102 cases of coronary heart disease (CHD) were divided randomly into two groups, 70 cases were given orally the Buyang Huanwu Decoction (BYHWD) for 15 days and were compared with 32 control patients. The effect of BYHWD in treating angina pectoris and the change of EKG before and after the treatment were observed. The results were as follows: in BYHWD group the serum level of lipoperoxide (LPO), apolipoprotein (apo) B100, LPO/SOD (superoxide dismutase) and apo B100/apo A1 were lowered remarkably, the serum of SOD and apo A1 were elevated significantly (P < 0.01) comparing with the control group. The total effective rate of treating angina pectoris was 91.4%. But the difference was insignificant compared with the control group (P < 0.05). The EKG improvement rate was 85.7% in BYHWD group, the difference was very significant comparing with control group (P < 0.05). The results indicated that BYHWD had a good effect on removing the oxygen free radicals, reducing the injury of LPO and regulating the apolipoprotein metabolism in the patients with CHD. Therefore BYHWD is an effective TCM remedy for CHD.

Despite alarming obesity levels in the Arabian Peninsula, its population lacks convincingly identified genetic determinants of obesity. A genome-wide association study was performed for obesity-related anthropometric traits in Arabs and to decipher mechanisms by which the variants mediate traits.

The Illumina HumanOmniExpress BeadChip was used to genotype 1,353 Arab individuals (largely with Class I obesity) from Kuwait. Genome-wide association tests for obesity-related anthropometric traits were performed. Top associations were tested for replication in an independent cohort (1,176 unrelated Arabs). Resultant variants were investigated for interactions with obesity-related plasma biomarkers. Pathway analysis was performed on genes harboring markers in linkage disequilibrium (LD) with identified variants.

The rs9606756[c.67A>G,p.Ile23Val] variant from TCN2 was associated with waist circumference (WC) at nearly genome-wide significance (P = 8.92E-08). WC was inversely related with Apo-A1 or high-density lipoprotein levels; individuals with the AG genotype exhibited stronger relationship than those with the reference AA genotype. Interaction involving the AG genotype (effect allele = G) significantly contributed to an increase in anthropometric traits (particularly WC). Genes harboring single-nucleotide polymorphisms in LD with rs9606756 mapped onto an interaction network (with TP53 as central element) of established obesity/diabetes-related protein components.

The TCN2 variant acts as a risk factor for WC in the Arab population. The variant mediates obesity-related anthropometric traits via interactions with Apo-A1/high-density lipoprotein or TP53.

BACKGROUND

Atherosclerotic cardiovascular disease is currently a cause of mortality in some parts of the world. The ATP-Binding Cassette Transporter (ABCA1) gene prepares instructions to produce the ATP-binding cassette transporter protein whose operation is for export of phospholipids and cholesterol, outside cells where they are limited to Apolipoprotein A1 (apoA1). Increased ABCA1 activity could inhibit atherosclerosis.

OBJECTIVE

In the present study, the effect of aerobic exercise was investigated on gene expression and biochemical parameters.

METHODS

The participants included 36 inactive women, which were randomly assigned to control (CON) and experimental (EX) groups. The EX group performed 12 weeks of aerobic exercise and the CON group remained inactive. Fasting blood samples were collected 24 hours before the first session and 48 hours after completion of the course. The ABCA1 and APOA1 gene expressions were measured using semi-quantitative-RT-PCR. Data were analyzed by the SPSS software (version 18).

RESULTS

A significant increase in blood ABCA1 (EX group P < 0.002, t = - 9.876) and Apo A-I (EX group P < 0.05, t = 2.76) gene expression was shown following the 12 weeks of training. Plasma high-density lipoprotein-cholesterol (HDL-C) concentration increased (P < 0.001, t = 4.90 respectively) while plasma low-density lipoprotein-cholesterol (LDL-C) concentration decreased (P < 0.001, t = 4.27) in the EX group compared with the CON group.

CONCLUSIONS

Aerobic exercises can increase ABCA1 and APO-A1 gene expression. Induction of these genes can effectively prevent cardiovascular disease.

To pick up serum high risk lithogenic factors predisposing one to gallstone formation and protective factors against gallstone formation in gallbladder. We compared serum lipid and apolipoprotein level of patients with gallbladder stone (stone group) with that of patients without gallbladder stone (control group). The correlation between serum lipid, apolipoprotein level and bile lipid level, cholesterol saturated index (CSI), characteristics of lipidemia in different kinds of gallbladder stones were studied. The results showed that the increase of serum Apo A1, C2 and E level in the stone group was more significant than in the control group. But there was no statistical significance in TC, TG, LDL-C, HDL-C, Apo A2, B, C3 level between the stone and control groups. These results suggested that serum apolipoproteins perhaps are more sensitive parameters than serum lipids in distinguishing patients with stones from those without stones. There were different profiles of serum lipid and apolipoproteins in different chemical types of gallbladder stones. Increased level in serum LDL-C, Apo B and ratio of LDL-C/HDL-C were characterized by an index for cholesterol stone, otherwise that in serum TG and Apo C2 an index for pigment stones. There was a positive correlation between serum total cholesterol (TC) or Apo B, C2, C3 and cholesterol amount or CSI in gallbladder bile. Therefore, TC, Apo B, C2, C3 could be considered as high risk lithogenic factors. A positive correlation existed between serum HDL-C and lecithin in gallbladder or common bile duct (CBD) bile as well as between HDL-C and bile acids in CBD bile. Thus, HDL-C might be a protective factor against gallstone formation in gallbladder.

