Bioactive Phytoconstituents and Their Therapeutic Potentials in the Treatment of Haematological Cancers: A Review.

Haematological (blood) cancers are the cancers of the blood and lymphoid forming tissues which represents approximately 10% of all cancers. It has been reported that approximately 60% of all blood cancers are incurable. Despite substantial improvement in access to detection/diagnosis, chemotherapy and bone marrow transplantation, there is still high recurrence and unpredictable but clearly defined relapses indicating that effective therapies are still lacking. Over the past two decades, medicinal plants and their biologically active compounds are being used as potential remedies and alternative therapies for the treatment of cancer. This is due to their anti-oxidant, anti-inflammatory, anti-mutagenic, anti-angiogenic, anti-cancer activities and negligible side effects. These bioactive compounds have the capacity to reduce proliferation of haematological cancers via various mechanisms such as promoting apoptosis, transcription regulation, inhibition of signalling pathways, downregulating receptors and blocking cell cycle. This review study highlights the mechanistic and beneficial effects of nine bioactive compounds (quercetin, ursolic acid, fisetin, resveratrol, epigallocatechin gallate, curcumin, gambogic acid, butein and celastrol) as potential remedies for chemoprevention of haematological cancers. The study provides useful insights on the effectiveness of the use of bioactive compounds from plants for chemoprevention of haematological cancers.

In silico Structure Prediction, Molecular Docking, and Dynamic Simulation of Plasmodium falciparum AP2-I Transcription Factor.

Plasmodium falciparum Apicomplexan Apetala 2 Invasion (PfAP2-I) transcription factor (TF) is a protein that regulates the expression of a subset of gene families involved in P. falciparum red blood cell (RBC) invasion. Inhibiting PfAP2-I TF with small molecules represents a potential new antimalarial therapeutic target to combat drug resistance, which this study aims to achieve. The 3D model structure of PfAP2-I was predicted ab initio using ROBETTA prediction tool and was validated using Save server 6.0 and MolProbity. Computed Atlas of Surface Topography of proteins (CASTp) 3.0 was used to predict the active sites of the PfAP2-I modeled structure. Pharmacophore modeling of the control ligand and PfAP2-I modeled structure was carried out using the Pharmit server to obtain several compounds used for molecular docking analysis. Molecular docking and postdocking studies were conducted using AutoDock vina and Discovery studio. The designed ligands' toxicity predictions and in silico drug-likeness were performed using the SwissADME predictor and OSIRIS Property Explorer. The modeled protein structure from the ROBETTA showed a validation result of 96.827 for ERRAT, 90.2% of the amino acid residues in the most favored region for the Ramachandran plot, and MolProbity score of 1.30 in the 98th percentile. Five (5) best hit compounds from molecular docking analysis were selected based on their binding affinity (between -8.9 and -11.7 Kcal/mol) to the active site of PfAP2-I and were considered for postdocking studies. For the absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties, compound MCULE-7146940834 had the highest drug score (0.63) and drug-likeness (6.76). MCULE-7146940834 maintained a stable conformation within the flexible protein's active site during simulation. The good, estimated binding energies, drug-likeness, drug score, and molecular dynamics simulation interaction observed for MCULE-7146940834 against PfAP2-I show that MCULE-7146940834 can be considered a lead candidate for PfAP2-I inhibition. Experimental validations should be carried out to ascertain the efficacy of these predicted best hit compounds.

Polygenic Risk Score in African populations: progress and challenges.

Polygenic Risk Score (PRS) analysis is a method that predicts the genetic risk of an individual towards targeted traits. Even when there are no significant markers, it gives evidence of a genetic effect beyond the results of Genome-Wide Association Studies (GWAS). Moreover, it selects  single nucleotide polymorphisms (SNPs) that  contribute to the disease with low effect size  making it more precise at individual level risk prediction. PRS  analysis addresses the shortfall of GWAS by taking into account the SNPs/alleles with  low effect size but play an indispensable role to the observed phenotypic/trait variance.  PRS analysis has  applications that investigate the genetic basis of several traits, which includes rare diseases. However, the accuracy of PRS analysis depends on the genomic data of the underlying population. For instance, several studies  show   that obtaining higher prediction power of PRS analysis is challenging for non-Europeans. In this manuscript, we review the conventional PRS methods and their application to sub-Saharan African communities. We conclude that  lack of sufficient GWAS data and tools is  the limiting factor of applying PRS analysis to sub-Saharan populations.   We recommend developing Africa-specific PRS methods and tools for estimating and analyzing  African population data   for clinical  evaluation of PRSs of interest and predicting  rare diseases.

