Monocyte to high-density lipoprotein cholesterol ratio as a predictor of the activity of thyroid-associated ophthalmopathy

AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified into two groups based on clinical activity score(CAS)scoring criteria:high CAS group(n=62,the CAS score was≥3);low CAS group(n=25,the CAS score was<3).In addition,a group of healthy people(n=114)were included to compared the MHR.Proptosis,MHR,average signal intensity ratio(SIR),average lacrimal gland(LG)-SIR,average extraocular muscles(EOM)area from 87 patients with TAO were calculated in magnetic resonance imaging(MRI),and compared between these two groups.Correlation testing was utilized to evaluate the association of parameters among the clinical variables.RESULTS:Patients in high CAS group had a higher proptosis(P=0.041)and MHR(P=0.048).Compared to the healthy group,the MHR in the TAO group was higher(P=0.001).Correlation testing declared that CAS score was strongly associated with proptosis and average SIR,and MHR was positively associated with CAS score,average SIR,and average LG-SIR.The area under the receiver operating characteristic curve(AUC)of MHR was 0.6755.CONCLUSION:MHR,a novel inflammatory biomarker,has a significant association with CAS score and MRI imaging(average SIR and LG-SIR)and it can be a new promising predictor during the active phase of TAO.

Synthetic high-density lipoprotein(sHDL):a bioinspired nanotherapeutics for managing periapical bone inflammation

Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.

Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity

Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various inflammation-related diseases.The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.Methods Based on hepatic ultrasound,a total of 504 children with obesity(357 with NAFLD and 147 without NAFLD)were included in the study.The correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s analyses.Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.Results The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD[0.52(0.44-0.67)versus 0.44(0.34-0.57),P<0.001].Multivariate stepwise logistic regression analysis demonstrated that the MHR[odds ratio(OR):1.033,95%confidence interval(CI):1.015-1.051;P<0.001]was an independent predictor of NAFLD in childhood obesity patients,as were age(OR:1.205,95%CI:1.059-1.371;P=0.005],waist circumference[OR:1.037,95%CI:1.008-1.067;P=0.012],and alanine transaminase[OR:1.067,95%CI:1.045-1.089;P<0.001].Additionally,MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.Conclusion The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.

Correlation of Helicobacter pylori infection with high-density lipoprotein cholesterol levels and pulse wave conduction velocity

Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's disease.However,the relationship between HP and lipid metabolism and atherosclerosis remains unclear.This study aims to investigate the association between H.pylori infection and high-density lipoprotein cholesterol levels and pulse wave conduction velocity.Methods:This is a report of a cross-sectional study that collected data from 2,827 participants.The data collected included results of life questionnaires,laboratory tests,13C-urea breath test(13C-UBT),and pulse wave conduction velocity test.Based on the results of the 13C-UBT test,the subjects were divided into two groups:the HP-uninfected group(HP−)and the HP-infected group(HP+).The study compared the differences in HDL-C levels and brachial-ankle pulse wave velocity(baPWV)between the two groups.One-way regression analysis was used to identify potential factors affecting HDL-C levels in the study population.Multiple regression equations were presented to analyze whether HP infection was an independent risk factor for abnormal HDL-C metabolism in the population.Results:Univariate analysis demonstrated that high-density lipoprotein cholesterol(HDL-C)levels were significantly lower in the HP+group compared to the HP−group,with a mean difference ofβ=−18.1 mg/dl(95%CI:−19.3 to−17.0,P<0.001).After adjusting for all variables,the HDL-C levels remained lower in the HP+group compared to the HP-group,with a mean difference ofβ=−17.4 mg/dl(95%CI:−18.2 to−16.7,P<0.001).These findings suggest that H.pylori infection is independently associated with abnormal HDL-C metabolism.Additionally,brachial-ankle pulse wave velocity(baPWV)was higher in the HP+group than in the HP−group on both sides.On the right side,the baPWV was 1,713.4±231.4 cm/s in the HP+group compared to 1,542.8±237.5 cm/s in the HP−group(t=−18.30,P<0.001).On the left side,the baPWV was 1,743.7±238.8 cm/s in the HP+group compared to 1,562.8±256.3 cm/s in the HP−group(t=−18.23,P<0.001).These results indicate a significant association between H.pylori infection and increased arterial stiffness,as measured by baPWV.Conclusion:Helicobacter pylori infection is associated with a decrease in high-density lipoprotein cholesterol levels and an increase in pulse wave conduction velocity.

