A Comparison of In Vitro Studies between Cobalt(III) and Copper(II) Complexes with Thiosemicarbazone Ligands to Treat Triple Negative Breast Cancer.

Metal complexes have gained significant attention as potential anti-cancer agents. The anti-cancer activity of [Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH 1 (where phen = 1,10-phenanthroline and MeATSC = 9-anthraldehyde-N(4)-methylthiosemicarbazone) and [Cu(acetylethTSC)Cl]Cl•0.25C2H5OH 2 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide) was investigated by analyzing DNA cleavage activity. The cytotoxic effect was analyzed using CCK-8 viability assay. The activities of caspase 3/7, 9, and 1, reactive oxygen species (ROS) production, cell cycle arrest, and mitochondrial function were further analyzed to study the cell death mechanisms. Complex 2 induced a significant increase in nicked DNA. The IC50 values of complex 1 were 17.59 µM and 61.26 µM in cancer and non-cancer cells, respectively. The IC50 values of complex 2 were 5.63 and 12.19 µM for cancer and non-cancer cells, respectively. Complex 1 induced an increase in ROS levels, mitochondrial dysfunction, and activated caspases 3/7, 9, and 1, which indicated the induction of intrinsic apoptotic pathway and pyroptosis. Complex 2 induced cell cycle arrest in the S phase, ROS generation, and caspase 3/7 activation. Thus, complex 1 induced cell death in the breast cancer cell line via activation of oxidative stress which induced apoptosis and pyroptosis while complex 2 induced cell cycle arrest through the induction of DNA cleavage.

In silico prediction of the possible antidiabetic and anti-inflammatory targets of Nymphaea lotus-derived phytochemicals and mechanistic insights by molecular dynamics simulations.

Nymphaea lotus is used traditionally for the treatment of diabetes and its complications. However, the mode of action and the likely bioactive phytochemicals involved are not yet fully explored. GC-MS analysis was employed to identify the inherent compounds in N. lotus leaves. To gain an insight into the antidiabetic mode of action of this plant, the identified phytochemicals were subjected to computational studies against four molecular targets of diabetes, dipeptidyl peptidase-4, glycogen synthase kinase 3, NADPH oxidase (NOX), sodium-glucose co-transporter-2, and one target of inflammation, cyclooxygenase-2. Compounds with notable binding affinity were subjected to druggability test. Results from molecular docking showed that seven of the compounds investigated exhibited druggability properties and had outstanding binding affinity values for these targets relative to values obtained for the respective standards of each of the targets. Analysis of the MD trajectories from a 100 ns atomistic run shows that the integrities of the complex systems were more stable and preserved throughout the simulation than the unbound protein. These results indicated that the antidiabetic and anti-inflammatory effects of these compounds might be via the inhibition of these targets, laying the foundation for further studies, such as in vitro and in vivo studies to fully validate the anti-diabetic agents from this plant.Communicated by Ramaswamy H. Sarma.

Heat Shock Factors in Protein Quality Control and Spermatogenesis.

Proper regulation of cellular protein quality control is crucial for cellular health. It appears that the protein quality control machinery is subjected to distinct regulation in different cellular contexts such as in somatic cells and in germ cells. Heat shock factors (HSFs) play critical role in the control of quality of cellular proteins through controlling expression of many genes encoding different proteins including those for inducible protein chaperones. Mammalian cells exert distinct mechanism of cellular functions through maintenance of tissue-specific HSFs. Here, we have discussed different HSFs and their functions including those during spermatogenesis. We have also discussed the different heat shock proteins induced by the HSFs and their activities in those contexts. We have also identified several small molecule activators and inhibitors of HSFs from different sources reported so far.

Diagnostic and therapeutic biomarkers in colorectal cancer: a review.

Colorectal cancer (CRC) is a public health concern and the second most common type of cancer among men and women causing a significant mortality. Biomarkers closely linked to the disease morbidity could holds potential as diagnostic and/or prognostic biomarker for the disease. This review provides an overview of recent advances in the search for colorectal cancer biomarkers through genomics and proteomics according to clinical function and application. Specifically, a number of biomarkers were identified and discussed. Emphasis was placed on their clinical applications relative to the diagnosis and prognosis of CRC. The discovery of more sensitive and specific markers for CRC is an urgent need, and the study of molecular targets is extremely important in this process, as they will allow for a better understanding of colorectal carcinogenesis, identification and validation of potential genetic signatures.

COVID-19 pandemic: an online-based survey of knowledge, perception, and adherence to preventive measures among educated Nigerian adults.

