BACKGROUND The association between the uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and mental health among individuals with type 2 diabetes mellitus(T2DM)has not been thoroughly investigated.AIM To exa...BACKGROUND The association between the uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and mental health among individuals with type 2 diabetes mellitus(T2DM)has not been thoroughly investigated.AIM To examine the link between UHR and symptoms of depression and anxiety in patients with T2DM.METHODS A cross-sectional analysis was carried out from March 2023 to April 2024,involving participants diagnosed with T2DM.Data on sociodemographic characteristics,clinical parameters,and UHR values were systematically gathered.The Self-Rating Depression Scale(SDS)and Self-Rating Anxiety Scale(SAS)were utilized to evaluate depressive and anxiety symptoms,respectively.To assess the relationships between UHR and SDS/SAS scores,linear regression models were employed,incorporating adjustments for potential confounding variables.Additionally,smooth curve fitting and threshold effect analyses were conducted to explore potential nonlinear relationships.RESULTS A total of 285 patients with T2DM were included.Initial univariate analysis demonstrated a significant positive correlation between elevated UHR levels and higher SDS and SAS scores.Multivariate regression analysis revealed that a one-unit rise in UHR was associated with a 1.13-point increase in SDS scores(95%CI:0.69-1.58)and a 0.57-point increase in SAS scores(95%CI:0.20-0.93).After controlling for confounders,UHR remained positively correlated with SDS(β=1.55,95%CI:0.57-2.53)and SAS(β=0.72,95%CI:0.35-1.09).Nonlinear analysis identified critical thresholds at UHR values of 5.02 for SDS and 4.00 for SAS,beyond which the relationships between UHR and psychological symptom scores became markedly stronger(P<0.05).CONCLUSION Higher UHR levels are significantly linked to exacerbated depressive and anxiety symptoms in patients with T2DM.These results indicate that UHR may function as a promising biomarker to identify individuals at greater risk of mental health complications within this population.展开更多
BACKGROUND The association between the serum uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and cardiovascular disease(CVD)risk in Asian populations with metabolic dysfunction-associated steatotic liver d...BACKGROUND The association between the serum uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and cardiovascular disease(CVD)risk in Asian populations with metabolic dysfunction-associated steatotic liver disease(MASLD)remains insufficiently elucidated.AIM To investigate the relevance and dose-responsive relationship between UHR and 10-year CVD risk among Asian MASLD patients.METHODS In this retrospective analysis,3901 MASLD patients were enrolled based on established screening criteria.As measured by the Framingham risk score,participants were stratified according to their 10-year CVD risk.The association between UHR and CVD risk was evaluated using binary logistic regression,while dose-response patterns were explored through restricted cubic spline(RCS)modeling.The discriminatory capability of UHR,in comparison with conventional biomarkers,was further examined by receiver operating characteristic curve analysis.RESULTS Multivariable-adjusted analyses revealed that elevated UHR levels were significantly associated with an increased likelihood of intermediate-to-high CVD risk.RCS modeling demonstrated a linear dose-response relationship between UHR and the Framingham risk score(P for nonlinearity=0.114).Sex-stratified RCS analyses further indicated that this linear association persisted among males(P for nonlinearity=0.167)but was not statistically significant in females(P for nonlinearity=0.476).Further stratified analyses revealed that the association was particularly pronounced among younger individuals(<50 years),males,and those with central obesity,whereas it was attenuated in older adults(≥50 years)and females.Receiver operating characteristic analysis demonstrated that UHR outperformed individual biomarkers in predicting 10-year CVD risk,showing an area under the curve of 0.655(95%confidence interval:0.635-0.674).CONCLUSION UHR functioned as an independent predictor of 10-year CVD risk in Asian patients with MASLD,demonstrating a linear dose-response association and superior discriminative performance relative to conventional biomarkers,especially among younger individuals,males,and those with central obesity.展开更多
AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells. METHODS: Recombinant complex of HDL and aclacinomycin (rHDL-ACM) was...AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells. METHODS: Recombinant complex of HDL and aclacinomycin (rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine. Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles, morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method. RESULTS: The density range of rHDL-ACM was 1.063-1.210 g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%. Encapsulated efficiencies of rHDL-ACM were more than 90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26±5.62 nm by measure of 110 rHDL-ACM particles in the range of diameter of lipoproteins. rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 μg/mL (P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 ug/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM (1.68 nmol/L vs3 nmol/L). Compared to L02 hepatocytes, a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 μg/mL.Cytotoxicity of the rHDL-ACM to SMMC- 7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5μg/mL (P<0.01). IC50 for SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L), showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells. CONCLUSION: rHDL-ACM complex keeps the basic physical and biological binding properties of native HDL and shows a preferential cytotoxicity for SMMC-7721 hepatoma to normal L02 hepatocytes, HDL is a potential carrier for delivering lipophilic antitumoral drug to hepatoma cells.展开更多
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 ...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展开更多
Objective:Disturbances in lipid and lipoprotein profiles in patients after kidney transplantation (Tx) are still not understood. Methods:Serum levels of lipids,lipoprotein,triglyceride-rich lipoproteins (TRLs),and hig...Objective:Disturbances in lipid and lipoprotein profiles in patients after kidney transplantation (Tx) are still not understood. Methods:Serum levels of lipids,lipoprotein,triglyceride-rich lipoproteins (TRLs),and high-density lipoprotein (HDL) particles were determined,lipid and lipoprotein ratios were calculated,and their relationships in Tx patients with hypertriglyceridemia (HTG) and lower apolipoprotein AI (apoAI) concentration were examined. Serum lipid and lipoprotein levels were measured in 109 Tx patients and 89 healthy subjects. HDL particle levels were de-termined by enzyme-linked immunosorbent assay (ELISA). Results:Tx patients had disturbed concentration,com-position,and metabolism of TRLs and HDL particles. Multivariance analysis showed significant and positive correlation between HDL cholesterol/apoAI (HDL-C/apoAI) and HDL-C/HDL ratios,which indicates that both ratios could sensi-tively reflect changes in the HDL subclasses and their distribution into smaller size particles. In Tx patients,the de-creased HDL-C/apoAI ratio indicates that,along with the decreased apoAI concentration,the HDL-C level is de-creased. However,a low HDL-C/HDL ratio indicates that HDL particles in Tx patients transport lesser content of HDL-C but more triglyceride (TG) (high TG/HDL ratio),and thus are hypercatabolized and removed; therefore,con-centration of HDL particles in serum was decreased. Conclusion:The decrease of HDL-C/apoAI ratio seems to be a good marker of HDL subclass distribution into smaller size particles.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
Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipop...Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein （HDL） reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein （ox-LDL） and anti-ox-LDL, and paraoxonase-1 （PON-1） activity in HD （n=33） and Tx （n=71） patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I （apoA-I） and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios （total cholesterol （TC）/HDL-C, LDL-C/HDL-C, triglyceride （TG）/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL） were atherogenic. The Spearman＇s rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level （R=0.363, P=0.004）, and negatively with TC （R=-0.306, P=0.012）, LDL-C （R=-0.283, P=0.020）, and non-HDL-C （R=-0.263, P=0.030） levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and de- creased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-13-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.展开更多
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 cholester...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.展开更多
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 ...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.展开更多
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 compo...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.展开更多
BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the gastrointestinal tract.Lipid metabolism,as an important part of material and energy circulation,is well known to play a crucial role in CRC.AIM To ex...BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the gastrointestinal tract.Lipid metabolism,as an important part of material and energy circulation,is well known to play a crucial role in CRC.AIM To explore the relationship between serum lipids and CRC development and identify aberrantly expressed cholesterol metabolism genes in CRC.METHODS We retrospectively collected 843 patients who had confirmed CRC and received surgical resection from 2013 to 2015 at the Cancer Hospital of the Chinese Academy of Medical Sciences as our research subjects.The levels of serum total cholesterol(TC),triglycerides,low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),LDL-C/HDL-C and clinical features were collected and statistically analyzed by SPSS.Then,we used the data from Oncomine to screen the differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and used Gene Expression Profiling Interactive Analysis to confirm the candidate DEGs.PrognoScan was used to analyze the prognostic value of the DEGs,and Search Tool for the Retrieval of Interacting Genes was used to construct the protein-protein interaction network of DEGs.RESULTS The serum HDL-C level in CRC patients was significantly correlated with tumor size,and patients whose tumor size was more than 5 cm had a lower serum HDL-C level(1.18±0.41 mmol/L vs 1.25±0.35 mmol/L,P<0.01)than their counterparts.In addition,TC/HDL(4.19±1.33 vs 3.93±1.26,P<0.01)and LDL-C/HDL-C(2.83±1.10 vs 2.61±0.96,P<0.01)were higher in patients with larger tumors.The levels of HDL-C(P<0.05),TC/HDL-C(P<0.01)and LDL-C/HDL-C(P<0.05)varied in different stages of CRC patients,and the differences were significant.We screened 14 differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and confirmed that lipoprotein receptor-related protein 8(LRP8),PCSK9,low-density lipoprotein receptor(LDLR),MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in cancer tissue.Higher expression of LDLR(HR=3.12,95%CI:1.77-5.49,P<0.001),ABCA1(HR=1.66,95%CI:1.11-2.48,P=0.012)and OSBPL1A(HR=1.38,95%CI:1.01-1.89,P=0.041)all yielded significantly poorer DFS outcomes.Higher expression of FDXR(HR=0.7,95%CI:0.47-1.05,P=0.002)was correlated with longer DFS.LDLR,ABCA1,OSBPL1A and FDXR were involved in many important cellular function pathways.CONCLUSION Serum HDL-C levels are associated with tumor size and stage in CRC patients.LRP8,PCSK9,LDLR,MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in CRC.Among them,LDLR,ABCA1,OSBPL1A and FDXR were valuable prognostic factors of DFS and were involved in important cellular function pathways.展开更多
The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studie...The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studies, however, have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism. The present review provides an overview of the roles of sphingosine 1-phosphate (S1P)/S1P receptor and apolipoprotein A-I/scavenger receptor class B type I systems in the anti-atherogenic HDL actions. In addition, the physiological significance of the existence of S1P in the HDL particles is discussed.展开更多
The association between high-density lipoprotein cholesterol（HDL-C） and mortality in patients with acute aortic dissection（AAD） is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patient...The association between high-density lipoprotein cholesterol（HDL-C） and mortality in patients with acute aortic dissection（AAD） is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group（n=585）, low HDL-C group（n=343） had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group（21.6% vs. 12.6%, log-rank=10.869, P=0.001）. After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference（adjusted hazard ratio, 1.23; 95% confidence interval, 0.86–1.77; P=0.259）. Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.展开更多
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 ma...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.展开更多
Developing natural nano-platforms with high biocompatibility and natural targeting ability represents great significance for drug delivery.High-density lipoprotein(HDL),a natural lipid-protein complex,plays important ...Developing natural nano-platforms with high biocompatibility and natural targeting ability represents great significance for drug delivery.High-density lipoprotein(HDL),a natural lipid-protein complex,plays important roles in physiological activities,particularly in reverse cholesterol transport(RCT)and be closely associated with atherosclerotic cardiovascular diseases.Recent studies have demonstrated that HDLs have the potential to serve as ideal drug carriers.Recombinant HDLs(r HDLs)have been used to encapsulate substances such as small interfering RNA(siRNA),drugs,and contrast agents,fully utilizing the biocompatibility and targeting