ALBERT

Description: Background: Dyslipidemia is a key independent modifiable risk factor for Cardiovascular Disease, which is a leading contributor to morbidity and mortality in most developed and developing countries. This study was designed to investigate the current epidemiological features of dyslipidemia among adults in rural China. Methods: Between January 2013 and August 2013, we conducted a cross-sectional study involving 11,956 subjects with age 〉=35 years in a general Chinese population. Permanent residents of the population were invited to participate in the study and the response rate was at 85.3%. Dyslipidemia was identified based on serum lipids levels following the standards proposed by the National Cholesterol Education Program Adult Treatment Panel III. Multivariate logistic regression analysis was used to evaluate the associated risk factors for dyslipidemia. Results: Within the study population, 16.4% had high TC, 13.8% had low HDL-C, 7.6% had high LDL-C, and 17.3% had high TG concentrations. Prevalence of lipid abnormality (including borderline dyslipidemia and dyslipidemia) was 47.8%, 13.8%, 25.7% and 30.7% for TC, HDL-C, LDL-C and TG, respectively. Detailed analysis indicated that 36.9% of this population had at least one type of dyslipidemia and 64.4% had at least one type of abnormal lipid concentration. Thus, this study observed an alarmingly higher prevalence of lipid abnormality, in a relatively large population, compared to previous studies. Further, we determined that not all of the risk factors studied, including age, gender, hypertension, diabetes mellitus, obesity, smoking, drinking, education level, marital status, and family income, influenced dyslipidemia to the same extent. Conclusions: Our present study, in a population of 11,956 adults in Liaoning Providence, demonstrated a very high prevalence of dyslipidemia, which represented an alarming rise since the publication of our previous study and other similar studies around the world, which report lower levels. We also examined various risk factors for dyslipidemia, many of which are modifiable risk factors for Cardiovascular Disease (CVD), to provide a comprehensive view that will help in designing strategies to slow the rapid spread and promote effective measures to treat dyslipidemia. Our ultimate goal is to prevent the increasing prevalence of lipid abnormality and reduce the burden of CVD in rural China.

Description: Background: Recent studies have demonstrated a relationship between fructose consumption and risk of developing metabolic syndrome. Mechanisms by which dietary fructose mediates metabolic changes are poorly understood. This study compared the effects of fructose, glucose and sucrose consumption on post-postprandial lipemia and low grade inflammation measured as hs-CRP. Methods: This was a randomized, single blinded, cross-over trial involving healthy subjects (n = 14). After an overnight fast, participants were given one of 3 different isocaloric drinks, containing 50 g of either fructose or glucose or sucrose dissolved in water. Blood samples were collected at baseline, 30, 60 and 120 minutes post intervention for the analysis of blood lipids, glucose, insulin and high sensitivity C-reactive protein (hs-CRP). Results: Glucose and sucrose supplementation initially resulted in a significant increase in glucose and insulin levels compared to fructose supplementation and returned to near baseline values within 2 hours. Change in plasma cholesterol, LDL and HDL-cholesterol (measured as area under curve, AUC) was significantly higher when participants consumed fructose compared with glucose or sucrose (P 〈 0.05). AUC for plasma triglyceride levels however remained unchanged regardless of the dietary intervention. Change in AUC for hs-CRP was also significantly higher in subjects consuming fructose compared with those consuming glucose (P 〈 0.05), but not sucrose (P = 0.07). Conclusion: This study demonstrates that fructose as a sole source of energy modulates plasma lipids and hsCRP levels in healthy individuals. The significance of increase in HDL-cholesterol with a concurrent increase in LDL-cholesterol and elevated hs-CRP levels remains to be delineated when considering health effects of feeding fructose-rich diets.Registration number for clinical trials: ACTRN12614000431628

Description: Background: Comparable to commercial expensive high-fat diets, cholesterol-cholate-butterfat (CCB) diet has also been used to induce hyperlipidemia in rats. Our objective was to explore its influence on multiple organs. Consequence of fasting was also analysed. Methods: Rats in groups 1 and 2 received normal diet (ND) whereas groups 3 and 4 received CCB-diet. Food was withdrawn daily for two hours from groups 2 (ND-F) and 4 (CCB-F). Blood was collected at fourth and sixth week for biochemical estimation; Morris water maze was done in the sixth week for learning ability and memory; after which aortae were isolated for vascular reactivity. Results: Apart from hyperlipidemia, CCB also induced hyperglycemia with marked increase in hepatic enzymes: gamma-glutamyl transferase (GGT), alanine and aspartate aminotransferase (ALT and AST); and vascular biomarkers: uric acid (UA), phosphorus and alkaline phosphatase (ALP). Isolated aortae, pre-contracted with phenylephrine, were less responsive to acetylcholine indicating endothelial dysfunction - serum nitric oxide (NO) production was limited with subsequent inhibition of endothelial NO synthase. CCB diet also compromised learning ability. CCB-coupled fasting potentiated hyperlipidemia but prevented memory-loss. Conclusion: We introduce CCB-diet for multi-organ dysfunction in rats, and propose its use for research on cardiovascular diseases and associated manifestations involving immense interplay of integrated pathways.

Description: Background: The disorder of triglyceride (TG) metabolism leading to hypertriglyceridemia is an independent risk factor for coronary artery disease (CAD). Variants in the apolipoprotein C3 (APOC3) gene were found to be associated with elevated TG levels. The purpose of this study was to investigate the effect of two polymorphisms (1100 C/T and 3238 C/G) of APOC3 on plasma lipid and risk of CAD in a Chinese population. Methods: The study population consisted of 600 patients with CAD and 600 age- and gender-matched controls. The APOC3 gene polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Patients with CAD had a significantly higher frequency of APOC3 3238 GG genotype [odds ratio (OR) =1.64, 95% confidence interval (CI) =1.10, 2.43; P = 0.01] and APOC3 3238 G allele (OR =1.27, 95% CI =1.04, 1.55; P = 0.02) than controls. The findings are still emphatic by the Bonferroni correction. When stratifying by hyperlipidemia, CAD patients with hyperlipidemia had a significantly higher frequency of APOC3 3238 GG genotype (OR =1.73, 95% CI =1.13, 2.64; P = 0.01) than without hyperlipidemia. The APOC3 3238 G allele was significantly associated with increasing plasma TG levels and very-low-density lipoprotein cholesterol (VLDL-C) levels both in cases and controls (P 〈 0.001). Conclusions: The APOC3 3238 G allele might contribute to an increased risk of CAD as a result of its effect on TG and VLDL-C metabolism.

Description: Background: This study investigated anti-obesity effects of seven different solvent (n-hexane, toluene, dicholoromethane, ethyl acetate, absolute methanol, 80% methanol and deionized water) extracts of germinated brown rice (GBR) on pancreatic lipase activity, adipogenesis and lipolysis in 3T3-L1 adipocytes. Methods: GBR were extracted separately by employing different solvents with ultrasound-assisted. Pancreatic lipase activity was determined spectrophotometrically by measuring the hydrolysis of p-nitrophenyl butyrate (p-NPB) to p-nitrophenol at 405nm. Adipogenesis and lipolysis were assayed in fully differentiated 3T3-L1 adipocytes by using Oil Red O staining and glycerol release measurement. Results: GBR extract using hexane showed the highest inhibitory effect (13.58 +/- 0.860%) at concentration of 200mug/ml followed by hexane extract at 100mug/ml (9.98 +/- 1.048%) while ethyl acetate extract showed the lowest (2.62 +/- 0.677%) at concentration of 200mug/ml on pancreatic lipase activity. Water extract at 300mug/ml showed 61.55 +/- 3.824% of Oil Red O staining material (OROSM), a marker of adipogenesis. It significantly decrease (p 〈 0.05) lipid accumulation than control (OROSM = 100%), follow by ethyl acetate extract at 300mug/ml (OROSM = 65.17 +/- 3.131%). All the GBR extracts induced lipolysis with 1.22-1.83 fold of greater glycerol release than control. Conclusions: GBR extracts especially the least polar and intermediate polar solvent extracts exhibited inhibitory effect on pancreatic lipase, decrease fat accumulation by adipocyte differentiation inhibition, and stimulate lipolysis on adipocytes. Therefore, GBR could be furthered study and developed as a functional food in helping the treatment and/or prevention of obesity.

Description: Background: Corn peptides (CPs) are a novel food prepared from corn gluten meal, which is a main by-product of the corn starch industry. Recently, significant beneficial effects of CPs on early alcoholic liver injury in rats and on acute alcoholic injury in mice were observed. To our knowledge, the present study is the first report showing that CPs supplementation has beneficial effects on lipid profile, oxidative stress and alcoholic liver injury in men with chronic alcohol consumption. Methods: A 9-week, randomized, double-blind, placebo-controlled study was conducted between September 2011 and August 2012 to assess the hepatoprotective effect of CPs. A total of 161 men were randomized to receive CPs (n = 53), whey protein (n = 54), or corn starch placebo (n = 54) at the same dose of 2 g twice daily. 146 participants completed the study. Serum lipid profile, serum markers of liver injury, oxidative stress and inflammation, and fatty liver based on the results of abdominal ultrasonography were assessed at the beginning and end of the intervention. Results: CPs supplementation (4 g/d) for 9 weeks significantly lowered serum levels or activities of total cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase, malondialdehyde and tumor necrosis factor-alpha, and significantly increased serum activities of superoxide dismutase and glutathione peroxidase, but the same dose of whey protein and corn starch (placebo) did not demonstrate these effects. Conclusions: Our results indicate that CPs may have protective effects on alcohol-induced liver damage via modulation of lipid metabolism and oxidative stress. CPs may potentially be used as a functional food for the management of alcoholic liver disease in subjects with chronic alcohol consumption.

Description: Background: Fish oil is a popular nutritional product consumed in Hong Kong. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the two main bioactive components responsible for the health benefits of fish oil. Market survey in Hong Kong demonstrated that various fish oil capsules with different origins and prices are sold simultaneously. However, these capsules are labelled with same ingredient levels, namely EPA 180 mg/g and DHA 120 mg/g. This situation makes the consumers very confused. To evaluate the quality of various fish oil capsules, a comparative analysis of the contents of EPA and DHA in fish oil is crucial. Methods: A gas chromatography-mass spectrometry (GC-MS) method was developed for identification and determination of EPA and DHA in fish oil capsules. A comprehensive validation of the developed method was conducted. Ten batches of fish oil capsules samples purchased from drugstores of Hong Kong were analyzed by using the developed method. Results: The present method presented good sensitivity, precision and accuracy. The limits of detection (LOD) for EPA and DHA were 0.08 ng and 0.21 ng, respectively. The relative standard deviation (RSD) values of EPA and DHA for precision tests were both less than 1.05%; and the recovery for accuracy test of EPA and DHA were 100.50% and 103.83%, respectively. In ten fish oil samples, the contents of EPA ranged from 39.52 mg/g to 509.16 mg/g, and the contents of DHA ranged from 35.14 mg/g to 645.70 mg/g. Conclusion: The present method is suitable for the quantitative analysis of EPA and DHA in fish oil capsules. There is a significant variation in the contents of the quantified components in fish oil samples, and there is not a linear relationship between price and contents of EPA and DHA. Strict supervision of the labelling of the fish oil capsules is urgently needed.

Description: Background: Cardiovascular diseases (CVD) and metabolic alterations are among the majors public health concern that have been reported in people living with HIV infections. Factors contributing to cardio metabolic syndrome in HIV include body fat distribution, dyslipidemia, insulin resistance, cardiovascular dysfunction and inflammation. To determine the effect of Spirulina platensis (Cyanobacteriaceae) supplementation versus local diet on lipid profile in HIV-infected antiretroviral-naive patients. Methods: A prospective single-blind, randomized, multicentre study was conducted from February 2010 to December 2012. A total of 320 HIV antiretroviral-naive patients were screened and 169 were recruited in this study. Patients were randomized and received either Spirulina supplementation combined with local diet (n = 82) or local diet only (n = 87). Age, weight, body mass index (BMI), lipid profile, CD4 count, and local food intake variables were assessed on three separate occasions (three, six and twelve months). Results: An average age of the patients was 35.6 +/- 9 years. The majority of participants were female 67.1%. Regarding the lipid profile, there is a significant increase in HDL-cholesterol and a significant decrease in total cholesterol, LDL-cholesterol and triglycerides in the group of patients who consumed Spirulina platensis. A change in the atherogenic index defined by the ratio CT/HDL-C substitutable by LDL-C/HDL-C and the TC/HDL decreased significantly from 10.83 at baseline to 2.22 after 12 months (p = 0.21 and p

Description: Background: To identify the chemical structure of Coreopsis tinctoria extracts and their effect and mechanism on reducing blood lipid in hyperlipemia mice. Methods: The flavonoids were extracted from Coreopsis tinctoria. The chemical structure was identified by HPLC. 59 mice were divided randomly into 5 groups. (group 1: normal diet control; group 2: hyperlipemia model; group 3: hyperlipemia mice treated with Coreopsis tinctoria, low dose 100 mg/kg; group 4: hyperlipemia mice treated with Coreopsis tinctoria high dose group 200 mg/kg; group 5 hyperlipemia mice treated with Fenofibrate. After 2 week of hyperlipid diet, the treatment of Coreopsis tinctoria and Fenofibrate were given for another 6 weeks with continuous hyperlipid diet. The TC, TG, HDL, histology, adipose differentiation-related protein (ADRP) expression in different groups were compared. Results: Compared with normal diet group, TC, TG in hyperlipemia model group increased ( P 〈 0. 01). After treatment with Coreopsis tinctoria low dose group, high dose group, TC of the hyperlipemia mice decreased (P 〈 0. 05) without increasing AST, ALT and ALP. Fenofibrate can also decrease TC and TG but increase AST, ALT and ALP. Expression of hepatic ADRP increased in hyperlipemia mice. Coreopsis tinctoria high dose group 200 mg/kg can inhibit ADRP as Fenofibrate does. Conclusion: The flavonoids from Coreopsis tinctoria extracts can reduce blood lipid without liver function damage, showing better anti- hyperlipemia effect than Fenofibrate by down-regulating ADRP.

Description: Background: Oral fat tolerance test (OFTT) has been widely used to assess the postprandial lipemia in human beings, but there is few studies concerning OFTT in nonhuman primates. This study is designed to explore the feasibility of OFTT in rhesus monkeys. Methods: In a cross-over study, a total of 8 adult female rhesus monkeys were fed with normal monkey diet (NND), high sugar high fat diet (HHD), and extremely high fat diet (EHD), respectively. Each monkey consumed NND, HHD and EHD respectively, each weighing 60 g. Serial blood samples were collected at 1, 2, 3, 4, 5, and 6 h after ingesting each kind of food. Triglyceride, cholesterol, glucose, and insulin at each time point were measured. The area under the curve of triglyceride (TG-AUC) and triglyceride peak response (TG-PR) were also calculated. Results: All monkeys ingested 3 kinds of foods within 15 minutes. TG-AUC and TG-PR of HHD group were higher than those of the other two groups. Postprandial triglyceride levels at 2, 3, 4, and 5 hours in HHD group during OFTT were also higher than those in NND and END group. Conclusions: HHD diet can be used in OFTT for nonhuman primates.

Description: Background: Few clinical studies have focused on the efficacy of lipid-lowering therapies in patients 〉=65 years. Methods: After stabilization on atorvastatin 10 mg, hypercholesterolemic subjects 〉=65 years at high/very high risk for CHD and not at LDL-C

Description: Background: Acute myocardial infarction and stroke are more likely to occur in the early morning. Circadian pacemakers are considered to be involved in the process. Many peripheral tissues and cells also contain clock systems. In this study, we examined whether the primary cultured human plaque-derived vascular smooth muscle cells (VSMCs) process circadian rhythmicity; furthermore, we investigated the expression difference of clock genes between normal human carotid VSMCs and human plaque-derived VSMCs. Methods: Fifty-six human carotid plaques provided the atherosclerotic tissue, and 21 samples yielded viable cultured primary VSMCs. The normal carotid VSMCs were cultured from donors' normal carotids. The mRNA levels of the target genes were measured by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: After serum shock, both types of cells showed clear circadian expressions of Bmal1, Cry1, Cry2, Per1, Per2, Per3 and Rev-erbalpha mRNA; meanwhile the Clock mRNA show a rhythmic expression in plaque-derived SMCs but not in normal carotid VSMCs. The expression levels of these main clock genes were significantly attenuated in human plaque-derived VSMCs compared with normal human carotid VSMCs. The rhythm of Bmal1 mRNA in plaque-derived VSMCs was changed. Conclusion: The present results demonstrate that the human plaque-derived VSMCs possess different circadian rhythmicity from that of normal carotid VSMCs. The rhythm changes of clock genes in plaque-derived VSMCs may be involved in the process of atherosclerosis and finally promote the rupture of plaque.

Description: Nichols et al. (Lipids Health Dis 13:2, 2014) raised concern about the higher n-6 concentration in fish oil used in our recent study which is different from typical commercial fish oils (Ramprasath et al. Lipids Health Dis 12:178, 2013). The aim of our study was to compare the effect of consumption of similar amount of n-3 PUFA from krill and fish oil with placebo on plasma and RBC fatty acids. As the concentration of n-3 PUFA in the fish oil utilised was higher than that in krill oil, we deemed it important to keep consistent the concentration of n-3 PUFA and volumes to be administered to participants between krill versus fish oils. As such, the fish oil used in the study was diluted with corn oil. Although the n-6 PUFA concentration in fish oil was higher compared to traditionally used fish oil, consumption of the fish oil used in our study actually reduced the total n-6 PUFA in plasma and RBC to a similar extent as did krill oil. Overall, our conclusion was that the increases in plasma and RBC concentrations of EPA and DHA along with improvement in the omega-3 index observed with consumption of krill oil compared with fish oil are due to differences in absorption and bioavailability based on the structural difference of the two oils rather than their n-6 PUFA content.