OBJECTIVE

To determine lipid target achievements of low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apo B) in the Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolemia (CEPHEUS) in Arabian Gulf States patients with high and highest risk according to the joint Consensus Statement of the American Diabetes Association (ADA) and American College of Cardiology Foundation (ACC).

METHODS

CEPHEUS was conducted in patients (≥ 18 years of age) in six Middle Eastern countries between November 2009 and July 2010 on lipid lowering drugs (LLDs). Serum samples collected included total cholesterol (TC), LDL-C, HDL-C, triglycerides (TGs), apo B, and apolipoprotein A1 (apo A1).

RESULTS

The overall mean age of the cohort (n = 5275) was 56 ± 13 years, 58% (n = 3060) were male and 69% (n = 3635) were highest risk. LDL-C target was achieved in 25%, non-HDL-C in 36% and apo B in 38% of patients in the highest risk cohort compared with LDL-C 46%, non-HDL-C 58% and apo B 51% in the high risk group. In patients with TGs ≥ 2.2 mmol/L, LDL-C target was achieved in 16% and apo B in 15% of patients in the highest risk group compared with LDL-C 32% and apo B 22% in the high risk cohort.

CONCLUSIONS

Despite being on LLDs, a large proportion of high and highest risk patients in the Arabian Gulf are not at recommended lipid targets and remain at a substantial residual risk for cardiovascular diseases. Apo B may be used as an additional target in patients with triglycerides ≥ 2.2 mmol/L. The findings should be interpreted in light of the study's limitations.

UNASSIGNED

Lipoprotein-associated phospholipase A2 (Lp-PLA2) which is believed to play a role in atherosclerotic inflammatory process due to its function in hydrolysis of phospholipids and release of pro-inflammatory products, is considered as a novel biomarker for vascular risk. In this study we aimed to investigate the alterations in Lp-PLA2 and its relationship with other cardiovascular risk factors in patients with testosterone deficiency.

UNASSIGNED

Forty hypogonadic male and 30 healthy male aged between 18-50 years were enrolled in this study. Height-weight, waist-to-hip circumference, body mass index (BMI) blood pressure, and body fat measurements were performed in all subjects. Blood glucose, albumin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, high sensitive C-reactive protein (hs-CRP), apo-A1, apo-B, fibrinogen, insulin, total testosterone, sex hormone binding globulin (SHBG), small dense low-density lipoprotein (sd-LDL), paraoxonase 1, oxidized low-density lipoprotein (ox-LDL) and Lp-PLA 2 values were measured. Free and bioavailable testosterone levels were calculated. Data management was carried out with the statistical program SAS Version 9.2. Statistical evaluations were performed using Analysis of Variance (ANOVA), Kruskal-Wallis test, Wilcoxon test, correlation analysis and chi-square analysis. P values <0.05 were considered statistically significant.

UNASSIGNED

In patients with hypogonadism, significant increase in Lp-PLA2 levels were accompanied with risk factors of atherosclerosis, such as increase in total cholesterol, apo-B, sd-LDL, weight, BMI, body fat percentage, and decrease in paraoxonase 1 levels. Although the differences were not significant, similarly ox-LDL, hs-CRP, triglyceride, LDL-cholesterol levels were found to be higher in patients with hypogonadism compared to the control group. The mean level of Lp-PLA2 was the highest when compared with the group of secondary hypogonadism with the lowest testosterone level.

UNASSIGNED

Our study has demonstrated that the testosterone deficiency increases cardiovascular risk via its effects on lipid metabolism and Lp-PLA2 can be used to assess this risk.

OBJECTIVE

To determine the influence of lipid concentration, lipid particle size, and total abdominal fat (TAF) on postprandial lipemic response (PPLr) in persons with spinal cord injury (SCI).

METHODS

Thirty-five persons with SCI (17 paraplegia, 18 tetraplegia) and 18 able-bodied (AB) individuals participated. Following a 10-hour fast, blood was drawn for lipids, apolipoprotein (apo) A1 and B concentrations, and low-density (LSP) and high-density (HSP) lipoprotein particle sizes. A high-fat milkshake was consumed (∼1.3 g fat/kg). Blood was drawn at 2, 4, and 6 hours to determine PPLr, (triglyceride (TG) area under the curve). TAF and visceral (VF) fat were measured by ultrasonography; total body fat (TBF) by dual-energy X-ray absorptiometry. Differences between the groups were determined by independent sample t-tests. Pearson correlation coefficients determined the relationship among PPLr and lipids, and TAF.

RESULTS

There were no significant differences in fasting TG, low-density lipoprotein (LDL), apoB, TAF, or PPLr values between the groups. In SCI, PPLr significantly correlated with: apoB (r = 0.63, P < 0.01, LSP (r = 0.57, P < 0.01), and TAF (r = 0.36, P < 0.01). After controlling for age and duration of injury, PPLr significantly correlated with apoB (r = 0.66, P = 0.001), TBF (r = 0.45, P = 0.03), VF (r = 0.66, P = 0.02), and TAF (r = 0.56, P = 0.007).