ability of r HDL in the body and providing new strategies for drug delivery and disease treatment.In this review,we discussed in detail the basic principles of HDL as a drug delivery system,the mechanisms of targeted drug delivery,and several methods for preparing HDL nanoparticles.Afterward,we comprehensively reviewed the applications of HDL as a drug carrier in cardiovascular diseases,cancer treatment(such as glioblastoma,breast cancer,hepatocellular carcinoma and urologic cancers)and some other fields.Finally,we reviewed the therapeutic effects and safety of HDL nanoparticles in clinical studies.Through a review and summary of these research advances,we aim to fully understand the potential of HDL as a drug carrier in clinical applications,providing valuable references and guidance for future research and expedites the translational application of HDL as drug carriers.展开更多
BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which ...BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.展开更多
This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco’s modified Eagle’s medium(D...This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco’s modified Eagle’s medium(DMEM) containing glucose of various concentrations.The cells were divided into 3 groups in terms of different glucose concentrations in the cultures:Control group(5.6 mmol/L glucose),high glucose concentration groups(16.7 mmol/L and 30 mmol/L glucose).ATP-binding cassette transporter A1(ABCA1) mRNA expression in the macrophages was detected by semi-quantitative RT-PCR 24,48 and 72 h after glucose treatment.The results showed that ABCA1 mRNA expression in the 16.7 mmol/L glucose group was not significantly different from that in the control group at all testing time points(P>0.05 for each).In the 30 mmol/L glucose group,macrophage ABCA1 mRNA expression was not changed significantly at 24 h(P=0.14),but was substantially decreased by 40.4% at 48 h(P=0.009) and by 48.1% at 72 h(P=0.015) as compared with that in the control group.It was concluded that ABCA1 is of vital importance for HDL-C biogenesis.High glucose may hamper HDL-C biogenesis by decreasing ABCA1 expression,which contributes to low HDL-C level in diabetes.展开更多
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 infla...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.展开更多
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 int...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.展开更多
BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.Howeve...BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.展开更多
基金Supported by Science and Technology Program of Quzhou,China,No.2022K67Zhejiang Medical Association Clinical Research Fund Project,No.2024ZYC-A526and the Research Project of Quzhou People’s Hospital,No.KYQD2024-006.
文摘BACKGROUND The association between the uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and mental health among individuals with type 2 diabetes mellitus(T2DM)has not been thoroughly investigated.AIM To examine the link between UHR and symptoms of depression and anxiety in patients with T2DM.METHODS A cross-sectional analysis was carried out from March 2023 to April 2024,involving participants diagnosed with T2DM.Data on sociodemographic characteristics,clinical parameters,and UHR values were systematically gathered.The Self-Rating Depression Scale(SDS)and Self-Rating Anxiety Scale(SAS)were utilized to evaluate depressive and anxiety symptoms,respectively.To assess the relationships between UHR and SDS/SAS scores,linear regression models were employed,incorporating adjustments for potential confounding variables.Additionally,smooth curve fitting and threshold effect analyses were conducted to explore potential nonlinear relationships.RESULTS A total of 285 patients with T2DM were included.Initial univariate analysis demonstrated a significant positive correlation between elevated UHR levels and higher SDS and SAS scores.Multivariate regression analysis revealed that a one-unit rise in UHR was associated with a 1.13-point increase in SDS scores(95%CI:0.69-1.58)and a 0.57-point increase in SAS scores(95%CI:0.20-0.93).After controlling for confounders,UHR remained positively correlated with SDS(β=1.55,95%CI:0.57-2.53)and SAS(β=0.72,95%CI:0.35-1.09).Nonlinear analysis identified critical thresholds at UHR values of 5.02 for SDS and 4.00 for SAS,beyond which the relationships between UHR and psychological symptom scores became markedly stronger(P<0.05).CONCLUSION Higher UHR levels are significantly linked to exacerbated depressive and anxiety symptoms in patients with T2DM.These results indicate that UHR may function as a promising biomarker to identify individuals at greater risk of mental health complications within this population.