Description: Background: Current guidelines recommend measuring plasma lipids in fasting patients. Recent studies, however, suggest that variation in plasma lipid concentrations secondary to fasting time may be minimal. Objective of the present study was to investigate the impact of fasting time on plasma lipid concentrations (total cholesterol, HDL and LDL cholesterol, triglycerides). A second objective was to determine the effect of non-alcoholic fatty liver disease exerted on the above-mentioned lipid levels.MethodSubjects participating in a population-based cross-sectional study (2,445 subjects; 51.7% females) were questioned at time of phlebotomy regarding duration of pre-phlebotomy fasting. Total cholesterol, LDL and HDL cholesterol, and triglycerides were determined and correlated with length of fasting. An upper abdominal ultrasonographic examination was performed and body-mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Subjects were divided into three groups based on their reported fasting periods of 1-4 h, 4-8 h and 〉 8 h. After application of the exclusion criteria, a total of 1,195 subjects (52.4% females) were included in the study collective. The Kruskal-Wallis test was used for continuous variables and the chi-square test for categorical variables. The effects of age, BMI, WHR, alcohol consumption, fasting time and hepatic steatosis on the respective lipid variables were analyzed using multivariate logistic regression. Results: At multivariate analysis, fasting time was associated with elevated triglycerides (p = 0.0047 for 1-4 h and p = 0.0147 for 4-8 h among females; p 〈 0.0001 for 1-4 h and p = 0.0002 for 4-8 h among males) and reduced LDL cholesterol levels (p = 0.0003 for 1-4 h and p = 0.0327 for 4-8 h among males). Among males, hepatic steatosis represents an independent factor affecting elevated total cholesterol (p = 0.0278) and triglyceride concentrations (p = 0.0002). Conclusion: Total and HDL cholesterol concentrations are subject to slight variations in relation to the duration of the pre-phlebotomy fasting period. LDL cholesterol and triglycerides exhibit highly significant variability; the greatest impact is seen with the triglycerides. Fasting time represents an independent factor for reduced LDL cholesterol and elevated triglyceride concentrations. There is a close association between elevated lipids and hepatic steatosis.

Description: : Obstructive sleep apnea syndrome (OSAS) is strongly associated with the increasing prevalence of cerebrovascular events and metabolic syndrome. A growing number of studies have shown OSAS is an independent factor for insulin resistance, glucose intolerance and type2 diabetes. However, relationship of OSAS with dysglycemia is complex and still remains poorly understood. Glucose transporter 4 (GLUT4) gene is Human and rodents' main glucose transporter sensitive to insulin, and therefore confirmation of candidate gene polymorphisms and association with OSAS is needed. Aim of our study was to assess whether GLUT4 gene polymorphisms are associated with OSAS. Methods: Patients hospitalized at People's Hospital of Xinjiang were selected from January to December 2010. A total of 568 Han subjects who possibly exist OSAS base on a history and physical examination were completed the polysomnography, 412of whom (72.5%) were diagnosed with OSAS, and 156 individuals were confirmed without OSAS (27.5%). 96 severe OSAS patients chosen from OSAS were used for DNA sequencing in functional domain. Blood samples were collected from all subjects and genotyping was performed on DNA extracted from blood cells. Results: We performed GLUT4 genome sequencing, found 4 mutated sites. And finally selected three mutated sites such as rs5415, rs4517 and rs5435, according to principle of linkage disequilibrium (r2 〉 0.8) and minimum gene allele frequency 〉 5%. All SNPs satisfied HEW (P 〉 0.05). Our study demonstrated a significant association of GLUT4 SNPrs5417 allele with OSAS, compared with controls (P 〈 0.05). Haplotype H1 (TCC) and H3 (CCC) defined as SNPrs5415, rs4517 and rs5435 are marginally associated with OSAS (P 〈 0.05). Frequencies of C haplotype of rs5417 in OSAS were higher than in controls. After adjustment for confounding factors, (AC + AA) genotype significantly reduces prevalence of OSAS, compared with CC genotype. Level of awake blood oxygen and lowest blood oxygen of (AA + AC) genotype was significantly superior to those of CC genotype. Conclusions: Our study demonstrates GLUT4 gene SNPrs5417 is associated with OSAS in hypertensive population. Carriers of AA + AC have less prevalence of obstructive sleep apnea syndrome than that of CC carriers.

Description: Lipids and cholesterol in particular, have long been associated with breast cancer (BC) onset and progression. However, the causative effects of elevated lipid levels and breast cancer remain largely undisclosed and were the subject of the present study.We took advantage of well-established in vitro and in vivo models of cholesterol enrichment to exploit the mechanism involved in LDL-cholesterol favouring BC growth and invasiveness. We analyzed its effects in models that mimic different BC subtypes and stages.Our data show that LDL-cholesterol (but not HDL-cholesterol) promotes BC cells proliferation, migration and loss of adhesion, hallmarks of the epithelial to mesenchymal transition. In vivo studies modeling cholesterol levels showed that breast tumors are consistently larger and more proliferative in hypercholesterolemic mice, which also have more frequently lung metastases. Microarray analysis revealed an over expression of intermediates of Akt and ERK pathways suggesting a survival response induced by LDL, confirmed by WB analyses. Gene expression analysis also evidenced an activation of ErbB2 signaling pathway and decreased expression of adhesion molecules (cadherin-related family member3, CD226, Claudin 7 and Ocludin) in the cells exposed to LDL.Together, the present work shows novel mechanistic evidence that high LDL-cholesterol levels promote BC progression. These data provide rationale for the clinical control of cholesterol levels in BC patients.

Description: Background: Exogenously hypercholesterolemic (ExHC) rats develop hypercholesterolemia and low hepatic triacylglycerol (TAG) levels when dietary cholesterol is loaded. The responsible gene Smek2 was identified via linkage analysis using the original strain Sprague-Dawley (SD) rats. In this study, we compared SD and ExHC rats to investigate a relationship between hypercholesterolemia and the low hepatic TAG levels observed in ExHC rats. Methods: Male 4-weeks-old ExHC and SD rats were fed a 1 % cholesterol diet for 1 week. Serum and liver parameters were analyzed. Gene expression and enzyme activities related to TAG metabolism were also assessed. Results: We reproducibly observed higher serum cholesterol and lower hepatic TAG levels in ExHC rats than in SD rats. Golgi apparatus in the livers of ExHC rats secreted beta-very-low-density lipoprotein (beta-VLDL) that had higher cholesterol ester (CE) and lower TAG content than those in the beta-VLDL secreted by SD rats. Gene expression related to fatty acid and TAG synthesis in ExHC rats was lower than that in SD rats. Enzymatic activities for fatty acid synthesis were also relatively lower in ExHC rats. Moreover, the fatty acid composition of hepatic and serum CE in ExHC rats showed that these CEs were not modified after secretion from the liver despite the similar activities of serum lecithin-cholesterol acyltransferase (LCAT) in ExHC rats to those in SD rats. Conclusions: Low production of liver TAG and secretion of CE-rich, TAG-poor beta-VLDL without modification by LCAT in the circulation contributed to hypercholesterolemia induced by dietary cholesterol in ExHC rats.

Description: Background: Studies investigating the association between the apolipoprotein E (APOE) gene polymorphism and the risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. Methods: Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratio (OR) and 95% confidence interval (CI) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. Results: This meta-analysis included 11 case-control studies, which included 1,238 ICH cases and 3,575 controls. The combined results based on all studies showed that ICH cases had a significantly higher frequency of APOE epsilon4 allele (OR= 1.42, 95% CI= 1.21,1.67, P

Description: Background: Single-nucleotide polymorphisms (SNPs) around the apolipoprotein A5 gene (APOA5) have pleiotropic effects on the levels of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C). APOA5 SNPs have also been associated with metabolic syndrome (MS). Here, we constructed haplotypes with SNPs spanning APOA5 and ZNF259, which are approximately 1.3 kb apart, to perform association analyses with the risk for MS and the levels of TG and HDL-C in terms of a TG:HDL-C ratio. Methods: The effects of three constructed haplotypes (TAA, CGG, and CGA, in the order of rs662799, rs651821, and rs6589566) on the TG:HDL-C ratio and MS were estimated using multiple regression analyses in 2,949 Koreans and in each gender separately (1,082 men and 1,867 women). Results: The haplotypes, CGG and CGA, were associated with the TG:HDL-C ratio and the risk of MS development in both genders. That is, the minor alleles of the rs662799 and rs651821 in APOA5, irrespective of which allele was present at rs6589566, had the marked effects. Interestingly, a C-G-A haplotype at these three SNPs had the most marked effects on the TG:HDL-C ratio and the risk of MS development in women. Conclusions: We have identified the novel APOA5-ZNF259 haplotype manifesting sex-dependent effects on elevation of the TG:HDL-C ratio as well as the increased risk for MS.

Description: Background: Recently, it has been found that Fructus Schisandra Chinensis (FSC), a Chinese herbal medicine, and its related compounds have a profound impact on lipid metabolism process. FSC can be divided into two parts, i.e., seed and pulp. The current study aimed to examine the effect of aqueous extracts of FSC pulp (AqFSC-P) on serum/hepatic lipid and glucose levels in mice fed with a normal diet (ND) or a high cholesterol/bile salt diet (HCBD). Methods: The AqFSC-P used in the present study was fractionated into supernatant (SAqFSC-P) and precipitate (PAqFSC-P) separated by centrifugation. Male ICR mice were fed with ND or HCBD, without or with supplementation of 1%, 3%, or 9% (w/w) SAqFSC-P or PAqFSC-P for 10 days. Biomarkers were determined according to the manufacturer's instruction. Results: Supplementation with SAqFSC-P or PAqFSC-P significantly reduced serum and hepatic triglyceride levels (approximately 40%) in ND- and/or HCBD-fed mice. The supplementation with SAqFSC-P or PAqFSC-P reduced hepatic total cholesterol levels (by 27 - 46%) in HCBD-fed mice. Supplementation with SAqFSC-P or PAqFSC-P markedly lowered hepatic glucose levels (by 13 - 30%) in ND- and HCBD-fed mice. SAqFSC-P decreased serum alanine aminotransferase (ALT) activity, but PAqFSC-P increased hepatic protein contents in ND-fed mice. Bicylol, as a positive control, reduced ALT activity. In addition, mice supplemented with FSC-P or bicylol showed a smaller body weight gain and adipose tissue mass as compared to the respective un-supplemented ND- or HCBD-fed mice. Conclusion: The results indicate that SAqFSC-P and PAqFSC-P produce hepatic lipid- and glucose-lowering as well as serum TG-lowering effects in hypercholesterolemic mice. FSC pulp may provide a safe alternative for the management of fatty liver and/or lipid disorders in humans.

Description: Background: Polymorphisms in the LPA gene were associated with coronary artery disease (CAD). However, there are differences in the allelic frequencies, Lp(a) levels, and significant association with CAD according to ethnic groups. In this scenario, the main aim of this study was to assess the influence of the LPA polymorphisms on coronary lesions in Brazilian patients. Methods: 1,394 consecutive patients submitted to coronary angiography to study suggestive CAD and twenty coronary segments were scored. Genotyping for the LPA rs10455872 and rs3798220 polymorphisms were performed by high resolution melting analysis. Results: The frequencies of the rs10455872 G and rs3798220 C variant alleles were 6.4% and 6.2%, respectively. LPA rs10455872 G variant allele was associated with higher odds ratio of having coronary lesions in an adjusted model (OR = 2.02, 95%CI = 1.10-3.72, p = 0.02). Scores of coronary lesions (extension, severity, and Gensini scores) were significantly different among rs10455872 genotype groups. Coronary lesions was not associated with LPA rs3798220 (OR = 1.09, 95%CI = 0.67-1.76, p = 0.73) and scores of coronary lesions were not different among rs3798220 genotypes. Conclusions: We confirmed the association of the LPA rs10455872 with CAD in a large sample of Brazilian patients. For the LPA rs3798220, our finding is consistent with studies which showed the lack of this genetic association.

Description: Background: Lipoprotein associated phospholipase A2 (Lp-PLA2) is a novel biomarker for cardiovascular risk prediction. Whether increased Lp-PLA2 level is associated with re-stenosis after stent-placement is unclear. Methods: Totally 326 participants eligible for stent-placement were enrolled and divided into two groups according to baseline Lp-PLA2 levels (named normal and elevated groups). Baseline characteristics and clinical outcomes were compared between normal and elevated groups. The relationships between Lp-PLA2 and other risk factors with re-stenosis were evaluated. Results: Only the between-group difference of Lp-PLA2 was significant (123.2 +/- 33.6 ng/mL vs 336.8 +/- 85.4 ng/mL, P 〈 0.001) while other demographic and clinical characteristics between these two groups were comparable. Approximately 55.1% and 58.5% of participants in normal and elevated groups presented with acute coronary syndrome, and the percentage of tri-vessels stenoses was significantly higher in elevated group (40.8% vs 32.1%, P = 0.016). Nearly 96.0% and 94.0% of participants in normal and elevated Lp-PLA2 groups were placed with drug-eluting stents, and the others were with bare-metal stents. After 1 year's follow-up, the incidence of clinical end-points was comparable (13.3% vs 15.4%, P = 0.172). Nevertheless, the incidence of re-stenosis was marginally higher in elevated Lp-PLA2 group (8.5% versus 4.6%, P = 0.047). With multivariate analysis, after adjustment for other risk factors, Lp-PLA2 remained an independent predictor for re-stenosis with a hazard ratio of 1.140. No synergistic effect between Lp-PLA2 and other risk factors for re-stenosis was found. Conclusion: Increased Lp-PLA2 level is associated with an increased risk of re-stenosis. Lp-PLA2 assessment may be useful in predicting subjects who are at increased risk for re-stenosis.

Description: Background: Alterations or mutations in the lipoprotein lipase (LPL) gene contribute to severe hypertriglyceridemia (HTG). This study reported on two patients in a Chinese family with LPL gene mutations and severe HTG and acute pancreatitis. Methods: Two patients with other five family members were included in this study for DNA-sequences of hyperlipidemia-related genes (such as LPL, APOC2, APOA5, LMF1, and GPIHBP1) and 43 healthy individuals and 70 HTG subjects were included for the screening of LPL gene mutations. Results: Both patients were found to have a compound heterozygote for a novel LPL gene mutation (L279V) and a known mutation (A98T). Furthermore, one HTG subject out of 70 was found to carry this novel LPL L279V mutation. Conclusions: The data from this study showed that compound heterozygote mutations of A98T and L279V inactivate lipoprotein lipase enzymatic activity and contribute to severe HTG and acute pancreatitis in two Chinese patients. Further study will investigate how these LPL gene mutations genetically inactivate the LPL enzyme.

Description: Background: Apolipoprotein M (apoM), as a novel apolipoprotein which is mainly expressed in liver and kidney tissues, is associated with development and progression of atherosclerosis and diabetes. Our group have recently shown that Dihydrocapsaicin(DHC)can significantly decrease atherosclerotic plaque formation in apoE-/- mice. However, the effect and possible mechanism of DHC on apoM expression remain unclear. Methods: HepG2 cells were treated with 0 muM, 25 muM, 50 muM and 100 muM DHC for 24 h or were treated with 100 muM DHC for 0, 6, 12, and 24 h, respectively. The mRNA levels and protein levels were measured by real-time quantitative PCR and western blot analysis, respectively. Results: We found that DHC markedly decreased expression of apoM at both mRNA and protein level in HepG2 cells in a dose-dependent and time-dependent manner. Expression of Foxa2 was decreased while expression of LXRalpha was increased by DHC treatment in HepG2 cells. In addittion, overexpression of Foxa2 markedly compensated the inhibition effect induced by DHC on apoM expression. LXRalpha small interfering RNA significantly abolished the inhibition effect which induced by DHC on apoM expression. The liver of C57BL/6 mice treated with DHC had significantly lower expression of apoM. Furthermore, the liver had lower expression of Foxa2 while had higher expression of LXRalpha. Conclusions: DHC could down-regulate apoM expression through inhibiting Foxa2 expression and enhancing LXRalpha expression in HepG2 cells.

Description: Background: The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. Methods: We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. Results: The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Conclusions: Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol absorption inhibition with STAEST. Serum plant sterol concentrations decrease dose-dependently in response to plant stanols suggesting that the higher the plant stanol dose, the more cholesterol absorption is inhibited and the greater the reduction in LDL cholesterol level is that can be achieved.Trial Registration numbers: Clinical Trials Register # NCT00698256 [ref 17]

Description: Background: The role of triglyceride (TG) in predicting the outcomes in diabetic patients with coronary artery disease (CAD) has not been well investigated. Methods: A total of 329 cases with stable angina pectoris (SAP) were prospectively enrolled and followed up for an average of 12 months. They were classified into the two groups according to the cut-off values of predicting early outcome of fasting TG level (low group =1.2 mmol/L, n = 226). The relationship between the TG levels and early outcomes were evaluated. Results: High TG group showed severer lipid profile and elevated inflammatory markers. During an average of 12-month follow-up, 47 out of 329 patients suffered from pre-specified outcomes. Area under the receivers operating characteristic curve suggested that TG, similar to serum Hemoglobin A1C (HbA1C), was a significant predictor of early outcome for diabetic patients with SAP (P = 0.002). In Cox regression models, after adjusted age, gender, body mass index, other lipid parameters, fasting blood glucose, high sensitivity C-reactive protein, neutrophil count and HbA1C, TG remained as an independent predictor of adverse prognosis. Conclusions: High level of fasting TG (〉=1.2 mmol/L) was an independent predictor for early outcome of diabetic patients with SAP as like as HBA1c and number of affected coronary arteries in the era of revascularization and statin therapeutics.

Description: Background: Genome-wide association studies found low plasma levels of 25-hydroxyvitamin D and vitamin D receptor (VDR) polymorphisms associated with a higher prevalence of pathological changes in the intestine such as chronic inflammatory bowel diseases. Methods: In this study, a proteomic approach was applied to understand the overall physiological importance of vitamin D in the small intestine, beyond its function in calcium and phosphate absorption. Results: In total, 569 protein spots could be detected by two-dimensional-difference in-gel electrophoresis (2D-DIGE), and 82 proteins were considered as differentially regulated in the intestinal mucosa of VDR-deficient mice compared to that of wildtype (WT) mice. Fourteen clearly detectable proteins were identified by MS/MS and further analyzed by western blot and/or real-time RT-PCR. The differentially expressed proteins are functionally involved in cell proliferation, cell adhesion and cell migration, stress response and lipid transport. Mice lacking VDR revealed higher levels of intestinal proteins associated with proliferation and migration such as the 37/67 kDa laminin receptor, collagen type VI (alpha 1 chain), keratin-19, tropomyosin-3, adseverin and higher levels of proteins involved in protein trafficking and stress response than WT mice. In contrast, proteins that are involved in transport of bile and fatty acids were down-regulated in small intestine of mice lacking VDR compared to WT mice. However, plasma and liver concentrations of cholesterol and triglycerides were not different between the two groups of mice. Conclusion: Collectively, these data imply VDR as an important factor for controlling cell proliferation, migration and stress response in the small intestine.