Aims: One of the ways to manage the current coronavirus disease 2019 (COVID-19) pandemic is to monitor the public knowledge, risk perceptions, adherence to preventive measures, and level of preparedness behaviors. This is important in resource-limited countries. This study determined the knowledge and perception regarding COVID-19; adherence to COVID-19 preventive measures; as well as predictors of self-perceived risk of contracting COVID-19 among Nigerian adults. Methods: A cross-sectional study was conducted among Nigerian adults ≥18 years using an online survey. A convenience sampling method was utilized to recruit a total of 1022 study participants. The participants were recruited using the authors' social media networks. Data were analyzed using descriptive and inferential statistics at a 5% level of statistical significance. Results: Generally, a high proportion of respondents had correct knowledge about COVID-19. However, only approximately half (49.8% and 49.9%) had correct knowledge that obesity was a risk factor for COVID-19 and that antibiotics cannot be used to treat COVID-19. Most (84.1%) did not have a self-perceived risk of contracting COVID-19. Most (81.0%) have been avoiding crowded places and 61.3% washed their hands frequently. Predictors of self-perceived risk of COVID-19 were age 40-59 years (OR 2.05, CI 1.217-3.435), ≥ 60 years (OR 4.68, CI 1.888-11.583), and visiting crowded places (OR 2.27, CI 1.499-3.448). Conclusion: Our study recommends more rigorous public health education aimed at improving COVID-19 outbreak response in Nigeria. In addition, physical and social distancing should be emphasized across all age groups with additional focus on the older population.

Toxoplasmosis in pregnancy: a neglected bane but a serious threat in Nigeria.

Toxoplasmosis is a global health threat in which occurrence in pregnant women poses grave consequences to fetal wellbeing. Studies on prenatal Toxoplasma gondii infection are generally limited in sub-Saharan African countries, including Nigeria. The risk of transmission of toxoplasmosis is very high in Nigeria due to the favourable climatic conditions and prevailing behavioural and socio-economic factors that could aid transmission. Currently, there are no systematic and organized procedures for diagnosis and treatment of maternal toxoplasmosis in Nigeria. These conditions forecast possible unabated transmission in many areas and exponential impact on associated adverse events of the disease during pregnancy. This paper highlights the importance of early diagnosis and treatment during pregnancy which may forestall subsequent development of infection in children delivered by infected mothers. Inclusion of toxoplasmosis control policy in the routine antenatal care of pregnant women is therefore strongly recommended.

Urinary aflatoxin exposure monitoring in rural and semi-urban populations in Ogun state, Nigeria.

Aflatoxins are a major class of fungal toxins that have food safety importance due to their economic and health impacts. This pilot aflatoxin exposure biomonitoring study on 84 individuals was conducted in a rural (Ilumafon) and a semi-urban community (Ilishan Remo) of Ogun state, Nigeria, to compare aflatoxin exposures among the two population cohorts. First morning urine samples were obtained from the participants, and the urinary aflatoxin M1 (AFM1) levels were measured by a quantitative Helica Biosystems Inc. ELISA kit assay. About 99% (83 out of 84) of the urine samples had detectable AFM1 levels in the range of 0.06 to 0.51 ng mL-1 (median: 0.27 ng mL-1). The mean urinary AFM1 levels were significantly (p = 0.001) higher in the semi-urban population (0.31 ± 0.09 ng mL-1) compared to the rural population (0.24 ± 0.07 ng mL-1). There were, however, no significant differences in mean urinary AFM1 levels of males and females, and among children, adolescents and adults. This study indicates high aflatoxin exposure to the extent of public health concerns in the studied populations. Thus, more efforts are required for aflatoxin exposure monitoring and control in high-risk regions.

In vitro ovicidal activity of poly lactic acid curcumin-nisin co-entrapped nanoparticle against Fasciola spp. eggs and its reproductive toxicity.

BACKGROUND: Curcumin and nisin have been widely reported for their antibacterial and anticancer potency. However, their therapeutic applications are hampered by several factors, which necessitate their development into nanosize ranges for improved delivery and activities. Their incorporation into a single nanosynthesized form may suggest desirable efficacy on parasites. The aim of the study was to assess the ovicidal activity of the curcumin-nisin polylactic acid (PLA) entrapped nanoparticle on the Fasciola eggs and its reproductive toxicity. METHODS: The nanoparticle was formulated by double emulsion method. The eggs of the adult Fasciola spp. were exposed to different concentrations (0.3125-5 mg/mL) of the nanoparticle to monitor hatchability. Mice were exposed to 0.5 mL of the formulated drug at varying concentrations (10-20 mg/kg) and then sacrificed for sperm morphology assay. RESULTS: The mean particle size, polydispersity index, and drug entrapment efficiency of the formulated drug were 288.4±24.3 nm, 0.232, and 51.7%, respectively. The highest nanoparticulate concentration (5 mg/mL) showed the least percentage egg hatching (41.7%) compared with the other treatment groups and positive control (albendazole) (45.1%). The aberrations observed in sperm cells were not concentration-dependent and no significant differences were observed in the mean aberrations between the nanoparticulate drug-exposed groups and the negative control (p>0.05). CONCLUSIONS: The results confirmed the ovicidal activity of the curcumin-nisin nanoparticulate drug against the Fasciola species. The formulation also showed no toxicity to sperm cells. More robust studies on anti-fascioliasis activity of the drug on adult Fasciola spp. and in vivo and in vitro toxicity studies are recommended.

