Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholestero...Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.展开更多
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...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.展开更多
In low-density steel,κ-carbides primarily precipitate in the form of nanoscale particles within austenite grains.However,their precipitation within ferrite matrix grains has not been comprehensively explored,and the ...In low-density steel,κ-carbides primarily precipitate in the form of nanoscale particles within austenite grains.However,their precipitation within ferrite matrix grains has not been comprehensively explored,and the second-phase evolution mechanism during aging remains unclear.In this study,the crystallographic characteristics and morphological evolution ofκ-carbides in Fe-28Mn-10Al-0.8C(wt%)low-density steel at different aging temperatures and times and the impacts of these changes on the steels’microhardness and properties were comprehensively analyzed.Under different heat treatment conditions,intragranularκ-carbides exhibited various morpho-logical and crystallographic characteristics,such as acicular,spherical,and short rod-like shapes.At the initial stage of aging,acicularκ-carbides primarily precipitated,accompanied by a few spherical carbides.κ-Carbides grew and coarsened with aging time,the spherical carbides were considerably reduced,and rod-like carbides coarsened.Vickers hardness testing demonstrated that the material’s hardness was affected by the volume fraction,morphology,and size ofκ-carbides.Extended aging at higher temperatures led to an increase in carbide size and volume fraction,resulting in a gradual rise in hardness.During deformation,the primary mechanisms for strengthening were dislocation strengthening and second-phase strengthening.Based on these findings,potential strategies for improving material strength are proposed.展开更多
The elemental distribution and microstructure near the surface of high-Mn/Al austenitic low-density steel were investigated after isothermal holding at temperatures of 900-1200℃ in different atmospheres,including air...The elemental distribution and microstructure near the surface of high-Mn/Al austenitic low-density steel were investigated after isothermal holding at temperatures of 900-1200℃ in different atmospheres,including air,N_(2),and N_(2)+CO_(2).No ferrite was formed near the surface of the experimental steel during isothermal holding at 900 and 1000℃ in air,while ferrite was formed near the steel sur-face at holding temperatures of 1100 and 1200℃.The ferrite fraction was larger at 1200℃ because more C and Mn diffused to the sur-face,exuded from the steel,and then reacted with N and O to form oxidation products.The thickness of the compound scale increased owing to the higher diffusion rate at higher temperatures.In addition,after isothermal holding at 1100℃ in N_(2),the Al content near the surface slightly decreased,while the C and Mn contents did not change.Therefore,no ferrite was formed near the surface.However,the near-surface C and Al contents decreased after holding at 1100℃in the N_(2)+CO_(2)mixed atmosphere,resulting in the formation of a small amount of ferrite.The compound scale was thickest in N_(2),followed by the N_(2)+CO_(2)mixed atmosphere,and thinnest in air.Overall,the element loss and ferrite fraction were largest after holding in air at the same temperature.The differences in element loss and ferrite frac-tion between in N_(2) and N_(2)+CO_(2)atmospheres were small,but the compound scale formed in N_(2) was significantly thicker.According to these results,N_(2)+CO_(2)is the ideal heating atmosphere for the industrial production of high-Mn/Al austenitic low-density steel.展开更多
AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV...AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of high-density lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1b infection decreases the numbers of medium, small, and very small LDL particles.展开更多
Thermal interface materials(TIMs) play a vital role in the thermal management of electronic devices and can significantly reduce thermal contact resistance(TCR). The TCR between the solid–liquid contact surface is mu...Thermal interface materials(TIMs) play a vital role in the thermal management of electronic devices and can significantly reduce thermal contact resistance(TCR). The TCR between the solid–liquid contact surface is much smaller than that of the solid–solid contact surface, but conventional solid–liquid phase change materials are likely to cause serious leakage. Therefore, this work has prepared a new formstable phase change thermal interface material. Through the melt blending of paraffin wax(PW) and low-density polyethylene(LDPE), the stability is improved and it has an excellent coating effect on PW. The addition of aluminum(Al) powder improves the low thermal conductivity of PW/LDPE, and the addition of 15wt% Al powder improves the thermal conductivity of the internal structure of the matrix by 67%. In addition, the influence of the addition of Al powder on the internal structure, thermal properties, and phase change behavior of the PW/LDPE matrix was systematically studied. The results confirmed that the addition of Al powder improved the thermal conductivity of the material without a significant impact on other properties, and the thermal conductivity increased with the increase of Al addition. Therefore, morphologically stable PW/LDPE/Al is an important development direction for TIMs.展开更多
Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in th...Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.展开更多
Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from...Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from sera df normal lipidemic donors was separated bysequential ultracentrifugation. The separated human IDL 1 mg·mL^(-1) in phosphate buffer saline, pH7.4, was incubated with cupric sulfate (10 μmol·L^(-1) ) at 37℃ for 10 h in the presence orabsence of various concentrations of Iso. Malondialdehyde (MDA) formation, vitamin E consumption,electrophoretic mobility of LDL, mitochondria] membrane potential of mouse peritoneal macrophages,phagocytosis of neutral red, and release of nitric oxide (NO) from macrophages were determined byvarious methods. Results Iso 1 - 100 μmol·L^(-1) significantly inhibited the increase of MDAformation, vitamin E consumption and electrophoretic mobility of LDL induced by Cu^(2+) in aconcentration-dependent manner. The injury of the mitochondrial membrane potential of mouseperitoneal macrophages due to incubation with ox-LDL (0.1 mg·mL^(-1)) at 37℃ for 12 h was markedlyprotected by 10 μmol·L^(-1) Iso. After pretreat-ment of the macrophages with 10 μmol · L^(-1)of Iso and then exposure to ox-LDL for 4 h, the reduction of phagocytosis of neutral red and releaseof NO in response to lipopolysaccharide (IPS) stimulation were significantly prevented. ConclusionIso has protective action against Cu^(2+) - mediated LDL peroxidation and ox-LDL induced toxicity tomacrophages in vitro.展开更多
Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-de...Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in pest-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.展开更多
It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been det...It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been determined.The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein(HDL)as well as oxLDL in untreated patients with coronary atherosclerosis(AS).Thirty-six subjects were enrolled in this study.O f them,18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls.The plasma lipid profile,lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively.The results showed that pitavastatin treatment indeed not only decreased LDL-C,total cholesterol(TC),triglycerides(TG)and apolipoprotein B(ApoB)levels,and increased HDL cholesterol(HDL-C),but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions.Meanwhile,pitavastatin could decrease plasma oxLDL levels.Furthermore,a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment.We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.展开更多
Objective To investigate the association between low-density lipoprotein receptor-related protein 5 (LRPS) variants (rs12363572 and rs4930588) and type 2 diabetes mellitus (T2DM) in Han Chinese. Methods A total ...Objective To investigate the association between low-density lipoprotein receptor-related protein 5 (LRPS) variants (rs12363572 and rs4930588) and type 2 diabetes mellitus (T2DM) in Han Chinese. Methods A total of 1842 T2DM cases (507 newly diagnosed cases and 1335 previously diagnosed cases) and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms (SNPs). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to describe the strength of the association by logistic regression. Results In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index (BMI), the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype ~ was associated with reduced risk of T2DM (OR 0.820, 95% CI 0.732-0.919). In addition, rs12363572 was associated with BMI (P〈0.001) and rs4930588 was associated with triglyceride levels (P=0.043) in 507 newly diagnosed T2DM cases but not in healthy controls. Conclusion No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM.展开更多
Oxidative stress may play a significant role in the pathogenesis of heart failure(HF).Antibodies to oxidized low-density lipoprotein(oxLDL Abs) reflect an immune response to LDL over a prolonged period and may represe...Oxidative stress may play a significant role in the pathogenesis of heart failure(HF).Antibodies to oxidized low-density lipoprotein(oxLDL Abs) reflect an immune response to LDL over a prolonged period and may represent long-term oxidative stress in HF.The oxLDL plasma level is a useful predictor of mortality in HF patients,and measurement of the oxLDL Abs level may allow better management of those patients.Antibodies to oxLDL also significantly correlate with the New York Heart Association score.Hypercholesterolemia,smoking,hypertension,and obesity are risk factors for atherosclerotic coronary heart disease(CHD) leading to HF,but these factors account for only onehalf of all cases,and understanding of the pathologic process underlying HF remains incomplete.Nutrients with antioxidant properties can reduce the susceptibility of LDL to oxidation.Antioxidant therapy may be an adjunct to lipid-lowering,angiotensin converting enzyme inhibition and metformin(in diabetes) therapy for the greatest impact on CHD and HF.Observational data suggest a protective effect of antioxidant supple-mentation on the incidence of HD.This review summarizes the data on oxLDL Abs as a predictor of morbidity and mortality in HF patients.展开更多