Description: IntroductionApolipoprotein E (apoE) is a member of apolipoprotein family, and its gene polymorphisms seem to have some impact among patients with cardiovascular disease. However, its role in the lower extremity deep venous thrombosis (LEDVT) has not been well studied. The objective of this study was to investigate the potential association between APOE gene polymorphisms and LEDVT.Materials and methods: A hospital-based case-control study was conducted in 300 patients with LEDVT by color-flow Doppler ultrasound and 300 age- and gender-matched healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the APOE gene polymorphisms. Results: Patients with LEDVT had a significantly higher frequency of APOE E3/E4 genotype [odds ratio (OR) =1.48, 95% confidence interval (CI) = 1.05, 2.10; P = 0.03] than healthy controls. When stratifying by family history of LEDVT, it was found that patients with positive family history of LEDVT had a significantly higher frequency of APOE E3/E4 genotype (OR =1.68, 95% CI = 1.04, 0.95; P = 2.70). When stratifying by smoking status, presence of varicose veins, type 2 diabetes mellitus and any hormone administration before, no significant differences were found in any groups. Conclusion: Our study suggested that APOE E3/E4 genotype was associated with a higher LEDVT risk. Additional studies are needed to confirm this finding.

Description: Background: The PPAR alpha and PPAR gamma are the key messengers responsible for the translation of nutritional stimuli into changes for the expression of genes, particularly genes involved in lipid metabolism. However, the associations between PPAR alpha / gamma polymorphisms and lipid serum levels in the general population were rarely studied, and the conclusions were conflicting. The objective was to investigate the associations of the PPAR alpha and PPAR gamma polymorphisms with dyslipidemia. Methods: 820 subjects were randomly selected from the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province cohort populations. The logistic regression model was used to examine the association between these polymorphisms and dyslipidemia. SNPstats was used to explore the haplotype association analyses. Results: In the codominant and log-additive models, rs1800206, rs1805192 and rs3856806 were all associated with dyslipidemia (P 〈 0.005). When the most common haplotype L-G (established by rs1800206, rs4253778) was treated as the reference group, the V-G haplotype was associated with dyslipidemia (P 〈 0.001), higher TC and TG levels (P 〈 0.01). Moreover, when compared to Pro-C haplotype (established by rs1805192, rs3856806), the Pro-T, Ala-C, Ala-T haplotypes were associated with dyslipidemia (p 〈 0.001). A-T haplotype was associated with higher TC levels, (p 〈 0.01), and the P-T, A-C, A-T haplotypes were associated with higher TG levels (p 〈 0.01). Conclusions: PPAR alpha and PPAR gamma polymorphisms and haplotypes may be the genetic risk factors for dyslipidemia.

Description: ObjectiveTo elucidate the effects of natural dietary components on the inflammatory and metabolic consequences of obesity, we examined the effects of unripe, ripe and industrial acerola juice (Malpighia emarginata DC.) on the relevant inflammatory and lipolysis proteins in the adipose tissue of mice with cafeteria diet-induced obesity.Materials/methods: Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13 weeks. Afterwards, the CAF-fed animals were divided into five subgroups, each of which received a different supplement for one further month (water, unripe acerola juice, ripe acerola juice, industrial acerola juice, or vitamin C) by gavage. Enzyme-linked immunosorbent assays, Western blotting, a colorimetric method and histology were utilized to assess the observed data. Results: The CAF water (control obese) group showed a significant increase in their adiposity indices and triacylglycerol levels, in addition to a reduced IL-10/TNF-alpha ratio in the adipose tissue, compared with the control lean group. In contrast, acerola juice and Vitamin C intake ameliorated the weight gain, reducing the TAG levels and increasing the IL-10/TNF-alpha ratio in adipose tissue. In addition, acerola juice intake led to reductions both in the level of phosphorylated JNK and to increases in the phosphorylation of IkappaBalpha and HSLser660 and in the expression of PeriA in adipose tissue. Conclusion: Taken together, these results suggest that acerola juice reduces low-grade inflammation and ameliorates obesity-associated defects in the lipolytic processes.

Description: Background: Cross-sectional studies have suggested that serum omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) are related to favorable lipoprotein particle concentrations. We explored the associations of serum n-3 and n-6 PUFAs with lipoprotein particle concentrations and sizes in a general population cohort at baseline and after 6 years.FindingsThe cohort included 665 adults (274 men) with a 6-year follow-up. Nutritional counseling was given at baseline. Serum n-3 and n-6 PUFAs and lipoprotein particle concentrations and the mean particle sizes of VLDL, LDL, and HDL were quantified by nuclear magnetic resonance (NMR) spectroscopy for all baseline and follow-up samples at the same time. Concentrations of n-3 and n-6 PUFAs were expressed relative to total fatty acids. At baseline, n-3 PUFAs were not associated with lipoprotein particle concentrations. A weak negative association was observed for VLDL (P = 0.021) and positive for HDL (P = 0.011) particle size. n-6 PUFA was negatively associated with VLDL particle concentration and positively with LDL (P 〈 0.001) and HDL particle size (P 〈 0.001). The 6-year change in n-3 PUFA correlated positively with the change in particle size for HDL and LDL lipoproteins but negatively with VLDL particle size. An increase in 6-year levels of n-6 PUFAs was negatively correlated with the change in VLDL particle concentration and size, and positively with LDL particle size. Conclusion: Change in circulating levels of both n-3 and n-6 PUFAs, relative to total fatty acids, during 6 years of follow-up are associated with changes in lipoprotein particle size and concentrations at the population level.

Description: Background: Atherosclerosis constitutes the leading contributor to morbidity and mortality in cardiovascular and cerebrovascular diseases. Lipid deposition and inflammatory response are the crucial triggers for the development of atherosclerosis. Recently, microRNAs (miRNAs) have drawn more attention due to their prominent function on inflammatory process and lipid accumulation in cardiovascular and cerebrovascular disease. Here, we investigated the involvement of miR-21 in lipopolysaccharide (LPS)-induced lipid accumulation and inflammatory response in macrophages. Methods: After stimulation with the indicated times and doses of LPS, miR-21 mRNA levels were analyzed by Quantitative real-time PCR. Following transfection with miR-21 or anti-miR-21 inhibitor, lipid deposition and foam cell formation was detected by high-performance liquid chromatography (HPLC) and Oil-red O staining. Furthermore, the inflammatory cytokines interleukin 6 (IL-6) and interleukin 10 (IL-10) were evaluated by Enzyme-linked immunosorbent assay (ELISA) assay. The underlying molecular mechanism was also investigated. Results: In this study, LPS induced miR-21 expression in macrophages in a time- and dose-dependent manner. Further analysis confirmed that overexpression of miR-21 by transfection with miR-21 mimics notably attenuated lipid accumulation and lipid-laden foam cell formation in LPS-stimulated macrophages, which was reversely up-regulated when silencing miR-21 expression via anti-miR-21 inhibitor transfection, indicating a reverse regulator of miR-21 in LPS-induced foam cell formation. Further mechanism assays suggested that miR-21 regulated lipid accumulation by Toll-like receptor 4 (TLR4) and nuclear factor-kappaB (NF-kappaB) pathway as pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-kappaB (PDTC) strikingly dampened miR-21 silence-induced lipid deposition. Additionally, overexpression of miR-21 significantly abrogated the inflammatory cytokines secretion of IL-6 and increased IL-10 levels, the corresponding changes were also observed when silencing miR-21 expression, which was impeded by preconditioning with TLR4 antibody or PDTC. Conclusions: Taken together, these results corroborated that miR-21 could negatively regulate LPS-induced lipid accumulation and inflammatory responses in macrophages by the TLR4-NF-kappaB pathway. Accordingly, our research will provide a prominent insight into how miR-21 reversely abrogates bacterial infection-induced pathological processes of atherosclerosis, indicating a promising therapeutic prospect for the prevention and treatment of atherosclerosis by miR-21 overexpression.

Description: Background: The aim of this study was to estimate associations between inflammatory markers and obesity indices in normo- and hypertensive subjects. Methods: 65 obese adult subjects were divided into two groups: (A) of hypertensives (n = 54) and (B) of normotensives (n = 11). Waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI) and tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and high sensitivity C-reactive protein (hsCRP) serum concentrations were estimated. Results: In group A WHtR was higher (0.69 +/- 0.07 vs 0.63 +/- 0.06; p 〈 0.01), hsCRP correlated with BMI and WHtR (r = 0.343; p = 0.011 and r = 0.363; p 〈 0.01, respectively). BAI correlated with hsCRP in group A and B (r = 0.329; p 〈 0.05 and r = 0.642; p 〈 0.05; respectively) and in females and males (r = 0.305; p = 0.05 and r = 0.44; p 〈 0.05, respectively). In females hsCRP was higher (3.2 +/- 2.2 mg/l vs 2.1 +/- 1.5 mg/l; p 〈 0.05). In patients without lipid lowering treatment hsCRP and IL-6 were higher (3.2 +/- 1.7 mg/l vs 2.4 +/-2.2 mg/l; p = 0.01 and 15.9 +/- 7.2 pg/ml vs 13.6 +/- 9.9 pg/ml; p 〈 0.01, respectively). Conclusions: WHtR is a sensitive index associated with chronic inflammation in obese hypertensive subjects. BAI correlates with hsCRP independently of hypertension and sex. hsCRP is more sensitive marker associated with obesity than IL-6 and TNF-alpha. Lipid lowering treatment influence chronic inflammation.

Description: Background: Some experimental animal studies reported that vanadium had beneficial effects on blood total cholesterol (TC) and triglyceride (TG). However, the relationship between vanadium exposure and lipid, lipoprotein profiles in human subjects remains uncertain. This study aimed to compare the serum lipid and lipoprotein profiles of occupational vanadium exposed and non-exposed workers, and to provide human evidence on serum lipid, lipoprotein profiles and atherogenic indexes changes in relation to vanadium exposure. Methods: This cross-sectional study recruited 533 vanadium exposed workers and 241 non-exposed workers from a Steel and Iron Group in Sichuan, China. Demographic characteristics and occupational information were collected through questionnaires. Serum lipid and lipoprotein levels were measured for all participants. The ratios of total cholesterol to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) to HDL-C and apoB to apoA-I were used as atherogenic indexes. A general linear model was applied to compare outcomes of the two groups while controlling possible confounders and multivariate logistic regression was performed to evaluate the relationship between low HDL-C level, abnormal atherogenic index and vanadium exposure. Results: Higher levels of HDL-C and apoA-I could be observed in the vanadium exposed group compared with the control group (P 〈 0.05). Furthermore, atherogenic indexes (TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios) were found statistically lower in the vanadium exposed workers (P 〈 0.05). Changes in HDL-C, TC/HDL-C, and LDL-C/HDL-C were more pronounced in male workers than that in female workers. In male workers, after adjusting for potential confounding variables as age, habits of smoking and drinking, occupational vanadium exposure was still associated with lower HDL-C (OR 0.41; 95% CI, 0.27-0.62) and abnormal atherogenic index (OR 0.38; 95% CI, 0.20-0.70). Conclusion: Occupational vanadium exposure appears to be associated with increased HDL-C and apoA-I levels and decreased atherogenic indexes. Among male workers, a significantly negative association existed between low HDL-C level, abnormal atherogenic index and occupational vanadium exposure. This suggests vanadium has beneficial effects on blood levels of HDL-C and apoA-I.

Description: Background: Dyslipidemia and abnormal phospholipid metabolism are frequent in uremic patients and increase their risk of cardiovascular disease (CVD): omega-3 polyunsaturated fatty acids (PUFAs) may reduce this risk in the general population. In this study we compared the plasma and erythrocyte cell membrane composition of PUFAs in a group of Caucasian hemodialysis (HD) patients and in a control group of healthy subjects and evaluated the erythrocyte/cell membrane fatty acid ratio as a marker of the dietary intake of phospholipids. The relationship between omega-3 and omega-6 fatty acids and the possible differences in PUFAs concentrations were also investigated.Methods and results: After obtaining a fully informed consent, a total of ninety-nine HD patients and 160 non uremic control subjects from "Tor Vergata" University Hospital were enrolled into the study. None of them took antioxidant drugs or dietary supplements for at least 90 days prior to the observation. Blood samples were analysed by gas-chromatographic coupled to a mass spectrometric detector.The daily intake of total calories, proteins, lipids and carbohydrates is significantly lower in HD patients than in controls (p 〈 0.001). Most plasma and erythrocyte PUFA were also reduced significantly in HD patients (p 〈 0.001). Conclusions: Our results suggest that many classes of PUFAs are lacking in HD patients, due to the removal of nutrients during the dialysis and to persistent malnutrition. A dietary treatment addressed to increase plasma omega-3 PUFAs and to optimize omega-6/omega-3 ratio may exert a protective action and reduce the risk of CVD in HD patient.

Description: Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays an important role in the pathophysiology of atherosclerosis and thrombosis. This study is aimed at evaluating the potential association of 3'-UTR-C188T and G501C in LOX-1 gene with cerebral infarction. Methods: A total of 386 patients with cerebral infarction and 386 healthy controls were included in the study, which were unrelated Chinese Han population in the Liaoning Province of northern China. The single nucleotide polymorphisms, 3'-UTR-C188T and G501C, were analyzed by polymerase chain reaction-ligation detection reaction method. Results: The frequencies of CC + GC genotype, GC genotype and C allele of G501C in the patients with cerebral infarction were significantly higher than those in the controls (P 〈 0.01, P 〈 0.01, P = 0.04, respectively). These correlations still remained after adjusting for confounding risk factors of cerebral infarction. In addition, no significant association was observed between 3'-UTR-C188T and cerebral infarction. Conclusions: The study indicated that the G501C variant in LOX-1 gene may be associated with susceptibility to cerebral infarction, independent of other common risk factors, in northern Chinese Han population.

Description: Background: In castration-resistant prostate cancer (CRPC), recent evidence has demonstrated the persistence of the intratumoral androgens. The multi-step androgen synthesis pathway originates from cholesterol, which can be obtained by cells from several major sources including intracellular synthesis through an enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). The inhibition of this enzyme by the use of statins has been investigated in prostate cancer as a possible therapeutic target for blocking the de novo androgen synthesis resulting in decreased tumor growth. However, the effectiveness of statins in CRPC has not been investigated. Methods: Castration-resistant C4-2 and androgen-sensitive LNCaP cells were treated with Simvastatin for 48 hours. Dose-dependent responses to Simvastatin were analyzed using cell proliferation and cytotoxicity assays. Cellular growth curve was generated using haemocytometer. HMGCR activity was assessed using 14C-acetic acid detected by thin layer chromatography, and the protein expression was quantified using western blot analysis. Intracellular cholesterol and prostate specific antigen (PSA) levels were quantified using enzyme-linked immunosorbent assays (ELISA). Results: Significant decrease in cell viability and growth curve observed at 75 muM of Simvastatin compared to no treatment group in the castration-resistant C4-2 cells. HMGCR activity was significantly decreased up to 50% and 70% at 50 muM and 75 muM of Simvastatin respectively compared to the vehicle control in C4-2 cells. Simvastatin did not affect the protein expression. 80% decrease in the amount of total intracellular cholesterol levels was observed in 75 muM Simvastatin treatment group compared to vehicle control. PSA secretion levels were significantly reduced in the C4-2 cell line at 50 muM and 75 muM of Simvastatin compared to vehicle control. Conclusion: The inhibition of HMGCR via Simvastatin lowered the viability of castration-resistant C4-2 cells. Simvastatin's ability to limit the endogenous supply of cholesterol contributes to the effects seen in cell viability.

Description: Background: Metabolic syndrome is now widely appreciated as a cluster of metabolic abnormalities such as visceral obesity, hypertension, hyperglycemia and dyslipidemia. To date, incidence of metabolic syndrome is continuously increasing worldwide.In addition, low vegetable consumption has recently become a serious issue in Japan. Furthermore, Japan is facing a shortfall in places offering food that can help prevent metabolic syndrome in the first place. Our study is designed to influence these developments. We conducted a non-randomized controlled trial by offering a Japanese-style healthy lunch menu to middle-aged men in a workplace cafeteria. This menu was designed to prevent and reduce metabolic syndrome. Methods: This intervention study took the form of a non-randomized controlled trial. Participants chose the control or intervention group. The control group consumed their habitual lunches without restriction and only nutrient contents were assessed. The intervention group received a Japanese-style healthy lunch at a workplace cafeteria for 3 months. The participants worked in offices at a city hall and mostly had low levels of physical activity. Data of 35 males (control group: 7 males, intervention group: 28 males, mean age: 47.2 +/- 7.9 years) were collected and analyzed. Results: We obtained an effective outcome by demonstrating that ongoing intake of a Japanese-style healthy lunch decreased blood pressure and serum lipids and increased plasma ghrelin levels. The results grew more pronounced as intake of Japanese-style healthy lunches increased in frequency. Conclusions: This study presents new empirical data as a result of an original intervention program undertaken in Japan. A Japanese-style healthy lunch menu containing many vegetables consumed can help prevent and/or improve metabolic syndrome.

Description: Background: This study was performed to understand the possible therapeutic activity of Terminalia panniculata ethanolic extract (TPEE) on non alcoholic fatty liver in rats fed with high fat diet. Methods: Thirty six SD rats were divided into 6 groups (n = 6): Normal control (NC), high fat diet (HFD), remaining four groups were fed on HFD along with different doses of TPEE (100,150 and 200 mg/kg b.wt) or orlistat, for ten weeks. Liver tissue was homogenized and analyzed for lipid profiles, activities of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) content. Further, the expression levels of FAS and AMPK-1alpha were also studied in addition to histopathology examination of liver tissue in all the groups. Results: HFD significantly increased hepatic liver total cholesterol (TC), triglycerides (TG), free fatty acids (FFA) and MDA but decreased the activities of SOD and CAT which were subsequently reversed by supplementation with TPEE in a dose-dependent manner. In addition, TPEE administration significantly down regulated hepatic mRNA expression of FAS but up regulated AMPK-1alpha compared to HFD alone fed group. Furthermore, western blot analysis of FAS has clearly demonstrated decreased expression of FAS in HFD + TPEE (200 mg/kg b.wt) treated group when compared to HFD group at protein level. Conclusions: Our biochemical studies on hepatic lipid profiles and antioxidant enzyme activities supported by histological and expression studies suggest a potential therapeutic role for TPEE in regulating obesity through FAS.

Description: Background: The goal of the study is to investigate the association between the APOA5 polymorphisms and haplotypes with Arterial Hypertension (AHT) in Moroccan patients. Methods: The study was performed in 283 subjects, 149 patients with AHT and 134 controls. All subjects were genotyped for the APOA5 -1131 T 〉 C (rs662799), 56C 〉 G (rs3135506) and c.553G 〉 T (rs2075291) polymorphisms. Results: There was a strong association between -1131 T 〉 C and 56C 〉 G polymorphisms with AHT. The -1131 T 〉 C and 56C 〉 G polymorphisms were significantly associated with increased systolic blood pressure (SBP) and triglycerides (TG) levels. There were 4 haplotypes with a frequency higher than 5%, constructed from APOA5 polymorphisms, with the following order: -1131 T 〉 C, 56C 〉 G and c.553G 〉 T. Haplotype H1 (TCG) was associated with decreased risk of AHT, whereas the haplotypes H2 (CCG) and H4 (CGG) were significantly associated with an increased risk of AHT. Carriers of H1 haplotype had a lower SBP and DBP and TG. In contrast, significant elevated SBP, DBP and TG were found in H4 haplotypes carriers. Conclusions: Our data demonstrate for the first time that several common SNPs in the APOA5 gene and their haplotypes are closely associated with modifications of blood pressure and serum lipid parameters in the AHT patient.

