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A common molecular variant of the angiotensinogen gene had been reported to predispose some ethnic groups to hypertension. This case-control study was designed to determine the frequency and association of the angiotensinogen M235T allele with hypertension in residents of Calabar and Uyo cities, south-south Nigeria. The study involved 1308 subjects, 612 patients and 696 controls. The M235T variant was investigated using an allele specific polymerase chain reaction and enzymatic digestion to determine allele frequencies. Hypertensinogenic factors such as dietary habits, physical activity, smoking and drinking habits were assessed using questionnaires. Descriptive statistics, chi-square and multiple regression analysis were used to analyze the data obtained. The M235T allele frequency was high (0.94 for hypertensives and 0.96 for controls) though it was not associated with hypertension status. The odds ratio for hypertension was 0.64 (95% confidence interval: 0.39-1.06) there were no significant differences between the genotype frequency of hypertensives and controls. By multiple regression, Hypertension was observed to be associated with age and was a predictor for systolic blood pressure in both patient r2= 0.359; p< 0.05 and control groups r2= 0.26. [ABSTRACT FROM AUTHOR]

Background: The absence of antibodies specific for the 19 kDa C-terminal domain of merozoite surface protein 1 (MSP119) has been associated with high-density malaria parasitaemia in African populations. The hypothesis that a high prevalence and/or level of anti-MSP119 antibodies that may inhibit erythrocyte invasion would be present in apparently healthy individuals who harbour a sub-microscopic malaria infection was tested in this study. Methods: Plasma samples were collected from residents in a region in Nigeria hyperendemic for malaria, who had no detectable parasitaemia by microscopy. Using a competition-based enzyme-linked-immunosorbent assay with two invasion-inhibitory monoclonal antibodies (mAbs) 12.10 and 12.8, the levels and prevalence of specific antibodies were measured. The minimum multiplicity of infection was determined using PCR. The prevalence of anaemia was also measured. Results: Plasma samples from 85% of individuals contained antibodies that bound to MSP119. The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p < 0.0001) and mean titre of anti-MSP119 antibodies (Spearman correlation test, p < 0.001) in the samples. Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP119 antibodies that competed with mAb 12.10. Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04). Conclusions: In the search for correlates of protection against malaria, which will be essential to evaluate clinical trials of malaria vaccines based on MSP1, this study examines some potential assays and the factors that need to taken into account during their evaluation, using samples from individuals naturally exposed to malaria infection. [ABSTRACT FROM AUTHOR]

The aetiology of OSCC remains unclear, however, aberrant methylation of CpG island promoters of tumor suppressor genes have been identified as contributory developmental pathways in several cancers. The aim of this study was to determine the presence of RUNX3 gene methylation and how its association with patients' demographic variables such as gender, age, histologic class and tumor location could be of diagnostic value for OSCC. Sixty-seven formalin-fixed paraffin-embedded (FFPE) solid tissue blocks of OSCC, and nine blocks of benign oral lesions of epithelial origin retrieved from the archives of the Department of Oral Pathology, University College Hospital, Ibadan, South-West Nigeria were used for the analyses. Frequency of CpG island methylation in the promoter region of RUNX3 was determined by methylation-specific polymerase chain reaction (MSP). Association between gender, age, tumor location, histologic class and promoter methylation in RUNX3 was assessed with Pearson's X2 test. Overall, 45% (30/67) of OSCC demonstrated methylation in the RUNX3 promoter indicating a high frequency of methylation of the CpG island promoter region of RUNX3. There was no association between gender, age, histologic class and promoter methylation in RUNX3 (P > 0.05), however a significant association was observed between tumor location and promoter methylation of RUNX3 (P < 0.05). Aberrant methylation of the CpG island promoter region of RUNX3 together with tumor location could therefore be critical in the development and diagnosis of OSCC. [ABSTRACT FROM AUTHOR]

