Hepatitis C virus relies on lipoproteins for its life cycle

Hepatitis C virus(HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production.

Regulation of ApoE Gene Expression in Mouse Peritoneal Macrophages by VLDL

Mouse peritoneal macrophages (MPM) were incubated with ApoEpoor VLDL or ApoE-rich VLDL at same concentrations for 24 h. The ApoE mR NA content increased in both groups than that in control and the highest ApoEmRNA content was seen in MPM incubated with ApoE-poor VLDL. The results suggest that VLDL could stimuIate ApoE gene expression in MPM and the ApoE poor VLDL has more pronounced effect. We think that the ApoE secreted byMPM may be incorporated into VLDL, especially the ApoE-poor VLDL, and thereby enhance the uptake of those lipoproteins by MPM or other local cells via ApoE-mediated receptor pathways.

鸡Apo VLDLⅡ基因内含子多态性与肉质关联分析

根据鸡Apo VLDLⅡ基因3个内含子序列设计9对引物,采用PCR-SSCP技术对如皋黄鸡、安卡肉鸡2个品种进行多态性检测,探讨其与肉质的相关性。结果表明:Apo VLDLⅡ基因内含子1发生了3处突变,分别为2522处A/C、2705处A/C及2793处C/T。突变对应的基因型在这2个品种间的分布差异极显著(P<0.01);单个引物所对应的不同基因型间肉质性状差异不显著(P>0.05),不同合并基因型在嫩度、pH和肉色3个性状上差异显著(P<0.05)。

鸡Apo VLDLⅡ基因内含子Ⅰ的多态性研究

本研究根据鸡Apo VLDL-Ⅱ基因内含子Ⅰ的基因序列设计3对引物,分别采用PCR-RFLP、PCR-SSCP技术对文昌鸡、如皋黄鸡、丝羽乌骨鸡、安卡肉鸡及红色原鸡5个鸡种进行多态性研究。结果表明,鸡Apo VLDL-Ⅱ基因内含子Ⅰ存在4处突变,分别为:1950处G/A、2522处A/C、2705处A/C及2793处C/T。统计结果显示:安卡肉鸡基因型频率的分布与如皋黄鸡、红色原鸡存在显著差异,文昌鸡基因型频率的分布与乌骨鸡差异不显著,除安卡肉鸡外所有鸡种均处于Hardy-Weinberg平衡状态。

金定鸭Apo VLDL Ⅱ基因多态性及其与生产性能的关联分析

根据鸡和鸭Apo VLDL Ⅱ基因序列设计3对特异性引物,对金定鸭外显子1、2和4编码区进行扩增,利用PCR-SSCP方法检测单核苷酸多态及其对体重、体尺、屠宰性能、肉品质、总蛋白、血清三酰甘油和总胆固醇的遗传效应。结果表明:外显子1和2未检测到多态;外显子4检测到3种基因型,即AA、AB和BB,AA为优势基因型,A为优势等位基因,序列比对发现在内含子3内发生G47A和G136A突变,外显子4编码区内发生C228T突变,为无义突变;该基因座的遗传杂合度为0.28,属中等遗传杂合度,基因型分布符合Hardy-Weinberg平衡;AA基因型个体的胸肌水分显著高于BB基因型,AB基因型个体的肌肉剪切力值显著高于BB基因型,而其他指标在各基因型间差异均不显著,推测该片段的多态位点可能对肉品质有一定的影响。

High-density lipoproteins:an emerging target in the prevention of cardiovascular disease

High-density lipoproteins （HDLs） have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their beneficial influence on the arterial wall. A number of exciting therapeutic strategies have been developed that target HDL and its ability to protect against the development of atherosclerotic plaque. This paper will review how the promotion of the functional properties of HDL inhibits the formation of atherosclerotic plaque and stabilises lesions in patients with established disease.

High density lipoproteins and type 2 diabetes:Emerging concepts in their relationship

Patients with type 2 diabetes mellitus(T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular(CV) disease. High density lipoproteins(HDL) are protective against atherosclerosis. Low levels of HDL cholesterol(HDL-C) independently contribute to CV risk. Patients with T2 DM not only exhibit low HDL-C, but also dysfunctional HDL. Furthermore, low concentration of HDL may increase the risk for the development of T2 DM through a decreased β cell survival and secretory function. In this paper, we discuss emerging concepts in the relationship of T2 DM with HDL.

Metabolism of high density lipoproteins in liver cancer

Liver plays a vital role in the production and catabolism of plasma lipoproteins. It depends on the integrity of cellular function of liver, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs these processes are impaired and high-density lipoproteins are changed.