A novel low-density lipoprotein adsorbent was prepared simply by directly phosphonating porous cellulose beads. Tests in vitro demonstrated that this adsorbent showed quite good adsorption performance for selective re...A novel low-density lipoprotein adsorbent was prepared simply by directly phosphonating porous cellulose beads. Tests in vitro demonstrated that this adsorbent showed quite good adsorption performance for selective removal of low-density lipoprotein from human plasma. The effects of preparation conditions on the lipoprotein sorption properties of the resulted adsorbent were investigated. The adsorption dynamics was also examined.展开更多
Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive...Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke.Therefore,OLR1 is likely involved in the progress of intracerebral hemorrhage.In this study,we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model.OLR1 small interfering RNA(10μL;50 pmol/μL)was injected into the right basal ganglia to knock down OLR1.Twenty-four hours later,0.5 U collagenase type VII was injected to induce intracerebral hemorrhage.We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma,neuron loss,inflammatory reaction,and oxidative stress in rat brain tissue.We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway.Therefore,silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage.These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage.展开更多
AIM: To investigate whether intravitreal injection of oxidized low-density lipoprotein(OxLDL) can promote laserinduced choroidal neovascularization(CNV) formation in mice and the mechanism involved, thereby to develop...AIM: To investigate whether intravitreal injection of oxidized low-density lipoprotein(OxLDL) can promote laserinduced choroidal neovascularization(CNV) formation in mice and the mechanism involved, thereby to develop a better animal model.METHODS: C57BL6/J mice were randomized into three groups. Immediately after CNV induction with 532 nm laser photocoagulation, 1.0 μL of OxLDL [100 μg/m L in phosphate-buffered saline(PBS)] was intravitreally injected, whereas PBS and the same volume low-density lipoprotein(LDL;100 μg/m L in PBS) were injected into the vitreous as controls. Angiogenic and inflammatory cytokines were measured by quantitative real-time polymerase chain reaction(q RT-PCR) and Western blotting(WB) after 5 d, and CNV severity was analyzed by choroid flat mount and immunofluorescence staining after 1wk. In vitro, retinal pigment epithelial(RPE) cell line(ARPE19) were treated with OxLDL(LDL as control) for 8 h. Angiogenic and inflammatory cytokine levels were measured. A specific inhibitor of lectin-like oxidized low-density lipoprotein receptor 1(LOX1) was used to evaluate the role of LOX1 in this process.RESULTS: At 7 d after intravitreal injection of 1 μL(100 μg/mL) OxLDL, T15-labeled OxLDL was mainly deposited around the CNV area, and the F4/80-labeled macrophages, the CD31-labeled vascular endothelial cells number and CNV area were increased. Meanwhile, WB and qR T-PCR results showed that vascular endothelial growth factor(VEGF), CC chemokine receptor 2(CCR2), interleukin-6(IL-6), IL-1β, and matrix metalloproteinase 9(MMP9) expressions were increased, which was supported by in vitro experiments in RPE cells. LOX1 inhibitors significantly reduced expressions of inflammatory factors IL-1β and VEGF. CONCLUSION: A modified laser-induced CNV animal model is established with intravitreal injection of 1 μL(100 μg/mL) of OxLDL at 7 d, which at least partially through LOX1. This animal model can be used as a simple model for studying the role of OxLDL in age-related macular degeneration.展开更多
BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modif...BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection.The relationship between cholesterol,APOE alleles,and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIM To investigate the role of APOE-ε2,-ε3,and-ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODS A total of 299 treatment-na?ve HCV patients were included in this retrospective study.Patients were stratified in chronic hepatitis C(CHC)(n=206)and spontaneous clearance(SC)(n=93).A clinical record was registered.Biochemical tests were assessed by dry chemistry assay.APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTS Total cholesterol,low-density lipoprotein cholesterol(LDL-c),triglycerides,and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOEε4 allele(12.4%vs 7.3%).SC patients were overweight(54.8%).Theε4 allele was associated with SC(OR=0.55,95%CI:0.31-0.98,P=0.042)and mild fibrosis(F1-F2)in CHC patients(OR 0.091,95%CI 0.01-0.75,P=0.020).LDL-c≥101.5 mg/dL(OR=0.20,95%CI:0.10-0.41,P<0.001)and BMI≥26.6 kg/m2(OR=0.37,95%CI:0.18-0.76,P<0.001)were associated with SC status;while ALT≥50.5 IU/L was negatively associated(OR=5.67,95%CI:2.69-11.97,P<0.001).CONCLUSION In SC patients,the APOEε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.展开更多