Methanol extract of Nymphaea lotus ameliorates carbon tetrachloride-induced chronic liver injury in rats via inhibition of oxidative stress.

BACKGROUND: Nymphaea lotus (NL) is an aquatic perennial plant used traditionally in the management of various liver diseases. In this study, the protective effect of methanol extract of NL against carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats was investigated. METHODS: Male Wistar rats were assigned into six groups of five rats each. Group I received corn oil (0.5 mL p.o.) and served as control, group II received CCl4 (1 mL/kg i.p., 1:3 in corn oil), group III received NL (200 mg/kg), and groups IV, V, and VI received CCl4+NL (50, 100, and 200 mg/kg, respectively) for 6 weeks. Twenty-four hours after the last exposure, rats were bled and killed. RESULTS: The activities of alanine aminotransaminase (ALT), aspartate aminotransferase (AST), and levels of total bilirubin (TB) in the serum, thiobarbituric acid reactive substances (TBARS), superoxide dismutase, catalase, glutathione peroxidase (GPx) and glutathione (GSH) in the liver, and histopathology of the liver were determined using standard procedures. NL significantly (p<0.05) lowered the levels of ALT, AST, and TB and exhibited antioxidant potentials in rats exposed to CCl4 relative to the control values. Specifically, NL at 100 and 200 mg/kg significantly (p<0.05) increased CCl4-induced decrease in hepatic GSH and GPx and also decreased the level of hepatic TBARS in CCl4-intoxicated rats. Histopathological findings revealed cellular infiltration and fibrosis in rats that received CCl4 only, which were ameliorated in rats that received NL+CCl4. CONCLUSIONS: The data suggest that NL exhibited hepatoprotective effects in CCl4-intoxicated rats via antioxidative mechanism.

Trichomonas vaginalis infection in Nigerian pregnant women and risk factors associated with sexually transmitted infections.

Trichomoniasis poses a public health threat to pregnant women and neonatal health. This study evaluated Trichomonas vaginalis and other common sexually transmitted infections (STIs) status in pregnant women, and risk factors associated with them. The study was cross-sectional and descriptive and a total of 198 pregnant women were recruited for T. vaginalis screening by microscopic examination. Questionnaires were also administered to 108 pregnant women to access information related to socio-demography and other factors associated with STI transmission. The overall prevalence of T. vaginalis was 18.7%. While prevalence of T. vaginalis was neither age nor parity dependent (p > 0.05), women in their first trimester showed significantly higher prevalence of trichomoniasis compared to women in their second and third trimesters (p < 0.05). The frequency of STIs was lowest (18.2%) and highest (71.4%) in age groups ≥ 39 and 15-20 years, respectively. Low levels of education, multiple sexual partners, lack of knowledge on partners' STI history, and having sex under the influence of alcohol or drugs were risk factors of for STIs (p < 0.05). We found a high prevalence of T. vaginalis in pregnant women, with those at an early gestational age at greater risk. The improved education of women on safe sex and the need to know partners' STI status are advocated.

Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal bioassays.

Spondias mombin (Linn), Nymphaea lotus (Linn) and Luffa cylindrica (Linn) (syn Luffa aegyptiaca Mill) are plants traditionally used as food ingredients and in the management of diseases, including cancer, in Nigeria. Despite the therapeutic potentials attributed to these plants, reports on their genotoxicity are scanty. In this study, the genotoxicity of the aqueous and hydro-methanol extract of these plants was evaluated using mouse bone marrow micronucleus and sperm morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was first used to assess acute toxicity of the aqueous and hydro-methanol extracts in Swiss albino mice. For each extract, there were five groups of mice (n=4/group) treated with different concentrations of the extract as against the negative and positive control group for the genotoxicity study. In the antigenotoxicity study, five groups of mice were exposed to five different concentrations of the extracts along with 60 mg/kg of methyl methane sulfonate (MMS), which was used to induce genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in the genotoxicity and antigenotoxicity groups. Administration of each of the extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in mice. At the concentrations tested, all the extracts, except aqueous S. mombin, increased micronucleated polychromatic erythrocytes. The aqueous and hydro-methanol extracts of N. lotus increased the frequency of aberrant sperm cells. All the extracts were also able to ameliorate MMS induced genotoxicity in bone marrow cells of the exposed mice. The results showed the potential of the extracts to induce somatic and germ cell mutation in male mice. The extracts also ameliorated the genotoxic effect of MMS.