The prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet may be an important risk factor for thrombotic events. The daily intake of an anti-thrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to test tomato extracts for anti-thrombotic effects and to identify those varieties that have such an effect. A shear-induced platelet-function test (haemostatometry) was used to test anti-thrombotic potential in vitro. Extracts from those tomato varieties that showed a significant anti-thrombotic activity in vitro were further assessed in vivo, using a laser-induced thrombosis test in mice. One tomato variety (KG99-4) showed significant anti-thrombotic activity both in vitro and in vivo. KG99-4 inhibited not only platelet-rich thrombus formation but also had a thrombolytic effect. It is concluded that haemostatometry can detect and classify the anti-thrombotic potential of fruits and vegetables and offers a simple way of screening for such effects.
A previous genome-wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC (odds ratio [OR] = 1.26, P = 4.13 × 10-9). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.
The human glycoprotein PC-1 codon Q121 allele has been correlated with insulin resistance, but not with type 2 diabetes or obesity. We investigated the prevalence of PC-1 Q121 in the Dominican Republic population (755 subjects studied) and whether this variant is associated with insulin resistance, obesity, or type 2 diabetes. The prevalence of PC-1 Q121 was high compared with that in other populations. The proportions of genotypes detected were: KK, 21.6%; KQ, 48.3%; and QQ, 30.1%. This compares to approximately 74%, 24%, and 2% in other populations. Among nonobese, nondiabetic subjects, the insulin response of KQ (P = 0.027) and QQ (P = 0.031) subjects was greater during the oral glucose tolerance test than that of KK subjects, whereas plasma glucose profiles were comparable. The Q allele was more prevalent in obese type 2 diabetics than in controls (P = 0.026; odds ratio = 1.56). Multiple regression analysis, after adjusting for age, gender, and body mass index, showed the QQ genotype to be associated with type 2 diabetes (P = 0.043; odds ratio = 2.74), but not obesity (P = 0.068). These results indicate that the PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic, contributing to both insulin resistance and type 2 diabetes.
Resveratrol is one of the major polyphenolics in red wine that has been shown to exert the preventive effects against cardiovascular diseases. The effect of trans-resveratrol (t-RES) administered as an ingredient of the diet on the atherothrombotic tendency was assessed in genetically hypercholesterolemic mice after laser-induced damage on endothelium. Mice lacking both apolipoprotein E and low-density lipoprotein receptor (apoE-/-/LDLR-/-) were fed with a high-fat diet with or without t-RES (9.6 and 96 mg/kg diet) for 8 weeks. The atherosclerotic tendency was morphometrically analyzed in their aortae. The thrombotic tendency was determined by inducing thrombus by the irradiation of a helium-neon laser on carotid arteries of these mice with injection of Evans blue. Atherosclerotic area and thrombus size were evaluated by image analyzing in a computer system. Even though the plasma concentrations of lipids (total cholesterol and triacylglycerol) did not change in the control and t-RES groups, a significant decrease (approximately 30%) in the formation of atheroma was observed in the aortae of the t-RES group. The size of laser-induced thrombus that mostly consisted of platelet aggregates was significantly reduced (approximately 25%) in the t-RES group compared with that in the control group. Thus, t-RES orally administrated with a high-fat diet in apoE-/-/LDLR-/- mice significantly suppressed atherosclerosis in their aortae and reduced the laser-induced thrombosis in their carotid arteries.
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