Selective Removal of Low-Density Lipoproteins from Blood by Induced Precipitation with AAS in Vitro(Ⅰ)

1 INTRODUCTION It’s evident that high level of cholesterol in blood is associated with the formation and devel-opment of familial hypercholestrolemia(FH)and atherosclerosis(AS).In general,choles-terol in blood is mainly combined with low-density lipoproteins(LDL),very low-densitylipoproteins(VLDL)and high density lipoproteins(HDL).About 60%-80% cholesterolexists in LDL and VLDL.LDL and VLDL have been recognized as the principal

Effect of low-density lipoproteins, spermatozoa concentration and glycerol on functional and motility parameters of bull spermatozoa during storage at 4℃

An extender has been developed with low-density lipoproteins （LDLs） that eliminates the microbial risks associated with the use of whole egg yolk. The objective of this study was to assess the effects of substituting egg yolk with LDLs for use as an extender in sperm preservation at 4 ℃, as well as on spermatozoa motility, plasma membrane and acrosome integrity, at two different concentrations （80×10^6 and 240× 10^6 sperm per ml） for 8 days and to evaluate glycerol toxicity in both extenders. A total of 12 ejaculates were collected from three bulls. Spermatozoa motility was examined using computer-assisted semen analysis. Plasma membrane integrity was determined using the hypo-osmotic swelling test and acrosome integrity with the fluorescein isothiocyanate-Pisum sativum agglutinin test. The semen was subsequently divided into four aliquots and diluted with Tris-egg yolk-glycerol （TEG）, Tris-egg yolk without glycerol （TE）, LDL with glycerol （LDL＋） and LDL without glycerol （LDL-）, at 80×10^6 and 240 ×10^6sperm per ml. This study showed that the LDL＋ and LDL- extenders were more effective at preserving spermatozoa motility, plasma membrane integrity and acrosome integrity than TEG and TE （P〈0.05） during 8 days of incubation. After 3 days of incubation, a toxicity of glycerol was observed in TEG, whereas no significant difference was observed between LDL＋ and LDL-. We can therefore conclude that the LDL extender can be used to refrigerate semen at 4 ~C instead of TEG and TE at 80×10^6and 240×10^6 sperm per ml for elite bulls. This finding can be used to define a policy for the storage of high-quality bull semen.

146名血脂正常的成人血清HDL-C VLDL-C及LDL-C测定与分析

对146名血脂正常的成人血清HDL-C、LDL-C及VLDL-C进行了测定。结果显示:HDL-C为56.0±14.2,LDL-C为87.2±25.1,VLDL-C为23.1±7.9 mg/dl,均呈正态分布,有随年龄增长而升高的趋向,除HDL-C女性显著高于男性(P<0.05)外,其余未见性别差异。对国人与欧州人胆固醇在各脂蛋白中分布的比较提示,其分布的差异可能是国人动脉粥样硬化发生明显低于欧州人的重要原因。

ApoB-containing lipoproteins promote infectivity of chlamydial species in human hepatoma cell line

AIM:To evaluate the direct binding of two main chlamydial biovars(C.trachomatis and C.pneumoniae) to plasma lipoproteins and its effect on chlamydial infection rate in human hepatoma cell line(HepG2 cells). METHODS:Murine plasma lipoproteins were fractionated and isolated using fast-performance liquid chromatography(FPLC),spotted on nitrocellulose membrane and incubated with chlamydial suspensions. Direct binding of chlamydial particles to lipoprotein fractions has been studied using lipopolysaccharide-specific antibodies in immuno-dot blot binding assay and immunoprecipitation analysis.Immunostaining protocol as well as flow cytometry analysis have been employed to study the infectivity rate of chlamydial species in HepG2 cells. RESULTS:Elementary bodies of both C.trachomatis and C.pneumoniae bind ApoB-containing fractions of plasma lipoproteins.That binding becomes stronger when heat-denatured FPLC fractions are used, suggesting a primary role of apolipoproteins in interaction between chlamydial particle and lipoprotein. Both chlamydial biovars efficiently propagate in human hepatoma cell line-HepG2 cells even in serum free conditions forming late-stage inclusion bodies and releasing extracellular elementary bodies.Preincubation of C.trachomatis and C.pneumoniae with native ApoB-containing lipoproteins enhances the rate of chlamydial infection in HepG2 cells.CONCLUSION:A productive infection caused by C. trachomatis and C.pneumoniae may take place in human-derived hepatocytes revealing hepatic cells as possible target in chlamydial infection.Obtained results may suggest the participation of lipoprotein receptors in the mechanism of attachment and/or entry of chlamydial particles into target cells.

