Effect of Dietary Cholesterol and Fat on Cell Cholesterol Transfer to Postprandial Plasma in Hyperlipidemic Men

Postprandial chylomicrons are potent ultimate acceptors of cell membrane cholesterol and are believed to accelerate reverse cholesterol transport (RCT). We compared the effects of meals rich in polyunsaturated fat (PUFA) and either high (605 mg) or low (151 mg) in cholesterol and a meal rich in dairy fat (DF) in the form of cream on net in vitro transport of red blood cell (RBC) membrane cholesterol to 4 and 6 h postprandial plasma in eight normotriglyceridemic (NTG-H) and eight hypertriglyceridemic (HTG-H) men with mild to moderate hypercholesterolemia. In HTG-H men, cell cholesterol accumulation in 6-h postprandial plasma was significantly (P = 0.02) less after the PUFA-HC meal compared with the other meals. The significant (P < 0.001) increase in cell plus endogenous cholesterol accumulation in the triglyceride-rich lipoprotein (TRL) fraction of 4 h postprandial plasma incubated with RBC was significantly (P = 0.007) higher after the PUFA-HC meal compared with DF meal in HTG-H men. In NTG-H men, cholesterol accumulation in plasma and plasma lipoproteins in the presence and absence of RBC was not significantly affected by the type of meal ingested. These data suggest that addition of large amounts of cholesterol to a PUFA meal may impair diffusion-mediated transport of cell membrane cholesterol to postprandial plasma and that replacing DF with PUFA in a meal increases postprandial lipemia and may potentially increase cholesterol accumulation in atherogenic postprandial TRL in HTG-H men.     

Celastrus Orbiculatus Thunb. Reduces Lipid Accumulation by Promoting Reverse Cholesterol Transport in Hyperlipidemic Mice

Previously, we found that Celastrus orbiculatus Thunb. (COT) decreases athero‐susceptibility in lipoproteins and the aorta of guinea pigs fed a high‐fat diet, and increases high‐density lipoprotein (HDL). In the present study, we investigated the effect of COT in reducing lipid accumulation and promoting reverse cholesterol transport (RCT) in vivo and vitro. Healthy male mice were treated with high‐fat diet alone, high‐fat diet with COT (10.0 g/kg/d), or general fodder for 6 weeks. Serum levels of total cholesterol (TC), triglyceride (TG), HDL‐C, non‐HDL‐C, and ³H‐cholesterol in plasma, liver, bile, and feces were determined. Pathological changes and the levels of TC and TG in liver were examined. The expression of hepatic genes and protein associated with RCT were analyzed. COT administration reduced lipid accumulation in the liver, ameliorated the pathological changes, and lessened liver injury, the levels of TG, TC, and non‐HDL‐C in plasma were decreased significantly, and COT led to a significant increase in plasma HDL‐C and apolipoprotein A (apoA1). ³H‐cholesterol in plasma, liver, bile, and feces was also significantly increased in COT‐treated mice compared to controls. Both mRNA and protein expression of SRB1, CYP7A1, LDLR, ATP‐binding cassette transporters ABCA1, ABCG5, and LXRα were improved in COT‐treated mice. An in vitro isotope tracing experiment showed that COT and its bioactive ingredients, such as celastrol, ursolic acid, oleanolic acid, and quercetin, significantly increased the efflux of ³H‐cholesterol. They also increased the expression of SRB1, ABCA1, and ABCG1 significantly in macrophages. Our findings provided a positive role of COT in reducing lipid accumulation by promoting RCT. These effects may be achieved by activating the SRB1 and ABC transporter pathway and promoting cholesterol metabolism via the CYP7A1 pathway in vivo. The effective ingredients in vitro are celastrol, ursolic acid, oleanolic acid, and quercetin.     

