Effects of different mycotoxins on humans, cell genome and their involvement in cancer (Review)

The chemical nature of most of the mycotoxins makes them highly liposoluble compounds that can be absorbed from the site of exposure such as from the gastrointestinal and respiratory tract to the blood stream where it can be dissimilated throughout the body and reach different organs such as the liver and kidneys. Mycotoxins have a strong tendency and ability to penetrate the human and animal cells and reach the cellular genome where it causes a major mutagenic change in the nucleotide sequence which leads to strong and permanent defects in the genome. This defect will eventually be transcribed, translated and lead to the development of cancer. In this review, the chemical and physical nature of mycotoxins, the action of mycotoxins on the cellular genome and its effect on humans, mycotoxins and their carcinogenicity and mycotoxins research gaps are discussed, and new research areas are suggested. The research review posed various questions. What are the different mycotoxins that can cause cancer, what is the role of mycotoxins in causing cancer and what types of cancers can be caused by mycotoxins? These questions have been selected due to the significant increase in the mycotoxin contamination and the cancer incidence rate in the contemporary world. By revealing and understanding the role of mycotoxins in developing cancer, measures to reduce the risks and incidents of cancer could be taken

Photocatalytic Degradation of Phenol using Visible light Activated Ag-AgBr-Hydrotalcite Composite

Water pollution is one of the persistent environmental challenges that continues to impact numerous communities worldwide. As such, several sustainable remediation technologies have been developed over the years to increase water supply through reuse. Visible light activated photocatalysis is one such technology that aptly remediates refractory organic pollutants from various water matrices. In this study, a composite Ag-AgBr-LDH photocatalyst was synthesized. The physical and chemical properties of the catalyst were elucidated using a range of characterization techniques. The photocatalytic activity of the material was tested on simulated phenol contaminated water, and degradation efficiencies as high as 92% were achieved at neutral pH and a catalyst loading of 2 g/L. The synthesized photocatalyst nanocomposite material proved to be a feasible catalyst for degradation of phenolic contaminants in water under visible light irradiation

Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans

The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans. Previous studies showed that the C. albicans ICL1 genes, which encode the glyoxylate cycle enzymes isocitratelyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid and were repressed by 2% glucose. In contrast to S. cerevsiae, the enzyme CaIcl1 was not destabilised by glucose, resulting with its metabolite remaining at high levels. Further glucose addition has caused CaIcl1 to lose its signal and mechanisms that trigger destabilization in response to glucose. Another purpose of this study was to test the stability of the Icl1 enzyme in response to the dietary sugars, fructose, and galactose. In the present study, the ICL1 mRNAs expression was quantified using Quantitative Real Time PCR, whereby the stability of protein was measured and quantified using Western blot and phosphoimager, and the replacing and cloning of ICL1 ORF by gene recombination and ubiquitin binding was conducted via co-immuno-precipitation. Following an analogous experimental approach, the analysis was repeated using S. cerevisiaeas a control. Both galactose and fructose were found to trigger the degradation of the ICL1 transcript in C. albicans. The Icl1 enzyme was stable following galactose addition but was degraded in response to fructose. C. albicans Icl1 (CaIcl1) was also subjected to fructose-accelerated degradation when expressed in S. cerevisiae, indicating that, although it lacks a ubiquitination site, CaIcl1 is sensitive to fructose-accelerated protein degradation. The addition of an ubiquitination site to CaIcl1 resulted in this enzyme becoming sensitive to galactose-accelerated degradation and increases its rate of degradation in the presence of fructose. It can be concluded that ubiquitin-independent pathways of fructose-accelerated enzyme degradation exist in C. albicans

Inhibitory effect of Labisia pumila leaf extract on angiogenesis via down-regulation of vascular endothelial growth factor