基金Supported by Shanghai Health and Medical Center Star Talent Program,No.2023QMX01 and No.2023QMX11.
文摘BACKGROUND The association between the serum uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and cardiovascular disease(CVD)risk in Asian populations with metabolic dysfunction-associated steatotic liver disease(MASLD)remains insufficiently elucidated.AIM To investigate the relevance and dose-responsive relationship between UHR and 10-year CVD risk among Asian MASLD patients.METHODS In this retrospective analysis,3901 MASLD patients were enrolled based on established screening criteria.As measured by the Framingham risk score,participants were stratified according to their 10-year CVD risk.The association between UHR and CVD risk was evaluated using binary logistic regression,while dose-response patterns were explored through restricted cubic spline(RCS)modeling.The discriminatory capability of UHR,in comparison with conventional biomarkers,was further examined by receiver operating characteristic curve analysis.RESULTS Multivariable-adjusted analyses revealed that elevated UHR levels were significantly associated with an increased likelihood of intermediate-to-high CVD risk.RCS modeling demonstrated a linear dose-response relationship between UHR and the Framingham risk score(P for nonlinearity=0.114).Sex-stratified RCS analyses further indicated that this linear association persisted among males(P for nonlinearity=0.167)but was not statistically significant in females(P for nonlinearity=0.476).Further stratified analyses revealed that the association was particularly pronounced among younger individuals(<50 years),males,and those with central obesity,whereas it was attenuated in older adults(≥50 years)and females.Receiver operating characteristic analysis demonstrated that UHR outperformed individual biomarkers in predicting 10-year CVD risk,showing an area under the curve of 0.655(95%confidence interval:0.635-0.674).CONCLUSION UHR functioned as an independent predictor of 10-year CVD risk in Asian patients with MASLD,demonstrating a linear dose-response association and superior discriminative performance relative to conventional biomarkers,especially among younger individuals,males,and those with central obesity.
基金Supported by the National Natural Science Foundation of China,No. 39770164
文摘AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells. METHODS: Recombinant complex of HDL and aclacinomycin (rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine. Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles, morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method. RESULTS: The density range of rHDL-ACM was 1.063-1.210 g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%. Encapsulated efficiencies of rHDL-ACM were more than 90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26±5.62 nm by measure of 110 rHDL-ACM particles in the range of diameter of lipoproteins. rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 μg/mL (P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 ug/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM (1.68 nmol/L vs3 nmol/L). Compared to L02 hepatocytes, a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 μg/mL.Cytotoxicity of the rHDL-ACM to SMMC- 7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5μg/mL (P<0.01). IC50 for SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L), showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells. CONCLUSION: rHDL-ACM complex keeps the basic physical and biological binding properties of native HDL and shows a preferential cytotoxicity for SMMC-7721 hepatoma to normal L02 hepatocytes, HDL is a potential carrier for delivering lipophilic antitumoral drug to hepatoma cells.
文摘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
基金Project (Nos. PW 55/09 and DS 41/09) supported by the Department of Laboratory Diagnostics, Medical University of Lublin, Poland
文摘Objective:Disturbances in lipid and lipoprotein profiles in patients after kidney transplantation (Tx) are still not understood. Methods:Serum levels of lipids,lipoprotein,triglyceride-rich lipoproteins (TRLs),and high-density lipoprotein (HDL) particles were determined,lipid and lipoprotein ratios were calculated,and their relationships in Tx patients with hypertriglyceridemia (HTG) and lower apolipoprotein AI (apoAI) concentration were examined. Serum lipid and lipoprotein levels were measured in 109 Tx patients and 89 healthy subjects. HDL particle levels were de-termined by enzyme-linked immunosorbent assay (ELISA). Results:Tx patients had disturbed concentration,com-position,and metabolism of TRLs and HDL particles. Multivariance analysis showed significant and positive correlation between HDL cholesterol/apoAI (HDL-C/apoAI) and HDL-C/HDL ratios,which indicates that both ratios could sensi-tively reflect changes in the HDL subclasses and their distribution into smaller size particles. In Tx patients,the de-creased HDL-C/apoAI ratio indicates that,along with the decreased apoAI concentration,the HDL-C level is de-creased. However,a low HDL-C/HDL ratio indicates that HDL particles in Tx patients transport lesser content of HDL-C but more triglyceride (TG) (high TG/HDL ratio),and thus are hypercatabolized and removed; therefore,con-centration of HDL particles in serum was decreased. Conclusion:The decrease of HDL-C/apoAI ratio seems to be a good marker of HDL subclass distribution into smaller size particles.