Description: Background: Statin therapy results in regression and stabilization of coronary artery plaques, and reduces the incidence of coronary artery disease. However, statin therapy does not effectively halt the accumulation of necrotic core in all patients. The purpose of the present study was to identify the predictors associated with necrotic core progression during statin therapy. Methods: Coronary atherosclerosis in non-culprit lesions was evaluated using virtual histology intravascular ultrasound at baseline and 8 months after statin therapy. One hundred nineteen patients were divided into 2 groups based on necrotic core progression or regression during an 8-month follow-up period. Results: Patients with necrotic core progression had higher serum lipoprotein(a) [Lp(a)] levels than patients with regression at baseline (16 mg/dL vs. 12 mg/dL, p = 0.02) and at the 8-month follow-up (17 mg/dL vs. 10 mg/dL, p = 0.006). Patients with necrotic core progression had a higher fibro-fatty plaque volume (1.28 mm3/mm vs. 0.73 mm3/mm, p = 0.002), and less necrotic core (0.56 mm3/mm vs. 1.04 mm3/mm, p 〈 0.0001) and dense calcium (0.35 mm3/mm vs. 0.56 mm3/mm, p = 0.006) plaque volumes at baseline than patients with regression. Multivariate logistic regression analysis showed that Lp(a) was a significant independent predictor associated with necrotic core progression during statin therapy (odds ratio [OR]: 3.514; 95% confidence interval [CI]: 1.338-9.228; p = 0.01). Conclusions: Serum Lp(a) is independently associated with necrotic core progression in statin-treated patients with angina pectoris.

Description: Background: Fatty acid-binding protein 2 (FABP2) is an intracellular protein expressed exclusively in the enterocytes of proximal small intestine. FABP2 has a high affinity for saturated and unsaturated long-chain fatty acids and is believed to be involved in the absorption and transport of dietary fatty acids. Methods: This is a case-control study conceded in 438 T2DM cases and 460 subjects with normal glucose levels and non-obese considered as healthy controls. Allelic discrimination was performed using TaqMan single-nucleotide polymorphism genotyping was carried out by real time-polymerase chain reaction (RT-PCR) assays using purified DNA. Results: Clinical data and anthropometric measurements except age, weight, height, body mass index and hips of the patients were significantly different from those of the controls (p 〈 0.05).Statistical analyses failed to show any type of significant association of the polymorphism between cases and controls. However logistic regression analyses was suggests that the TT genotype is significantly associated with male patients (p = 0.001, Table 1). None of the allele or genotypes of FABP2 A54T was associated with T2DM cases versus the controls (AT genotype, OR = 0.85 (0.64-1.12), p = 0.25; TT genotype, OR = 0.66 (0.39-1.11), p = 0.11; T allele, 0.82 (0.67-1.02), p = 0.08). Conclusion: In conclusion, this study suggests that the above named variant in FABP2 gene is not potential contributor to the risk of T2DM and related traits in a Saudi population. However TT genotype is a risk factor for the disease in males.

Description: Background: This study aimed to determine early postoperative changes of plasma polyunsaturated fatty acids (PUFAs) following laparoscopic sleeve gastrectomy (LSG). Methods: Ten obese patients (mean BMI: 51.10 +/- 11.59 kg/m2) underwent LSG and eleven normal weight control patients (mean BMI: 24.37 +/- 2.33 kg/m2) underwent laparoscopic abdominal surgery. Fasting blood samples were collected prior to surgery, at day 1 after surgery and after postoperation oral feeding. Plasma levels of arachidonic acid (AA, C20:4n6), dihomo-gamma-linolenic acid (DGLA, C20:3n6), eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Prostaglandin E2 (PGE2) was measured in serum samples by enzyme immunoassay. Results: A significant decrease was observed in insulin and HOMA IR levels in sleeve gastrectomy patients after postoperation oral feeding compared to preoperation. Plasma AA levels and AA/EPA ratio were significantly increased in sleeve gastrectomy patients after postoperation oral feeding compared to postoperation day 1. Serum PGE2 levels and AA/DHA ratio was significantly higher in sleeve gastrectomy patients at preoperation, postoperation day 1 and after postoperation oral feeding when compared to control group patients. Conclusion: Increased peripheral insulin sensitivity associated with LSG may play a role in the significant increase of plasma AA levels in sleeve gastrectomy patients following postoperation oral feeding. The significant increase in PGE2 levels and AA/DHA ratio in sleeve gastrectomy group patients also confirms the presence of a proinflammatory state in obesity.

Description: Background: We have previously demonstrated that carrying the apolipoprotein (apo) E epsilon 4 (E4+) genotype disrupts omega-3 fatty acids (n - 3 PUFA) metabolism. Here we hypothesise that the postprandial clearance of n - 3 PUFA from the circulation is faster in E4+ compared to non-carriers (E4-). The objective of the study was to investigate the fasted and postprandial fatty acid (FA) profile of triacylglycerol-rich lipoprotein (TRL) fractions: Sf 〉400 (predominately chylomicron CM), Sf 60 - 400 (VLDL1), and Sf 20 - 60 (VLDL2) according to APOE genotype. Methods: Postprandial TRL fractions were obtained in 11 E4+ (epsilon3/epsilon4) and 12 E4- (epsilon3/epsilon3) male from the SATgenepsilon study following high saturated fat diet + 3.45 g/d of docosahexaenoic acid (DHA) for 8-wk. Blood samples were taken at fasting and 5-h after consuming a test-meal representative of the dietary intervention. FA were characterized by gas chromatography. Results: At fasting, there was a 2-fold higher ratio of eicosapentaenoic acid (EPA) to arachidonic acid (P = 0.046) as well as a trend towards higher relative% of EPA (P = 0.063) in the Sf 〉400 fraction of E4+. Total n - 3 PUFA in the Sf 60 - 400 and Sf 20 - 60 fractions were not APOE genotype dependant. At 5 h, there was a trend towards a time x genotype interaction (P = 0.081) for EPA in the Sf 〉400 fraction. When sub-groups were form based on the level of EPA at baseline within the Sf 〉400 fraction, postprandial EPA (%) was significantly reduced only in the high-EPA group. EPA at baseline significantly predicted the postprandial response in EPA only in E4+ subjects (R2 = 0.816). Conclusion: Despite the DHA supplement contain very low levels of EPA, E4+ subjects with high EPA at fasting potentially have disrupted postprandial n - 3 PUFA metabolism after receiving a high-dose of DHA.Trial registration: Registered at clinicaltrials.gov as NCT01384032.

Description: Background: Several studies have identified APOB as a candidate gene predisposing individuals to dyslipidemia. Polymorphisms including the signal peptide (rs11279109), codon 2488 XbaI (rs1042031), codon 3611 MspI (rs693), codon 4154 EcoRI (rs1801701) and the 3' variable number of tandem repeats have been reported to be associated with dyslipidemia in several populations. With limited studies on Arabs, this study aimed to investigate the genetic association of APOB polymorphisms and assess the potential influence of minor and rare alleles on serum lipid levels in the Kuwaiti population. Methods: A total of 795 Kuwaiti subjects, documented with phenotypic data and fasting serum lipid levels, were genotyped for the five polymorphisms using PCR, PCR-RFLP and gene fragment analysis. Genotype and allele association with variation in serum lipid levels as well as haplotypes were analyzed using chi-square test, univariate and logistic regression analysis. Results: Analysis of the genotype and allele frequencies distribution revealed a significant positive association between the APOB signal peptide and 3611 MspI polymorphisms with increased levels of triglycerides (statistical power of 80%). Haplotype analysis further supported the findings by showing that carriers of haplotypes (IX-M-E+M) had significantly lower mean (SD) TG levels (0.86 +/- 0.07) as compared to non-carriers (1.01 +/- 0.02). Significance was also observed with regards to positive family history of hypercholesterolemia. Conclusion: The results imply a "protective role" for two alleles (rs11279109 and rs1801701) in which logistic regression analysis showed a significant half-fold decrease in the risk for heterozygotes of rs11279109 and an 8.8 fold decrease in the risk for homozygous M-M- of rs1801701 of having lower TG levels (

Description: Background: Deregulated secretion of adipokines contributes to subclinical systemic inflammation associated with type 2 diabetes mellitus (T2DM). However, the mechanisms underlying are not fully understood. Hydrogen sulfide (H2S), as an endogenous gasotransmitter, possesses an anti-inflammation activity. The aim of this study was to examine the possible involvement of H2S in high glucose induced adipokine secretion in 3T3-L1 adipocytes. Methods: The expression of cystathionine-gamma-lyase (CSE), the H2S-forming enzyme, was evaluated by Western-blotting and real-time PCR. The secretion of TNF-, MCP-1 and adiponectin was determined by radioimmunoassay and enzyme-linked immunosorbent assay (ELISA), respectively. Lentiviral empty vector and vector expressing mouse CSE were used for in vitro transduction. Results: High glucose (HG) significantly decreased CSE expression at both protein and mRNA levels in mature 3T3-L1 adipocytes. In parallel, HG significantly increased secretion of MCP-1 while decreasing secretion of adiponectin, but had no effect on secretion of TNF-. HG induced changes in MCP-1 and adiponectin secretion were partly attenuated by forced expression of CSE or sodium hydrosulfide (NaHS), a source of exogenous H2S. Conclusion: High glucose induces aberrant secretion of adipokines in mature 3T3-L1 adipocytes, favoring inflammation. The mechanism is partly related to inhibition of CSE/ H2S system.

Description: Background: The aim of the present meta-analysis of cohort studies was to focus on monounsaturated fat (MUFA) and cardiovascular disease, cardiovascular mortality as well as all-cause mortality, and to distinguish between the different dietary sources of MUFA. Methods: Literature search was performed using the electronic databases MEDLINE, and EMBASE until June 2nd, 2014. Study specific risk ratios and hazard ratios were pooled using a inverse variance random effect model. Results: Thirty-two cohort studies (42 reports) including 841,211 subjects met the objectives and were included. The comparison of the top versus bottom third of the distribution of a combination of MUFA (of both plant and animal origin), olive oil, oleic acid, and MUFA:SFA ratio in each study resulted in a significant risk reduction for: all-cause mortality (RR: 0.89, 95% CI 0.83, 0.96, p = 0.001; I2 = 64%), cardiovascular mortality (RR: 0.88, 95% CI 0.80, 0.96, p = 0.004; I2 = 50%), cardiovascular events (RR: 0.91, 95% CI 0.86, 0.96, p = 0.001; I2 = 58%), and stroke (RR: 0.83, 95% CI 0.71, 0.97, p = 0.02; I2 = 70%). Following subgroup analyses, significant associations could only be found between higher intakes of olive oil and reduced risk of all-cause mortality, cardiovascular events, and stroke, respectively. The MUFA subgroup analyses did not reveal any significant risk reduction. Conclusion: The results indicate an overall risk reduction of all-cause mortality (11%), cardiovascular mortality (12%), cardiovascular events (9%), and stroke (17%) when comparing the top versus bottom third of MUFA, olive oil, oleic acid, and MUFA:SFA ratio. MUFA of mixed animal and vegetable sources per se did not yield any significant effects on these outcome parameters. However, only olive oil seems to be associated with reduced risk. Further research is necessary to evaluate specific sources of MUFA (i.e. plant vs. animal) and cardiovascular risk.

Description: Background: An important inter-individual variability in the response of insulin sensitivity following a fish oil supplementation has been observed. The objective was to examine the associations between single nucleotide polymorphisms (SNPs) within sterol regulatory element binding transcription factor 1 (SREBF1) gene and the response of insulin sensitivity to a fish oil supplementation. Methods: Participants (n = 210) were recruited in the greater Quebec City area and followed a 6-week fish oil supplementation protocol (5 g/day: 1.9-2.2 g EPA; 1.1 g DHA). Insulin sensitivity was assessed by the quantitative insulin sensitivity check index (QUICKI). Three tag SNPs (tSNPs) within SREBF1 gene were genotyped according to TAQMAN methodology. Results: Three tSNPs (rs12953299, rs4925118 and rs4925115) covered 100% of the known genetic variability within SREBF1 gene. None of the three tSNPs was associated with either baseline fasting insulin concentrations (rs12953299, rs4925118 and rs4925115) (p = 0.29, p = 0.20 and p = 0.70, respectively) or QUICKI (p = 0.20, p = 0.18 and p = 0.76, respectively). The three tSNPs (rs12953299, rs4925118 and rs4925115) were associated with differences in the response of plasma insulin levels (p = 0.01, p = 0.005 and p = 0.004, respectively) and rs12953299 as well as rs4925115 were associated with the insulin sensitivity response (p = 0.009 and p = 0.01, respectively) to the fish oil supplementation, independently of the effects of age, sex and BMI. Conclusions: The genetic variability within SREBF1 gene has an impact on the insulin sensitivity in response to a fish oil supplementation.Trial registration: clinicaltrials.gov: NCT01343342.

Description: Background: Many drugs are substrates for P-glycoprotein (P-gp) and interactions involving P-gp may be relevant to clinical practice. Co-administration with P-gp inhibitors or inducers changes the absorption profile as well as the risk for drug toxicity, therefore it is important to evaluate possible P-gp alterations. The purpose of this study was to investigate the effect of two novel cholesterol-lowering agents, disodium ascorbyl phytostanol phosphate (DAPP) and nanostructured aluminium silicate (NSAS), a protonated montmorillonite clay, on mdr-1 gene expression and its protein, P-glycoprotein (P-gp) within Caco-2 cells. Methods: The effects of DAPP and NSAS on the regulation of mdr-1 gene, P-gp protein expression and activity within Caco-2 cells, were determined using cell viability and cytotoxicity tests, RT-PCR, Western Blot analysis and bi-directional transport studies. Results: We observed a significant down-regulation of mdr-1 mRNA (e.g. 38.5 +/- 17% decrease vs. control at 10 muM DAPP and 61.2 +/- 25% versus control at 5 muM DAPP; n = 6, P* 〈 0.05) within Caco-2 cells. Western Blot analysis of P-gp expression showed that changes in mdr-1 gene expression lead to correlating changes in P-gp protein expression. This down-regulation of P-glycoprotein also resulted in decreased activity of P-glycoprotein compared to untreated control. In contrast, when Caco-2 cells were treated with NSAS, no changes in mdr-1 gene expression, P-gp protein expression nor P-gp activity were observed. Conclusions: DAPP but not NSAS decreases P-gp mediated drug efflux through decreased mdr-1 gene expression and consequently decreased P-gp protein expression. These findings have to be taken into consideration when DAPP is concurrently given with other drugs that are substrates for P-gp since drug-drug interactions harbour a safety issue and alter bioavailability profiles.NSAS does not have any P-gp altering properties and therefore might not affect drug-drug interactions. We conclude from this study that NSAS might make a safer drug candidate compared to DAPP for lowering LDL-cholesterol.

Description: Background: Diabetic retinopathy, the main microvascular complications of diabetes and one of the leading causes of blindness worldwide. Interesting reports on the role of inflammatory/proangiogenic high mobility group 1 (HMGB-1) cytokine and phospholipases A2 (PLA2) in neovascularization have diverted our concentration to reveal whether HMGB-1 and PLA2 plays role in diabetic retinopathy. Methods: We performed our study in streptozotocin (STZ)-induced diabetic rat model. The expression levels of the cytokines, chemokines, and cell adhesion molecules in retinal tissues were evaluated by quantitative RT-PCR. HMGB-1 and PLA2 protein levels along with VEGF, TNF-alpha, IL-1beta and ICAM-1 levels were also measured. Results: We observed the retinal pericytes, endothelial injury/death and breakdown of blood-retinal barrier (BRB). The protein expression of HMGB-1, PLA2 and IL-1beta were significantly increased in micro vessels from retina of diabetic rats. Diabetic rats had also high retinal levels of VEGF, ICAM-1 and TNF-alpha. Further investigation revealed that pericyte death is mediated by HMGB-1-induced cytotoxic activity of glial cells, while HMGB-1 can directly mediate endothelial cell death. Similarly, increased expression of PLA2 represents the diabetic mediated alteration of BRB, perhaps up regulating the VEGF. Conclusions: Our data suggest that HMGB-1 and PLA2 involved in retinal pericyte and endothelial injury and cell death in diabetic retinopathy. From this study, we suggest that HMGB-1 and PLA2 may be interesting targets in managing diabetic retinopathy.

Description: Background: Sphingolipids are increasingly recognized to play a role in insulin resistance and diabetes. Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated.FindingsWe analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 1-deoxySLs were significantly higher in the groups with T2DM but not different between T1DM and controls. In contrast to patients with T2DM, 1-deoxSL levels are not elevated in T1DM. Conclusions: Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels.

Description: Background: Waist circumference, a metabolic syndrome (MetSy) criterion, is not routinely measured in clinical practice making early identification of individuals with MetSy challenging. It has been argued that ratios of commonly measured parameters such as lipids and lipoproteins may be an acceptable alternative for identifying individuals with MetSy. The objective of our study was to explore clinical utility of lipid ratios to identify men and women with MetSy; and to explore the association between lipid ratios and the number of MetSy components. Methods: Men and women (N = 797) of Aboriginal, Chinese, European, and South Asian origin (35-60 years), recruited across ranges of body mass index (BMI), with no diagnosed cardiovascular disease (CVD) or on medications to treat CVD risk factors were assessed for anthropometrics, family history of CVD, MetSy components (waist circumference, blood pressure, glucose, triglycerides (TG), high-density-lipoprotein-cholesterol (HDL-C)), low-density-lipoprotein-cholesterol (LDL-C), nonHDL-C, and health-related behaviours. Results: Mean levels of lipid ratios significantly increased with increasing number of MetSy components in men and women (p 〈 0.05). After adjustment for age, ethnicity, smoking, alcohol consumption, physical activity, family history of CVD and BMI, (and menopausal status in women), all lipid ratios were associated with the number of MetSy components in men and women (Poisson regression, p 〈 0.001). Compared to the rest of the lipid ratios (ROC curve analysis), TG/HDL-C was best able to discriminate between individuals with and without MetSy (AUC = 0.869 (95%CI: 0.830, 0.908) men; AUC = 0.872 (95%CI: 0.832, 0.912) women). The discriminatory power of TC/HDL-C and nonHDL-C/HDL-C to identify individuals with MetSY was the same (for both ratios, AUC = 0.793 (95%CI: 0.744, 0.842) men; 0.818 (95%CI: 0.772, 0.864) women). Additionally, LDL-C/HDL-C was a good marker for women (AUC = 0.759 (95%CI: 0.706, 0.812)), but not for men (AUC = 0.689 (95%CI: 0.631, 0.748)). Based on a multiethnic sample, we identified TG/HDL-C cut-off values of 1.62 in men and 1.18 in women that were best able to discriminate between men and women with and MetSY. Conclusions: Our results indicate that TG/HDL-C is a superior marker to identify men and women with MetSy compared to TC/HDL-C, LDL-C/HDL-C, and nonHDL-C/HDL-C.