Background The correlation among the ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol(LDL-C/HDL-C), total cholesterol/high-density lipoprotein cholesterol(TC/HDL-C) and thin-cap fibro...Background The correlation among the ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol(LDL-C/HDL-C), total cholesterol/high-density lipoprotein cholesterol(TC/HDL-C) and thin-cap fibroatheroma has not yet been established. Methods It was a single center, retrospective observational study. In total, we recruited 421 patients(82.4% men;mean age 65.73 ± 10.44 years) with one culprit vessel which determined by intravascular optical coherence tomography(OCT). The thinnest-capped fibroatheroma(TCFA) group was defined as lipid contents in > 2 quadrants, with the thinnest fibrous cap measuring less than 65 μm. Univariate and multivariate logistic regression were carried out to explore the relationship between lipoprotein ratios, TCFA and other characteristics of plaque. To compare different ratios, the area under curve(AUC) of receiver-operating characteristic(ROC) curve was assessed. Results OCT was performed in 421 patients(TCFA group(n = 109), non-TCFA group(n = 312)). LDL-C/HDL-C in the TCFA group was significantly higher than in the non-TCFA group(2.95 ± 1.20 vs. 2.43 ± 0.92, P < 0.05), as was TC/LDL in TCFA and non-TCFA group(4.57 ± 1.58 vs. 4.04 ± 1.13, P < 0.05). Both LDL-C/HDL-C(OR: 1.002(1.002-1.003), P < 0.05) and TC/HDL-C(OR: 1.001(1.001-1.004), P < 0.05) were considered independent factors for the prediction of TCFA according to the logistic regression. Based on the AUC comparison, LDL-C/HDL-C and TC/HDL-C had no significant difference statistically(LDL-C/HDL-C AUC: 0.63;TC/HDL-C AUC: 0.61;P = 0.10) for the prediction of TCFA. Conclusions LDL-C/HDL-C and TC/HDL-C could be the independent factors for predicting the presence of TCFA, indicating coronary plaque vulnerability in CAD patients. Moreover, TC/HDL-C also showed a comparative performance for the prediction of TCFA as LDL-C/HDL-C.展开更多
OBJECTIVE To investigate the associations between the blood concentrations of low-density lipoprotein cholesterol(LDL-C)and the clinical features of haemorrhagic stroke.METHODS This study analysed the data from patien...OBJECTIVE To investigate the associations between the blood concentrations of low-density lipoprotein cholesterol(LDL-C)and the clinical features of haemorrhagic stroke.METHODS This study analysed the data from patients with acute haemorrhagic stroke at a comprehensive stroke centre from 2013 to 2018.Patients were stratified into three groups according to their baseline LDL-C levels:<70,70 to<100 and≥100 mg/dL.We used multivariate logistic regression models to analyse the associations between LDL-C and the risks of having severe neurological deficits(National Institute Health Stroke Scale[NIHSS]scores≥15)and unfavourable outcomes(modified Rankin Scale[mRS]scores>2)at discharge.RESULTS Six-hundred and six patients were analysed.Their median age was 58 years.Among the patients,75(12%)patients had LDL-C levels<70 mg/dL,194(32%)patients had LDL-C levels between 70 to<100 mg/dL and the other 337(56%)patients had LDL-C levels≥100 mg/dL.Patients with higher LDL-C levels were less likely to suffer severe neurological deficits(LDL-C:70 to<100 vs.<70 mg/dL,adjusted odds ratio[OR]:0.29,95%CI:0.15–0.57;LDL-C:≥100 vs.<70 mg/dL,adjusted OR=0.27,95%CI:0.15–0.51)and to have unfavourable outcomes at discharge(LDL-C:70 to<100 vs.<70 mg/dL,adjusted OR=0.50,95%CI:0.29–0.87 and LDL-C:≥100 vs.<70 mg/dL,adjusted OR=0.46,95%CI:0.28–0.78).CONCLUSIONS An LDL-C level<70 mg/dL was independently associated with severe neurological deficits of haemorrhagic stroke and may increase the risks of unfavourable outcomes at discharge.展开更多
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 mai...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展开更多
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 substitutin...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.展开更多
基金supported by the National Key R&D Program of China (2022YFE0196200)the National Natural Science Foundation of China–Deutsche Forschungsgemeinschaft of Germany (31761133021)+3 种基金the National Natural Science Foundation of China (31970469 and 31701794)the earmarked fund for Modern Agro-industry Technology Research System, China (2023CYJSTX01-20)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi, China (2017104)the Fund for Shanxi “1331 Project”, China
文摘Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.
基金supported by the National Natural Science Foundation of China,No.82201460(to YH)Nanjing Medical University Science and Technology Development Fund,No.NMUB20210202(to YH).
文摘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.
基金supported by the National Key Research and Development Program of China(No.2023YFB3711702).