CONCLUSIONS

Although concentrations of LDL cholesterol and apoB were not different between SCI and AB groups, LSP, apoB, and TAF correlated with PPLr in persons with SCI. ApoB was associated with a greater PPLr in those with motor complete SCI, after controlling for age and duration of injury.

Hypertriglyceridemia is an independent risk factor for coronary artery disease (CAD) and is also commonly associated with other coronary risk factors, ie, small, dense low-density lipoprotein (LDL) particles and low plasma levels of high-density lipoprotein cholesterol (HDL-C). Dietary fat restriction is recommended for the prevention of nutrition-related cancers. Low-fat, high-carbohydrate intake can increase plasma triglyceride (TG) and decrease HDL-C. In general, plasma TG levels are inversely related to the particle size of LDL. We investigated the effects of dietary fat restriction on the concentration and particle size of plasma lipoproteins in 14 healthy postmenopausal women (aged 61 +/- 11 years). During a 4-month period of eucaloric controlled feeding, dietary fat was reduced stepwise from a habitual intake of 33% +/- 8% to 23% and then to 14% of daily energy. Changes in the plasma lipid level and particle size of very-low-density lipoprotein (VLDL), LDL, and HDL were determined at the end of each dietary phase. Increasing carbohydrate intake without weight loss was associated with an increase in plasma TG (1.86 +/- 0.30 v 2.47 +/- 0.37 mmol/L) and decreases in total cholesterol (5.82 +/- 0.25 v 5.40 +/- 0.21 mmol/L), LDL-C (3.07 +/- 0.18 v 2.61 +/- 0.21 mmol/L), HDL-C (1.42 +/- 0.1 v 1.24 +/- 0.1 mmol/L), and apolipoprotein (apo) A1 (5.14 +/- 0.25 v 4.61 +/- 0.36 mmol/L), whereas plasma apo B did not change. The particle size of VLDL increased (42.7 +/- 1.4 v 47.0 +/- 0.9 nm). However, there was no change in either LDL (25.1 +/- 0.2 v 25.3 +/- 0.2 nm) or HDL particle size. Although at each level of dietary fat intake LDL particle size correlated inversely with plasma TG and apo B, there was no relationship between the increase in plasma TG and LDL particle size. These results show that hypertriglyceridemia caused by a eucaloric high-carbohydrate intake is not associated with a decrease in LDL particle size. Therefore, carbohydrate-induced hypertriglyceridemia may not have the same atherogenic potential as genetic hypertriglyceridemias.

High-density lipoproteins (HDL) exert anti-atherosclerotic effects via reverse cholesterol transport, yet this salutary property is impaired in the setting of inflammation. GlycA, a novel integrated glycosylation marker of five acute phase reactants, is linked to cardiovascular (CV) events. We assessed the hypothesis that GlycA is associated with measures of impaired HDL function and that dysfunctional HDL may contribute to the association between GlycA and incident CV events. Baseline measurements of HDL cholesterol (HDL-C), HDL particle concentration (HDL-P), apoliprotein A1 (Apo A1), cholesterol efflux capacity, GlycA and high-sensitivity C-reactive protein (hs-CRP) were obtained from the Dallas Heart Study, a multi-ethnic cohort of 2643 adults (median 43 years old; 56% women, 50% black) without cardiovascular disease (CVD). GlycA was derived from nuclear magnetic resonance imaging. Participants were followed for first nonfatal MI, nonfatal stroke, coronary revascularization, or CV death over a median of 12.4 years (n = 197). The correlation between GlycA and hs-CRP was 0.58 (p < 0.0001). In multivariate models with HDL-C, GlycA was directly associated with HDL-P and Apo A1 and inversely associated with cholesterol efflux (standardized beta estimates: 0.08, 0.29, -0.06, respectively; all p ≤ 0.0004) GlycA was directly associated with incident CV events (adjusted hazard ratio (HR) for Q4 vs. Q1: 3.33, 95% confidence interval (CI) 1.99, 5.57). Adjustment for cholesterol efflux mildly attenuated this association (HR for Q4 vs. Q1: 3.00, 95% CI 1.75 to 5.13). In a multi-ethnic cohort, worsening inflammation, as reflected by higher GlycA levels, is associated with higher HDL-P and lower cholesterol efflux. Impaired cholesterol efflux likely explains some of the association between GlycA and incident CV events. Further studies are warranted to investigate the impact of inflammation on HDL function and CV disease.

BACKGROUND

HDL cell cholesterol efflux capacity has been documented as superior to HDL cholesterol (HDL-C) in predicting cardiovascular disease risk. HDL functions relate to its composition. Compositional assays are easier to perform and standardize than functional tests and are more practical for routine testing. Our goal was to compare measurements of HDL particles by 5 different separation methods.