Changes Induced by Physical Activity, Weight Loss and Calorie Restriction in Body Composition, Lipoproteins and Functional Capacity in Obese Congolese Women

Background. The effects of physical exercises combined with a low-calorie diet on weight loss, body composition, lipoproteins profile, and physical fitness had been well described. However, Central Africa’s studies investigating these kinds of diets and exercise regimens are lacking. Objective. To investigate the effects of adding 14-weeks exercises to a hypocaloric diet on changes in body composition, lipoproteins concentrations, and physical capacities in obese Congolese women. Population and Methods. In total, 34 obese women aged 30 - 39 years (mean age: 33.7 ± 2.4 years) assigned to 14-weeks training program and low energy ketogenic diet. Body composition was assessed using classic methods and impedancemetry. Fasting plasma glucose (FPG) and fasting serum insulin were assessing using enzymatic colorimetric and radioim-munoradiometric methods. HOMA-IR and lipoproteins concentrations were assessed using standardized laboratory methods. VO2peak was measured on a treadmill during a progressive exercise test. Speed, cadence and stride length were measured along the 10-m level walkway. Muscular endurance was measured using the tests of sit-up and inflections-extensions of elbows. All the variables of the study were assessed at the beginning, in the 7-weeks, and in the 14-weeks of training methods. Results. Declines in body weight (16%), percent fat (12.1%), fat weight (26.4%), abdominal fat (34.2%), and waist circumference (10.4%) were found. A significant decrease in FPG (13%), fasting serum insulin (60.9%), HOMA-IR (64.7%), total cholesterol (12.2%), LDL-cholesterol (20.3%), triglycerides (92.8%), and VLDL-triglycerides (17.5%) was shown. In contrast, significant increase in HDL-cholesterol (27.13%) was found. The peak oxygen consumption VO2peak relative to body weight improved more in the 14-weeks training program (13.4%). Obese women exhibited higher values in the 14-weeks training program for speed gait (16.5%), cadence (9.1%), and stride length (15.7%) during normal walk and rapid walk. Weight loss combined with a low-calorie diet and 14-weeks training program improved significantly muscular endurance capacities. Conclusion. Exercise added to hypocaloric diet leads to decreases in body composition, to improve in insulin sensitivity, to enhancement of VO2peak and functional fitness. This may be helpful for the treatment of the metabolic complications of abdominal obesity.

Nanotechnologies meeting natural sources:Engineered lipoproteins for precise brain disease theranostics

Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,because of their inherent blood-brain barrier permeability and lesion-homing capability,have been identified as promising strategies for high-performance theranostics of brain diseases.However,the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes,which can be critical for individual therapeutics and clinical translation.To address these issues,lipoprotein-inspired nano drug-delivery systems(nano-DDSs),which have been learned from nature,have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions.In this review,the barriers in brain disease treatment,advantages of state-of-the-art lipoprotein-inspired nano-DDSs,and bio-interactions of such nano-DDSs are highlighted.Furthermore,the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized.Specifically,the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed.Finally,the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles,such as exosomes,cell membranes,and bacteria,are discussed.

Role of VLDL Receptor in the Process of Foam Cell Formation

The role of very low density lipoprotein receptor (LVLDR) in the process of foam cell formation was investigated. After the primary cultured mouse peritoneal macrophages were incubated with VLDL, β VLDL or low density lipoprotein (LDL), respectively for 24 h and 48 h, foam cells formation was identified by oil red O staining and cellular contents of triglyceride (TG) and total cholesterol (TC) were determined. The mRNA levels of LDLR, LDLR related protein (LRP) and VLDLR were detected by semi quantitative RT PCR. The results demonstrated that VLDL, β VLDL and LDL could increase the contents of TG and TC in macrophages. Cells treated with VLDL or β VLDL showed markedly increased expression of VLDLR and decreased expression of LDLR, whereas LRP was up regulated slightly. For identifying the effect of VLDL receptor on cellular lipid accumulation, ldl A7 VR cells, which expresses VLDLR and trace amount of LRP without functional LDLR, was used to incubate with lipoproteins for further examination. The results elucidated that the uptake of triglyceride rich lipoprotein mediated by VLDLR plays an important role in accumulation of lipid and the formation of foam cells.