Description: Background: Atherogenic dyslipoproteinemia is one of the most important risk factor for atherosclerotic changes development. Hypothyroidism is one of the most common causes of secondary dyslipidemias which results from reduced LDL clearance and therefore raised levels of LDL and apoB. Association between small dense LDL (sdLDL) presentation and thyroid status has been examinated using polyacrylamide gel electrophoresis for lipoprotein subfractions evaluation. Methods: 40 patients with diagnosed autoimmune hypothyroidism and 30 patients with autoimmune hyperthyroidism were treated with thyroxine replacement or thyreo-suppressive treatment. In both groups lipid profiles, LDL subractions, apolipoproteins (apoA1, apoB), apoA1/apoB ratio and atherogenic index of plazma (AIP) were examined before treatment and in state of euthyreosis. Results: Thyroxine replacement therapy significantly reduced levels of total cholesterol (TC), LDL, triglycerides (TG) and also decreased levels of sdLDL (8,55+/-11,671 vs 0,83+/-1,693mg/dl;p

Description: Background: Several studies have analyzed the association of body mass index (BMI) with either the prevalence or incidence of type 2 diabetes (T2D), but no study from Europe or North America has yet analyzed and compared the association of BMI with both incident and prevalent T2D cases. Methods: Stratified logistic regression was used to calculate odds ratios (OR), and stratified Cox proportional hazards regression was used to calculate hazard ratios (HR) of the effect of BMI on the prevalence, and incidence of T2D. Wald chi-square statistics were applied when comparing the risk estimates. Results: Among prevalent T2D cases, overweight women (BMI 25-29.9 kg/m2) had an OR of 2.83 (95% confidence interval [CI], 1.92-4.18) and obese women (BMI 〉=30 kg/m2) had an OR of 12.12 (95% CI, 8.32-17.68) when compared with normal weight women (BMI

Description: Background: Micronutrients in rapeseed such as polyphenols, tocopherols, phytosterols and phospholipids in rapeseed exert potential benefit to atherosclerosis. Some part of these healthy components substantially lost during the conventional refining processing. Thus some new processing technologies have been developed to produce various endogenous micronutrient-enriched optimized rapeseed oils. The aim of this study is to assess whether optimized rapeseed oils have positive effects on the atherosclerosis risk factors in rats fed a high-fat diet. Methods: Rats received experiment diets containing 20% fat and refined rapeseed oil or optimized rapeseed oils obtained with various processing technologies as lipid source. After 10 weeks of treatment, plasma was assayed for oxidative stress, lipid profiles and imflammation. Results: Micronutrients enhancement in optimized rapeseed oils significantly reduced plasma oxidative stress, as evaluated by the significant elevation in the activities of CAT and GPx as well as the level of GSH, and the significant decline in lipid peroxidation. Optimized rapeseed oil with the highest micronutrient contents obtained by microwave pretreatment-cold pressing reduced the levels of TG, TC and LDL-C as well as IL-6 and CRP in plasma. Conclusions: These results suggest that optimized rapeseed oils may contribute to prevent atherogenesis and make them very promising functional food in cardiovascular health promotion.

Description: Background: High-density lipoprotein (HDL) has been shown to confer cardiovascular protection in clinical and epidemiologic studies. Emerging evidence suggests that many of the cardioprotective functions of HDL may be due to the phospholipid sphingosine-1-phosphate (S1P).Presentation of the hypothesisHDL-S1P binds to S1P receptors in the heart, activating PI3K/Akt signaling and myocyte survival. PI3K/Akt is a classic signaling modulator of autophagy. Excessive autophagy due to cell death and cardiomyocyte loss may contribute to impaired heart function during pressure overload-induced heart failure. Therefore, we hypothesize that HDL-S1P may suppress excessive autophagy of cardiomyocytes through activation of PI3K/Akt signaling. Further, reconstituted HDL (including S1P) may protect heart function during pressure overload-induced heart failure.Testing the hypothesisWe will design the following experiments to test this hypothesis. (1) We will treat cells and mice with PI-3 kinase inhibitors to examine if HDL-S1P downregulates expression of Autophagy-related genes (ATGs) and proteins via activation of PI3K/Akt signaling. (2) We will use siRNA against S1P receptors or inhibitors of S1P receptors to determine which types of S1P receptors participate in this mechanism. (3) We will also examine if reconstituted HDL (including S1P) improves heart function during pressure overload-induced heart failure by suppressing excessive autophagy of cardiomyocytes through activation of PI3K/Akt signaling.Implications of the hypothesisUnderstanding the autophagy signaling pathway modulated by HDL-S1P will make a major contribution to the field by identifying a novel mechanism for cardiovascular protection of high-density lipoprotein. Further, using reconstituted HDL to improve heart function would provide a novel therapeutic approach for pressure overload-induced heart failure.

Description: Background: Endothelial dysfunction is implicated in the initiation and progression of atherosclerosis. Whether atorvastatin combined with rosiglitazone has synergistic effects on endothelial function improvement in the setting of dyslipidemia is unknown. Methods: Dyslipidemia rat model was produced with high-fat and high-cholesterol diet administration. Thereafter, atorvastatin, rosiglitazone or atorvastatin combined with rosiglitazone were prescribed for 2 weeks. At baseline, 6 weeks of dyslipidemia model production, and 2 weeks of medical intervention, fasting blood was drawn for parameters of interest evaluation. At the end, myocardium was used for 15-deoxy-delta-12,14-PGJ2 (15-d-PGJ2) assessment. Results: Initially, there was no significant difference of parameters between sham and dyslipidemia groups. With 6 weeks' high-fat and high-cholesterol diet administration, as compared to sham group, serum levels of triglyceride (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) were significantly increased. Additionally, nitric oxide (NO) production was reduced and serum levels of malondialdehyde (MDA), C-reactive protein (CRP) and asymmetric dimethylarginine (ADMA) were profoundly elevated in dyslipidemia group. After 2 weeks' medical intervention, lipid profile was slightly improved in atorvastatin and combined groups as compared to control group. Nevertheless, in comparison to control group, NO production was profoundly increased and serum levels of MDA, CRP and ADMA were significantly decreased with atorvastatin or rosiglitazone therapy. 15-d-PGJ2 expression of myocardium was also significantly elevated with atorvastatin or rosiglitazone treatment. Notably, these effects were further enhanced with combined therapy, suggesting that atorvastatin and rosiglitazone had synergistic effects on endothelial protection, and inflammation and oxidation amelioration. Conclusion: Atorvastatin and rosiglitazone therapy had synergistic effects on endothelium protection as well as amelioration of oxidative stress and inflammatory reaction in rats with dyslipidemia.

Description: Background: Previously, we identified three loci affecting HDL-cholesterol levels in a screen for ENU-induced mutations in mice and discovered two mutated genes. We sought to identify the third mutated gene and further characterize the mouse phenotype. Methods: We engaged, DNA sequencing, gene expression profiling, western blotting, lipoprotein characterization, metabolomics assessment, histology and electron microscopy in mouse tissues. Results: We identify the third gene as Ampd2, a liver isoform of AMP Deaminase (Ampd), a central component of energy and purine metabolism pathways. The causative mutation was a guanine-to-thymine transversion resulting in an A341S conversion in Ampd2. Ampd2 homozygous mutant mice exhibit a labile hypercholesterolemia phenotype, peaking around 9 weeks of age (251 mg/dL vs. wildtype control at 138 mg/dL), and was evidenced by marked increases in HDL, VLDL and LDL. In an attempt to determine the molecular connection between Ampd2 dysfunction and hypercholesterolemia, we analyzed hepatic gene expression and found the downregulation of Ldlr, Hmgcs and Insig1 and upregulation of Cyp7A1 genes. Metabolomic analysis confirmed an increase in hepatic AMP levels and a decrease in allantoin levels consistent with Ampd2 deficiency, and increases in campesterol and beta-sitosterol. Additionally, nephrotic syndrome was observed in the mutant mice, through proteinuria, kidney histology and effacement and blebbing of podocyte foot processes by electron microscopy. Conclusion: In summary we describe the discovery of a novel genetic mouse model of combined transient nephrotic syndrome and hypercholesterolemia, resembling the human disorder.

Description: Background: Our previous study has shown that regardless of a relatively high amount of cholesterol, squid homogenate lowers serum and hepatic cholesterol in animals. Since this work, we have developed a new method to inhibit autolysis of squid proteins with sodium citrate. This study aims to investigate how squid homogenate prepared with sodium citrate affects lipid metabolism in Sprague-Dawley rats at the molecular level. Methods: We prepared squid homogenate with sodium citrate to inhibit autolysis of squid protein. In Experiment 1 (Exp. 1), rats were given a cholesterol-free control diet or a squid diet, with squid homogenate added at the level of 5% as dietary protein for 4 weeks. Blood, the liver and adipose tissue were taken after 6 hours fasting. Serum and hepatic lipids and activities of enzymes related to lipid metabolism were measured. In Experiment 2 (Exp. 2), the above-mentioned diets had cholesterol added at the level of 0.1% and given to rats. Lipid parameters, enzyme activities, and gene expression of proteins involved in lipid metabolism in the liver and the small intestine were determined. In addition, feces were collected for two days at the end of Exp. 2 to measure fecal excretion of steroids. Results: In Exp.1, serum triglyceride and cholesterol were ~50% and ~20% lower, respectively, in the squid diet-fed rats than in the control diet-fed animals while hepatic cholesterol was ~290% higher in the squid diet-fed rats. When cholesterol was included into the diets (Exp. 2), serum lipids were significantly lower in the squid group while no difference of hepatic lipid was seen between two groups. Activities of hepatic lipogenic enzymes were significantly lower in rats on the squid diet while the enzyme responsible for fatty acid oxidation was not modified (Expt. 1 and 2). Hepatic level of mRNA of microsomal triglyceride transfer protein was significantly lower in the squid group. In the small intestine, the squid diet exhibited significantly lower gene expression of proteins involved in fatty acid transport and cholesterol absorption. Fecal secretion of acidic steroids, but not neutral steroids, was higher in rats fed the squid diet than in those fed the control diet. Conclusion: These results imply that newly-developed squid homogenate has hypolipidemic potential primarily through decreased absorption of bile acids in the small intestine and suppressed lipogenesis in the liver.

Description: Excessive energy storage of adipose tissue makes contribution to the occurrence and progression of obesity, which accompanies with multiple adverse complications, such as metabolic syndrome, cardiovascular diseases. It is well known that apolipoprotein E, as a component of lipoproteins, performs a key role in maintaining plasma lipoproteins homeostasis. Interestingly, apolipoprotein E is highly expressed in adipocyte and has positive relation with body fat mass. Apolipoprotein E knock-out mice show small fat mass compared to wild type mice. Moreover, adipocyte deficiency in apolipoprotein E shows impaired lipoproeteins internalization and triglyceride accumulation. Apolipopreotein E-deficient lipoproteins can not induce preadipocyte to form round full-lipid adipocyte, whereas apolipoprotein E-containing lipoproteins can. This article mainly reviews the modulation of apolipoprotein E synthesized by adipocyte and apolipoprotein E carried on lipoproteins in adipocyte triglyceride content.

Description: It has proven difficult to compare the bioavailability of krill oil (KO) vs. fish oil (FO) due to several of the characteristics of KO. These include the lower concentration of the active ingredients, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n3), in KO as well as differences in their ratio relative to FO as well as the red color due to astaxanthin. In addition, the lipid classes in which EPA and DHA are found are quite different with KO containing phospholipid, di- and tri-glycerides as well as non-esterified fatty acid forms and with FO being primarily triglycerides. No human study has yet been performed that matches the dose of EPA and DHA in a randomized, controlled trial with measures of bloodstream EPA and DHA content. However, several claims have been made suggesting greater bioavailability of KO vs. FO. These have largely been based on a statistical argument where a somewhat lower dose of KO has been used to result in a similar bloodstream level of EPA and/or DHA or their total. However, the magnitude of the dosage differential is shown to be too small to be expected to result in differing blood levels of the long chain n-3 PUFAs. Some studies which have claimed to provide equal doses of KO and FO have actually used differing amounts of the two major n-3 fatty acid constituents. It is concluded that there is at present no evidence for greater bioavailability of KO vs. FO and that more carefully controlled human trials must be performed to establish their relative efficacies after chronic administration.

Description: Background: Thymus algereinsis Boiss. et Reut. (Lamiaceae), popularly known as "mougecha" or "mazoukcha" is prolific in Mediterranean regions, mostly in North Africa, and is used in folk medicine to treat of stomach diseases. Methods: In this study, animals were induced with gastric ulcers using HCl/ethanol (0.3 M HCl/60% ethanol) and treated orally with essential oil of Thymus algereinsis (EOTa) in various doses ranging from 54 mg/kg body weight to 180 mg/kg body weight.Result: The dose found to be effective was 180 mg/kg body weight, since this dose brought about a maximum reduction in lesion index in female rats. In gastric tissues, levels of total glutathiones (GSH, GST and GPx) and thiobarbituric acid reactive substances (TBARS) were evaluated. The activities of the antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD) were measured. Histopathological changes were observed using a cross section of gastric tissue. Chemical analysis revealed the presence of 13 components accounting for 77.7% of the essential oil from dried leaves. Oral administration of EOTa (54, 117 and 180 ml/kg) inhibited HCl/ethanol-induced ulcers. Lesion index was significantly reduced in ulcer induced animals treated with EOTa (HCl/ethanol + EOTa) compared to those ulcerated with HCl/ethanol but with no treatment given. Females showed a greater resistance to ulcers and gastric lesions occurred less often than in males. GSH, pH, enzymic antioxidants, and adherent mucus content were all significantly increased. Conclusion: From the data presented in this study, it can be concluded that male rats are more sensitive to gastric ulcers induced by HCl / ethanol than females.

Description: Background: Epidemiological studies have shown that chronic kidney disease (CKD) is an important risk factor for atherosclerosis and cardiovascular disease (CAD). The aim of the study was to determine markers of increased risk of CAD and to achieve a better understanding of agents implicated in the process of atherosclerosis in CKD patients. Methods: The study group consisted of a total of 139 patients with CKD while the control group comprised 45 healthy volunteers. Concentrations of osteoprotegerin, osteopontin, osteocalcin, matrix gamma-carboxyglutamic acid (Gla) protein (MGP), fetuin A, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP 1), tissue inhibitor of metalloproteinase-2 (TIMP-2), ATP binding cassette transporter A1 (ABCA1), ATP binding cassette transporter G1 (ABCG1) and renalase were measured by the ELISA method. Results: We observed decreased levels of fetuin A (control vs. CKD group: 37.5 vs. 33.2 ng/ml, p=0.018), and increased concentrations of osteocalcin (control vs. CKD group: 9.1+/-6.0 vs. 13.6+/-10.3 ng/ml, p=0.05), MMP-2 (113.1+/-75.0 vs. 166.0+/-129.9 ng/ml, p=0.045), TIMP-2 (22.1+/-5.1 vs. 25.4+/-7,0 ng/ml, p=0.005) and renalase (251.0+/-157 vs. 316.1+/-155.3 ng/ml, p=0.026). In patients with CKD (in comparison to control group), left ventricle ejection fraction: 53.0+/-3,5% vs. 48.5%, p=0.012) and calcification of the aortic valve (9.5% vs. 39.8%, p=0.008) were observed more frequently. Conclusions: Decreased levels of fetuin A and increased concentration of osteocalcin, renalase, MMP-2 and TIMP-2 suggest that these factors may be involved in the pathogenesis of CAD in patients with CKD. Significantly increased indices of cardiac hypertrophy and its dysfunction in patients with CKD are indicators of pathological mechanisms occurring in cardiovascular system in this group of patients.

Description: Background: Breast cancer is the most common cancer amongst Malaysian women. Both the disease and its treatment can disrupt the lives of the woman and adversely affect all aspects of life and thus can alter a woman's quality of life. The aim of this study was to examine the effect of virgin coconut oil (VCO) on the quality of life (QOL) of patients diagnosed with breast cancer. Methods: This was a prospective study of breast cancer patients admitted into the Oncology Unit of Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. The sample consisted of 60 patients with stage III and IV breast cancer allocated to either an intervention group (n = 30) or a control group (n = 30) using a simple random table. QOL was evaluated from the first cycle of chemotherapy to the sixth cycle, and data were collected using a validated Bahasa Malaysia version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-C30) and its breast-specific module (QLQ-BR 23). Results: The mean age of breast cancer patients was 50.2 (SD = 13.5) years. There were significant mean score differences for functioning and global QOL between groups (alpha 〈 0.01). The intervention group also had better scores for symptoms including fatigue, dyspnea, sleep difficulties, and loss of appetite compared to the control group. Although there are deteriorations for sexual enjoyment, the intervention group exhibited improvement in breast functioning and symptom scores for body image, sexual function, future perspective, breast symptoms, and systemic therapy side effects. Conclusion: VCO consumption during chemotherapy helped improve the functional status and global QOL of breast cancer patients. In addition, it reduced the symptoms related to side effects of chemotherapy.

Description: Background: The migration of T cell to atherosclerotic lesions is proposed to be involved in the pathogenesis of the atherosclerosis. Sphingosine 1-phosphate (S1P), a bioactive lysophospholipid released from activated platelets, exerts a variety of responses such as cell migration and proliferation, and reportedly induces T cell migration. Accordingly, platelet-T cell interactions may exist based on T cell responses triggered by platelet-derived S1P. Methods: S1P was measured using two-step lipid extraction followed by high-performance liquid chromatography (HPLC) separation while other phospholipids were determined by an enzymatic assay. The expression of S1P and lysophosphatidic acid receptors on Jurkat T cells was examined by RT-PCR and flow cytometry. Jurkat cell migration by S1P and the supernatant of activated platelets (SAP) was evaluated by a modified Boyden's chamber assay. Results: S1P1 receptor was confirmed to be expressed on Jurkat T cell by RT-PCR and flow cytometry. S1P at 10-100 nM induced strong Jurkat cell migration, which was inhibited by the S1P1 (and S1P3) antagonist VPC23019 and the Gi inactivator pertussis toxin (PTX). We found that the supernatant (releasate) of human platelets activated by collagen stimulation, which contains S1P abundantly, induced Jurkat cell migration and that the migration was inhibited by VPC23019 and PTX. In addition, human serum, into which platelet contents (including S1P) are fully released, induced the Jurkat cell migration, which was also inhibited by VPC23019. Conclusions: Our findings suggest that platelet-derived S1P induces Jurkat T cell migration possibly via S1P1. S1P may be a key molecule involved in the responses triggered by platelet-T cell interactions, including atherosclerosis.