METHODS

HDL subfractions were measured in 98 samples using vertical auto profiling (VAP), ion mobility (IM), nuclear magnetic resonance (NMR), native 2-dimensional gel electrophoresis (2D-PAGE), and pre-β1-ELISA. VAP measured cholesterol in large HDL2 and small HDL3; IM measured particle number directly in large, intermediate, and small HDL particles; NMR measured lipid signals in large, medium, and small HDL; 2D-PAGE measured apolipoprotein (apo) A-I in large (α1), medium (α2), small (α3-4), and pre-β1 HDL particles; and ELISA measured apoA-I in pre-β1-HDL. The data were normalized and compared using Passing-Bablok, Lin concordance, and Bland-Altman plot analyses.

RESULTS

With decreasing HDL-C concentration, NMR measured a gradually lower percentage of large HDL, compared with IM, VAP, and 2D-PAGE. In the lowest HDL-C tertile, NMR measured 8% of large HDL, compared with IM, 22%; VAP, 20%; and 2D-PAGE, 18%. There was strong discordance between 2D-PAGE and NMR in measuring medium HDL (R2 = 0.356; rc = 0.042) and small HDL (R2 = 0.376; rc = 0.040). The 2D-PAGE assay measured a significantly higher apoA-I concentration in pre-β1-HDL than the pre-β1-ELISA (9.8 vs 1.6 mg/dL; R2 = 0.246; rc = 0.130).

CONCLUSIONS

NMR agreed poorly with the other methods in measuring large HDL, particularly in low HDL-C individuals. Similarly, there was strong discordance in pre-β1-HDL measurements between the ELISA and 2D-PAGE assays.

OBJECTIVE

The present study is on line with our previous studies evaluating the influence of ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms on the lipid variables of Greek student-nurses. The current study was undertaken to (1) estimate the influence of variant(s) such as rs2066715 (V825I), R219K, R1587K, I883M of ABCA1 gene on lipid variables and (2) evaluate the effect of all four ABCA1 polymorphisms on common demographic parameters.

METHODS

The study population involved 432 unrelated nurses (86 men) who were genotyped for ABCA1 polymorphisms and correlated according to lipid variables [total cholesterol (TC), triglycerides (TGs), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) A] and demographic parameters (age, gender, BMI, waist circumference).

RESULTS

According to lipid variables concentration there was no difference between genotypes and alleles of V825I, R219K and I883M polymorphisms. The LDL-C concentration was 13% lower in RR compared with RK genotype (100.7 vs. 113.9 mg/dl, p=0.013) of R1587K gene polymorphism. In regression analysis the effects of age, gender and only R1587K gene polymorphism on LDL-C concentrations were proved significant. Additionally, LDL-C was increased (by 1.29 mg/dl on average) by every year of increase of age. Moreover, females had lower LDL-C concentrations as compared with males.

CONCLUSIONS

Findings suggested that only R1587K polymorphism of ABCA1 gene was associated with lipid variables, age, and gender of Greek nurses. These findings may be helpful in assessing the risk factors for premature coronary heart disease and distinct individuals with lower/higher atherosclerotic burden.

Beta-hydroxyacid dehydrogenase (β-HAD) genes have been identified in all sequenced genomes of eukaryotes and prokaryotes. Their gene products catalyze the NAD(+)- or NADP(+)-dependent oxidation of various β-hydroxy acid substrates into their corresponding semialdehyde. In many fungal and bacterial genomes, multiple β-HAD genes are observed leading to the hypothesis that these gene products may have unique, uncharacterized metabolic roles specific to their species. The genomes of Geobacter sulfurreducens and Geobacter metallireducens each contain two potential β-HAD genes. The protein sequences of one pair of these genes, Gs-βHAD (Q74DE4) and Gm-βHAD (Q39R98), have 65% sequence identity and 77% sequence similarity with each other. Both proteins are observed to reduce succinic semialdehyde, a 4-carbon substrate instead of the typical β-HAD 3-carbon substrate, to γ-hydroxybutyric acid. To further explore the structural and functional characteristics of these two β-HADs with a less frequently observed substrate specificity, crystal structures for Gs-βHAD and Gm-βHAD in complex with NADP(+) were determined to a resolution of 1.89 Å and 2.07 Å, respectively. The structures of both proteins are similar, composed of 14 α-helices and nine β-strands organized into two domains. Domain 1 (1-165) adopts a typical Rossmann fold composed of two α/β units: a six-strand parallel β-sheet surrounded by six α-helices (α1-α6) followed by a mixed three-strand β-sheet surrounded by two α-helices (α7 and α8). Domain 2 (166-287) is composed of a bundle of seven α-helices (α9-α1apo-NADP(+) and apo-substrate bound state suggests that NADP(+) binding effects a rigid body rotation between Domains 1 and 2. Bound near the Substrate-Binding and Catalysis Regions in two of the eight protomers in the asymmetric unit of Gm-βHAD is a glycerol molecule that may mimic features of bound biological substrates.

