µg/mL concentration. The peaks observed in the Fourier Transform Infra-Red Spectroscopy (FTIR) spectrum of control (naphthalene), which were absent in that of the metabolites, further established naphthalene degradation. Furthermore, Gas Chromatography-Mass Spectrometer (GCMS) revealed metabolites of single aromatic ring, such as 3,4-dihydroxybenzoic acid 4-hydroxylmethylphenol, which confirmed that the removal of naphthalene is by biodegradation. Tyrosinase induction and laccase activities suggested the involvement of these enzymes in naphthalene biodegradation by the bacterium. Conclusively, a strain of K. quasipneumoniae that can effectively remove naphthalene from contaminated environments has been isolated, and its biodegradation rate was doubled in the presence of non-ionic surfactant, tween-80.

Association of Dopamine Transporter Gene (DAT1) 40 bp 3' UTR VNTR Polymorphism (rs28363170) and Cannabis Use Disorder.

Introduction: Cannabis remains the most widely used illicit drug among Nigerians, often associated with psychiatric disorders. Since genetic predisposition has been implicated in substance use disorders, we, therefore, aimed at finding out the relationship between dopamine transporter gene (DAT1) polymorphism and cannabis use disorder. Methods: We recruited 104 patients from a tertiary psychiatric facility in Lagos, Nigeria, who were diagnosed with cannabis use disorder according to ICD-10 and 96 non-smokers as a comparative group. The smokers were screened with Cannabis Use Disorder Identification Test (CUDIT), and cannabis dependence was assessed with the Severity of Dependence Scale (SDS). Genotyping was carried out for the 40 bp 3' UTR VNTR of the DAT1 (rs28363170). Results: The frequencies of 9R/9R, 9R/10R, 10R/10R among non-smokers and smokers were 14 (14.3%), 25 (26.2%), 57 (59.5%) and 17 (16.3%), 54 (51.9%), 33 (31.7%) respectively. The genotype distribution was in Hardy Weinberg equilibrium (HWE) only in the smokers' population (χ² = 1.896, P = .166). Individuals with the 10R allele were almost twice as likely as the 9R carriers to smoke cannabis (OR = 1.915, 95% CI: 1.225-2.995). However, this polymorphism was not associated with the quantity of cannabis smoked, age at onset of smoking, CUDIT, and SDS scores. Conclusion: The DAT VNTR polymorphism was associated with cannabis smoking but not cannabis use disorder.

Prevalence of Factor V Leiden G1691A and Prothrombin G20210A Gene Mutation Among Pregnant Women: Experience from a Multi-Center Study in Nigeria.

INTRODUCTION: Inherited thrombophilia and venous thromboembolism (VTE) have been closely linked to adverse pregnancy outcomes such as preeclampsia/eclampsia contributing to increased maternal and perinatal morbidity and mortality. There is, however, little genetic data from Africa including Nigeria that explores the prevalence of common VTE genetic risk markers such as factor V Leiden mutation (FVL G1691A) and prothrombin gene mutation (F2 G20210A) among pregnant women in Nigeria. PURPOSE: To determine the prevalence and distribution of FVL G1691A and F2 G20210A in pregnant women in Lagos, Nigeria. PATIENTS AND METHODS: This hospital-based cross-sectional pilot study was conducted among pregnant women between 1 July 2019 and 31 August 2020. The genotype of interest was determined through amplification by polymerase chain reaction using G1691A of FV and prothrombin A20210G specific primers. Descriptive data were presented using Stata version 15 (Stata Corp) statistical software. RESULTS: Of the 400 recruited participants, 397 and 389 samples were successfully processed for FVL G1691A and F2 G20210A mutations, respectively. Three participants had FVL heterozygous mutation; thus, the prevalence of heterozygous mutation of FVL among the study participants was 0.76%, 95% CI: 0.002-0.023%, n=3/397. There was no F2 G20210A mutation detected among the study participants. CONCLUSION: This study indicates that screening for factor V Leiden mutation and prothrombin gene mutation in pregnancy might not be of any clinical significance among Nigerian women. However, carrying out a genome-wide associated study is recommended to determine the true impact of these two common inherited thrombophilias in this population.

Genetic polymorphisms in malaria vaccine candidate Plasmodium falciparum reticulocyte-binding protein homologue-5 among populations in Lagos, Nigeria.