文摘In low-density steel,κ-carbides primarily precipitate in the form of nanoscale particles within austenite grains.However,their precipitation within ferrite matrix grains has not been comprehensively explored,and the second-phase evolution mechanism during aging remains unclear.In this study,the crystallographic characteristics and morphological evolution ofκ-carbides in Fe-28Mn-10Al-0.8C(wt%)low-density steel at different aging temperatures and times and the impacts of these changes on the steels’microhardness and properties were comprehensively analyzed.Under different heat treatment conditions,intragranularκ-carbides exhibited various morpho-logical and crystallographic characteristics,such as acicular,spherical,and short rod-like shapes.At the initial stage of aging,acicularκ-carbides primarily precipitated,accompanied by a few spherical carbides.κ-Carbides grew and coarsened with aging time,the spherical carbides were considerably reduced,and rod-like carbides coarsened.Vickers hardness testing demonstrated that the material’s hardness was affected by the volume fraction,morphology,and size ofκ-carbides.Extended aging at higher temperatures led to an increase in carbide size and volume fraction,resulting in a gradual rise in hardness.During deformation,the primary mechanisms for strengthening were dislocation strengthening and second-phase strengthening.Based on these findings,potential strategies for improving material strength are proposed.
基金gratefully acknowledge the financial support from the National Natural Science Foundation of China(No.U20A20270)China Postdoctoral Science Foundation(No.2022M722486).We would like to thank Dr.Wei Yuan at the Analytical&Testing Center of Wuhan University of Science and Technology for the help on EPMA analyses.
文摘The elemental distribution and microstructure near the surface of high-Mn/Al austenitic low-density steel were investigated after isothermal holding at temperatures of 900-1200℃ in different atmospheres,including air,N_(2),and N_(2)+CO_(2).No ferrite was formed near the surface of the experimental steel during isothermal holding at 900 and 1000℃ in air,while ferrite was formed near the steel sur-face at holding temperatures of 1100 and 1200℃.The ferrite fraction was larger at 1200℃ because more C and Mn diffused to the sur-face,exuded from the steel,and then reacted with N and O to form oxidation products.The thickness of the compound scale increased owing to the higher diffusion rate at higher temperatures.In addition,after isothermal holding at 1100℃ in N_(2),the Al content near the surface slightly decreased,while the C and Mn contents did not change.Therefore,no ferrite was formed near the surface.However,the near-surface C and Al contents decreased after holding at 1100℃in the N_(2)+CO_(2)mixed atmosphere,resulting in the formation of a small amount of ferrite.The compound scale was thickest in N_(2),followed by the N_(2)+CO_(2)mixed atmosphere,and thinnest in air.Overall,the element loss and ferrite fraction were largest after holding in air at the same temperature.The differences in element loss and ferrite frac-tion between in N_(2) and N_(2)+CO_(2)atmospheres were small,but the compound scale formed in N_(2) was significantly thicker.According to these results,N_(2)+CO_(2)is the ideal heating atmosphere for the industrial production of high-Mn/Al austenitic low-density steel.
文摘AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P < 0.001), as was that of high-density lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P < 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P < 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P < 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1b infection decreases the numbers of medium, small, and very small LDL particles.
基金supported by the National Natural Science Foundation of China, China (No. 51874047)the Key Science and Technology Project of Changsha City, China (No. kq2102005)+1 种基金the Special Fund for the Construction of Innovative Province in Hunan Province, China (No. 2020RC3038)the Changsha City Fund for Distinguished and Innovative Young Scholars, China (No. kq1802007)。
文摘Thermal interface materials(TIMs) play a vital role in the thermal management of electronic devices and can significantly reduce thermal contact resistance(TCR). The TCR between the solid–liquid contact surface is much smaller than that of the solid–solid contact surface, but conventional solid–liquid phase change materials are likely to cause serious leakage. Therefore, this work has prepared a new formstable phase change thermal interface material. Through the melt blending of paraffin wax(PW) and low-density polyethylene(LDPE), the stability is improved and it has an excellent coating effect on PW. The addition of aluminum(Al) powder improves the low thermal conductivity of PW/LDPE, and the addition of 15wt% Al powder improves the thermal conductivity of the internal structure of the matrix by 67%. In addition, the influence of the addition of Al powder on the internal structure, thermal properties, and phase change behavior of the PW/LDPE matrix was systematically studied. The results confirmed that the addition of Al powder improved the thermal conductivity of the material without a significant impact on other properties, and the thermal conductivity increased with the increase of Al addition. Therefore, morphologically stable PW/LDPE/Al is an important development direction for TIMs.
基金State Key Clinical Specialty Construction Project,China
文摘Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.