Description: Background: Polyunsaturated fatty acid (PUFA) intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, the relationship between the PUFA and inflammatory factors in the healthy vegetarians were not clear. We aimed to investigate the plasma fatty acids status, and its association with plasma inflammatory factors in Chinese vegetarians and omnivores. Methods: A total of 89 male vegetarians and 106 male omnivores were participated the study. Plasma concentrations of inflammatory factors were detected by ELISA, and as standard methods fatty acids were extracted and determined by chromatography. Results: Compared with omnivores, vegetarians have significant higher interleukin-6 (IL-6), plasma n-6 PUFA, n-6/n-3, and 18:3n-3; while they have significant lower leukotriene B4 (LTB4), cyclo-oxygenase-2 (COX2) and prostaglandin E2 (PGE2), 20:5n-3, 22:5n-3, 22:6n-3, and n-3 PUFA. In vegetarians, plasma 20:4n-6 was significant positively related to TNF-alpha. LTB4 was significantly positively related to plasma 22:6n-3, and negatively associated with n-6 PUFA. Conclusion: Vegetarians have higher plasma n-6 PUFA and IL-6, but lower LTB4, n-3 PUFA, 22:6n-3, COX2 and PGE2 levels. It would seem appropriate for vegetarians to increase their dietary n-3 PUFA, while reduce dietary n-6 PUFA and thus reduce the risk of chronic inflammatory-related diseases.

Description: Background: Hypercholesterolemia is a well-established risk factor for the development of kidney injury. Considering that female sex hormones may play a preventative role in both cardiovascular and renal diseases, the aim of the present study was to evaluate the effects of female sex hormones on hypercholesterolemia-induced renal dysfunction. Methods: Apolipoprotein E-deficient (ApoE) and C57 control female mice underwent an ovariectomy (OVX) or sham surgery and after 2 months, creatinine clearance, uremia and proteinuria were determined. Renal oxidative stress and lipid deposition were also quantified. Values are presented as mean +/- SEM. Statistical analyses were performed using Two-way ANOVA followed by Tukey's post hoc test. Results: Creatinine clearance (muL/min) was similar between C57 (171 +/- 17) and ApoE (140 +/- 26) mice underwent sham surgery. OVX resulted in a reduced glomerular filtration rate in both C57 (112 +/- 8, ~ - 35%, p 〈 0.05) and ApoE (61 +/- 10, ~ - 56%, p 〈 0.05) animals. Plasma levels of urea (mg/dL) were higher in both ApoE groups (Sham: 73 +/- 7; OVX: 73 +/- 8, p 〈 0.05) when compared to C57 animals (Sham: 49 +/- 3; OVX: 60 +/- 4), with no changes among ovariectomized groups. Proteinuria levels (mg/24 h) were similar between C57 (Sham: 25.1 +/- 5.7; OVX: 33.7 +/- 4.7) and ApoE sham animals (26.4 +/- 3.5), however, 24-h urine protein excretion was augmented in ApoE OVX animals (49.6 +/- 5.8, p 〈 0.05). Histological kidney analysis demonstrated that the absence of female sex hormones resulted in increased oxidative stress, which was more severe in ApoE mice (C57 Sham: 9.2 +/- 0.4; C57 OVX: 22.9 +/- 1.0; ApoE Sham: 13.9 +/- 0.7; ApoE OVX: 34.0 +/- 1.4 au x 103, p 〈 0.05). As expected, ApoE mice presented higher lipid deposition, which was not affected by OVX (C57 Sham: 0 +/- 0; C57 OVX: 0 +/- 0; ApoE Sham: 6.8 +/- 1.6; ApoE OVX: 5.2 +/- 0.8% x 10-2, p 〈 0.05). Ovariectomy resulted in a similar reduction in ER-alpha protein expression in the renal cortex (C57: 0.78 +/- 0.04; ApoE: 0.81 +/- 0.04 au, p 〈 0.05) when compared to sham animals (C57:1.00 +/- 0.04; ApoE: 1.03 +/- 0.03 au). Conclusion: Taken together these data indicate that female sex hormones may delay hypercholesterolemia-induced renal dysfunction and emphasizes the importance of plasma cholesterol control in post-menopausal women.

Description: Background: Aerobic exercise can decrease postprandial triglyceride (TG) concentrations but the relationship between exercise-induced energy deficits and postprandial lipemia is still unclear. The aim of the present study was to examine the effect of a single bout of aerobic exercise, with and without energy replacement, on postprandial lipemia and on peripheral blood mononuclear cell (PBMC) mRNA expression of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) receptors and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Methods: Nine healthy male humans completed three two-day trials in a random order. On day 1, volunteers rested (CON), completed 60 minutes of treadmill walking at 50% of VO2peak (EX) or completed the same bout of walking but with the energy replaced afterwards with a glucose solution (EXG). On day 2, volunteers rested and consumed a high fat test meal in the morning. Results: Total and incremental TG AUC were significantly lower on the EXG (P 〈 0.05) and EX (P 〈 0.05) trials than the CON trial with no difference between the two exercise trials. No significant difference was observed in VLDL or LDL receptor mRNA expression among the trials (P 〉 0.05). Conclusions: In conclusion, energy replacement by glucose did not affect the decrease in postprandial TG concentrations observed after moderate intensity exercise and exercise does not affect changes in PBMC HMGCR, VLDL and LDL receptor mRNA expression.

Description: Background: To determine the effects of post-challenge hyperglycemia potentiate low-density lipoprotein cholesterol (LDL) particles on the risk of arterial stiffness in non-diabetic adults. Methods: During 2009-2011, 592 adults without clinical diabetes (fasting glucose

Description: Background: Shark liver oil (SLO) contains both alkylglycerols (AKG) and squalene and is an ancient remedy among the fishermen on the west coast of Norway and Sweden. Literature reports showed that alkyglycerols enhance Fc-receptor mediated phagocytosis, increase humoral immune response and delay hypesensivity reactions. Methods: On this background we performed an open spontaneous study on 40 very old aged surgical patients preoperatively treated with alkyglycerols (500mg twice a day for 4 weeks), in order to reduce the risks of operation, counteracting the postoperative inflammatory and anergic conditions thus achieving quick and plain recovery. To better understand the possible therapeutic impact of alkyglycerols we compared on a case/control basis treated versus untreated patients submitted contemporarily to the identical operation and exposed to the same environmental and seasonal risks. Results: The onset of complications was reduced in the alkyglycerols treated group and the compliance to the natural treatment was excellent without any serious adverse effect. WBC count and IgG significant increase (respectively p

Description: Background: Elevated serum Mead acid as a proportion of total fatty acids is an indirect marker of a deficiency of essential fatty acids (EFA). The aim of the study was to evaluate the symptoms and nutrition of food-allergic children with elevated or normal serum Mead acid. Methods: Serum fatty acid compositions from 400 children were studied by clinical indications, mostly by suspicion of deficiency of EFA due to inadequate nutrition. A Mead acid level exceeding 0.21% (percentage of total fatty acids) was considered to be a specific sign of an insufficient EFA supply. From a total of 31 children with elevated Mead acid (MEADplus group), 23 (74%) had food allergy. The symptoms and dietary restrictions of this MEADplus group of food allergic children were compared to 54 age-and sex-matched controls with food allergy but normal Mead acid proportions (MEADminus group) before and 6 months after the serum fatty acid determination. Results: At the beginning of the 6-month follow-up, 44% of the food allergic children in both MEADplus and MEADminus groups were on an elimination diet. These diets did not differ between the two groups and we were not able to document an association between the severity of elimination diet and elevated Mead acid proportion. However, the MEADplus children were on average more symptomatic than MEADminus children. In the MEADplus group, food allergy presented with skin symptoms in 100% (vs. 70% in the MEADminus group, p 〈 0.001) and with vomiting or diarrhea in 70% (vs. 44% in the MEADminus group, p 〈 0.05). Clinical suspicion of malnutrition resulted in increase in the use of vegetable oil and milk-free margarine in both groups from

Description: Background: To investigate relationship between glycated hemoglobin (HbA1c) level and coronary artery disease (CAD) severity Methods: Observational study was conducted and 573 participants were enrolled and baseline characteristics were collected. Clinical presentations in terms of stable angina, unstable angina or acute myocardial infarction were diagnosed. All participants were performed coronary angiography to figure out the numbers of coronary artery stenosis in terms of none-stenosis ( 〈 50% stenosis), single or multiple vessels stenoses (〉= 50% stenosis). All participants were divided into subgroups according to two categories in terms of severity of clinical presentation (stable angina, unstable angina, or acute myocardial infarction) and the number of coronary artery stenosis (none, single, and multiple vessels). Primary endpoint was to evaluate relationship between baseline HbA1c value and CAD severity. Results: Consistent to previous studies, participants with CAD had more risk factors such as elderly, smoking, low HDL-C and high CRP levels. Notably, HbA1c level was more prominent in CAD group than that without CAD. As compared to stable angina subgroup, HbA1c levels were gradually increased in unstable angina and acute myocardial infarction groups. Similar trend was identified in another category in terms of higher HbA1c level corresponding to more vessels stenoses. Multivariate regression analyses showed that after adjusted for traditional risk factors as well as fasting blood glucose, HbA1c remained strongly associated with the severity of CAD. Nonetheless, there was no significant association when CRP was accounted for. Conclusion: HbA1c may be a useful indicator for CAD risk evaluation in non-diabetic adults.

Description: Background: The aim of present study is to investigate the hypocholesterolemic effects of the oat components other than the beta-glucan in rats fed with a hypercholesterolemic diet. Methods: Four-week-old male Wister rats were divided into 6 groups of 7 rats each with similar mean body weights and serum cholesterol concentrations. Rats were fed with the experimental diets containing 10% oats flour for 30 days. Food intake was recorded and monitored everyday to ensure the similar contents of protein, starch, lipid and cellulose in all groups. The lipids levels in serum, liver, and faeces were determined. Results: The plasma total cholesterol concentrations in different oat groups were significantly reduced compared with the control group, and the effects were different among oat groups. The decrease extent of plasma total cholesterol and low-density lipoprotein-cholesterol concentrations increased with the increase of the proteins and lipids contents. Moreover, liver total cholesterol and cholesterol ester contents were markedly decreased. The fecal bile acids concentrations in the oat groups were significantly increased. Oat proteins had lower Lysine/Arginin (0.59 ~ 0.66) and Methionin/Glycine (0.27 ~ 0.35) ratio than casein (Lysine/Arginin, 2.33; Methionin/Glycine, 1.51). Oat lipids contained higher contents of total Vitamin E and plant sterols than that in soybean oil. Conclusion: These results indicated that dietary oat improved hypercholesterolemia by increasing the excretions of fecal bile acids, and this improvement was not only related to beta-glucan, but also attributed to the lipids and proteins. Oat proteins decreased serum total cholesterol and low-density lipoprotein-cholesterol contents due to their low Lysine/Arginin and Methionin/Glycine ratio. The co-existence of oleic acid, linoleic, vitamin E, or plant sterols accounted for the hypocholesterolemic properties of oat lipids.

Description: Background: Based on previous observations a potential resort in the therapy of the particularly radioresistant glioma would be its treatment with unsaturated fatty acids (UFAs) combined with irradiation. Methods: We evaluated the effect of different UFAs (arachidonic acid (AA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and oleic acid (OA)) on human U87 MG glioma cell line by classical biochemical end-point assays, impedance-based, real-time cellular and holographic microscopic analysis. We further analyzed AA, DHA, and GLA at morphological, gene and miRNA expression level. Results: Corresponding to LDH-, MTS assays and real-time cytoxicity profiles AA, DHA, and GLA enhanced the radio sensitivity of glioma cells. The collective application of polyunsaturated fatty acids (PUFAs) and irradiation significantly changed the expression of EGR1, TNF-alpha, NOTCH1, c-MYC, TP53, HMOX1, AKR1C1, NQO1, while up-regulation of GADD45A, EGR1, GRP78, DDIT3, c-MYC, FOSL1 were recorded both in response to PUFA treatment or irradiation alone. Among the analyzed miRNAs miR-146 and miR-181a were induced by DHA treatment. Overexpression of miR-146 was also detected by combined treatment of GLA and irradiation. Conclusions: Because PUFAs increased the radio responsiveness of glioma cells as assessed by biochemical and cellular assays, they might increase the therapeutic efficacy of radiation in treatment of gliomas. We demonstrated that treatment with DHA, AA and GLA as adjunct to irradiation up-regulated the expression of oxidative-stress and endoplasmic reticulum stress related genes, and affected NOTCH1 expression, which could explain their additive effects.

Description: Background: Cytochrome P450 (CYP) 2C9 is expressed in the vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which have the crucial role in the modulation of cardiovascular homeostasis. We sought to assess the association between the human CYP2C9 gene and coronary artery disease (CAD) in Xinjiang Han Population of China. Methods: 301 CAD patients and 220 control subjects were genotyped for 4 single-nucleotide polymorphisms (SNPs) of the human CYP2C9 gene (rs4086116, rs2475376, rs1057910, and rs1934967) by a Real-Time PCR instrument. The datas were assessed for 3 groups: total, men, and women via diplotype-based case-control study. Results: For women, the distribution of genotypes, dominant model and alleles of SNP2 (rs2475376) showed significant difference between the CAD patients and control participants (p = 0.033, P = 0.010 and p = 0.038, respectively). The significant difference of the dominant model (CC vs CT + TT) was retained after adjustment for covariates in women (OR: 2.427, 95 % confidence interval [CI]: 1.305-4.510, p = 0.005). The haplotype (C-T-A-C) and the diplotypes (CTAC/CTAC) in CYP2C9 gene were lower in CAD patients than in control subjects (p* = 0.0016, and p* = 0.036 respectively). The haplotype (C-C-A-T) was higher in the CAD patients than in the control subjects in women (p* = 0.016). Conclusions: CC genotype of rs2475376 and C-C-A-T haplotype in CYP2C9 may be a risk genetic marker of CAD in women. T allele of rs2475376, the haplotype (C-T-A-C) and the diplotype (CTAC/CTAC) could be protective genetic markers of CAD for women in Han population of China.

Description: Background: The cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) gene is expressed in the vascular endothelium, which metabolizes arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs). 20-HETE mediates cardiovascular homeostasis and growth response in vascular smooth muscle cells (VSMCs) as well as the anti-platelet effect. EETs are potent endogenous vasodilators and inhibitors of vascular inflammation. This study assessed the association between human CYP1A1 gene polymorphisms and coronary artery disease (CAD) in the Uygur and Han in China. Methods: Two independent case-control studies that recruited Han (389 patients with CAD and 411 controls) and Uygur participants (293 patients with CAD and 408 controls) analyzed the relationship between CYP1A1 single nucleotide polymorphisms (SNPs: rs4886605, rs12441817, rs4646422 and rs1048943) and CAD. All patients with CAD and controls were genotyped for the four SNPs of CYP1A1 using TaqMan SNP genotyping assays. Results: In the Uygur group, the distribution of the dominant model(CC vs CT + TT) of rs4886605 for the total sample and the males was significantly different between CAD patients and control participants (P = 0.001 and P = 0.012, respectively), The difference remained significant after a multivariate adjustment (P = 0.018, P = 0.015, respectively). The rs12441817 was also associated with CAD in a dominant model for all participants (P = 0.003) and men (P = 0.012), and the difference remained significant after a multivariate adjustment (P = 0.016, P = 0.002, respectively). However, we did not observe differences in the Uygur females and Han group with regard to the allele frequency or genotypic distribution of rs4886605 and rs12441817 between patients with CAD and control participants. Patients with CAD did not significantly differ from the control participants with regard to the distributions of rs4646422 and rs1048943 genotypes, the dominant model, the recessive model, or allele frequency in the Han and Uygur groups. Conclusion: Both rs4886605 and rs12441817 SNPs of the CYP1A1 gene are associated with CAD in the Uygur population of China.

Description: Background: Psychosocial stress is one of the risk factors for atherosclerosis. As occlusal disharmony induces psychological stress, we hypothesized that psychological stress by occlusal disharmony accelerates atherosclerosis. The aim of this study was to investigate the effects of occlusal disharmony on the initiation of atherosclerosis in apolipoprotein E (apoE) knockout rats. Methods: Fourteen male apoE-knockout rats (age; 8 weeks) (Sprague-Dawley strain background) were divided into two groups of seven rats: the occlusal disharmony group and the no treatment (control) group. In the occlusal disharmony group, the maxillary molar cusps were cut off for the 8-week experimental period. Results: In the occlusal disharmony group, the percentages of the area of total aortic lumen occupied by plaques and lipid were significantly higher than those in the control group (p 〈 0.05, t-test). The occlusal disharmony group also showed significantly higher serum levels of very low-density lipoprotein-cholesterol (VLDL) and low-density lipoprotein-cholesterol (LDL), plasma levels of corticosterone (1.9, 1.3 and 1.3 times, respectively), higher aortic protein expression levels of vascular cell adhesion molecule-1 (VCAM1) and intercellular adhesion molecule-1 (ICAM1) (1.5 and 1.4 times, respectively), and higher aortic gene expression of levels of VCAM1 and Toll-like receptor 4 (TLR4) (1.9 and 4.3 times, respectively), as compared to the control group (p 〈 0.05). However, there were no significant differences in serum levels of oxidized LDL, reactive oxygen metabolites and C-reactive protein between the two groups. Conclusion: In apoE knockout rats, occlusal disharmony may induce VCAM1, ICAM1 and TLR4 expression and accelerate the initiation of atherosclerosis.