Purpose: To investigate the anti-angiogenic activity of a methanol leaf extract of Labisia pumila (ME), and its bioactive water fraction (WF), using in vitro models.Methods: The antioxidant activity and total phenolic contents of ME and WF were assessed using DPPH and Folin–Ciocalteu reagents. Antiproliferative effects of extracts towards human umbilical vein endothelial cells (HUVECs) were evaluated using MTT assay. Isolated rat aortic ring and matrigel tube formation assays were performed to assess the antiangiogenic potential of Me and its WF. Levels of VEGF protein in the cell lysates were measured using ELISA kit.Results: Among all the extracts prepared, ME and its WF showed higher total phenolic contents and exhibited moderate antioxidant effects. Significant (p < 0.001) suppression of microvessels outgrowth with half-maximal concentration (IC50) values of 20 and 26 μg/mL for ME and WF, was observed in rat aortic ring assay. ME and its WF halted proliferation and tube formation capacity of HUVECs in in vitro assays. Marked reduction in VEGF levels was observed in lysates of HUVECs treated with ME and its WF.Conclusion: Labisia pumila leaf extract and its water fraction halted angiogenesis by blocking VEGF secretion leading to inhibition of endothelial cells proliferation and differentiation which is suggested to be due to its phenolic antioxidant contents.Keywords: Labisia pumila, Anti-angiogenesis, Antioxidant, Tube formation, Rat aort

Pharmacokinetics and antiangiogenic studies of potassium koetjapate in rats

© 2020 Purpose: Koetjapic acid is an active compound of a traditional medicinal plant, Sandoricum koetjape. Although koetjapic acid has a promising anticancer potential, yet it is highly insoluble in aqueous solutions. To increase aqueous solubility of koetjapic acid, we have previously reported a chemical modification of koetjapic acid to potassium koetjapate (KKA). However, pharmacokinetics of KKA has not been studied. In this study, pharmacokinetics and antiangiogenic efficacy of KKA are investigated. Methods: Pharmacokinetics of KKA was studied after intravenous and oral administration in SD rats using HPLC. Anti-angiogenic efficacy of KKA was investigated in rat aorta, human endothelial cells (EA.hy926) and nude mice implanted with matrigel. Results: Pharmacokinetic study revealed that KKA was readily absorbed into blood and stayed for a long time in the body with Tmax 2.89 ± 0.12 h, Cmax 7.24 ± 0.36 μg/mL and T1/2 1.46 ± 0.03 h. The pharmacological results showed that KKA significantly suppressed sprouting of microvessels in rat aorta with IC50 18.4 ± 4.2 μM and demonstrated remarkable inhibition of major endothelial functions such as migration, differentiation and VEGF expression in endothelial cells. Further, KKA significantly inhibited vascularization in matrigel plugs implanted in nude mice. Conclusions: The results indicate that bioabsorption of KKA from oral route was considerably efficient with longer retention in body than compared to that of the intravenous route. Further, improved antiangiogenic activity of KKA was recorded which could probably be due to its increased solubility and bioavailability. The results revealed that KKA inhibits angiogenesis by suppressing endothelial functions and expression of VEGF

Neuroprotective and anti-inflammatory effects of Rhus coriaria extract in a mouse model of ischemic optic neuropathy

Modulating oxidative stresses and inflammation can potentially prevent or alleviate the pathological conditions of diseases associated with the nervous system, including ischemic optic neuropathy. In this study we evaluated the anti-neuroinflammatory and neuroprotective activities of Rhus coriaria (R. coriaria) extract in vivo. The half maximal inhibitory concentration (IC50) for DPPH, ABTS and \u3b2-carotene were 6.79 \ub1 0.009 \u3bcg/mL, 10.94 \ub1 0.09 \u3bcg/mL, and 6.25 \ub1 0.06 \u3bcg/mL, respectively. Retinal ischemia was induced by optic nerve crush injury in albino Balb/c mice. The anti-inflammatory activity of ethanolic extract of R. coriaria (ERC) and linoleic acid (LA) on ocular ischemia was monitored using Fluorescence Molecular Tomography (FMT). Following optic nerve crush injury, the mice treated with 400 mg/kg of ERC and LA exhibited an 84.87% and 86.71% reduction of fluorescent signal (cathepsin activity) respectively. The results of this study provide strong scientific evidence for the neuroprotective activity of the ERC, identifying LA as one of the main components responsible for the effect. ERC may be useful and worthy of further development for its adjunctive utilization in the treatment of optic neuropathy

Motivational determinants of physical activity in disadvantaged populations with (pre)diabetes: a cross-cultural comparison