Myocardial infarction (MI) is a leading major health problem with increased morbidity and mortality worldwide. The present study investigates isoproterenol (ISO) induced MI and the beneficial role of Aegle marmelos fruit extract (AMFE) in rats. Our results indicated the significant augmentation of plasma nitric oxide (NOx) levels, C-reactive protein (CRP), homocysteine, apolipoprotein B (apo-B), cardiac tissue lipid peroxidation and liver 3-hydroxy-3 methyl glutaryl CoA (HMG-CoA) reductase activity in ISO treated rats (85mg/kg b.wt) with a concomitant decrease in plasma apolipoprotein A1 (apo-A), lipase activity, paraoxonase-1 activity and cardiac tissue taurine levels when compared with controls. However, pretreatment of ISO administered rats with AMFE (150mg/kg b.wt/day for 45 days) markedly brought the observed alterations toward near normal level indicating its protective role against MI. Further, we have extended our studies to study the interaction of important phytocompounds, marmesin, marmin, umbelliferone and impertonin, present in AMFE with key enzymes, HMG-CoA reductase, iNOS, lipoprotein lipase and paraoxonase using AutoDock4. Molecular docking analysis indicated that HMG-CoA reductase, inducible nitric oxide synthase (iNOS) and lipoprotein lipase formed a strong enzyme ligand complex with impertonin. While the marmesin showed strong interaction with paraoxonase enzyme. In conclusion, our results suggest that AMFE acts as a strong protective agent against ISO-induced MI, and the bioactive compounds are responsible for this protective action which is confirmed by molecular docking studies.

We have assessed early indicators of arterial disease in patients with glycogen storage disease type III (GSD III; McKusick 232400), investigating the plasma lipid and lipoprotein profile and endothelial function. Eleven patients, aged 10-39 years, were recruited together with age-, sex- and smoking status-matched controls. Brachial artery responses were assessed by high-resolution ultrasonographic measurement of the diameter of the brachial artery at baseline, after reactive hyperaemia and in response to sublingual glyceryl trinitrate (GTN). The means of plasma cholesterol (total and HDL and LDL subfractions), triglycerides, apo-A1, apo-B, Lp(a) and the atherogenic index were similar in both groups. Cardiac troponin I was below the lower limits of detection (< 0.03 g/L) in all subjects. The GSD III patients had similar body mass index (BMI) and brachial artery diameter to the control group (BMI 22.6 +/- 5.6 vs 22.3 +/- 5 kg/m2; brachial artery diameter 3.4 +/- 0.5 vs 3 +/- 0.7 mm). When compared to the baseline diameter, the maximal flow-mediated dilatation of the brachial artery after reactive hyperaemia was 9.3% +/- 2.1% (mean +/- SD) in the GSD III patients and 6.5% +/- 3.5% in the control group, a difference of 1.8% (95% CI 0.07% to 5.5%). The maximal dilatation of the brachial artery after GTN administration was 18.3% +/- 6.4% in the GSD III patients and 17.9% +/- 6.5% in the control group, a difference of 0.4% (95% CI-6.9% to 7.7%). In conclusion, we found no evidence of abnormal plasma lipid and lipoprotein profile or endothelial dysfunction in patients with GSD III. They are unlikely to be at increased risk of premature atherosclerosis.

Lipoprotein-associated phospholipase A₂ (Lp-PLA2) is a new specific vascular inflammation biomarker that is carried by the lipoproteins in the blood and plays a prominent role in the pathogenesis of atherosclerosis. Increased Lp-PLA2 levels and impaired Lp-PLA2 distribution across high-density lipoprotein (HDL) and non-HDL lipoproteins have been reported in diabetic patients, which is associated with the increase in cardiovascular disease (CVD) risk. This study is aimed at investigating the effect of alpha lipoic acid (ALA), as an antioxidant with potential cardioprotective properties, on the Lp-PLA2 mass and its distribution in diabetic patients. In a double-blind, randomized, placebo-controlled clinical trial, seventy diabetic patients were randomly allocated to ALA (1200 mg ALA as two 600 mg capsules/day) and placebo (two maltodextrin capsules/day) groups. The serum levels of total Lp-PLA2 mass, HDL-Lp-PLA2, oxidized low-density lipoproteins (ox-LDL), apolipoprotein A1 (apo A1), lipid profiles, fasting blood sugar (FBS), and insulin were measured, and apolipoprotein B- (apoB-) associated Lp-PLA2 and homeostasis model of assessment index (HOMA-IR) were calculated at the baseline and after 8 weeks of intervention. ALA significantly decreased the ox-LDL, total Lp-PLA2 mass, apoB-associated Lp-PLA2, and percent of apoB-associated Lp-PLA2 and triglyceride and increased the percent of HDL-Lp-PLA2 compared with the placebo group but had no significant effect on HDL-Lp-PLA2 mass, apo A1, lipid profiles, and glycemic indices. There was a positive correlation between the reduction in the ox-LDL level and total Lp-PLA2 mass in the ALA group. In conclusion, ALA may decrease the CVD risk by reducing the ox-LDL and Lp-PLA2 mass and improving the Lp-PLA2 distribution among lipoproteins in type 2 diabetic patients.