A model for fast electron-driven high-density plasma in the double-cone ignition scheme

A model for fast electron-driven high-density plasma is proposed to describe the effect of injected fast electrons on the temperature and inner pressure of the plasma in the fast heating process of the double-cone ignition(DCI)scheme.Due to the collision of the two low-density plasmas,the density and volume of the high-density plasma vary.Therefore,the ignition temperature and energy requirement of the high-density plasma vary at different moments,and the required energy for hot electrons to heat the plasma also changes.In practical experiments,the energy input of hot electrons needs to be considered.To reduce the energy input of hot electrons,the optimal moment and the shortest time for injecting hot electrons with minimum energy are analyzed.In this paper,it is proposed to inject hot electrons for a short time to heat the high-density plasma to a relatively high temperature.Then,the alpha particles with the high heating rate and PdV work heat the plasma to the ignition temperature,further reducing the energy required to inject hot electrons.The study of the injection time of fast electrons can reduce the energy requirement of fast electrons for the high-density plasma and increase the probability of successful ignition of the high-density plasma.

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.

Tandem hydroalkylation and deoxygenation of lignin-derived phenolics to synthesize high-density fuels

Lignin is the most abundant naturally phenolic biomass,and the synthesis of high-performance renewable fuel from lignin has attracted significant attention.We propose the efficient synthesis of high-density fuels using simulated lignin cracked oil in tandem with hydroalkylation and deoxygenation reactions.First,we investigated the reaction pathway for the hydroalkylation of phenol,which competes with the hydrodeoxygenation form cyclohexane.And then,we investigated the effects of metal catalyst types,the loading amount of metallic,acid dosage,and reactant ratio on the reaction results.The phenol hydroalkylation and hydrodeoxygenation were balanced when 180℃ and 5 MPa H_(2)with the alkanes yield of 95%.By extending the substrate to other lignin-derived phenolics and simulated lignin cracked oil,we obtained the polycyclic alkane fuel with high density of 0.918 g·ml^(-1)and calorific value of41.2 MJ·L^(-1).Besides,the fuel has good low-temperature properties(viscosity of 9.3 mm^(2)·s^(-1)at 20℃ and freezing point below-55℃),which is expected to be used as jet fuel.This work provides a promising way for the easy and green production of high-density fuel directly from real lignin oil.

Kinetic-Thermodynamic Promotion Engineering toward High-Density Hierarchical and Zn-Doping Activity-Enhancing ZnNiO@CF for High-Capacity Desalination

Despite the promising potential of transition metal oxides(TMOs)as capacitive deionization(CDI)electrodes,the actual capacity of TMOs electrodes for sodium storage is significantly lower than the theoretical capacity,posing a major obstacle.Herein,we prepared the kinetically favorable Zn_(x)Ni_(1−x)O electrode in situ growth on carbon felt(Zn_(x)Ni_(1−x)O@CF)through constraining the rate of OH^(−)generation in the hydrothermal method.Zn_(x)Ni_(1−x)O@CF exhibited a high-density hierarchical nanosheet structure with three-dimensional open pores,benefitting the ion transport/electron transfer.And tuning the moderate amount of redox-inert Zn-doping can enhance surface electroactive sites,actual activity of redox-active Ni species,and lower adsorption energy,promoting the adsorption kinetic and thermodynamic of the Zn_(0.2)Ni_(0.8)O@CF.Benefitting from the kinetic-thermodynamic facilitation mechanism,Zn_(0.2)Ni_(0.8)O@CF achieved ultrahigh desalination capacity(128.9 mgNaCl g^(-1)),ultra-low energy consumption(0.164 kW h kgNaCl^(-1)),high salt removal rate(1.21 mgNaCl g^(-1) min^(-1)),and good cyclability.The thermodynamic facilitation and Na^(+)intercalation mechanism of Zn_(0.2)Ni_(0.8)O@CF are identified by the density functional theory calculations and electrochemical quartz crystal microbalance with dissipation monitoring,respectively.This research provides new insights into controlling electrochemically favorable morphology and demonstrates that Zn-doping,which is redox-inert,is essential for enhancing the electrochemical performance of CDI electrodes.