Background Understanding motivational determinants of physical activity (PA) is essential to guide the implementation of PA at individual and population level. Knowledge about the cross-cultural generalizability of these determinants is lacking and they have mostly been studied as separate factors. This study compares a motivational process model across samples from diverse populations with, or at risk of diabetes. Methods Measurement invariance of barrier identified regulation, barrier self-efficacy and social support was assessed in a rural Ugandan sample (n = 712) and disadvantaged samples with high proportions of immigrants in urban South Africa (n = 566) and Sweden (n = 147). These motivational determinants were then compared through multigroup structural equation modeling. Results The studied motivational constructs showed scalar invariance. Latent mean levels of perceived social support and barrier self-efficacy were lower in South Africa and Sweden. Structural models (for different PA outcomes) were not consistent across settings except for the association between perceived social support and identified regulation. Identified regulation was only associated with vigorous PA in Uganda and with moderate PA in South Africa. The association between social support and PA outcomes ranged from weak to not significant and the association between self-efficacy and PA was not significant. Self-reported PA was highest in Uganda and lowest in Sweden. Self-reported vigorous PA was significantly related to lower hemoglobin A1c levels, while moderate PA was not. Conclusions Findings suggest that: 1) it is feasible to compare a motivational process model across diverse settings; 2) there is lower perceived social support and self-efficacy in the urban, migrant samples; 3) identified regulation is a more promising determinant of PA than self-efficacy or social support in these populations; 4) associations between motivational determinants and PA depend on the perceived type and/or intensity of PA; 5) perceived relatedness functions as a basic psychological need across diverse settings; and 6) people’s perception of the PA they perform depends on their perceived level of intensity of PA which would have major implications for health promotion

Wealth-based inequality in the continuum of maternal health service utilisation in 16 sub-Saharan African countries

BackgroundPersistent inequalities in coverage of maternal health services in sub-Saharan Africa (SSA), a region home to two-thirds of global maternal deaths in 2017, poses a challenge for countries to achieve the Sustainable Development Goal (SDG) targets. This study assesses wealth-based inequalities in coverage of maternal continuum of care in 16 SSA countries with the objective of informing targeted policies to ensure maternal health equity in the region.MethodsWe conducted a secondary analysis of Demographic and Health Survey (DHS) data from 16 SSA countries (Angola, Benin, Burundi, Cameroon, Ethiopia, Gambia, Guinea, Liberia, Malawi, Mali, Nigeria, Sierra Leone, South Africa, Tanzania, Uganda, and Zambia). A total of 133,709 women aged 15-49 years who reported a live birth in the five years preceding the survey were included. We defined and measured completion of maternal continuum of care as having had at least one antenatal care (ANC) visit, birth in a health facility, and postnatal care (PNC) by a skilled provider within two days of birth. We used concentration index analysis to measure wealth-based inequality in maternal continuum of care and conducted decomposition analysis to estimate the contributions of sociodemographic and obstetric factors to the observed inequality.ResultsThe percentage of women who had 1) at least one ANC visit was lowest in Ethiopia (62.3%) and highest in Burundi (99.2%), 2) birth in a health facility was less than 50% in Ethiopia and Nigeria, and 3) PNC within two days was less than 50% in eight countries (Angola, Burundi, Ethiopia, Gambia, Guinea, Malawi, Nigeria, and Tanzania). Completion of maternal continuum of care was highest in South Africa (81.4%) and below 50% in nine of the 16 countries (Angola, Burundi, Ethiopia, Guinea, Malawi, Mali, Nigeria, Tanzania, and Uganda), the lowest being in Ethiopia (12.5%). There was pro-rich wealth-based inequality in maternal continuum of care in all 16 countries, the lowest in South Africa and Liberia (concentration index = 0.04) and the highest in Nigeria (concentration index = 0.34). Our decomposition analysis showed that in 15 of the 16 countries, wealth index was the largest contributor to inequality in primary maternal continuum of care. In Malawi, geographical region was the largest contributor.ConclusionsAddressing the coverage gap in maternal continuum of care in SSA using multidimensional and people-centred approaches remains a key strategy needed to realise the SDG3. The pro-rich wealth-based inequalities observed show that bespoke pro-poor or population-wide approaches are needed