Description: Background: N-3 PUFAs have been demonstrated in vitro it could prevent the intestinal tight junctions (TJs) from the ischemia/re-perfusion injury and the inflammatory reaction injury. The purpose of this study was to evaluate the protection of n-3 PUFAs on the intestinal TJs in the rat model of hemorrhagic shock followed by resuscitation. Methods: Male SD rats (n = 72; 250 ~ 300 g) were randomly divided into 6 groups: SHAM, hemorrhagic shock (HS), hemorrhagic shock/resuscitation (HS/R), omega-6 group, omega-3 group and omega-3 treatment group. Shock was induced, and a mean arterial pressure was maintained at 35 to 40 mmHg for 60 minutes. Resuscitation was carried out by returning half of the shed blood and Ringer's lactate solution. In omega-6 and omega-3 group, Intralipid or fish oil (0.2 g/Kg), respectively, was infused 30 minutes after shock. And fish oil was infused with resuscitation in omega-3 treatment group. Half of each group was killed at 30 minutes and 4 hours after resuscitation, respectively. The serum samples and the intestinal sample was collected for further examination.Result: There is no difference between omega-3, omega-3 treatment and sham group in Chiu's score, but the other three groups have higher scores than they did. Compared with HS, HSR and omega-6 group, omega-3 and omega-3 treatment group showed most intact in intestinal mucoscal villi and TJs through HE, SEM and LSCM. The levels of IL-6 and TNF-alpha of bowel tissue in omega-3 and omega-3 treatment group were significantly lower than HS and HSR groups'. At the time point of 30 min, the levels of serum endotoxin were dramatically higher in HS[ideographic comma]HSR and omega-6 groups when compared with omega-3, omega-3 treatment and sham group. However, it in omega-3 group was greater than sham and HS group until 4 hours. Conclusion: Fish oil pretreatment before resuscitation showed a beneficial effect to the intestinal TJs and atteunated inflammation after H/R in HS/R rat model and is better than omega-6 PUFAs did.

Description: Background: GP78 is a membrane-anchored ubiquitin ligase mediating the degradation of 3-hydroxy-3-methyl-glutaryl-CoA coenzyme A reductase (HMGCR) and Insig-1, which was very essential for the synthesis of cholesterol process. Cholesterol levels have a causal role in the development of cardiovascular disease. The aim of the present study was to assess the association between the human gp78 gene polymorphism and coronary artery disease (CAD) in a Han and Uygur population of China. Methods: We used two independent case-control studies: a Han population (602 CAD patients and 572control subjects) and a Uygur population (374 CAD patients and 376control subjects). All CAD patients and controls were genotyped for the same three single nucleotide polymorphisms (SNPs) (rs731119, rs2617849and rs2440472) of gp78 gene by a Real-time PCR instrument. Results: In the Han population, for total and men, the distribution of SNP3 (rs2440472) alleles and the dominant model (AA vs AG + GG) and recessive model (GG vs AG + AA) showed a significant difference between CAD and control participants (for allele: P = 0.003 and P = 0.002, respectively; for dominant model: P = 0.041 and P = 0.026, respectively; for recessive model: p = 0.004 and p = 0.004, respectively).The significant difference in both the two models was retained after adjustment for covariates (for dominant model OR:0.760, 95% confidence interval [CI]:0.584-0.99, P = 0.042; OR:0.686, 95% CI: 0.498-0.946, P = 0.022, respectively; for recessive model OR: 1.451, 95%CI: 1.067-1.974, P = 0.018; OR: 1.789, 95% CI: 1.219-2.627, P = 0.000). Our data was also assessed via haplotype-based case-control studies. For the Han population, for total, The G-T-G haplotype in CAD was significantly higher than that in the control group (P = 0.02), and the G-C-A haplotype in CAD was significantly lower than that in the control group (P = 0.0443), And for man, the G-T-G haplotype in CAD was significantly higher than that in the control group (P = 0.0048). Conclusions: The GG genotype and G allele of rs2440472 in gp78 gene could be a risk genetic marker of CAD in Han population in China.

Description: Background: Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease in diabetic patients. Increasing evidence from studies in the rodents has suggested that this disease is associated with increased oxidative stress due to hyperglycemia. In the present study, we evaluated the renoprotective, anti-oxidative and anti-apoptotic effects of the flavonoid quercetin in C57BL/6 J model of DN. Methods: DN was induced by streptozotocin (STZ, 100 mg/kg/day, for 3 days) in adult C57BL/6 mice. Six weeks later, mice were divided into the following groups: diabetic mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks), diabetic mice treated with vehicle (DV) or non-treated non-diabetic (ND) mice. Results: Quercetin treatment caused a reduction in polyuria (~45%) and glycemia (~35%), abolished the hypertriglyceridemia and had significant effects on renal function including, decreased proteinuria and high plasma levels of uric acid, urea and creatinine, which were accompanied by beneficial effects on the structural changes of the kidney including glomerulosclerosis. Flow cytometry showed a decrease in oxidative stress and apoptosis in DN mice. Conclusion: Taken together, these data show that quercetin effectively attenuated STZ-induced cytotoxicity in renal tissue. This study provides convincing experimental evidence and perspectives on the renoprotective effects of quercetin in diabetic mice and outlines a novel therapeutic strategy for this flavonoid in the treatment of DN.

Description: Background: Diabetes is characterized by chronic hyperglycemia and disturbances of carbohydrate, lipid and protein metabolism. We aimed to research association between serum lipid profile and blood glucose, hypothesizing that early detection and treatment of lipid abnormalities can minimize the risk for atherogenic cardiovascular disorder and cerebrovascular accident in patients with type 2 diabetes mellitus. Methods: Fasting blood glucose (FBG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TG) and glycated haemoglobin (HbA1c) levels were evaluated. A hepatic ultrasound was performed for every diabetic to evaluate hepatosteatosis. The study was done from January 2014 to June 2014 among 132 patients with T2DM who were admitted to outpatient clinic of Family Medicine department in a university hospital. The patients whose taking multi-vitamin supplementation or having hepatic, renal or metabolic bone disorders (including parathyroid related problems) were excluded from the study for the reason that those conditions might affect the carbohydrate and lipid metabolism in diabetes. Test of significance was calculated by unpaired student's t test between cases and controls. Correlation studies (Pearson's correlation) were performed between the variables of blood glucose and serum lipid profile. Significance was set at p

Description: Background: Low serum amylase levels have been reported in patients with metabolic syndrome (MS), diabetes, and asymptomatic non-alcoholic fatty liver disease (NAFLD). However, no study has yet indicated the serum amylase levels in NAFLD with MS. The aim of the present study was to evaluate serum amylase levels in NAFLD patients with and without MS, and to explore a possible association between serum amylase levels with the components of MS and the degree of hepatic fibrosis in NAFLD patients. Methods: Our study included 713 NAFLD participants (180 females and 533 males) and 304 healthy control participants (110 females and 194 males). The diagnosis of NAFLD was based on ultrasonography, and advanced fibrosis was assessed by the FIB-4 index. Results: Serum amylase levels were significantly lower in NAFLD patients with MS compared with NAFLD patients without MS and healthy controls (42, 45, and 53 IU/L, respectively). The serum amylase levels of patients with elevated glucose, elevated triglycerides, and low high density lipoprotein cholesterol patients were significantly lower than in case of normal parameters (both p 〈 0.05). Multivariate logistic regression analysis showed that a relative serum amylase level increase was an independent factor predicting advanced fibrosis (FIB-4 〉=1.3) in NAFLD participants (OR: 1.840,95% CI: 1.117-3.030, p=0.017). Conclusions: Compared with NAFLD patients without MS and healthy controls, serum amylase levels were significantly lower in NAFLD patients with MS. Moreover, a relative serum amylase increase may be an independent factor of more advanced hepatic fibrosis.

Description: Background: Ingestion of polyunsaturated fatty acids (PUFAs) has been proposed to influence several chronic diseases including coronary heart disease (CHD) and type-2 diabetes (T2D).There is strong evidence that omega-3 (n-3) PUFAs provide protection against CHD and biomarkers of atherosclerosis. In contrast, there is more limited and inconsistent data for T2D. Few studies have examined the impact of n-3 PUFA-containing botanical oils on T2D. Methods: Fifty-nine subjects with early-stageT2D or metabolic syndrome participated in an 8-week, randomized, single-blind, parallel intervention study and were provided PUFA-containing oils. Individuals received either corn oil (CO), a botanical oil (BO) combination (borage [Borago officinalis L.]/echium oil [Echium plantagineum L.]) or fish oil (FO). The BO combination was enriched in alpha-linolenic, gamma-linolenic, and stearidonic acids and the FO in eicosapentaenoic and docosahexaenoic acids. Serum fatty acids and other serum lipids(triglycerides and total, HDL and LDL cholesterol), as well as markers of inflammation (leptin, and C-reactive protein) and glucose regulation (glucose and hemoglobin A1c) were assessed from fasting participants at baseline and after the intervention. Results: Compliance was verified by expected increases in specific PUFAs in each of the three oil arms. Participants in the CO group showed no differences in serum lipids, markers of inflammation or glucose regulation between pre- and post-treatment measures. Supplementation with BO significantly lowered total and LDL cholesterol levels and FO reduced serum triglycerides, hemoglobin A1c and increased HDL-cholesterol. Conclusion: Short-term dietary supplementation with BO and FO improved biomarkers associated with T2D/metabolic syndrome.Trial registration: Clinicaltrial.gov NCT01145066

Description: Background: Atorvastatin and poly-unsaturated fatty acid (PUFA) are beneficial for lipid-modification, whether atorvastatin plus PUFA could confer better improvement on dyslipidemia and endothelium function is unknown. Methods: Dyslipidemia model of 40 rabbits were produced with atherogenic diet, and thereafter saline, atorvastatin, PUFA, or atorvastatin plus PUFA were prescribed for 1 week. Ten rabbits given normal diet served as the sham group. Parameters of interest including lipid profiles, endothelium function (nitric oxide, NO) and activation (solution vascular-cellular adhesion molecule, (sVCAM) and intracellular adhesion molecule, (sICAM)), markers of inflammation (C-reactive protein, CRP) and oxidation (malondialdehyde, MDA) were compared among groups. Results: There was no significant difference of parameters among groups at the initial. With 1 week of atherogenic diet administration, serum levels of lipid profiles, sVCAM and sICAM, CRP and MDA were significantly increased, accompanying with profound NO reduction, as compared to the sham group. After 1 week of medical intervention, as compared to the control group (saline administration), dyslipidemia and endothelium function were modestly improved with either atorvastatin or PUFA therapy. Nevertheless, these efficacies were further and significantly enhanced with combined therapy when compared to the control group (p 〈 0.005), suggesting that there was synergistic effects of atorvastatin and PUFA co-therapy in rabbits with dyslipidemia. Conclusion: Atorvastatin plus PUFA therapy could immediately contribute to better improvement of lipid-modification and endothelium function in rabbits with dyslipidemia.

Description: Background: Plasma PCSK9 levels was positively associated with low-density lipoprotein (LDL) cholesterol (LDL-C) and atherosclerosis, while PCSK9 may also be implicated in the metabolism of lipoprotein subfractions. The study was to examine the association of plasma PCSK9 with lipoprotein subfractions in patients with stable coronary artery disease (CAD). Methods: A total of 281 consecutive, stable CAD patients who were not treated with lipid-lowering drugs were enrolled. The baseline clinical characteristics were collected, the plasma PCSK9 levels were determined using ELISA, and the LDL and high-density lipoprotein (HDL) subfractions were analyzed by Lipoprint System. The association of plasma PCSK9 levels with the lipoprotein subfractions was investigated. Results: In the overall population, plasma PCSK9 levels were positively associated with the concentration of LDL-C, intermediate LDL-C, small LDL-C, and LDL score, while negatively correlated with mean LDL particle size. PCSK9 levels were positively associated with the concentration of HDL-C, intermediate HDL-C and small HDL-C. Multivariable regression analysis revealed that the plasma PCSK9 levels were significantly and independently associated with the concentration of intermediate LDL-C (beta = 0.152, p = 0.013), small LDL-C (beta = 0.179, p = 0.004), LDL score (beta = 0.121, p = 0.043), and mean LDL particle size (beta = -0.130, p = 0.035), while not HDL subfractions. Interestingly, when investigated in male and female patients separately, these relationships were only found in male but not in female, and the small HDL-C exhibited an association with PCSK9 levels in male patients (beta = 0.149, p = 0.045). Conclusions: PCSK9 levels were independently associated with the changes of lipoprotein subfractions, suggesting a potential interaction between PCSK9 and lipoprotein subfractions in CAD.

Description: Background: The bioactive lysophospholipids phosphatidic acid (PA), lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have been implicated in mediating cell migration, proliferation and apoptosis, inflammation, angiogenesis and fibrosis. This study was conducted to measure the levels of PA, LPA, LPA-producing enzymes phospholipase A1/A2 (PLA1A / PLA2, respectively) and acylgylycerol kinase (AGK), the S1P receptor S1PR1, the S1P catabolising enzyme S1P lyase (SPL) and 5-lipoxygenase in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR). In addition, we investigated the correlations between the levels of PA and LPA and the levels of the inflammatory and endothelial dysfunction biomarker soluble vascular cell adhesion molecule-1 (sVCAM-1). Methods: Vitreous samples from 34 PDR and 29 nondiabetic patients were studied by biochemical and enzyme-linked immunosorbent assays and Western blot analysis. Results: PA, LPA and sVCAM-1 levels in vitreous samples from PDR patients were significantly higher than those in nondiabetic patients. Significant correlations were observed between levels of LPA and levels of PA and sVCAM-1. Western blot analysis revealed a significant increase in the expression of PLA1A, AGK, S1PR1 and SPL in vitreous samples from PDR patients compared to nondiabetic controls, whereas PLA2 and 5-lipoxygenase were not detected. Conclusions: Our findings suggest that the enzymatic activities of PLA1A and AGK might be responsible for increased synthesis of LPA in PDR and that PLA1A, but not PLA2 is responsible for deacylation of PA to generate LPA. S1PR1 and SPL might regulate inflammatory, angiogenic and fibrogenic responses in PDR.

Description: Background: Micronutrients in oil reduce one or more risk factors of cardiovascular diseases, while the contents of micronutrients in oil are relatively poor, which is insufficient to reverse the metabolic disorders at different stages of progress. The aim of this study was to investigate the effects of endogenous micronutrients in optimized cold-pressed rapeseed oil and restoratively added or fortified micronutrients in traditional refined rapeseed oil (restoring micronutrients to be nearly equal to or significantly higher than levels in crude rapeseed oil) on the antioxidant status and lipid profile in high-fat fed rats. Methods: Male Wistar rats were fed high-fat diets containing different rapeseed oils for 4 weeks, including the standard refined rapeseed oil(SRO), optimized cold-pressed rapeseed oil(CRO) and the traditional refined rapeseed oil with restorative addition or fortification of micronutrients (LF, HF-SRO). Results: CRO exhibited significant increases in contents of tocopherols (+13%), phytosterols (+34%), polyphenols (+92%) and phospholipids (+725%) compared with SRO, as well as the total antioxidant capacities (+82-125%) (p 〈 0.05). While the HF-SRO revealed improved antioxidant properties in vitro than the CRO, which was comparable to LF-SRO. Significant improved plasma antioxidant capacities and lipid peroxidation evaluated by T-AOC, GSH, tocopherols and MDA were found in rats fed HF-SRO when compared with CRO and LF-SRO (p 〈 0.05). Furthermore, HF-SRO also decreased the plasma and hepatic TC levels compared to CRO and LF-SRO, accompanying higher fecal cholesterol excretion (p 〈 0.05). Conclusion: The standard refined rapeseed oil with fortification, not restorative addition of micronutrients was comparable to the optimized cold-pressed rapeseed oil in improving the antioxidant status and lipid profile of high-fat fed rats.

Description: Background: Parkinson's disease is a neurodegenerative disorder that is being characterized by the progressive loss of dopaminergic neurons of the nigrostriatal pathway in the brain. The protective effect of omega-6 fatty acids are unclear. There are lots of contradictions in the literature with regard to the cytoprotective role of arachidonic acid. To date, there is no solid evidence that shows the protective role of omega-6 fatty acids in Parkinson's disease. In the current study, the potential of two omega-6 fatty acids (i.e. arachidonic acid and linoleic acid) in alleviating 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity in PC12 cells was examined. Methods: Cultured PC12 cells were either treated with MPP+ alone or co-treated with one of the omega-6 fatty acids for 1 day. Cell viability was then assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Cells treated with 500 muM MPP+ for a day reduced cell viability to ~70% as compared to control group. Linoleic acid (50 and 100 muM) significantly reduced MPP+-induced cell death back to ~85-90% of the control value. The protective effect could be mimicked by arachidonic acid, but not by ciglitazone. Conclusions: Both linoleic acid and arachidonic acid are able to inhibit MPP+-induced toxicity in PC12 cells. The protection is not mediated via peroxisome proliferator-activated receptor gamma (PPAR-gamma). Overall, the results suggest the potential role of omega-6 fatty acids in the treatment of Parkinson's disease.

Description: Background: Evidence from in vitro and animal studies indicates that conjugated linoleic acid (CLA) possesses anti-diabetic properties, which appear to be attributed to cis-9, trans-11 CLA, the major CLA isomer in ruminant fat. However, there is a shortage of studies addressing CLA from natural source. The present study aimed to evaluate the effects of butter naturally enriched in cis-9, trans-11 CLA on parameters related to glucose tolerance, insulin sensitivity and dyslipidemia in rats. Methods: Forty male Wistar rats were randomly assigned to the following dietary treatments (n = 10/group), for 60 days: 1) Normal fat-Soybean oil (NF-So): diet containing 4.0% soybean oil (SO); 2) High Fat-Control Butter (HF-Cb): diet containing 21.7% control butter and 2.3% SO; 3) High Fat-CLA enriched Butter (HF-CLAb): diet containing 21.7% cis-9, trans-11 CLA-enriched butter and 2.3% SO; and 4) High fat-Soybean oil (HF-So): diet containing 24.0% SO. HF-Cb and HF-CLAb diets contained 0.075% and 0.235% of cis-9, trans-11 CLA, respectively. Results: HF-CLAb-fed rats had lower serum insulin levels at fasting than those fed with the HF-Cb diet, while the PPARgamma protein levels in adipose tissue was increased in HF-CLAb-fed rats compared to HF-Cb-fed rats. Furthermore, R-QUICK was lower in HF-Cb than in NF-So group, while no differences in R-QUICK were observed among NF-So, HF-CLAb and HF-So groups. Serum HDL cholesterol levels were higher in HF-CLAb-fed rats than in those fed NF-So, HF-Cb and HF-So diets, as well as higher in NF-So-fed rats than in HF-Cb and HF-So-fed rats. HF-CLAb, HF-Cb and HF-So diets reduced serum LDL cholesterol levels when compared to NF-So, whereas serum triacylglycerol levels were increased in HF-CLAb. Conclusion: Feeding rats on a high-fat diet containing butter naturally enriched in cis-9, trans-11 CLA prevented hyperinsulinemia and increased HDL cholesterol, which could be associated with higher levels of cis-9, trans-11 CLA, vaccenic acid, oleic acid and lower levels of short and medium-chain saturated fatty acids from butter naturally modified compared to control butter. On the other hand CLA-enriched butter also increased serum triacylglycerol levels, which could be associated with concomitant increases in the content of trans-9 and trans-10 C18:1 isomers in the CLA-enriched butter.