文摘Aim To study the effect of Isorhapontigenin (Iso) on copper-mediatedperoxidation of human low-density lipoprotein (LDL) and on the toxicity of oxidized LDL (ox-LDL) tomouse macrophages in vitro. Methods Human LDL from sera df normal lipidemic donors was separated bysequential ultracentrifugation. The separated human IDL 1 mg·mL^(-1) in phosphate buffer saline, pH7.4, was incubated with cupric sulfate (10 μmol·L^(-1) ) at 37℃ for 10 h in the presence orabsence of various concentrations of Iso. Malondialdehyde (MDA) formation, vitamin E consumption,electrophoretic mobility of LDL, mitochondria] membrane potential of mouse peritoneal macrophages,phagocytosis of neutral red, and release of nitric oxide (NO) from macrophages were determined byvarious methods. Results Iso 1 - 100 μmol·L^(-1) significantly inhibited the increase of MDAformation, vitamin E consumption and electrophoretic mobility of LDL induced by Cu^(2+) in aconcentration-dependent manner. The injury of the mitochondrial membrane potential of mouseperitoneal macrophages due to incubation with ox-LDL (0.1 mg·mL^(-1)) at 37℃ for 12 h was markedlyprotected by 10 μmol·L^(-1) Iso. After pretreat-ment of the macrophages with 10 μmol · L^(-1)of Iso and then exposure to ox-LDL for 4 h, the reduction of phagocytosis of neutral red and releaseof NO in response to lipopolysaccharide (IPS) stimulation were significantly prevented. ConclusionIso has protective action against Cu^(2+) - mediated LDL peroxidation and ox-LDL induced toxicity tomacrophages in vitro.
基金This work was supported in part by funding from the National Natural Science Foundation of China (No. 30800845), the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (No. R3100105), and the NIH grants RR00169 and RR13439. We thank Dr. M. Anton for providing the detailed protocols of LDL and HDL extraction.
文摘Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in pest-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.
基金This work was supported,in part,by Capital Special Foundation of Clinical Application Research(No.Z121107001012015)Capital Health Development Fund(No.201614035)+1 种基金CAMS Major Collaborative Innovation Project(No.2016-I2M-1-011)PUMC Youth Fund(No.3332018200).
文摘It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein(LDL)cholesterol(LDL-C),but its impact on lipoprotein subfractions and oxidized low-density lipoprotein(oxLDL)has not been determined.The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein(HDL)as well as oxLDL in untreated patients with coronary atherosclerosis(AS).Thirty-six subjects were enrolled in this study.O f them,18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls.The plasma lipid profile,lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively.The results showed that pitavastatin treatment indeed not only decreased LDL-C,total cholesterol(TC),triglycerides(TG)and apolipoprotein B(ApoB)levels,and increased HDL cholesterol(HDL-C),but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions.Meanwhile,pitavastatin could decrease plasma oxLDL levels.Furthermore,a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment.We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.
基金supported by the National Natural Science Foundation of China(No.81072359)Natural Science Foundation of Guangdong Province(No.S2013010016791)+1 种基金Science and Technology Development Foundation of Shenzhen(No.JCYJ20120613112221107 and JCYJ20130326110246234)Natural Science Foundation of Shenzhen University(No.801-00035911)
文摘Objective To investigate the association between low-density lipoprotein receptor-related protein 5 (LRPS) variants (rs12363572 and rs4930588) and type 2 diabetes mellitus (T2DM) in Han Chinese. Methods A total of 1842 T2DM cases (507 newly diagnosed cases and 1335 previously diagnosed cases) and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms (SNPs). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to describe the strength of the association by logistic regression. Results In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index (BMI), the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype ~ was associated with reduced risk of T2DM (OR 0.820, 95% CI 0.732-0.919). In addition, rs12363572 was associated with BMI (P〈0.001) and rs4930588 was associated with triglyceride levels (P=0.043) in 507 newly diagnosed T2DM cases but not in healthy controls. Conclusion No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM.
文摘Oxidative stress may play a significant role in the pathogenesis of heart failure(HF).Antibodies to oxidized low-density lipoprotein(oxLDL Abs) reflect an immune response to LDL over a prolonged period and may represent long-term oxidative stress in HF.The oxLDL plasma level is a useful predictor of mortality in HF patients,and measurement of the oxLDL Abs level may allow better management of those patients.Antibodies to oxLDL also significantly correlate with the New York Heart Association score.Hypercholesterolemia,smoking,hypertension,and obesity are risk factors for atherosclerotic coronary heart disease(CHD) leading to HF,but these factors account for only onehalf of all cases,and understanding of the pathologic process underlying HF remains incomplete.Nutrients with antioxidant properties can reduce the susceptibility of LDL to oxidation.Antioxidant therapy may be an adjunct to lipid-lowering,angiotensin converting enzyme inhibition and metformin(in diabetes) therapy for the greatest impact on CHD and HF.Observational data suggest a protective effect of antioxidant supple-mentation on the incidence of HD.This review summarizes the data on oxLDL Abs as a predictor of morbidity and mortality in HF patients.