A review on the clinical trials of repurposing therapeutic drugs, mechanisms and preventive measures against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly transmittable pathogenic viral infection that causes a disease known as COVID-19. It is a pandemic and public health challenge ravaging the world today. Unfortunately, with the daily increase of infected individuals, there is no known drug approved for the treatment of COVID-19. However, there are therapeutic drugs with the potentials to inhibit endocytic pathways, suppress ribonucleic acid (RNA) polymerase activities, and reduce the replication of SARS-CoV-2. These drugs modifications are aimed at reducing inflammation, time of recovery, and number of deaths. This review is aimed at providing updated information on the clinical manifestations, diagnosis, preventive measures and therapeutic drugs used against SARS-CoV-2. The finding of this review revealed that some of these drugs are transmembrane protease, serine 2, and angiotensin-converting enzyme 2 inhibitors with the capacity to block the entrance/replication of SARS-CoV-2 in a host cell and therefore, may be promising in preventing the spread and mortality of SARS-CoV-2. However, these drugs may cause detrimental health effects such as toxic and non-efficacy issues. Therefore great caution should be employed by health professionals when prescribing these drugs to COVID-19 patients.

Anti-inflammatory and antioxidant activities of fractions and compound from Ricinodendron heudelotii (Baill.).

Medicinal plants have been documented over the years to play vital role in promoting human health. The study evaluated the anti-inflammatory and anti-oxidant activities of different fractions and isolated compound from Ricinodendron heudelotii leaves. The leaves of Ricinodendron heudelotii were extracted with ethanol and further partitioned sequentially using petroleum ether, ethylacetate and butanol. Bioassay-guided fractionation of the ethylacetate fraction was done using repeated column chromatographic technique while the structural elucidation of pure compound was carried out using mass spectra, 13C and 1H NMR analyses. Antioxidant potential of the fractions and isolated compound were evaluated with 2,2-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays and anti-inflammatory effect of fractions was measured by their inhibitory potency on nitric oxide (NO). Corilagin, an amorphous tannin was isolated and structurally elucidated. Corilagin showed scavenging effect against ABTS and DPPH radicals which vary in a dose dependent manner. It also showed an antioxidant potential with IC50 value of 0.003 mg/mL comparable to vitamin C 0.001 mg/mL) used as standard. The butanol and ethylacetate fractions exhibited significant (p < 0.05) NO inhibition of 60 and 69% respectively after treatment of RAW 264.7 macrophages with lipopolysaccharide. These results demonstrated the role of isolated corilagin as a promising potent antioxidant while the ethylacetate and butanol fractions suppressed the expression of an inflammation mediator by inhibiting nitric oxide.

Gene Expression Profiling Analysis Reveals Putative Phytochemotherapeutic Target for Castration-Resistant Prostate Cancer.

Prostate cancer is the leading cause of cancer death among men globally, with castration development resistant contributing significantly to treatment failure and death. By analyzing the differentially expressed genes between castration-induced regression nadir and castration-resistant regrowth of the prostate, we identified soluble guanylate cyclase 1 subunit alpha as biologically significant to driving castration-resistant prostate cancer. A virtual screening of the modeled protein against 242 experimentally-validated anti-prostate cancer phytochemicals revealed potential drug inhibitors. Although, the identified four non-synonymous somatic point mutations of the human soluble guanylate cyclase 1 gene could alter its form and ligand binding ability, our analysis identified compounds that could effectively inhibit the mutants together with wild-type. Of the identified phytochemicals, (8'R)-neochrome and (8'S)-neochrome derived from the Spinach (Spinacia oleracea) showed the highest binding energies against the wild and mutant proteins. Our results identified the neochromes and other phytochemicals as leads in pharmacotherapy and as nutraceuticals in management and prevention of castration-resistance prostate cancers.

Cytotoxic Effects of Compounds Isolated from Ricinodendron heudelotii.

