Growth-inhibitory and cell cycle-arresting properties of the rice bran constituent tricin in human-derived breast cancer cells in vitro and in nude mice in vivo

Tricin, a flavone found in rice bran, inhibits the growth of human-derived malignant MDA-MB-468 breast tumour cells at submicromolar concentrations. As part of the exploration of tricin as a potential cancer chemopreventive agent, we investigated the duration and cell cycle specificity of growth inhibition elicited by tricin in vitro and the effect of tricin on the development of MDA-MB-468 tumours grown in immune-compromised MF-1 mice in vivo. Preincubation of MDA-MB-468 cells with tricin (1-40 microM) for 72 h compromised cell growth after tricin removal, and such irreversibility was not observed in human breast-derived nonmalignant HBL-100 cells. Tricin (>/=5 microM) arrested MDA-MB-468 cells in the G2/M phase of the cell cycle without inducing apoptosis as adjudged by annexin V staining. In nude mice consumption of tricin with the diet (0.2%, w w(-1)) from 1 week prior to MDA-MB-468 cell implantation failed to impede tumour development. Steady-state levels of tricin in plasma, breast tumour tissue and intestinal mucosa, as measured by HPLC, were 0.13 microM and 0.11 and 63 nmol g(-1), respectively. Cells were exposed to tricin (0.11, 1.1 or 11 microM) in vitro for 72 h and then implanted into mice. The volume of tumours in animals bearing cells pre-exposed to 11 microM tricin was less than a third of that in mice with control cells, while tumours from cells incubated with 0.1 or 1.1 microM tricin were indistinguishable from controls. These results suggest that the potent breast tumour cell growth-inhibitory activity of tricin in vitro does not directly translate into activity in the nude mouse bearing the MDA MB-468 tumour. While the results do not support the notion that tricin is a promising candidate for breast cancer chemoprevention, its high levels in the gastrointestinal tract after dietary intake render exploration of its ability to prevent colorectal carcinogenesis propitious

The prevalence of diabetes and prediabetes in the adult population of Jeddah, Saudi Arabia- a community-based survey

BACKGROUND: Type 2 (T2DM) is believed to be common in Saudi Arabia, but data are limited. In this population survey, we determined the prevalence of T2DM and prediabetes. MATERIALS AND METHODS: A representative sample among residents aged ≥ 18 years of the city of Jeddah was obtained comprising both Saudi and non-Saudi families (N = 1420). Data on dietary, clinical and socio-demographic characteristics were collected and anthropometric measurements taken. Fasting plasma glucose and glycated hemoglobin (HbA1c) were used to diagnose diabetes and prediabetes employing American Diabetes Association criteria. Multiple logistic regression analysis was used to identify factors associated with T2DM. RESULTS: Age and sex standardized prevalence of prediabetes was 9.0% (95% CI 7.5-10.5); 9.4% (7.1-11.8) in men and 8.6% (6.6-10.6) in women. For DM it was 12.1% (10.7-13.5); 12.9% (10.7-13.5) in men and 11.4% (9.5-13.3) in women. The prevalence based on World Population as standard was 18.3% for DM and 11.9% for prediabetes. The prevalence of DM and prediabetes increased with age. Of people aged ≥50 years 46% of men and 44% of women had DM. Prediabetes and DM were associated with various measures of adiposity. DM was also associated with and family history of dyslipidemia in women, cardiovascular disease in men, and with hypertension, dyslipidemia and family history of diabetes in both sexes. DISCUSSION: Age was the strongest predictor of DM and prediabetes followed by obesity. Of people aged 50 years or over almost half had DM and another 10-15% had prediabetes leaving only a small proportion of people in this age group with normoglycemia. Since we did not use an oral glucose tolerance test the true prevalence of DM and prediabetes is thus likely to be even higher than reported here. These results demonstrate the urgent need to develop primary prevention strategies for type 2 diabetes in Saudi Arabia

Progression of coronary calcification in healthy postmenopausal women

BACKGROUND: Coronary artery calcium score incrementally improves coronary risk prediction beyond that provided by conventional risk factors. Limited information is available regarding rates of progression of coronary calcification in women, particularly those with baseline scores above zero. Further, determinants of progression of coronary artery calcification in women are not well understood. This study prospectively evaluated rates and determinants of progression of coronary artery calcium score in a group of healthy postmenopausal women. METHODS: We determined coronary calcium score by computed tomography and recorded demographic, lifestyle and health characteristics of 914 postmenopausal women, a subset of those enrolled in the Women's Health Initiative Observational Study. The 305 women with calcium score ≥10 Agatston units at baseline were invited for repeat scan. This analysis includes the 94 women who underwent second scans. RESULTS: Mean age of study participants was 65 ± 9 years (mean ± SD), body mass index was 26.1 ± 6.1 kg/m(2), and baseline calcium score was 162 ± 220 Agatston units. Mean interval between scans was 3.3 ± 0.7 years. A wide range of changes in coronary calcium score was observed, from -53 to +452 Agatston units/year. Women with lower scores at baseline had smaller annual increases in absolute calcium score. Coronary calcium scores increased 11, 31 and 79 Agatston units/year among women with baseline calcium score in the lowest, middle and highest tertiles. In multivariate analysis, age was not an independent predictor of absolute change in coronary calcium score. Hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use at baseline was a negative predictor (p = 0.015), whereas baseline calcium score was a strong, positive predictor (p < 0.0001) of progression of coronary calcification. CONCLUSION: Among postmenopausal women with coronary calcium score ≥ 10 Agatston units, rates of change of coronary calcium score varied widely. In multivariate analysis, statin use was a negative independent determinant, whereas baseline calcium score was a strong positive predictor of annual change in coronary calcium score