BACKGROUND: Vaccines are the most reliable alternative to elicit sterile immunity against malaria but their development has been hindered by polymorphisms and strain-specificity in previously studied antigens. New vaccine candidates are therefore urgently needed. Highly conserved Plasmodium falciparum reticulocyte-binding protein homologue-5 (PfRH5) has been identified as a potential candidate for anti-disease vaccine development. PfRH5 is essential for erythrocyte invasion by merozoites and crucial for parasite survival. However, there is paucity of data on the extent of genetic variations on PfRH5 in field isolates of Plasmodium falciparum. This study described genetic polymorphisms at the high affinity binding polypeptides (HABPs) 36718, 36727, 36728 of PfRH5 in Nigerian isolates of P. falciparum. This study tested the hypothesis that only specific conserved B and T cell epitopes on PfRH5 HABPs are crucial for vaccine development. METHODS: One hundred and ninety-five microscopically confirmed P. falciparum samples collected in a prospective cross-sectional study of three different populations in Lagos, Nigeria. Genetic diversity and haplotype construct of Pfrh5 gene were determined using bi-directional sequencing approach. Tajima's D and the ratio of nonsynonymous vs synonymous mutations were utilized to estimate the extent of balancing and directional selection in the pfrh5 gene. RESULTS: Sequence analysis revealed three haplotypes of PfRH5 with negative Tajima's D and dN/dS value of - 1.717 and 0.011 ± 0.020, respectively. A single nucleotide polymorphism, SNP (G → A) at position 608 was observed, which resulted in a change of the amino acid cysteine at position 203 to tyrosine. Haplotype and nucleotide diversities were 0.318 ± 0.016 and 0.0046 ± 0.0001 while inter-population genetic differentiation ranged from 0.007 to 0.037. Five polypeptide variants were identified, the most frequent being KTKYH with a frequency of 51.3%. One B-cell epitope, 151 major histocompatibility complex (MHC) class II T-cell epitopes, four intrinsically unstructured regions (IURs) and six MHC class I T-cell epitopes were observed in the study. Phylogenetic analysis of the sequences showed clustering and evidence of evolutionary relationship with 3D7, PAS-2 and FCB-2 RH5 sequences. CONCLUSIONS: This study has revealed low level of genetic polymorphisms in PfRH5 antigen with B- and T-cell epitopes in intrinsically unstructured regions along the PfRH5 gene in Lagos, Nigeria. A broader investigation is however required in other parts of the country to support the possible inclusion of PfRH5 in a cross-protective multi-component vaccine.

Pro-inflammatory Cytokine Response and Genetic Diversity in Merozoite Surface Protein 2 of Plasmodium falciparum Isolates from Nigeria.

BACKGROUND: Polymorphisms in Plasmodium falciparum merozoite surface protein-2 (msp-2) and associated parasite genetic diversity which varies between malaria-endemic regions remain a limitation in malaria vaccine development. Pro-inflammatory cytokines are important in immunity against malaria, understanding the influence of genetic diversity on cytokine response is important for effective vaccine design. METHODS: P. falciparum isolates obtained from 300 Nigerians with uncomplicated falciparum malaria at Ijede General Hospital, Ijede (IJE), General Hospital Ajeromi, Ajeromi (AJE) and Saint Kizito Mission Hospital, Lekki, were genotyped by nested polymerase chain reaction of msp-2 block 3 while ELISA was used to determine the pro-inflammatory cytokine response to describe the genetic diversity of P. falciparum. RESULTS: Eighteen alleles were observed for msp-2 loci. Of the 195 isolates, 61 (31.0%) had only FC27-type alleles, 38 (19.7%) had only 3D7-type alleles, and 49.3% had multiple parasite lines with both alleles. Band sizes were 275-625 bp for FC27 and 150-425 bp for 3D7. Four alleles were observed from LEK, 2 (375-425 bp) and 2 (275-325 bp) of FC27-and 3D7-types, respectively; 12 alleles from AJE, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively; while IJE had a total of 12 alleles, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively. Mean multiplicity of infection (MOI) was 1.54. Heterozygosity (HE) ranged from 0.77 to 0.87 and was highest for IJE (0.87). Cytokine response was higher among <5 years and was significantly associated with MOI (P > 0.05) but with neither parasite density nor infection type. CONCLUSION: P. falciparum genetic diversity is extensive in Nigeria, protection via pro-inflammatory cytokines have little or no interplay with infection multiplicity.

Decolorization of dyehouse effluent and biodegradation of Congo red by Bacillus thuringiensis RUN1.

A dye-decolorizing bacterium was isolated from a soil sample and identified as Bacillus thuringiensis using 16S rRNA sequencing. The bacterium was able to decolorize three different textile dyes, namely, Reactive blue 13, Reactive red 58, and Reactive yellow 42, and a real dyehouse effluent up to 80-95% within 6 h. Some non-textile industrially important dyes were also decolorized to different extents. Fourier transform infrared spectroscopy and gas chromatography-mass spectrometer analysis of the ethyl acetate extract of Congo red dye and its metabolites showed that the bacterium could degrade it by the asymmetric cleavage of the azo bonds to yield sodium (4- amino-3-diazenylnaphthalene-1-sulfonate) and phenylbenzene. Sodium (4-amino-3-diazenylnaphthalene-1-sulfonate) was further oxidized by the ortho-cleavage pathway to yield 2- (1-amino-2-diazenyl-2-formylvinyl) benzoic acid. There was induction of the activities of laccase and azoreductase during the decolorization of Congo red, which suggests their probable role in the biodegradation. B. thuringiensis was found to be versatile and could be used for industrial effluent biodegradation.