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.

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.

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.

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.

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.

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

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.

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.

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.

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.

The pleiotropic vasoprotective functions of high density lipoproteins(HDL)

The pleiotropic functions of circulating high density lipoprotein（HDL） on peripheral vascular health are well established. HDL plays a pivotal role in reverse cholesterol transport and is also known to suppress inflammation,endothelial activation and apoptosis in peripheral vessels. Although not expressed in the central nervous system, HDL has nevertheless emerged as a potential resilience factor for dementia in multiple epidemiological studies. Animal model data specifically support a role for HDL in attenuating the accumulation of P-amyloid within cerebral vessels concomitant with reduced neuroinflammation and improved cognitive performance. As the vascular contributions to dementia are increasingly appreciated, this review seeks to summarize recent literature focused on the vasoprotective properties of HDL that may extend to cerebral vessels, discuss potential roles of HDL in dementia relative to brainderived lipoproteins, identify gaps in current knowledge, and highlight new opportunities for research and discovery.

Carbamylated lipoproteins in diabetes

Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in lipoproteins.In addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in diabetes.Patients with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in diabetes.cLDL levels have been shown to predict cardiovascular events and all-cause mortality.cLDL facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair defects.Lastly,cLDL induces thrombus formation and platelet aggregation.On the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D patients.This relationship may be causative since the atheroprotective properties of HDL are altered after carbamylation.Thus,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit apoptosis.Taken together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.

Lipids, Lipoproteins and Apolipoproteins Abnormalities inPatients undergoing Dialysis

Twenty hemodialysis (HD) patients and 20 patients on continuous am-bulatory peritoneal dialysis (CAPD) were investigated for lipids, lipoproteins andapolipoproteins abnormalities. HD patients had elevated serum triglyceride, de-creased high-density lipoprotein cholesterol (HDL-C ) and apolipoprotein A-I(Apo A-I ), whi1e CAPD patients had elevated total cho1esterol, triglyceride,low-density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), Apo B/Apo A-Iratio, and decreased HDL-C, Apo A-I. Because of the molecular sievingeffects of peritoneum, CAPD have a negative effect on these abnormalities. CAPDpatients might be at greater risk of developing coronary artery disease than HD patients who are also at increased riskas compared with normals.

Influence of poloxamer 407 on fractional and subfractional composition of serum lipoproteins of mice

Using a novel small-angle X-ray scattering (SAXS) method for determination of fractional and subfractional composition of lipoproteins (LPs), a significant elevation of total cholesterol-lipop- roteins (C-LP) and, especially, total triglyceride- lipoproteins (TG-LP), was shown in this work. Among the LP fractions, poloxamer 407 was shown to significantly increase proatherogenic total C-LDL, TG-LDL and, especially, their precursors C-VLDL and TG-VLDL, while only exhibiting a moderate increase in the antiatherogenic C-HDL and TG-HDL fractions. With regard to the VLDL subfractions, significant elevations were observed in both subfractions studied;namely, C-VLDL1-2 and C-VLDL3-5. Similar chang- es were noted in the TG-VLDL1-2 and TG- VLDL3-5 subfractions. The C-IDL and TG-IDL subfractions were increased significantly (?20- to 30- fold), while the C-LDL1-3 subfraction was moderately (?3- to 5-fold) increased at 48 hrs and at day 4. In the moderately elevated (?2- to 4-fold) anti-atherogenic HDL fraction, the C-HDL2 subfraction was increased more significantly (?4- fold) compared to the C-HDL3 subfraction;how- ever, both C-HDL subfractions returned to base- line by day 4. The elevation in the TG-HDL2 subfraction was observed only at 24 hrs. Mouse models of hyperlipidemia and atherosclerosis are useful to evaluate the role of “individual” LPs, as well as their fractions and subfractions, in hyperlipidemia and the genesis of atherosclerosis.

Relevance of plasma lipoproteins and small metabolites in assessment of nutritional status among patients with severe injuries

Background:This study aimed to identify plasma lipoproteins and small metabolites associated with high risk of malnutrition during intensive care unit(ICU)stay in patients with severe injuries.Methods:This observational prospective exploratory study was conducted at two level-1 trauma centers in the Netherlands.Adult patients(aged≥18 years)who were admitted to the ICU for more than 48 h between July 2018 and April 2022 owing to severe injuries(polytrauma,as defined by Injury Severity Scores of≥16)caused by blunt trauma were eligible for inclusion.Partial least squares discriminant analysis was used to analyze the relationship of 112 lipoprotein-related components and 23 small metabolites with the risk of malnutrition(mod-ified Nutrition Risk in Critically Ill score).Malnutrition was diagnosed based on Subjective Global Assessment scores.The relationship of lipoprotein properties and small metabolite concentrations with malnutrition(during ICU admission)was evaluated using mixed effects logistic regression.Results:Overall,51 patients were included.Lower(very)low-density lipoprotein([V]LDL)(free)cholesterol and phospholipid levels,low particle number,and higher levels of LDL triglycerides were associated with a higher risk of malnutrition(variable importance in projection[VIP]value>1.5).Low levels of most(V)LDL and intermediate-density lipoprotein subfractions and high levels of high-density lipoprotein Apo-A1 were associated with the diagnosis of malnutrition(VIP value>1.5).Increased levels of dimethyl sulfone,trimethylamine N-oxide,creatinine,N,N-dimethylglycine,and pyruvic acid and decreased levels of creatine,methionine,and acetoacetic acid were also indicative of malnutrition(VIP value>1.5).Overall,14 lipoproteins and 1 small metabolite were significantly associated with a high risk of malnutrition during ICU admission(P<0.05);however,the association did not persist after correcting the false discovery rate(P=0.35 for all).Conclusion:Increased triglyceride in several lipoprotein subfractions and decreased levels of other lipoprotein subfraction lipids and several small metabolites(involved in the homocysteine cycle,ketone body formation,and muscle metabolism)may be indicative of malnutrition risk.Following validation in larger cohorts,these indicators may guide institution of preventive nutritional measures in patients admitted to the ICU with severe injuries.