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Project(Nos.PW 55/09 and DS 41/10) supported by the Department of Laboratory Diagnostics,Medical University of Lublin,Poland
文摘Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed （HD） and post-renal transplant （Tx） patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein （HDL） reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein （ox-LDL） and anti-ox-LDL, and paraoxonase-1 （PON-1） activity in HD （n=33） and Tx （n=71） patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I （apoA-I） and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios （total cholesterol （TC）/HDL-C, LDL-C/HDL-C, triglyceride （TG）/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL） were atherogenic. The Spearman＇s rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level （R=0.363, P=0.004）, and negatively with TC （R=-0.306, P=0.012）, LDL-C （R=-0.283, P=0.020）, and non-HDL-C （R=-0.263, P=0.030） levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and de- creased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-13-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.
文摘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.
文摘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.
基金This project was supported by Grant 31200884 from the National Natural Science Foundation of China Grant 2016D016, 2016-ZQN-92, and 2016-2-75 from the Natural Science Foundation of Fujian and Grant 3502Z20154048, 3502Z20144061, and 3502Z20154047 from the Natural Scien- ce Foundation of Xiamen.
文摘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.
文摘BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the gastrointestinal tract.Lipid metabolism,as an important part of material and energy circulation,is well known to play a crucial role in CRC.AIM To explore the relationship between serum lipids and CRC development and identify aberrantly expressed cholesterol metabolism genes in CRC.METHODS We retrospectively collected 843 patients who had confirmed CRC and received surgical resection from 2013 to 2015 at the Cancer Hospital of the Chinese Academy of Medical Sciences as our research subjects.The levels of serum total cholesterol(TC),triglycerides,low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),LDL-C/HDL-C and clinical features were collected and statistically analyzed by SPSS.Then,we used the data from Oncomine to screen the differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and used Gene Expression Profiling Interactive Analysis to confirm the candidate DEGs.PrognoScan was used to analyze the prognostic value of the DEGs,and Search Tool for the Retrieval of Interacting Genes was used to construct the protein-protein interaction network of DEGs.RESULTS The serum HDL-C level in CRC patients was significantly correlated with tumor size,and patients whose tumor size was more than 5 cm had a lower serum HDL-C level(1.18±0.41 mmol/L vs 1.25±0.35 mmol/L,P<0.01)than their counterparts.In addition,TC/HDL(4.19±1.33 vs 3.93±1.26,P<0.01)and LDL-C/HDL-C(2.83±1.10 vs 2.61±0.96,P<0.01)were higher in patients with larger tumors.The levels of HDL-C(P<0.05),TC/HDL-C(P<0.01)and LDL-C/HDL-C(P<0.05)varied in different stages of CRC patients,and the differences were significant.We screened 14 differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and confirmed that lipoprotein receptor-related protein 8(LRP8),PCSK9,low-density lipoprotein receptor(LDLR),MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in cancer tissue.Higher expression of LDLR(HR=3.12,95%CI:1.77-5.49,P<0.001),ABCA1(HR=1.66,95%CI:1.11-2.48,P=0.012)and OSBPL1A(HR=1.38,95%CI:1.01-1.89,P=0.041)all yielded significantly poorer DFS outcomes.Higher expression of FDXR(HR=0.7,95%CI:0.47-1.05,P=0.002)was correlated with longer DFS.LDLR,ABCA1,OSBPL1A and FDXR were involved in many important cellular function pathways.CONCLUSION Serum HDL-C levels are associated with tumor size and stage in CRC patients.LRP8,PCSK9,LDLR,MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in CRC.Among them,LDLR,ABCA1,OSBPL1A and FDXR were valuable prognostic factors of DFS and were involved in important cellular function pathways.