血脂异常对脑梗死的影响

目的考察血脂异常对老年人脑梗死的影响。方法筛选100例脑梗死患者,年龄45～81岁,与100例健康受试者作对照,抽取受试者清晨空腹静脉血3mL,离心后将分离的血清置-25℃冰箱备用。采用双抗夹心ELISA法检测血清脂蛋白(a);氧化本科法检测血清总胆固醇(TC)和甘油三酯(TG);磷钨酸镁沉淀检测高密度脂蛋白(HDL-C);低密度脂蛋白(LDL-C)采用计算公式:LDL-C=TC-(TG/2.2 HDL-C);免疫比浊法检测载脂蛋白A、B(apoA、apoB)。结果脑梗死患者血清LPa、TC、TG、LDL-C、apoB水平显著高于对照组患者,血清HDL-C、apoA水平显著低于对照组,且患者组血清中各项脂质浓度异常发生率与对照组比较差异具有显著性,P<0.05。结论血脂异常与老年人脑梗死密不可分,调解血脂水平至正常对于预防和治疗老年人脑梗死具有重要义。     

Plasma Lipid Transfer Enzymes in Non-Diabetic Lean and Obese Men and Women

There are considerable differences in the plasma lipid profile between lean and obese individuals and between men and women. Little, however, is known regarding the effects of obesity and sex on the plasma concentration of enzymes involved in intravascular lipid remodeling. Therefore, we measured the immunoreactive protein mass of lipoprotein lipase (LPL), hepatic lipase (HL), cholesterol-ester transfer protein (CETP) and lecithin-cholesterol acyl transferase (LCAT) in fasting plasma samples from 40 lean and 40 obese non-diabetic men and premenopausal women. Women, compared with men, had ~5% lower plasma LCAT (p < 0.041), ~35% greater LPL (p = 0.001) and ~10% greater CETP (p = 0.085) concentrations. Obese, compared with lean individuals of both sexes, had ~30% greater plasma LCAT (p < 0.001), ~20% greater CETP (p < 0.001) and ~20% greater LPL (p = 0.071) concentrations. Plasma HL concentration was not different in lean men and women. Obesity was associated with increased (by ~50%) plasma HL concentration in men (p = 0.018) but not in women; consequently, plasma HL concentration was lower in obese women than obese men (p = 0.009). In addition, there were direct correlations between plasma lipid transfer enzyme concentrations and lipoprotein particle concentrations and sizes. There are considerable differences in basal plasma lipid transfer enzyme concentrations between lean and obese subjects and between men and women, which may be partly responsible for respective differences in the plasma lipid profile.     

Convection and segregation in vertically vibrated granular beds

Experiments and 3D simulations are performed to study the convection cells generated in spherical glass beads within a vertically vibrated container. Discrete element method is employed to simulate the response of glass beads under vertical vibration. Movement of mono-size spherical particles is simulated under different vibration conditions and results are validated in experiments. The patterns of convection cells are found to depend on different operating parameters, i.e. frequency, amplitude etc. The influence of modified container geometries on the behavior of particle movement is being studied. Outward tilted container walls lead to the reversal of the direction of convection cells but only in specially modified containers. Results obtained from 3D systems are in controversy to the results obtained in 2D systems as described in most of the previous works.     

脂联素对巨噬细胞ATP结合盒转运子A1表达及其功能的影响

目的探讨脂联素对巨噬细胞ATP结合盒转运子A1(ATP binding cassette transporter A1,ABCA1)及其上游调控因子肝脏X受体α(Liver X receptorα,LXRα)表达的影响及其在胆固醇逆转运(Reverse cholesterol transport,RCT)和抗动脉粥样硬化(Atherosclerosis,AS)中可能的作用机制。方法以不同浓度的脂联素(0、1、5、10μg/ml)体外培养巨噬细胞RAW264.7 24 h,RT-PCR法检测细胞中ABCA1和LXRα基因mRNA的转录水平,Western blot法检测细胞中ABCA1和LXRα蛋白的表达水平,闪烁计数法检测细胞内胆固醇的流出情况。结果脂联素能显著上调RAW264.7细胞中ABCA1和LXRα基因mRNA的转录水平及蛋白的表达水平(P<0.05),且呈浓度依赖性;脂联素能浓度依赖性地增加细胞内胆固醇的流出(P<0.05)。结论脂联素可通过LXRα途径上调巨噬细胞ABCA1基因的转录和翻译水平,促进胆固醇逆转运,延缓AS的发生、发展。     

Caveolae and Caveolin-1 Integrate Reverse Cholesterol Transport and Inflammation in Atherosclerosis

Lipid disorder and inflammation play critical roles in the development of atherosclerosis. Reverse cholesterol transport is a key event in lipid metabolism. Caveolae and caveolin-1 are in the center stage of cholesterol transportation and inflammation in macrophages. Here, we propose that reverse cholesterol transport and inflammation in atherosclerosis can be integrated by caveolae and caveolin-1.     