Low Stress TSV Arrays for High-Density Interconnection

In three-dimensional(3D)stacking,the thermal stress of through-silicon via(TSV)has a significant influence on chip performance and reliability,and this problem is exacerbated in high-density TSV arrays.In this study,a novel hollow tungsten TSV(W-TSV)is presented and developed.The hollow structure provides space for the release of thermal stress.Simulation results showed that the hollow W-TSV structure can release 60.3%of thermal stress within the top 2 lm from the surface,and thermal stress can be decreased to less than 20 MPa in the radial area of 3 lm.The ultra-high-density(1600 TSV∙mm2)TSV array with a size of 640×512,a pitch of 25 lm,and an aspect ratio of 20.3 was fabricated,and the test results demonstrated that the proposed TSV has excellent electrical and reliability performances.The average resistance of the TSV was 1.21 X.The leakage current was 643 pA and the breakdown voltage was greater than 100 V.The resistance change is less than 2%after 100 temperature cycles from40 to 125℃.Raman spectroscopy showed that the maximum stress on the wafer surface caused by the hollow W-TSV was 31.02 MPa,which means that there was no keep-out zone(KOZ)caused by the TSV array.These results indicate that this structure has great potential for applications in large-array photodetectors and 3D integrated circuits.

Predictive value of intracranial high-density areas in neurological function

BACKGROUND Intracranial high-density areas(HDAs)have attracted considerable attention for predicting clinical outcomes;however,whether HDAs predict worse neurological function and mental health remains controversial and unclear,which requires further investigation.In this prospective study,96 patients with acute ischemic stroke(AIS)who accepted endovascular mechanical thrombectomy(EMT)were included.The enrolled patients underwent cranial computed tomography(CT)examination within 24 hours after EMT.Clinical data in terms of National Institutes of Health Stroke Scale(NIHSS),the 3-month modified Rankin Scale(mRS),self-rating depression scale(SDS),and self-rating anxiety scale(SAS)scores were collected and compared between patients with HDAs and non-HDAs and between patients with good and poor clinical prognosis.Compared to patients without HDAs,patients with HDAs presented severe neurological deficits(admission NIHSS score:18±3 vs 19±4),were more likely to have post-stroke disabilities(mRS<3:35%vs 62%),and suffered more severe depression(SDS score:58±16 vs 64±13)and anxiety disorder(SAS score:52±8 vs 59±10).Compared to patients with a good prognosis,patients with a poor prognosis presented severe neurological deficits(admission NIHSS score:17±4 vs 20±3),were more likely to have HDAs on CT images(64%vs 33%),and suffered more severe depression(SDS score:55±19 vs 65±11)and anxiety(SAS score:50±8 vs 58±12).Multivariate analysis revealed that HDAs were independent nega-tive prognostic factors.CONCLUSION In conclusion,HDAs on CT images predicted poor prognosis and severe depressive and anxiety symptoms in patients with AIS who underwent EMT.

Proso Millet Protein Elevates Plasma Level of High-Density Lipoprotein:A New Food Function of Proso Millet

We examined the effects of dietary proso-millet protein on plasma levels of high-density lipoprotein (HDL) cholesterol in different rats from animals reported in our previous studies. The results showed also, in this animal, that the ingestion of the millet protein elevates plasma levels of HDL-cholesterol like our earlier works. Taking into account the anti-atherogenic function of HDL, therefore, the millet protein would be useful as a new food ingredient which has the function that regulates cholesterol metabolism

OXIDIZED HIGH-DENSITY LIPOPROTEIN PROMOTES MATURATION AND MIGRATION OF BONE MARROW DERIVED DENDRITIC CELLS FROM C57BL/6J MICE