文摘A novel low-density lipoprotein adsorbent was prepared simply by directly phosphonating porous cellulose beads. Tests in vitro demonstrated that this adsorbent showed quite good adsorption performance for selective removal of low-density lipoprotein from human plasma. The effects of preparation conditions on the lipoprotein sorption properties of the resulted adsorbent were investigated. The adsorption dynamics was also examined.
基金supported by the National Natural Science Foundation of China,No.81971125(to ZYH).
文摘Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke.Therefore,OLR1 is likely involved in the progress of intracerebral hemorrhage.In this study,we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model.OLR1 small interfering RNA(10μL;50 pmol/μL)was injected into the right basal ganglia to knock down OLR1.Twenty-four hours later,0.5 U collagenase type VII was injected to induce intracerebral hemorrhage.We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma,neuron loss,inflammatory reaction,and oxidative stress in rat brain tissue.We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway.Therefore,silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage.These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage.
基金Supported by the National Natural Science Foundation of China (No.81470654)Science and Technology Plan of Natural Science Foundation of Shaanxi Province (No.2019SF-047)。
文摘AIM: To investigate whether intravitreal injection of oxidized low-density lipoprotein(OxLDL) can promote laserinduced choroidal neovascularization(CNV) formation in mice and the mechanism involved, thereby to develop a better animal model.METHODS: C57BL6/J mice were randomized into three groups. Immediately after CNV induction with 532 nm laser photocoagulation, 1.0 μL of OxLDL [100 μg/m L in phosphate-buffered saline(PBS)] was intravitreally injected, whereas PBS and the same volume low-density lipoprotein(LDL;100 μg/m L in PBS) were injected into the vitreous as controls. Angiogenic and inflammatory cytokines were measured by quantitative real-time polymerase chain reaction(q RT-PCR) and Western blotting(WB) after 5 d, and CNV severity was analyzed by choroid flat mount and immunofluorescence staining after 1wk. In vitro, retinal pigment epithelial(RPE) cell line(ARPE19) were treated with OxLDL(LDL as control) for 8 h. Angiogenic and inflammatory cytokine levels were measured. A specific inhibitor of lectin-like oxidized low-density lipoprotein receptor 1(LOX1) was used to evaluate the role of LOX1 in this process.RESULTS: At 7 d after intravitreal injection of 1 μL(100 μg/mL) OxLDL, T15-labeled OxLDL was mainly deposited around the CNV area, and the F4/80-labeled macrophages, the CD31-labeled vascular endothelial cells number and CNV area were increased. Meanwhile, WB and qR T-PCR results showed that vascular endothelial growth factor(VEGF), CC chemokine receptor 2(CCR2), interleukin-6(IL-6), IL-1β, and matrix metalloproteinase 9(MMP9) expressions were increased, which was supported by in vitro experiments in RPE cells. LOX1 inhibitors significantly reduced expressions of inflammatory factors IL-1β and VEGF. CONCLUSION: A modified laser-induced CNV animal model is established with intravitreal injection of 1 μL(100 μg/mL) of OxLDL at 7 d, which at least partially through LOX1. This animal model can be used as a simple model for studying the role of OxLDL in age-related macular degeneration.
基金Supported by Programa para el Desarrollo Profesional Docente(PRODEP)to Gonzalez-Aldaco K,No.UDG-PTC-1422Consejo Nacional de Ciencia y Tecnología(CONACYT)to Panduro A,No.2017-01-5254
文摘BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection.The relationship between cholesterol,APOE alleles,and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIM To investigate the role of APOE-ε2,-ε3,and-ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODS A total of 299 treatment-na?ve HCV patients were included in this retrospective study.Patients were stratified in chronic hepatitis C(CHC)(n=206)and spontaneous clearance(SC)(n=93).A clinical record was registered.Biochemical tests were assessed by dry chemistry assay.APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTS Total cholesterol,low-density lipoprotein cholesterol(LDL-c),triglycerides,and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOEε4 allele(12.4%vs 7.3%).SC patients were overweight(54.8%).Theε4 allele was associated with SC(OR=0.55,95%CI:0.31-0.98,P=0.042)and mild fibrosis(F1-F2)in CHC patients(OR 0.091,95%CI 0.01-0.75,P=0.020).LDL-c≥101.5 mg/dL(OR=0.20,95%CI:0.10-0.41,P<0.001)and BMI≥26.6 kg/m2(OR=0.37,95%CI:0.18-0.76,P<0.001)were associated with SC status;while ALT≥50.5 IU/L was negatively associated(OR=5.67,95%CI:2.69-11.97,P<0.001).CONCLUSION In SC patients,the APOEε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.