Background: Metabolic fingerprinting analysis can offer insights into underlying reactions in a biological system; hence it is crucial to the understanding of disease pathogenesis and could provide useful tools for discovering biomarkers. We sought to examine the urine and plasma metabolome in individuals affected by urogenital schistosomiasis and its associated-bladder pathologies. Methodology: Blood and midstream urine were obtained from volunteers who matched our inclusion criteria among residents from Eggua, southwestern Nigeria. Samples were screened by urinalysis, microscopy, PCR and ultrasonography, and categorised as advanced (urogenital schistosomiasis associated-bladder pathologies), infection-only (urogenital schistosomiasis alone) and controls (no infection and no pathology). Metabolites were extracted and data acquired with ultra high-performance liquid chromatography coupled with Thermo Q-Exactive orbitrap HRMS. Data was analysed with MetaboAnalyst, Workflow4Metabolomics, HMDB, LipidMaps and other bioinformatics tools, with univariate and multivariate statistics for metabolite selection. Principal findings: There were low levels of host sex steroids, and high levels of several benzenoids, catechols and lipids (including ganglioside, phosphatidylcholine and phosphatidylethanolamine), in infection-only and advanced cases (FDR<0.05, VIP>2, delta>2.0). Metabolites involved in biochemical pathways related to chorismate production were abundant in controls, while those related to choline and sphingolipid metabolism were upregulated in advanced cases (FDR<0.05). Some of these human host and Schistosoma haematobium molecules, including catechol estrogens, were good markers to distinguish infection-only and advanced cases. Conclusions: Altered glycerophospholipid and sphingolipid metabolism could be key factors promoting the development of bladder pathologies and tumours during urogenital schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity. Methodology: A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers. Results: A total of 1306 proteins and 9701 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70). Conclusion: These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Human schistosomiasis is a highly prevalent neglected tropical disease (NTD) caused by Schistosoma species. Research on the molecular mechanisms influencing the outcomes of bladder infection by Schistosoma haematobium is urgently needed to develop new diagnostics, therapeutics and infection prevention strategies. The objective of the research study was to determine the microbiome features and changes in urine during urogenital schistosomiasis and induced bladder pathologies. Methodology: Seventy participants from Eggua, southwestern Nigeria provided morning urine samples and were screened for urogenital schistosomiasis infection and bladder pathologies in a cross-sectional study. Highthroughput NGS sequencing was carried out, targeting the 16S V3 region. Filtered reads were processed and analyzed in a bioinformatics pipeline. Principal findings: The study participants (36 males and 34 females, between ages 15 and 65) were categorized into four groups according to status of schistosomiasis infection and bladder pathology. Data analytics of the next-generation sequencing reads revealed that Proteobacteria and Firmicutes dominated and had influence on microbiome structure of both non-infected persons and persons with urogenital schistosomiasis. Furthermore, gender and age influenced taxa abundance independent of infection or bladder pathology. Several taxa distinguished urogenital schistosomiasis induced bladder pathologies from urogenital schistosomiasis infection alone and from healthy persons, including known immune-stimulatory taxa such as Fusobacterium, Sphingobacterium and Enterococcus. Some of these significant taxa, especially Sphingobacterium were projected as markers of infection, while several genera including potentially beneficial taxa such as Trabulsiella and Weissella, were markers of the non-infected. Finally, expected changes in protein functional categories were observed to relate to cellular maintenance and lipid metabolism. Conclusion: The urinary microbiome is a factor to be considered in developing biomarkers, diagnostic tools, and new treatment for urogenital schistosomiasis and induced bladder pathologies. [ABSTRACT FROM AUTHOR]

Erythrocyte-binding antigens (EBAs) and P. falciparum reticulocyte-binding homologue proteins (PfRhs) are two important protein families that can vary in expression and utilization by P. falciparum to evade inhibitory antibodies. We evaluated antibodies at repeated time-points among individuals living in an endemic region in Nigeria over almost one year against these vaccine candidates. Antibody levels against EBA140, EBA175, EBA181, PfRh2, PfRh4, and MSP2, were measured by ELISA. We also used parasites with disrupted EBA140, EBA175 and EBA181 genes to show that all these were targets of invasion inhibitory antibodies. However, antigenic targets of inhibitory antibodies were not stable and changed substantially over time in most individuals, independent of age. Antibodies levels measured by ELISA also varied within and between individuals over time and the antibodies against EBA181, PfRh2 and MSP2 declined more rapidly in younger individuals (≤15 years) compared with older (>15). The breadth of high antibody responses over time was more influenced by age than by the frequency of infection. High antibody levels were associated with a more stable invasion inhibitory response, which could indicate that during the long process of formation of immunity, many changes not only in levels but also in functional responses are needed. This is an important finding in understanding natural immunity against malaria, which is essential for making an efficacious vaccine. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Chromolaena odorata, Tithonia diversifolia and Lawsonia inermis are medicinal plants used in treating malaria in traditional medicine system. Previous studies however showed that their dichloromethane, methanol (1:1) extracts were more active against Plasmodium parasite than the aqueous extracts. Aim of the study To determine the in vitro and in vivo antiplasmodial activity of dichloromethane, methanol (1:1) extracts of Chromolaena odorata, Tithonia diversifolia and Lawsonia inermis in combination and evaluate their safety using acute limit toxicity test. Materials and methods Dichloromethane, methanol (1:1) extracts of Chromolaena odorata, Tithonia diversifolia and Lawsonia inermis leaves were combined at ratios 1:1, 1:3, 3:1, 1:5 and 5:1 using in vitro semi-automated microdilution technique against P. falciparum Chloroquine sensitive (D6) and Chloroquine resistant (W2) strains, with chloroquine and artemisinin as controls. The in vivo antiplasmodial activity of the crude extracts was carried out singly, and in combination at the different combination ratios on Plasmodium berghei Anka infected Swiss albino mice using Peters' 4-day suppressive test. Acute toxicity test was done in mice at 5000 mg/kg. Results The in vitro combination of L . inermis and T. diversifolia (1:1) extracts against P. falciparum showed the highest synergy with IC 50 of 0.43±0.02 µg/mL and 2.55±0.19 µg/mL against D6 and W2 respectively; while the combination of C. odorata with T. diversifolia and L. inermis were antagonistic. A synergy with chemosuppression of 83.6% against P. berghei infected mice was observed in L. inermis and T. diversifolia (1:1) treated animals. In contrast to the in vitro result, combination of C. odorata with T. diversifolia and L . inermis showed some degrees of synergy in vivo . Extracts were not toxic at the concentration tested. Conclusion These findings rationalized the use of these plants in combination as antimalarials in traditional medicine. However, the combination of Chromolaena odorata with other medicinal plants should be used with caution because of its possible antagonistic effect. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "The microbiome in urogenital schistosomiasis and induced bladder pathologies" which appeared in the 2017 issue.