This study was designed to explore the in vitro anticancer effects of the bioactive compounds isolated from Ricinodendron heudelotii on selected cancer cell lines. The leaves of the plant were extracted with ethanol and partitioned in sequence with petroleum ether, ethyl acetate, and n-butanol. The ethyl acetate fraction was phytochemically studied using thin layer chromatography (TLC) and column chromatography (CC). Structural elucidation of pure compounds obtained from the ethyl acetate fraction was done using mass spectra, ¹H-NMR, and 13C-NMR analysis. The isolated compounds were subsequently screened using five different cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7, SW-480, and normal lung epithelial cell line, BEAS-2B, to assess their cytotoxic effects. Nine compounds were isolated and structurally elucidated as gallic acid, gallic acid ethyl ester, corilagin, quercetin-3-O-rhamnoside, myricetin-3-O-rhamnoside, 1,4,6-tri-O-galloyl glucose, 3,4,6-tri-O-galloyl glucose, 1,2,6-tri-O-galloyl glucose, and 4,6-di-O-galloyl glucose. Corilagin exhibited the most cytotoxic activity with an IC50 value of 33.18 µg/mL against MCF-7 cells, which were comparable to cisplatin with an IC50 value of 27.43 µg/mL. The result suggests that corilagin isolated from R. heudelotii has the potential to be developed as an effective therapeutic agent against the growth of breast cancer cells.

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.

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.

Factors influencing maternal mortality among rural communities in southwestern Nigeria.

BACKGROUND: Maternal mortality and morbidity reflect the status of population health and quality of life across nations. Poor understanding of the interplay of many antecedent factors, including sociocultural, economic and logistic factors, combined with an overwhelming poor health services delivery, is a basic challenge in several countries, particularly in rural settings where functional health care services are relatively scarce. There are still uncertainties as to the extent of this burden, owing to current challenges with information and data collation. This study aimed at identifying nonmedical factors associated with maternal mortality in rural and semiurban communities of southwestern Nigeria. METHODOLOGY: The study was carried out in Ado-Odo/Ota Local Government Area of Ogun State. A multistage sampling technique and an informant survey approach were used in the study. A total sample of 360 eligible respondents were selected randomly from 11 out of 16 political wards in the study area and interviewed through the administration of questionnaires. The data were processed using descriptive statistics and regression analyses. RESULTS: Place of consultation (P=0.000), who pays the treatment costs (P=0.000), awareness of pregnancy complications (P=0.002) and knowledge of the place of antenatal care treatment (P=0.000) significantly influenced maternal mortality (proxy by place of delivery of last birth). The F-statistic (15.100) confirmed the hypothesis that nonmedical factors influence maternal mortality. The correlation of predictor variables was significant at both the 0.01 level and the 0.05 level (2-tailed). CONCLUSION: Our findings suggest that in a rural community setting with a depleted health care system, health education tailored toward community culture, subsidized maternal health care services by the government and operators of private clinics, as well as empowering and improving the status of women may reduce maternal mortality and prompt better utilization and survival chances of women in the study area as well as in all of Nigeria.

An Estimate of the Incidence of Prostate Cancer in Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Prostate cancer (PCa) is rated the second most common cancer and sixth leading cause of cancer deaths among men globally. Reports show that African men suffer disproportionately from PCa compared to men from other parts of the world. It is still quite difficult to accurately describe the burden of PCa in Africa due to poor cancer registration systems. We systematically reviewed the literature on prostate cancer in Africa and provided a continent-wide incidence rate of PCa based on available data in the region. METHODS: A systematic literature search of Medline, EMBASE and Global Health from January 1980 to June 2015 was conducted, with additional search of Google Scholar, International Association of Cancer Registries (IACR), International Agency for Research on Cancer (IARC), and WHO African region websites, for studies that estimated incidence rate of PCa in any African location. Having assessed quality and consistency across selected studies, we extracted incidence rates of PCa and conducted a random effects meta-analysis. RESULTS: Our search returned 9766 records, with 40 studies spreading across 16 African countries meeting our selection criteria. We estimated a pooled PCa incidence rate of 22.0 (95% CI: 19.93-23.97) per 100,000 population, and also reported a median incidence rate of 19.5 per 100,000 population. We observed an increasing trend in PCa incidence with advancing age, and over the main years covered. CONCLUSION: Effective cancer registration and extensive research are vital to appropriately quantifying PCa burden in Africa. We hope our findings may further assist at identifying relevant gaps, and contribute to improving knowledge, research, and interventions targeted at prostate cancer in Africa.

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.

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.