Induction of Very Low Density Lipoprotein Receptor(VLDLR) Transcription by VLDL Is Mediated by the Extracellular Signal-Regulated Kinase Signaling Pathway

To elucidate the intracellular signaling pathways for VLDL-induced VLDLR transcription, Western blot analysis was used to examine phosphorylated ERK1/2 protein. It was found that that VLDL induced an increase in ERK1/2 activity in a protein kinase C (PKC)-dependent manner in murine RAW264. 7 macrophages. By using different protein kinases inhibitors or activators it was observed that the effect of VLDL-induced VLDL receptor transcription, which is monitored by RT-PCR analysis of VLDL receptor mRNA, was not affected by the inhibitor of p38 kinase and cAMP analog, but completely abolished by pretreatment of the cells with PD 98059, an inhibitor of MEK and GF 109203X, an inhibitor of PKC. These results demonstrated that the PKC/ERK1/2 cascade is the essential signaling pathway by which VLDL activates VLDL receptor mRNA expression.

Effect of Insulin on the Differential Expression of VLDL Receptor Isoforms of SGC7901 Cell and Its Biological Implication

This study examined the effect of insulin on the expression of very low density lipoprotein receptor (VLDLR) subtypes of SGC7901 cells and discussed its biological implication.In vitro, moderately or poorly-differentiated human gastric adenocarcinoma cell line SGC7901 was incubated with insulin for different lengths of time, and then the expression of protein and RNA level in VLDLR subtypes were detected by Western blotting and real-time PCR, respectively.The results showed that, at certain time interval, insulin could down-regulate expression of type Ⅰ VLDLR and up-regulate the expression of type Ⅱ VLDLR in SGC7901 cells, at both protein and RNA level.We are led to conclude that insulin serves as a regulator in maintaining the balance between glucose and lipid metabolism in vivo, possibly through its effect on the differential expression of VLDLR subtypes.

The Importance of Systemic Balance in Safeguarding Health: A Randomized Double-Blind Clinical Trial on VLDL, Triglycerides, Free T3, Leptin, Ghrelin, Cortisol and Visceral Adipose Tissue

The purpose of this clinical trial was to delineate some of the negative consequences of high BMI on health and explore the possibility of a solution. We analysed the blood test results of nine overweight adults with sedentary lifestyles, and an average BMI of 32.23. Results revealed a statistically significant reduction of visceral adipose tissue, very-low density lipoprotein (VLDL), and triglycerides. Testosterone, leptin, IGF-1 and Free T3 increased within the normal range, juxtaposed by cortisol and ghrelin that declined, but without dipping into abnormality. These findings have important implications during the COVID-19 pandemic, where optimal immunity is deemed necessary in limiting susceptibility to the virus. Recent research indicates that weight gain often escalates vulnerability to respiratory track disturbances, cardiovascular disease (CVD) and diabetes. Consequently, pre-existing conditions increase COVID-19 mortality rates. CVD and diabetes emerge out of hormonal imbalances that involve Free T3, leptin, ghrelin, testosterone, and cortisol. Physical training is decidedly the most acclaimed solution, yet, the least implemented one, due to procrastination, or demoralization after investing constant exhaustive effort with no immediately visible physical change. COVID-19 confinement exacerbates the tendency for inactivity, and promotes stress-eating behaviours. Moreover, strenuous exercise, necessary for visceral fat reduction, results in a negative cortisol/testosterone relationship that provokes caloric consumption and inflammation. Offering an alternative to exercise that effectively improves health, boosts metabolism, and controls appetite, may serve as a proactive, and preventive method that can safeguard health.

Expression of Monocyte Chemoattractant Protein-1 in Monocytes and Effects of Native and Oxidized Very Low Density Lipoproteins

Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capacity of human peripheral blood monocytes to express MCP-1 and effects of native very low density lipoprotein (VLDL) and oxidized VLDL(OX-VLDL) on the expression. The total RNA was extracted from cultured monocytes, which were exposed to VLDL and OX-VLDL, and the media conditioned by monocytes were collected. MCP-1 mRNA expression was examined by Northern blot analysis. MCP-1 protein in conditioned media was determined by using sandwich ELISA. The results showed that monocytes can express MCP-1 after a 24 h incubation at 37℃，and the expression was markedly increased by a exposure to OX-VLDL, whereas the expression was slightly increased when exposed to VLDL. It suggests that the capacity of monocytes to produce MCP-1 that recruits and activates circulating monocytes may be of considerable importance in atherogenesis, and oxidation of VLDL enhances its potential to promote atherogenesis.