Circulating Lipoproteins Mediate the Association Between Cardiovascular Risk Factors and Cognitive Decline:A Community‑Based Cohort Study

Cardiovascular health metrics are now widely recognized as modifable risk factors for cognitive decline and dementia.Metabolic perturbations might play roles in the linkage of cardiovascular diseases and dementia.Circulating metabolites profling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive decline.In a prospective community-based cohort in China(n=725),312 serum metabolic phenotypes were quantifed,and cardiovascular health score was calculated including smoking,exercise,sleep,diet,body mass index,blood pressure,and blood glucose.Cognitive function assessments were conducted in baseline and follow-up visits to identify longitudinal cognitive decline.A better cardiovascular health was signifcantly associated with lower risk of concentration decline and orientation decline(hazard ratio(HR):0.84–0.90;p<0.05).Apolipoprotein-A1,high-density lipoprotein(HDL)cholesterol,cholesterol ester,and phospholipid concentrations were signifcantly associated with a lower risk of longitudinal memory and orientation decline(p<0.05 and adjusted-p<0.20).Mediation analysis suggested that the negative association between health status and the risk of orientation decline was partly mediated by cholesterol ester and total lipids in HDL-2 and-3(proportion of mediation:7.68–8.21%,both p<0.05).Cardiovascular risk factors were associated with greater risks of cognitive decline,which were found to be mediated by circulating lipoproteins,particularly the medium-size HDL components.These fndings underscore the potential of utilizing lipoproteins as targets for early stage dementia screening and intervention.

Mycoplasma lipoproteins and Toll-like receptors

Mycoplasmas, the smallest free-living, self-replicating bacteria with diameters of 200 to 800 nm, have been reported to be associated with human diseases. It is well known that the mycoplasma lipoprotein/peptide is able to modulate the host immune system, whose N-terminal structure is an important factor in inducing immunity and distinguishing Toll-like receptors (TLRs). However, there is still no clear elucidation about the pathogenic mechanism of mycoplasma lipoprotein/peptide and the signaling pathway. Some researchers have focused on understanding the structures of these proteins and the relationships between their structure and biological function. This review provides an update on the research in this field.

MicroRNA alterations in senescent endothelial progenitor cells induced by remnant-like lipoproteins

Background Remnant-like lipoproteins （RLPs） have been demonstrated to accelerate the onset of endothelial progenitor cells （EPCs） senescence. Recent study has determined that microRNAs （miRNAs） were closely associated with cellular proliferation and senescence. This study aimed to examine whether RLPs lead to an alteration of miRNAs in senescent EPCs. Methods RLPs were prepared from plasma samples with immunoaffinity method. After 8 days of culture, EPCs were identified by flow cytometry analysis. Cells were incubated with RLPs for 72 hours. The senescent markers p161NK4a and senescence-associated beta-galactosidase （SA-^-gal） were detected by Western blotting analysis and 13-gal staining assay, respectively. A human miRNA microarray containing 723 miRNAs was used to detect the expression profile of miRNAs in control and senescent EPCs. The result from the above microarray was qualified by RT-PCR assay. Results RLPs dose-dependently up-regulated the protein level of p16INK4a in EPCs, and RLPs at a concentration of 100 pg/ml induced a significant increase in the percentage of SA-i3-gal-positive EPCs. Of 723 miRNAs, four miRNAs expressed differentially and significantly in RLPs-treated EPCs （P 〈0.05）, then their changes in expression were validated by real-time RT-PCR. Among them miR-148b and miR-155 were upregulated while miR-574-3p was down-regulated significantly when compared with control （P 〈0.01）. Conclusions RLPs result in the onset of EPCs senescence. Senescent EPCs induced by RLPs exhibit a different profile of miRNAs. These three miR-148b and miR-155 and miR-574-3p reach a significant difference when compared with control, indicating that microRNA might take part in RLPs-induced EPCs senescence.

Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this condition.The aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive impairment.We found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic stroke.In addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic stroke.Serum phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic stroke.Furthermore,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein levels.Although ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein levels.Taken together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion injury.Low-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s disease.However,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic stroke.To address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke models.First,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting analysis.We observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/reoxygenation.Second,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated virus.Low-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective phenotype.Finally,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte phenotype.These findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.