Dietary guidelines for the treatment of type 2 diabetes advocate the regular consumption of nuts and seeds. Key lipid abnormalities associated with diabetes include raised LDL-C, VLDL-C, and TAG concentrations and decreased concentrations of HDL-C. The fatty acid profiles of nuts and seeds differ and may potentially influence lipid outcomes in people with diabetes differently. To examine the effects of nut or seed consumption on lipid and lipoprotein markers of cardiovascular disease (CVD), we added almonds (AD) or sunflower kernels (SKD) to a recommended diet in a randomised crossover feeding study. Twenty-two postmenopausal women with type 2 diabetes consumed personalised diets, with the addition of 30 g/d of either almonds or sunflower kernels. All food was supplied for two periods of three weeks, separated by a four-week washout. There was a significant reduction in high-density lipoprotein cholesterol (HDL-C), triacylglycerol (TAG), and apolipoprotein (apo) A1 and B100 on the SKD compared to the AD. Total (TC) and low density lipoprotein cholesterol (LDL-C) decreased significantly on both diets from baseline, with no difference between diets. A diet with the addition of either almonds or sunflower kernels has clinically beneficial effects on lipid- and lipoprotein-mediated CVD risk.

The human circulation contains cell-free DNA and non-coding microRNA (miRNA). Less is known about the presence of messenger RNA (mRNA). This report profiles the human circulating mRNA transcriptome in people with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) to determine whether mRNA analytes can be used as biomarkers of liver disease. Using RNAseq and RT-qPCR, we investigate circulating mRNA in plasma from HCC and LC patients and demonstrate detection of transcripts representing more than 19,000 different protein coding genes. Remarkably, the circulating mRNA expression levels were similar from person to person over the 21 individuals whose samples were analyzed by RNAseq. Liver derived circulating transcripts such as albumin (ALB), apolipoprotein (APO) A1, A2 & H, serpin A1 & E1, ferritin light chain (FTL) and fibrinogen like 1 (FGL1) were significantly upregulated in HCC patient samples. Higher levels of some of these liver-specific transcripts in the plasma of HCC patients were confirmed by RT-qPCR in another cohort of 20 individuals. Several less abundant circulating transcripts associated with cancer were detected in most HCC samples, but not in healthy subjects. Liver specificity of circulating transcripts was confirmed by investigating their expression in HCC tumor and liver cancer cell lines. Liver specific mRNA sequences in the plasma were predominantly present outside circulating extracellular vesicles. Conclusions: The circulating "mRNA" transcriptome is remarkably consistent in diversity and expression from person to person. Detection of transcripts corresponding to disease selective polypeptides suggests the possibility that circulating mRNA can work as a biomarker analyte for cancer detection.

Keywords: biomarkers; circulating transcripts; extracellular vesicles; hepatocellular carcinoma; liver cirrhosis.

OBJECTIVE

Diabetic dyslipidemia is an important risk factor for the development of macrovascular complications. Recent clinical trials suggest that diabetics treated with glucagon-like peptide-1 (GLP-1) have normalized lipid levels, including an increase in plasma high-density lipoprotein cholesterol (HDLc) levels.

METHODS

To determine if GLP-1 (7-36 amide) and the GLP-1-like insulinotropic peptide exendin-4 regulate expression of apolipoprotein A-I (apo A-I), the primary anti-atherogenic component of high-density lipoprotein (HDL), HepG2 hepatocytes and Caco-2 intestinal cells, representative of tissues that express the majority of apo A-I, were treated with increasing amounts of each peptide and apo A-I gene expression was measured in the conditioned medium.

RESULTS

Apo A-I secretion increased in both GLP-1 and exendin-4-treated HepG2, but not Caco-2 cells, and this was accompanied by similar changes in apo A-I mRNA levels and apo A-I promoter activity. Induction of apo A-I promoter activity by GLP-1 and exendin-4 required an SP1-responsive element. Hepatic ATP binding cassette protein A1 (ABCA1) expression, but not scavenger receptor class B type1 receptor expression was also induced by GLP-1 and exendin-4.

CONCLUSIONS

These results suggest that GLP-1- and exendin-4-mediated changes in HDLc are likely due to changes in hepatic expression of apo A-I and ABCA1.

BACKGROUND

The purpose of gene expression analysis is to look for the association between regulation of gene expression levels and phenotypic variations. This association based on gene expression profile has been used to determine whether the induction/repression of genes correspond to phenotypic variations including cell regulations, clinical diagnoses and drug development. Statistical analyses on microarray data have been developed to resolve gene selection issue. However, these methods do not inform us of causality between genes and phenotypes. In this paper, we propose the dynamic association rule algorithm (DAR algorithm) which helps ones to efficiently select a subset of significant genes for subsequent analysis. The DAR algorithm is based on association rules from market basket analysis in marketing. We first propose a statistical way, based on constructing a one-sided confidence interval and hypothesis testing, to determine if an association rule is meaningful. Based on the proposed statistical method, we then developed the DAR algorithm for gene expression data analysis. The method was applied to analyze four microarray datasets and one Next Generation Sequencing (NGS) dataset: the Mice Apo A1 dataset, the whole genome expression dataset of mouse embryonic stem cells, expression profiling of the bone marrow of Leukemia patients, Microarray Quality Control (MAQC) data set and the RNA-seq dataset of a mouse genomic imprinting study. A comparison of the proposed method with the t-test on the expression profiling of the bone marrow of Leukemia patients was conducted.

RESULTS

We developed a statistical way, based on the concept of confidence interval, to determine the minimum support and minimum confidence for mining association relationships among items. With the minimum support and minimum confidence, one can find significant rules in one single step. The DAR algorithm was then developed for gene expression data analysis. Four gene expression datasets showed that the proposed DAR algorithm not only was able to identify a set of differentially expressed genes that largely agreed with that of other methods, but also provided an efficient and accurate way to find influential genes of a disease.