基金supported by Zhejiang Natural Science Foundation (LY18H020007 and LQ16H020001)National Natural Science Foundation of China (81500212 and 81800212)。
文摘Background The correlation among the ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol(LDL-C/HDL-C), total cholesterol/high-density lipoprotein cholesterol(TC/HDL-C) and thin-cap fibroatheroma has not yet been established. Methods It was a single center, retrospective observational study. In total, we recruited 421 patients(82.4% men;mean age 65.73 ± 10.44 years) with one culprit vessel which determined by intravascular optical coherence tomography(OCT). The thinnest-capped fibroatheroma(TCFA) group was defined as lipid contents in > 2 quadrants, with the thinnest fibrous cap measuring less than 65 μm. Univariate and multivariate logistic regression were carried out to explore the relationship between lipoprotein ratios, TCFA and other characteristics of plaque. To compare different ratios, the area under curve(AUC) of receiver-operating characteristic(ROC) curve was assessed. Results OCT was performed in 421 patients(TCFA group(n = 109), non-TCFA group(n = 312)). LDL-C/HDL-C in the TCFA group was significantly higher than in the non-TCFA group(2.95 ± 1.20 vs. 2.43 ± 0.92, P < 0.05), as was TC/LDL in TCFA and non-TCFA group(4.57 ± 1.58 vs. 4.04 ± 1.13, P < 0.05). Both LDL-C/HDL-C(OR: 1.002(1.002-1.003), P < 0.05) and TC/HDL-C(OR: 1.001(1.001-1.004), P < 0.05) were considered independent factors for the prediction of TCFA according to the logistic regression. Based on the AUC comparison, LDL-C/HDL-C and TC/HDL-C had no significant difference statistically(LDL-C/HDL-C AUC: 0.63;TC/HDL-C AUC: 0.61;P = 0.10) for the prediction of TCFA. Conclusions LDL-C/HDL-C and TC/HDL-C could be the independent factors for predicting the presence of TCFA, indicating coronary plaque vulnerability in CAD patients. Moreover, TC/HDL-C also showed a comparative performance for the prediction of TCFA as LDL-C/HDL-C.
基金the National Natural Science Foundation of China(No.82001242).
文摘OBJECTIVE To investigate the associations between the blood concentrations of low-density lipoprotein cholesterol(LDL-C)and the clinical features of haemorrhagic stroke.METHODS This study analysed the data from patients with acute haemorrhagic stroke at a comprehensive stroke centre from 2013 to 2018.Patients were stratified into three groups according to their baseline LDL-C levels:<70,70 to<100 and≥100 mg/dL.We used multivariate logistic regression models to analyse the associations between LDL-C and the risks of having severe neurological deficits(National Institute Health Stroke Scale[NIHSS]scores≥15)and unfavourable outcomes(modified Rankin Scale[mRS]scores>2)at discharge.RESULTS Six-hundred and six patients were analysed.Their median age was 58 years.Among the patients,75(12%)patients had LDL-C levels<70 mg/dL,194(32%)patients had LDL-C levels between 70 to<100 mg/dL and the other 337(56%)patients had LDL-C levels≥100 mg/dL.Patients with higher LDL-C levels were less likely to suffer severe neurological deficits(LDL-C:70 to<100 vs.<70 mg/dL,adjusted odds ratio[OR]:0.29,95%CI:0.15–0.57;LDL-C:≥100 vs.<70 mg/dL,adjusted OR=0.27,95%CI:0.15–0.51)and to have unfavourable outcomes at discharge(LDL-C:70 to<100 vs.<70 mg/dL,adjusted OR=0.50,95%CI:0.29–0.87 and LDL-C:≥100 vs.<70 mg/dL,adjusted OR=0.46,95%CI:0.28–0.78).CONCLUSIONS An LDL-C level<70 mg/dL was independently associated with severe neurological deficits of haemorrhagic stroke and may increase the risks of unfavourable outcomes at discharge.
文摘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
文摘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.