Advances in the Study of the Antiatherogenic Function and Novel Therapies for HDL

The hypothesis that raising high-density lipoprotein cholesterol (HDL-C) levels could improve the risk for cardiovascular disease (CVD) is facing challenges. There is multitudinous clear clinical evidence that the latest failures of HDL-C-raising drugs show no clear association with risks for CVD. At the genetic level, recent research indicates that steady-state HDL-C concentrations may provide limited information regarding the potential antiatherogenic functions of HDL. It is evident that the newer strategies may replace therapeutic approaches to simply raise plasma HDL-C levels. There is an urgent need to identify an efficient biomarker that accurately predicts the increased risk of atherosclerosis (AS) in patients and that may be used for exploring newer therapeutic targets. Studies from recent decades show that the composition, structure and function of circulating HDL are closely associated with high cardiovascular risk. A vast amount of data demonstrates that the most important mechanism through which HDL antagonizes AS involves the reverse cholesterol transport (RCT) process. Clinical trials of drugs that specifically target HDL have so far proven disappointing, so it is necessary to carry out review on the HDL therapeutics.     

SPF金黄仓鼠原代肾细胞的安全性

目的验证SPF金黄仓鼠原代肾细胞的安全性。方法采用ELISA法检测10种鼠源病毒血清抗体。通过细胞直接观察、细胞培养试验和血吸附病毒试验检测外源因子。并用直接XC蚀斑法、S+L检验法、电镜观察和双模板法以及联合培养与F-PERT法检测逆转录病毒及逆转录酶活性。结果10种鼠源病毒抗体为阴性,未检出外源因子、逆转录病毒和逆转录酶。结论SPF金黄仓鼠原代肾细胞作为乙型脑炎减毒活疫苗的生物原材料安全可靠。     

Optimization of a Reverse Osmosis System Using Genetic Algorithm

Abstract

Reverse Osmosis (RO) has found extensive application in industry as a highly efficient separation process. In most cases, it is required to select the optimum set of operating variables such that the performance of the system is maximized. In this work, an attempt has been made to optimize the performance of RO system with a cellulose acetate membrane to separate NaCl‐Water system using Genetic Algorithm (GA). The GAs are faster and more efficient than conventional gradient based optimization techniques. The optimization problem was to maximize the observed rejection of the solute by varying the feed flowrate and overall permeate flux across the membrane for a constant feed concentration. To model the system, a well‐established transport model for RO system, the Spiegler‐Kedem model was used. It was found that the GA converged rapidly to the optimal solution at the 8th generation. The effect of varying GA parameters like size of population, crossover probability, and mutation probability on the result was also studied. The algorithm converged to the optimum solution set at the 8th generation. It was also seen that varying the computational parameters significantly affected the results.     

Delayed Metabolism of Postprandial Triglyceride-Rich Lipoproteins in Subjects with Echolucent Carotid Plaques

Subjects with echolucent carotid plaques have an increased risk of ischemic cerebrovascular events independent of degree of stenosis. Low plasma lipoprotein lipase (LPL) activity promotes a proatherogenic lipid profile, and delayed chylomicron clearance is a risk factor for atherosclerosis. This study was conducted to determine plasma LPL activity and postprandial metabolism of triglycerides in relation to carotid plaque morphology. Plaque echogenicity was assessed by B-mode ultrasound and analysis of the grey scale median (GSM). Echolucent plaques were defined as GSM ≤ 63 (the median) and echogenic plaques as GSM > 63, and 57 subjects with carotid plaques and 38 subjects without carotid plaques were recruited. Blood samples were collected before and at 2-h interval for 8 h after a standard high fat meal. LPL activity and mass was determined before and after heparin administration. Postheparin LPL activity was decreased in subjects with echolucent plaques compared to subjects with echogenic plaques (P = 0.06) and to controls (P = 0.04). Plaque echogenicity increased linearly with increasing levels of postheparin LPL activity (P = 0.02) and mass (P = 0.03). Subjects with echolucent plaques had delayed postprandial clearance of chylomicron triglycerides compared to controls (P = 0.04). Low postheparin LPL activity due to attenuated mobilization of LPL from capillary endothelium may play an important role in the formation of echolucent plaques by modulation of postprandial lipids and subsequent fat accumulation in the arterial wall.