Testing of a Model with Latino Patients That Explains the Links Among Patient-Perceived Provider Cultural Sensitivity, Language Preference, and Patient Treatment Adherence

Introduction Disparities in treatment adherence based on race and ethnicity are well documented but poorly understood. Specifically, the causes of treatment nonadherence among Latino patients living in the USA are complex and include cultural and language barriers. Purpose The purpose of this study was to examine whether patients’ perceptions in patient-provider interactions (i.e., trust in provider, patient satisfaction, and patient sense of interpersonal control in patient-provider interactions) mediate any found association between patient-perceived provider cultural sensitivity (PCS) and treatment adherence among English-preferred Latino (EPL) and Spanish-preferred Latino (SPL) patients. Methods Data from 194 EPL patients and 361 SPL patients were obtained using questionnaires. A series of language-specific structural equation models were conducted to test the relationship between patient-perceived PCS and patient treatment adherence and the examined mediators of this relationship among the Latino patients. Results No significant direct effects of patient-perceived PCS on general treatment adherence were found. However, as hypothesized, several significant indirect effects emerged. Preferred language appeared to have moderating effects on the relationships between patient-perceived PCS and general treatment adherence. Conclusion These results suggest that interventions to promote treatment adherence among Latino patients should likely include provider training to foster patient-defined PCS, trust in provider, and patient satisfaction with care. Furthermore, this training needs to be customized to be suitable for providing care to Latino patients who prefer speaking Spanish and Latino patients who prefer speaking English

The influence of hip circumference on the relationship between abdominal obesity and mortality

Background Higher waist circumference and lower hip circumference are both associated with increased cardiovascular disease (CVD) risk, despite being directly correlated. The real effects of visceral obesity may therefore be underestimated when hip circumference is not fully taken into account. We hypothesized that adding waist and hip circumference to traditional risk factors would significantly improve CVD risk prediction

Alpha-santalol, a chemopreventive agent against skin cancer, causes G2/M cell cycle arrest in both p53-mutated human epidermoid carcinoma A431 cells and p53 wild-type human melanoma UACC-62 cells

<p>Abstract</p> <p>Background</p> <p>α-Santalol, an active component of sandalwood oil, has shown chemopreventive effects on skin cancer in different murine models. However, effects of α-santalol on cell cycle have not been studied. Thus, the objective of this study was to investigate effects of α-santalol on cell cycle progression in both p53 mutated human epidermoid carcinoma A431 cells and p53 wild-type human melanoma UACC-62 cells to elucidate the mechanism(s) of action.</p> <p>Methods</p> <p>MTT assay was used to determine cell viability in A431 cells and UACC-62; fluorescence-activated cell sorting (FACS) analysis of propidium iodide staining was used for determining cell cycle distribution in A431 cells and UACC-62 cells; immunoblotting was used for determining the expression of various proteins and protein complexes involved in the cell cycle progression; siRNA were used to knockdown of p21 or p53 in A431 and UACC-62 cells and immunofluorescence microscopy was used to investigate microtubules in UACC-62 cells.</p> <p>Results</p> <p>α-Santalol at 50-100 μM decreased cell viability from 24 h treatment and α-santalol at 50 μM-75 μM induced G₂/M phase cell cycle arrest from 6 h treatment in both A431 and UACC-62 cells. α-Santalol altered expressions of cell cycle proteins such as cyclin A, cyclin B1, Cdc2, Cdc25c, p-Cdc25c and Cdk2. All of these proteins are critical for G₂/M transition. α-Santalol treatment up-regulated the expression of p21 and suppressed expressions of mutated p53 in A431 cells; whereas, α-santalol treatment increased expressions of wild-type p53 in UACC-62 cells. Knockdown of p21 in A431 cells, knockdown of p21 and p53 in UACC-62 cells did not affect cell cycle arrest caused by α-santalol. Furthermore, α-santalol caused depolymerization of microtubules similar to vinblastine in UACC-62 cells.</p> <p>Conclusions</p> <p>This study for the first time identifies effects of α-santalol in G₂/M phase arrest and describes detailed mechanisms of G₂/M phase arrest by this agent, which might be contributing to its overall cancer preventive efficacy in various mouse skin cancer models.</p

Genetic Predictions of Prion Disease Susceptibility in Carnivore Species Based on Variability of the Prion Gene Coding Region

Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE) during the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD) remains an open question. Variation in the host-encoded prion protein (PrP(C)) largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrP(C) protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo) and pine marten (Martes martes) were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus) and mountain lion (Puma concolor) from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter

TbUNC119 and Its Binding Protein Complex Are Essential for Propagation, Motility, and Morphogenesis of Trypanosoma brucei Procyclic Form Cells

Flagellum-mediated motility of Trypanosoma brucei is considered to be essential for the parasite to complete stage development in the tsetse fly vector, while the mechanism by which flagellum-mediated motility is controlled are not fully understood. We thus compared T. brucei whole gene products (amino acid sequence) with Caenorhabditis elegans UNC (uncoordinated) proteins, in order to find uncharacterized motility-related T. brucei genes. Through in silico analysis, we found 88 gene products which were highly similar to C. elegans UNC proteins and categorized them as TbCEUN (T. brucei gene products which have high similarity to C. elegans UNC proteins). Approximately two thirds of the 88 TbCEUN gene products were kinesin-related molecules. A gene product highly similar to C. elegans UNC119 protein was designated as TbUNC119. RNAi-mediated depletion of TbUNC119 showed no apparent phenotype. However, knock-down analysis of both TbUNC119 and its binding protein (TbUNC119BP) which was found by yeast two-hybrid analysis showed characteristic phenotypes, including reduced motility, morphological change (extended cell shape), and cellular apoptosis. Based on the observed phenotypes, possible function of the TbUNC119 and TbUNC119BP is discussed