Objective To explore the influence of oxidized high-density lipoprotein （oxHDL） on the maturation and migration of bone marrow-derived dendritic cells （BMDCs） from C57BL/6J mice. Methods The C57BL/6J mice bone marrow cell suspension was prepared and purified. Recombinant granulocyte-macrophage colony-stimulating factor （rmGM-CSF） and recombinant interleukin-4 （rmlL-4） were used to promote monocytes to differentiate and suppress lymphocytes. Then 50μg/mL oxHDL was added to stimulate BMDCs, using 50μg/mL high-density lipoprotein （HDL） as homologous protein control, PBS as negative control, and 1 μg/mL lipopolysaccharide （LPS） as positive control. The CD86 and MHCII expression rates were detected with fluorescence-activated cell sorting （FACS）. Liquid scintillation counting （LSC） was used in mixed lymphocyte reactions （MLRs） to reflect the ability of BMDCs in stimulating the proliferation of homologous T cells, Levels of cytokines IL-12 and IL-10 were detected by ELISA. The cell migration was evaluated with the transwell system. Results Compared with PBS group, the expressions of CD86 and MHCII, counts per minute of MLRs, secretion of IL-12 and IL-10, and number of migrated cells in oxHDL group and LPS group significantly increased （all P 〈 0.05）, while the increment was less in oxHDL group than LPS group. The number of migrated cells in oxHDL group was about twice of that in HDL group. Conclusion OxHDL may promote the maturation and migration of BMDCs in vitro.

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.

Conversion of lignin oil and hemicellulose derivative into high-density jet fuel

Synthesizing high-density fuel from lignocellulose can not only achieve green and low-carbon development,but also expand the feedstock source of hydrocarbon fuel.Here,we reported a route of producing high-density fuel from lignin oil and hemicellulose derivative cyclopentanol through alkylation and hydrodeoxygenation,HY with SiO_(2)/Al_(2)O_(3) molar ratio of 5.3 was screened as the alkylation catalyst in the reaction of model phenolic compounds and mixtures,and the reaction conditions were optimized to achieve conversion of phenolic compounds higher than 87%and selectivity of bicyclic and tricyclic products higher than 99%.Then two phenolic pools simulating the composition of two typic lignin oils were studied to validate the alkylation and analyze the competition mechanism of phenolic compounds in mixture system.Finally,real lignin oil from depolymerized of beech powder was tested,and notably80%of phenolic monomers in the oil were converted into fuel precursor.After hydrodeoxygenation,the alkylated product was converted to fuel blend with a density of 0.91 g/mL at 20℃and a freezing point lower than-60℃,very promising as high density fuel.This work provides a facile and energyefficient way of synthesizing high-performance jet fuel directly from lignocellulosic derivatives,which decreases processing energy consumption and improve the utilization rate of feedstock.

QTL mapping for berry shape based on a high-density genetic map constructed by whole-genome resequencing in grape

Grape berry shape is an important agricultural trait.Clarifying its genetic basis is significant for cultivating grape varieties that meet market demands.However,the current study by forward genetics has not achieved in-depth results.Here,a high-density map was constructed to identify quantitative trait loci(QTLs)for berry shape.A total of 358709 polymorphic SNPs were obtained using whole-genome resequencing(WGS)based on 208 F2 individuals derived from round grape‘E42-6’and oblong grape‘Rizamat’.The 1635.65 cM high-density map was divided into 19 linkage groups with an average distance of 0.37 cM.Using this map,three significant QTLs for fruit shape index(ShI:ratio of berry length to berry width)identified over three years were mapped onto LG4 and LG5,including one stable QTL on Chr5 with the genomic region of 0.47–1.94 Mb.Combining with gene annotation and expression patterns based on RNA-seq data from two contrasting F2 individuals with round and oblong berry(their average ShI was 1.89 and 1.10,respectively)at four developmental stages,four candidate genes were selected from the above QTLs.They were mainly involved in DNA replication,cell wall modification,and phytohormone biosynthesis.Further analysis of RNA-seq data revealed that several important phytohormone synthesis and metabolic pathways were enriched based on differentially expressed genes(DEGs),which was consistent with the results of QTL mapping for genes related to plant hormone biosynthesis in the F2 population.Furthermore,a comparison of plant hormone content showed that there were significant differences in IAA and tZ content between the two contrasting F2 individuals at different developmental stages.Our findings provide molecular insights into the genetic variation in grape berry shape.Stable QTLs and their tightly linked markers offer the possibility of marker-assisted selection to accelerate berry shape breeding.

The role of low-density lipoprotein （LDL） and high-density lipoprotein （HDL） in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys

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.