CONCLUSIONS

In the paper, the well-established association rule mining technique from marketing has been successfully modified to determine the minimum support and minimum confidence based on the concept of confidence interval and hypothesis testing. It can be applied to gene expression data to mine significant association rules between gene regulation and phenotype. The proposed DAR algorithm provides an efficient way to find influential genes that underlie the phenotypic variance.

BACKGROUND

Cardiovascular disease (CVD) is the major cause of mortality and morbidity of hemodialysis (HD) and peritoneal dialysis (CAPD) patients. We aimed to investigate the cardiovascular risk factors and their correlation with CVD in groups of HD and CAPD patients.

METHODS

Thirty HD patients, 30 CAPD patients and 30 healthy controls were included in the study. Apolipoprotein A-l (apo A-l), apolipoprotein B (apo B), apolipoprotein(a) [Lp(a)] and high-sensitivity CRP (hs-CRP) were measured with a Beckman Coulter nephelometer, and homocysteine (Hcy) was determined with an Agilent HPLC analyzer. Lipid profile was determined with a Synchron LX 20 Pro analyzer.

RESULTS

Hcy levels were 41.9+/-19.4, 41.8+/-38.5 and 9.3+/-3.5 micromol/L; Lp(a) levels were 325+/-315, 431+/-367 and 130+/-97 mg/L; hs-CRP levels were 3.78+/-3.21, 4.34+/-3.39 and 2.07+/-1.67 mg/L; apo A1/apo B ratios were 1.46+/-0.6, 1.36+/-0.5 and 1.80+/-0.59; total cholesterol levels were 3.56+/-0.7, 4.84+/-1.1 and 4.39+/-0.5 mmol/L; triglycerides were 1.44+/-0.5, 1.60+/-0.8 and 0.85+/-0.5 mmol/L in the HD, CAPD and control groups, respectively.

CONCLUSIONS

HD and CAPD patients had higher Hcy, hs-CRP and Lp(a) levels and lower apo A/B ratios than controls. There was no significant difference between the HD and CAPD groups. Hypertension, age and hs-CRP showed a positive correlation with CVD.

Physical exercise may in vivo promote an increase of free radical formation. Low-density lipoproteins (LDL) are highly susceptible to oxidation, probably because of their high polyunsaturated fatty acid content, since lipid oxidation is an important factor in the genesis and development of atherosclerosis. The aim of the present study is to evaluate the effect in a group of adolescent gymnasts, of intense and regular physical exercise on lipid profile and redox status.

METHODS

All members of the Portuguese National Team of Rhythm Gymnastics (1996) (n = 20).

METHODS

1. Clinical evaluation 1.1 Anthropometric evaluation: weight, height, triceps, biceps, subscapular and supra- and supra-iliac skinfolds. NCHS were used as the standard of reference for weight and height, and Frisancho for the sum of skinfolds; 1.2. Evaluation of nutritional status (Quetelet body mass index) and body composition (Durnin and Siri). 2. Evaluation of biological parameters: a blood sample was collected after 12 hours fasting and 24 hours detraining, to evaluate: 2.1 Lipid profile: total cholesterol, high (HDL) and low (LDL) density lipoproteins, triglycerides, apolipoproteins A1 and B, were measured using internationally recommended laboratory methods; 2.2. Plasma trace elements: zinc, copper and selenium, by atomic absorption; 2.3 Red blood cell enzymes; transmembranar reductase (TMR), metahemoglobin reductase (MethaHbRed) and acid phosphatase, by spectrophotometry; 2.4. Redox status: MDA and MDA-LDL were evaluated by spectrophotometry. 3. Evaluation of eating habits: 24 hr recall.

RESULTS

Chronological age is 14.3 +/- 1.7 years. Nutritional assessment shows a mean value for height near the 50th percentile (99% +/- 3.8), and low mean values respectively for BMI (89.3% +/- 9) and sum of triceps and subscapular skinfolds (51.9% +/- 14). Study of lipid profile shows low mean values for total cholesterol (162.3 mg/dl +/- 27.7) LDL-cholesterol (87.6 mg/dl +/- 22.6) and Apo B (64.4 mg/dl +/- 11.5), but high values for HDL-cholesterol (61.3 mg/dl +/- 14.5) and Apo A1 (173.1 mg/dl +/- 25.1). We observe higher values for total cholesterol and LDL-cholesterol in those with lower Cu plasmatic levels. We also observe a negative significative correlation between MDA-LDL and Zn (r = -0.469), Cu (r = -0.524) and RTM (r = -0.608).

CONCLUSIONS

The AA concluded that in this group of gymnasts intense physical exercise induces, a favorable lipid profile, but a clear susceptibility to LDL peroxidation in those with lower plasma Cu and Zn values. It is possible that the negative correlation observed between MDA-LDL and TMR is caused by higher consumption of TMR induced by the action of exercise on the oxidative system.