Description: Background: Chronic kidney disease (CKD) is known to be one of the causes of cardiovascular disease and end-stage renal disease. Among the several treatable risk factors of CKD, that of dyslipidemia is relatively controversial. To clarify the association of polymorphisms in genes involved in lipid metabolism with the risk of CKD in the Japanese population, we used cross-sectional data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Methods: A total of 3,268 men and women, aged 35-69 years, were selected from J-MICC Study participants for inclusion in this study. Twenty-eight candidate single nucleotide polymorphisms (SNPs) were selected in 17 genes associated with the risk of lipid metabolism disorders, and genotyping of the subjects was conducted using the multiplex PCR-based invader assay. The prevalence of CKD was determined for stages 3-5 (defined as estimated glomerular filtration rate 30 and individuals with at least one minor allele of each genotype of OR 10.43 (95% CI:1.29-84.19) and 3.36 (0.87-13.01), respectively. Conclusions: Four polymorphisms in APOA5, TOMM40, and CETP were shown to be significantly associated with CKD risk, and a significant interaction between the two APOA5 SNPs and BMI on CKD risk was also demonstrated. This suggests the future possibility of personalized risk estimation for this life-limiting disease.

Description: Background: The main goal of this randomized controlled single-blinded pilot study was to study whether, independent of weight loss, a Palaeolithic-type diet alters characteristics of the metabolic syndrome. Next we searched for outcome variables that might become favourably influenced by a Paleolithic-type diet and may provide new insights in the pathophysiological mechanisms underlying the metabolic syndrome. In addition, more information on feasibility and designing an innovative dietary research program on the basis of a Palaeolithic-type diet was obtained. Methods: Thirty-four subjects, with at least two characteristics of the metabolic syndrome, were randomized to a two weeks Palaeolithic-type diet (n = 18) or an isoenergetic healthy reference diet, based on the guidelines of the Dutch Health Council (n = 14). Thirty-two subjects completed the study. Measures were taken to keep bodyweight stable. As primary outcomes oral glucose tolerance and characteristics of the metabolic syndrome (abdominal circumference, blood pressure, glucose, lipids) were measured. Secondary outcomes were intestinal permeability, inflammation and salivary cortisol. Data were collected at baseline and after the intervention. Results: Subjects were 53.5 (SD9.7) year old men (n = 9) and women (n = 25) with mean BMI of 31.8 (SD5.7) kg/m2. The Palaeolithic-type diet resulted in lower systolic blood pressure (-9.1 mmHg; P = 0.015), diastolic blood pressure (-5.2 mmHg; P = 0.038), total cholesterol (-0.52 mmol/l; P = 0.037), triglycerides (-0.89 mmol/l; P = 0.001) and higher HDL-cholesterol (+0.15 mmol/l; P = 0.013), compared to reference. The number of characteristics of the metabolic syndrome decreased with 1.07 (P = 0.010) upon the Palaeolithic-type diet, compared to reference. Despite efforts to keep bodyweight stable, it decreased in the Palaeolithic group compared to reference (-1.32 kg; P = 0.012). However, favourable effects remained after post-hoc adjustments for this unintended weight loss. No changes were observed for intestinal permeability, inflammation and salivary cortisol. Conclusions: We conclude that consuming a Palaeolithic-type diet for two weeks improved several cardiovascular risk factors compared to a healthy reference diet in subjects with the metabolic syndrome.Trial registration: Nederlands Trial Register NTR3002

Description: Background: Endothelial cell activation and dysfunction are the foundation of atherosclerosis, including coronary artery disease (CAD). Endothelial cell activation is mediated by the level of gene transcription. Early growth response 3 (Egr3) is a critical determinant of vascular endothelial growth factor (VEGF) signalling in activated endothelial cells. If endothelial cells are excessively activated, it may lead to vasculopathic diseases, such as pathologic angiogenesis, inflammation, and atherosclerosis. The aim of the present study was to assess the association between the Egr3 gene polymorphisms and CAD. Methods: Two independent case-control studies that involved the Han group (409 CAD patients and 351 control subjects) and the Uygur group (299 CAD patients and 303 control subjects) analysed the relationship between Egr3 SNPs (rs1996147 and rs1008949) and CAD. Genotyping was undertaken using the TaqMan SNP genotyping assay. Results: The entire Uygur group and the males in the Uygur group showed a higher frequency of the A allele (rs1996147) in CAD patients than in the control subjects (P = 0.003 and P = 0.005, respectively). Additionally, the distribution of the recessive model of rs1996147 (AA vs GG + AG) for the total sample and the males was significantly different between CAD patients and control participants (P = 0.002 and P = 0.003, respectively), and the difference remained statistically significant following multivariate adjustment (Total: OR = 1.705; 95% CI: 1.166-2.494, P = 0.006; males: OR = 1.908, 95% CI: 1.189-3.062, P = 0.007). However, for Uygur females, we did not observe a difference in the allele frequency or genotypic distribution of rs1996147 between CAD patients and control participants. Similarly, the distribution of the rs1996147 allele frequency or genotypes showed no significant difference between patients with CAD and control participants in the Han group. The distribution of rs1008949 genotypes, dominant model, recessive model, and allele frequency did not show a significant difference between patients with CAD and the control subjects in the Han and Uygur groups. Conclusion: rs1996147 may be a novel polymorphism of the Egr3 gene associated with CAD in males of the Chinese Uygur population.

Description: Background: Studies had investigated the relationships between endothelial lipase (EL) 584C/T polymorphism and high density lipoprotein cholesterol (HDL-C) level and coronary heart disease (CHD), but the results were controversial. To investigate a more authentic associations between EL 584C/T polymorphism and HDL-C level, and the risk of CHD, we performed this meta-analysis. Methods: We searched electric databases for all articles on the associations between EL 584 C/T polymorphism and HDL-C level, and CHD risk. Odds ratios (ORs) with 95% confidence interval (CI) were used to evaluate the strength of the association between the EL 584 C/T polymorphism and the CHD susceptibility. The pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of EL 584C/T polymorphism and HDL-C level. Begg's funnel plots and Egger's test were used to examine the publication bias. Results: For CHD association, the pooled OR was 0.829 (95% CI: 0.701-0.980, P = 0.028) for the dominant model and 0.882 (95% CI: 0.779-0.999, P = 0.049) for the allelic model. By meta-regression analysis, we found that only total sample size could influence the initial heterogeneity. When the subgroup analysis was carried out, we found that the protective effect only existed in the subgroups of relatively small sample size. Sensitivity analyses indicated that Tang's study influenced the overall results significantly. We calculated the pooled ORs again after excluding Tang's study and found the association between EL 584C/T polymorphism and the risk of CHD was not significant for any genetic model. For HDL-C level association, the carriers of 584 T allele had a higher HDL-C level than the non-carriers. The pooled SMD was 0.399 (95% CI: 0.094-0.704, P = 0.010). When the studies were stratified by ethnicity and total sample size, the positive effects existed in the Caucasians and in subgroups of larger sample size. No significant publication bias was found in the present meta-analysis. Conclusions: The results of the present meta-analysis suggest that the carriers of EL 584 T allele have a higher HDL-C level in Caucasian populations. Whereas, it might not be a protective factor for CHD.

Description: Background: The over-all age-adjusted prevalence of diabetes mellitus type 2 (DMT2) in Saudi Arabia is unprecedented at 31%. Aggressive measures should be done to curb down increasing incidence. In this prospective 6-month study we aim to determine whether a self-monitoring, life-style modification program that includes increased sunlight exposure confer improvement in vitamin D status and health benefits among adult Saudi overweight and obese patients with varying glycemic status. Methods: A total of 150 overweight and obese Saudi adults with varying glycemic status aged 30-60 years were included in this study. They were divided into 3 groups (Non-DMT2, Pre-diabetes and DMT2). Baseline anthropometrics and blood glucose were taken at baseline and after 6 months. Fasting blood sugar, lipid profile, calcium, albumin and phosphate were measured routinely. Serum 25(OH) vitamin D was measured using standard assays. Within the time period they were instructed to reduce total intake of fat, increased fiber intake and increase sun exposure. Results: In all groups there was a significant improvement in vitamin D levels as well as serum triglycerides, LDL- and total cholesterol. However, a significant increase in serum glucose levels was noted in the non-DMT2 group, and a significant decrease in HDL-cholesterol in both non-DMT2 and pre-diabetes group. In the pre-diabetes group, 53.2% were able to normalize their fasting blood levels after 6 months, with 8.5% reaching the DMT2 stage and 38.3% remaining pre-diabetic. In all groups there was a significant increase in the prevalence of hypertension. Conclusion: Improving vitamin D status with modest lifestyle modifications over a short-period translates to improvement in lipid profile except HDL-cholesterol among overweight and obese Saudi adults, but not BMI and blood pressure. Findings of the present study merit further investigation as to whether full vitamin D status correction can delay or prevent onset of DMT2.

Description: Background: The conversions of the n-3 and n-6 fatty acid of plant origin to the C20 and C22 very long chain fatty acids (LCPUFAs) is regulated by several cellular enzymes such as elongases and desaturases. Methods: Sixty-five male one-day old chickens (Ross 308) were randomly divided into four groups and given one of four diets; with or without linseed oil (LO), (the diets contained equal amounts of fat) and with low or high selenium (Se). Final body weight, amount of Se and fat in breast muscle, fatty acid profile, and gene expression for fatty acid desaturases (Fads1, Fads2, Fads9), HMG-CoA reductase, Acyl-CoA oxidase (Acox), carnitine palmitoyl transferase1 (Cpt1), superoxide dismutase (Sod) and glutathione peroxidase4 (Gpx4) were analyzed in all animals, and Gpx activity in whole blood was determined. Results: mRNA expression of elongases and desaturases in chicken breast muscle was not affected by feed rich in C18:3n-3. The highly positive correlation between amount of fat in breast muscle and the product/precursor indices of monounsaturated fatty acid synthesis, and the negative correlation between muscle fat and indices of LCPUFA synthesis should be further studied. Conclusion: mRNA expression in chicken breast muscle of elongases and desaturases was not affected by feed rich in C18:3n-3. The highly positive correlation between amount of fat in breast muscle and the product/precursor indices of monounsaturated fatty acid synthesis, and the negative correlation between muscle fat and indices of LCPUFA synthesis should be further studied.

Description: Background: Owing to the complexity of the antioxidant materials and their mechanism of actions, it is obvious that no single testing method is capable of providing a comprehensive picture of the antioxidant profile. The essential oil of the Thymus specie may still possess other important activities in traditional medicine, it can be used in the treatment of fever and cough. This essential oil may also have an anticancer activity. Methods: The essential oils aerial parts hydrodistilled from Thymus hirtus sp. algeriensis, were characterised by GC/MS analysis and the methanolic extracts were chemically characterized by HPLC method. The essence of thyme was evaluated for its antioxidant and antibacterial activity.Result: The Terpinen-4-ol are the principal class of metabolites (33.34%) among which 1.8-cineole (19.96%) and camphor (19.20%) predominate. In this study, quantitative values of antioxidant activity of crude methanolic extracts of Thymus hirtus sp. algeriensis were investigated. The essential oils was screened for their antibacterial activity against six common pathogenic microorganisms (Escherichia coli, Pseudomonas aeruginosa, Salmonella enteridis, Staphylococcus aureus, Bacillus subtilis and Listeria monocytogenes) by well diffusion method and agar dilution method (MIC). All the essences were found to inhibit the growth of both gram (+) and gram (-) bacteria organisms tested. These activities were correlated with the presence of phenolic compounds in active fractions. HPLC confirmed presence of phenolic compounds in methanol extracts. Conclusion: Methanol extracts and essential oils from aerial parts of Thymus hirtus sp. algeriensis, were examined for their potential as antioxidants. The technique for measuring antioxidant activity, which was developed using DPPH, ABTS and beta-carotene bleaching, produced results as found in established literatures. The present results indicate clearly that methanol extracts and essential oils from Thymus hirtus sp. algeriensis possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants, also their essential oil have an antibacterial effect.

Description: Background: Rho kinase over-activation is associated with nitric oxide (NO) reduction and atherosclerosis. Metformin is favorable for endothelial function improvement and cardiovascular outcomes. Whether cardio-protective effect of metformin is associated with Rho kinase activity is unknown. Methods: Hyperlipidemia model of rats were established accordingly. Thereafter, medical interventions in terms of atorvastatin, metformin or combined therapy were administered for 4 weeks. Laboratory parameters were compared among each groups at initial, 6 weeks of high-fat and high-cholesterol diet administration, and 4 weeks of medical intervention. Lineal regression analyses were performed. Results: No significant difference of laboratory parameters was observed initially. Six weeks of high-fat and high-cholesterol diet administration, serum levels of cholesterol, C-reactive protein (CRP) level, and Rho kinase activity were significantly increased while NO production was concomitantly reduced in comparison to the sham group. After 4 weeks of medical intervention, CRP level and Rho kinase activity were profoundly diminished while NO production was significantly enhanced in the atorvastatin and metformin groups, and these benefits were further enhanced with combined therapy. Lineal regression analyses showed that Rho kinase activity was negatively correlated with NO production but positively correlated with CRP level. Conclusion: In rats with hyperlipidemia, metformin and atorvastatin therapy is favorable for NO production and CRP reduction, which might be associated with Rho kinase activity decrease.

Description: Background: 3-Hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitors or statins are competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis. Currently, statins are used as first-line therapy in the treatment of diabetic dyslipidemia. However, effects of statins on beta cell function remains unclear. This study aims to examine effects of atorvastatin treatment on pancreatic beta cell function in obese C57BL/6 J mice and the possible mechanisms. Methods: Diet-induced obesity (DIO) C57BL/6 J mice were treated with atorvastatin (30 mg/kg/day) for 58 days. beta cell function was assessed by hyperglycemic clamp and the area of insulin-positive beta cells was examined by immunofluorescence. Gene expression was assessed by RT-PCR, and endoplasmic reticulum (ER) stress related proteins were examined by Western blot. Additionally, cell viability and apoptosis of the cholesterol-loaded NIT-1 cells were investigated after atorvastatin treatment. Results: Hyperglycemic clamp study revealed that glucose infusion rate (GIR) and insulin stimulation ratio in atorvastatin-treated DIO mice were markedly higher than control mice (P 〈 0.05, P 〈 0.01 vs. con), indicating preserved beta-cell sensitivity to glucose. Lipid profiles of plasma triglyceride (TG), pancreas TG and plasma cholesterol (CHO) were improved. Pancreas weight and weight index were improved significantly after atorvastatin treatment (P 〈 0.05 vs. con). Immunofluorescence results showed that atorvastatin-treated mice had significantly larger insulin-positive beta cell area (P 〈 0.05 vs. con). Furthermore, RT-PCR and western blot showed that the mRNA and protein expression of pancreatic and duodenal homeobox 1 (Pdx1) in the pancreas were upregulated (P 〈 0.001, P 〈 0.01 vs. con). Moreover, the expression level of ER stress markers of activating transcription factor 4 (ATF4), CCAAT-enhancer-binding protein homologous protein (CHOP) and phosphorylated eukaryotic initiation factor 2alpha (eIF2alpha) were downregulated in the pancreas of atorvastatin-treated mice (P 〈 0.001, P 〈 0.01, P 〈 0.01 vs. con). Besides, atorvastatin protected the pancreatic beta cell line of NIT-1 from cholesterol-induced apoptosis. Western blot showed increased expression of anti-apoptotic protein of B-cell lymphoma 2 (Bcl-2). Conclusion: Pancreatic beta cell function of obese C57BL/6 J mice was preserved after atorvastatin treatment, and this improvement may be attributed to enhanced pancreas proliferation and amelioration of pancreatic ER stress.

Description: Background: We aimed to comprehensively evaluate lipoprotein profile including lipid particle size following a lifestyle intervention in metabolic syndrome (MetS) volunteers and to assess the associations between lipoprotein subfractions and carotid-intima-media-thickness (CIMT) - a surrogate indicator of atherogenesis. Methods: 100 participants (50-70 years) from the RESOLVE trial, underwent a one-year follow-up beginning with a three-week residential program combining high exercise volume (15-20 h/week), restrictive diet (-500 kcal/day), and education. For baseline references, 40 aged-matched healthy controls were recruited. Independent associations between subfractions of lipoproteins and CIMT were evaluated using a generalized estimating equations model accounting for variation in correlations between repeated measures. The lipoprotein subfractions profile was assessed using Lipoprint(R) electrophoresis allowing to separate: the very low-density lipoprotein (VLDL) fraction, then the intermediate-density lipoprotein (IDL) C, B and A, the low-density lipoprotein (LDL) with subfractions 1 and 2 as large LDL and subfractions 3 to 7 as small dense LDL (sdLDL), and the high density lipoprotein (HDL) subfractions categorized into large, intermediate, and small HDL. Apolipoproteins A1 and B were also measured. Results: 78 participants completed the program. At baseline, apolipoproteins B/A1, VLDL, sdLDL and small HDL were higher in MetS than in healthy controls; IDL, LDL size, large and intermediate HDL were lower. Despite time-related regains during the follow-up, lipoprotein subfractions traditionally involved in cardiovascular risk, such as sdLDL, improved immediately after the residential program with values closest to those of healthy controls. CIMT improved throughout the lifestyle intervention. Conclusions: Lipoprotein subfractions traditionally involved in CVR, decreased after the 3-week residential program. During a 12 month follow-up, the time-related regains remained closer to the values of healthy controls than they were at baseline. CIMT improved throughout the lifestyle intervention. However, we failed to demonstrate a link between some lipoprotein subfractions and the atherogenicity directly measured from the wall thickness of arteries (CIMT). Further investigations are required to explore the atherogenicity of lipoprotein subfractions.Trial registration: NCT00917917

Description: Background: Serum lipids and the ratios are known to be associated with the cardiovascular diseases (CVD). However, the associations of serum lipids and the ratios related to arterial stiffness are unclear. We sought to compare the strength of these serum lipids and the ratios with arterial stiffness assessing by brachial-ankle pulse wave velocity (baPWV) in the middle-aged and elderly Chinese subjects. Methods: A total number of 1133 Chinese aged from 50 to 90 years old were recruited from Shanghai downtown district. The serum lipids, baPWV and major cardiovascular risk factors of the participants were measured. Results: Participants with high baPWV exhibited higher levels of non-HDL-c, TC/HDL-c, TG/HDL-c, LDL-c/HDL-c, and non-HDL-c/HDL-c, while HDL-c worked in the opposite direction (all P