Effect of low high-density lipoprotein levels on mortality of septic patients: A systematic review and meta-analysis of cohort studies

BACKGROUND:An increase in high-density lipoprotein(HDL)is well associated with a decreased cardiovascular risk,especially atherosclerosis.Recent studies suggest that lower levels of HDL may also be associated with an increased risk of sepsis and an increased rate of mortality in septic patients.However,this conclusion remains controversial.METHODS:MEDLINE,EMBASE,and CENTRAL databases were searched from inception to September 30,2019.All studies were conducted to evaluate the correlation of lipoprotein levels and the risk and outcomes of sepsis in adult patients.The primary outcomes were the risk and mortality of sepsis.RESULTS:Seven studies comprising 791 patients were included.Lower levels of HDL had no marked relevance with the risk of sepsis(odds radio[OR]for each 1 mg/dL increase,0.94;95%CI 0.86–1.02;P=0.078),whereas lower HDL levels were related to an increased mortality rate in septic patients(OR for below about median HDL levels,2.00;95%CI 1.23–3.24;P=0.005).CONCLUSION:This meta-analysis did not reveal a signifi cant association between lower HDL levels and an increase in the risk of sepsis,whereas it showed that lower HDL levels are associated with a higher mortality rate in septic adult patients.These findings suggest that HDL may be considered as a promising factor for the prevention and treatment of sepsis in the future.

Bone and high-density lipoprotein:The beginning of a beautiful friendship

There is a tight link between bone and lipid metabolic pathways.In this vein,several studies focused on the exploration of high-density lipoprotein(HDL)in the pathobiology of bone diseases,with emphasis to the osteoarthritis(OA)and osteoporosis,the most common bone pathologies.Indeed,epidemiological and in vitro data have connected reduced HDL levels or dysfunctional HDL with cartilage destruction and OA development.Recent studies uncovered functional links between HDL and OA fueling the interesting hypothesis that OA could be a chronic element of the metabolic syndrome.Other studies have linked HDL to bone mineral density.Even though at epidemiological levels the results are conflicting,studies in animals as well as in vitro experiments have shown that HDL facilitates osteoblastogensis and bone synthesis and most probably affects osteoclastogenesis and osteoclast bone resorption.Notably,reduced HDL levels result in increased bone marrow adiposity affecting bone cells function.Unveiling the mechanisms that connect HDL and bone/cartilage homeostasis may contribute to the design of novel therapeutic agents for the improvement of bone and cartilage quality and thus for the treatment of related pathological conditions.

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.

Glycation of high-density lipoprotein triggers oxidative stress and promotes the proliferation and migration of vascular smooth muscle cells

Background In type 2 diabetes mellitus （T2DM）, high-density lipoprotein （HDL） impairs its anti-atherogenic properties and even develops to a pro-inflammatory and pro-atherogenic phenotype because of abnormal compositions and modifications. In this study, we ex- amined the effects and the related mechanisms of glycation of HDL on the proliferation and migration of vascular smooth muscle cells （VSMCs）. Methods ＆ Results Glycated HDL （G-HDL） was modified with D-glucose （25 mmol/L） in vitro. Diabetic HDL （D-HDL） was isolated from T2DM patients. Rat VSMCs were isolated from the thoracic aortas. Human VSMCs were obtained from ScienCell Research Laboratories. Alpha-actin was detected through immunofiuorescence. VSMC proliferation was assayed by Cell Count. VSMC migration was determined by transwell chamber and scratch-wound assay. Intracellular reactive oxygen species （ROS） was detected based on ROS-medi- ated 2＇,7＇-dichlorofluorescein （DCFH-DA） fluorescence. Compared to native HDL （N-HDL）, G-HDL remarkably promoted VSMC prolif- eration and migration in the dose and time-dependent manners. In addition, G-HDL enhanced ROS generation in VSMCs. However, the ROS scavenger, N-acetylcysteine, efficiently decreased ROS production and subsequently inhibited the proliferation of VSMCs induced by G-HDL. Similarly, D-HDL from T2DM patients also promoted ROS release and VSMC proliferation and migration. Conclusions HDL either glycated in vitro or isolated from T2DM patients triggered VSMC proliferation, migration, and oxidative stress. These results might partly interpret the higher morbidity of cardiovascular disease in T2DM patients.