Olive oil, the principal fat of Mediterranean Diet, is known to improve several cardiovascular risk factors at relatively high doses together with intensive modifications of dietary habits. Since this is hard to obtain in the long term, an intervention with encapsulated oil supplements might be more feasible. Aim of this preliminary study was to investigate the effects of the supplementation of a moderate amount of encapsulated extra virgin olive oil vs a lower dose in mildly hypercholesterolemic subjects, as part of their established diet, on blood lipid profile. A prospective randomized study was performed. Thirty-four mildly hypercholesterolemic subjects [age, mean+/-SD: 46+/-7 yr; total cholesterol (TC): 235+/-28 mg/dl] were randomly assigned to receive 2 g (group A) or 4 g (group B) per os of extra-virgin olive oil for 3 months. TC, triglycerides (TG), LDL cholesterol, HDL cholesterol, apolipoprotein A1 (Apo-AI), apolipoprotein B (Apo-B), and atherogenic index of plasma (AIP) were evaluated at the beginning and at the end of the study. In group B, but not in group A, a significant reduction of Apo-B values (7%) was observed; TG concentrations showed a trend towards reduction and Apo-A1 values a trend towards increase (9%). A significant decrease in Apo-B/Apo-A1 ratio (p<0.01) was also observed in group B. Extra virgin olive oil supplementation significantly decreased AIP from baseline in group B (p<0.05). The results of the present study seem to suggest that the daily supplementation, on top of the normal diet, of at least 4 g of extra virgin olive oil, in mildly hypercholesterolemic subjects, is associated to favorable modifications of the plasmatic lipid profile.

Both exercise training and weight loss reduce cardiovascular risk, but the independent importance of the two strategies is unclear. We aimed to investigate independent and combined effects of exercise training and weight loss on lipoproteins and dyslipidemia in overweight sedentary men. Sixty individuals were randomized to 12 wk of endurance training (T), energy-reduced diet (D), training and energy increased diet (T-iD), or control (C). Equal energetic deficits (-600 kcal/day) were prescribed by exercise for T and caloric restriction for D. T-iD completed similar exercise but remained in energy balance due to the dietary replacement of calories expended during exercise. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo)B and A1, pre-β-HDL, and susceptibility of LDL-C to oxidation were measured. Body weight was reduced similarly between T (-5.9 ± 0.7 kg) and D (-5.2 ± 0.8 kg), whereas T-iD (-1.0 ± 0.5 kg) and C (0.1 ± 0.6 kg) remained weight stable. Plasma TC, LDL-C, and apolipoprotein B were reduced in T compared with C ( P < 0.001 for both), but this was not observed for D ( P>> 0.17). Changes in TC and LDL-C were associated with changes in body weight and body fat ( P < 0.01). In T-iD, increases in HDL-C and apolipoprotein A1 were observed ( P < 0.001). In conclusion, an exercise-induced decline in body weight reduces proatherogenic apoB-containing lipoproteins, whereas exercise compensated by energy intake increases the key component of reverse cholesterol transport, i.e., apoA1-containing HDL-C. NEW & NOTEWORTHY Exercise has additive effects in lowering plasma lipoprotein particles to diet-induced weight loss in individuals with increased cardiovascular risk. In the present study, we investigated whether training per se would have beneficial cardiovascular effects. We found that 3 mo of exercise-induced weight loss reduced proatherogenic lipoproteins, whereas endurance training without weight loss improved factors involved in reverse cholesterol transport in a group of overweight sedentary men.

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis and results in high morbidity and mortality in children. Diagnostic delay contributes to the poor outcome. There is an urgent need for new tools for the rapid diagnosis of TBM, especially in children. Methods: We collected serum samples from children in whom TBM was suspected at a tertiary hospital in Cape Town, South Africa. Children were subsequently classified as having TBM or no TBM using a published uniform research case-definition. Using a multiplex cytokine array platform, we investigated the concentrations of serum biomarkers comprising biomarkers that were previously found to be of value in the diagnosis of adult pulmonary TB (CRP, SAA, CFH, IFN-γ, IP-10, Apo-AI, and transthyretin) plus other potentially useful host biomarkers as diagnostic candidates for TBM. Findings: Out of 47 children included in the study, 23 (48.9%) had a final diagnosis of TBM and six were HIV infected. A modified version of the adult 7-marker biosignature in which transthyretin was replaced by NCAM1, diagnosed TBM in children with AUC of 0.80 (95% CI, 0.67-0.92), sensitivity of 73.9% (95% CI, 51.6-89.8%) and specificity of 66.7% (95% CI, 44.7-84.4%), with the other six proteins in the signature (CRP, IFN-γ, IP-10, CFH, Apo-A1, and SAA) only achieving and AUC of 0.75 (95% CI, 0.61-0.90) when used in combination. A new childhood TBM specific 3-marker biosignature (adipsin, Aβ42, and IL-10) showed potential in the diagnosis of TBM, with AUC of 0.84 (95% CI, 0.73-0.96), sensitivity of 82.6% (95 CI, 61.2-95.0%) and specificity of 75.0% (95% CI, 53.3-90.2%) after leave-one-out cross validation. Conclusion: A previously described adult 7-marker serum protein biosignature showed potential in the diagnosis of TBM in children. However, a smaller childhood TBM-specific 3-marker signature demonstrated improved performance characteristics. Our data indicates that blood-based biomarkers may be useful in the diagnosis of childhood TBM and requires further validation in larger cohort studies.