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Sutherlandia frutescens is a plant that is endemic to South Africa and is traditionally used for the treatment of cancer and many other ailments. Although previous studies have shown S. frutescens to exert anti-proliferative and apoptotic effects in human mammary adenocarcinoma- and leukemia cell lines, its potential cytotoxic effects on colon cancer cells have not yet been established. Moreover, limited information is available elucidating the major signaling pathways involved upon exposure to the herbal extract. The aim of this study was therefore to assess the cytotoxic effect of S. frutescens on the colon cancer cell line CaCo2, to investigate molecular role players of apoptosis and to assess the involvement of the PI3-K survival pathway. CaCo2 cells exposed to ethanolic extracts of S. frutescens showed significant decreased cell viability, indicated by reduced MTT reductive capacity, increased pyknosis as well as loss in cellular membrane integrity. Western blot analysis revealed a down-regulation in the PI3-K and Akt phosphorylation, a decrease in forkhead transcription factor (FKHR) phosphorylation as well as a concomitant induction of apoptosis. This study demonstrates that Sutherlandia treatment attenuates proliferation of colon cancer cells in vitro by the disruption of the key molecules in the PI-3K pathway thereby inducing apoptosis.

Background: Although roll-out of combined anti-retroviral treatment (cART) has blunted HIV-AIDS onset, studies show increased development of cardiovascular diseases (CVD) in HIV-infected individuals. This study aimed to identify changes in immune cells (T cells, monocyte subsets) and determine their relationship to: (a) classical markers of HIV progression (CD4 count, viral load), (b) immune activation status and coagulation, and (c) traditional lipid profile/subclasses. Methods: Eighty participants were recruited (Worcester, South Africa) and fasted blood collected to evaluate: a) traditional lipid profile, b) immune markers, c) monocyte subpopulations (non-classical, intermediate, classical) by flow cytometry together with tissue factor (marker: thrombus formation) and CD38 (marker:immune activation) expression on CD4 and CD8 T cells. Classical regulatory T cells (Treg) with activation markers (glycoprotein A repetitions predominant [GARP], special AT-rich sequence-binding protein 1) were assessed together with high-and low-density lipoprotein subclasses (Lipoprint). Findings: This study revealed four key findings in HIV-positive patients: a) co-expression of a coagulation marker (tissue factor) together with immune activation on CD4 and CD8 T cells (irrespective of cART), b) Treg cell activation and upregulated GARP contributing to persistent immune activation, c) Pro-atherogenic monocyte subset expansion; and d) Lipopolysaccharide binding protein (LBP) as a key modulator mediating immunometabolic perturbations. Interpretation: These findings alert to the future clinical management of HIV-positive patients and highlight the need for earlier therapeutic interventions to address chronic inflammation, immune activation and LBP-mediated lipid subclass effects. This strategy should decrease coagulation and lower CVD risk. Funding Statement: This work was supported by the Medical Research Council and Stellenbosch University [MFE]. Declaration of Interests: None declared. Ethics Approval Statement: This study complies with the Declaration of Helsinki and ethical approval was obtained from the Human Research Ethics Committee of Stellenbosch University and the Department of Health (Western Cape Government, South Africa). Prior to the study, all participants were informed about procedures and consent forms were signed by all.

Polymorphic N -acetyltransferase genes ( NAT1 and NAT2 ) determine rapid or slow acetylation phenotypes, which are believed to affect cancer risk related to environmental exposure. Black South Africans have a unique incidence pattern of environment-related cancers, but genetic characteristics of this population are mostly unknown. In this study, we compared NAT1 and NAT2 allele distributions in 101 Black South Africans and 112 UK Caucasians. Frequencies of the rapid alleles were significantly higher in Black South Africans for both NAT1 and NAT2 . Putative rapid NAT1 genotypes due to the presence of either NAT1 ∗ 10 or NAT1 ∗ 11 were found in 74.3% of Black South Africans (only NAT1 ∗ 10 ) and 42.0% of UK Caucasians ( P NAT2 analysis showed that the presence of NAT2 ∗ 4 , NAT2 ∗ 12A , NAT2 ∗ 12B , NAT2 ∗ 12C , and NAT2 ∗ 13 alleles provided significantly higher ( P =0.0001) frequency of rapid acetylation genotypes among Black South Africans (60.4%) than in the Caucasian group (33.9%). The rapid acetylation genotype in Caucasians usually depended on the NAT2 ∗ 4 allele presence. The significant differences in N -acetylation genotypes can be among the factors determining a distinctive cancer morbidity and mortality pattern observed in Black South Africans. Both further genetic characterization of different populations and development of preventive strategies adopted for ethnicities with different genetic backgrounds are needed to deal adequately with the emerging health care problems in developing multiethnic societies.

Nutritional status and risk factors for chronic diseases, including plasma fibrinogen and its determinants, of Africans in the Northwest Province of South Africa, have been studied in a cross-sectional survey. A representative sample of 1854 "apparently healthy" African men and women volunteers aged 15 years and older was recruited from 37 randomly selected sites throughout the Province and stratified for level of urbanisation. Information was collected using validated and culture-sensitive questionnaires. Fasting blood samples were drawn, and all measurements were done with standardised methodology using appropriate equipment, procedures, and controls. Fibrinogen concentration was measured in citrated plasma with the method of Clauss, using the ACL200 automated system and the international fibrinogen standard. The results revealed a population with a high mean plasma fibrinogen (3.17+/-1.10 g/L for HIV-negative men and 3. 64+/-1.12 g/L for HIV-negative women). Factors known to influence plasma fibrinogen, such as age, gender, smoking habit, and physical activity, were also observed in this population. Young rural men and women had the lowest fibrinogen level. Nasal snuff taking and HIV infection did not influence fibrinogen concentration. Multivariate analyses revealed that lower plasma fibrinogen was associated with low to normal body mass index in women, and with dietary intakes compatible with prudent dietary guidelines in men and women (low intakes of animal protein; trans fatty acids and higher intakes of plant protein; dietary fibre, vitamin E, and iron, and a high dietary P/S ratio). Subjects in the higher quartiles of plasma fibrinogen had significantly lower iron, vitamin E, and vitamin B6 (women) status. Increases in fibrinogen were associated with significant increases in serum lipids. Both under- and overnutrition seem to be associated with high plasma fibrinogen. It is concluded that overall nutritional status, possibly in addition to specific nutrients (and foods), influences plasma fibrinogen.

Genetic polymorphisms for apolipoprotein E (apo E) and methylenetetrahydrofolate reductase (MTHFR) are believed to modulate risk of coronary heart disease (CHD) acting through regulation of lipid and homocysteine metabolism, respectively. The distributions of apo E and MTHFR alleles in Black South Africans, a population with a low CHD incidence, and UK Caucasians from the Cambridge area, with a higher CHD incidence, were therefore compared. Clinically healthy volunteers (207), including 107 UK Caucasians from the Cambridge area and 100 Black South Africans, participated in the study. Apo E and MTHFR genotypes were determined in all of them. Analyses for serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and plasma fibrinogen were carried out in 65 UK Caucasians and 60 Black South Africans. The apo E epsilon4 allele, which is associated with elevated CHD risk, was present in 48% of Black South Africans compared to 20.8% of Caucasians (P < 0.0001); however, both total and LDL cholesterol levels in Black South Africans were 18-32% lower than in Caucasians with similar apo E genotypes. Hyperhomocysteinemia-causing MTHFR 677T variant was detected in only 20% of Black South Africans (no homozygotes) versus 56% of Caucasians with 12% homozygotes (P