基金Supported by Grants-in-Aid for scientific research from the Japan Society for the Promotion of Science,No.20015008,20054003,and 21390016
文摘The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studies, however, have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism. The present review provides an overview of the roles of sphingosine 1-phosphate (S1P)/S1P receptor and apolipoprotein A-I/scavenger receptor class B type I systems in the anti-atherogenic HDL actions. In addition, the physiological significance of the existence of S1P in the HDL particles is discussed.
基金supported by National Natural Science Foundation of China(No.81170259)
文摘The association between high-density lipoprotein cholesterol（HDL-C） and mortality in patients with acute aortic dissection（AAD） is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group（n=585）, low HDL-C group（n=343） had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group（21.6% vs. 12.6%, log-rank=10.869, P=0.001）. After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference（adjusted hazard ratio, 1.23; 95% confidence interval, 0.86–1.77; P=0.259）. Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.
基金Supported by the Foundation of Hunan Educational Committee (06C692)
文摘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.
基金the National Natural Science Foundation of China(Nos.52273128,82003450)the Natural Science Foundation of Guangdong Province(No.2022A1515220048)+2 种基金the Natural Science Foundation of Guizhou Province(Nos.Guizhou Province-ZK[2022]General 300,Guizhou Province-ZK[2023]General 244)the Xiangshan Talented Scientific Research Foundation of Zhuhai People’s Hospital(No.2023XSYC-01)Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment(No.2021B1212040004)。
文摘Developing natural nano-platforms with high biocompatibility and natural targeting ability represents great significance for drug delivery.High-density lipoprotein(HDL),a natural lipid-protein complex,plays important roles in physiological activities,particularly in reverse cholesterol transport(RCT)and be closely associated with atherosclerotic cardiovascular diseases.Recent studies have demonstrated that HDLs have the potential to serve as ideal drug carriers.Recombinant HDLs(r HDLs)have been used to encapsulate substances such as small interfering RNA(siRNA),drugs,and contrast agents,fully utilizing the biocompatibility and targeting ability of r HDL in the body and providing new strategies for drug delivery and disease treatment.In this review,we discussed in detail the basic principles of HDL as a drug delivery system,the mechanisms of targeted drug delivery,and several methods for preparing HDL nanoparticles.Afterward,we comprehensively reviewed the applications of HDL as a drug carrier in cardiovascular diseases,cancer treatment(such as glioblastoma,breast cancer,hepatocellular carcinoma and urologic cancers)and some other fields.Finally,we reviewed the therapeutic effects and safety of HDL nanoparticles in clinical studies.Through a review and summary of these research advances,we aim to fully understand the potential of HDL as a drug carrier in clinical applications,providing valuable references and guidance for future research and expedites the translational application of HDL as drug carriers.
基金The study was reviewed and approved by the Institutional Review Board of Chaohu Hospital Affiliated to AnhuiMedical University,Approval No.KYXM-202208-011.
文摘BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.
基金supported by a grant from the Scientific Research Foundation for the Returned Overseas Chinese Scholars by the State Education Ministry of China (No.2005383-6144)
文摘This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco’s modified Eagle’s medium(DMEM) containing glucose of various concentrations.The cells were divided into 3 groups in terms of different glucose concentrations in the cultures:Control group(5.6 mmol/L glucose),high glucose concentration groups(16.7 mmol/L and 30 mmol/L glucose).ATP-binding cassette transporter A1(ABCA1) mRNA expression in the macrophages was detected by semi-quantitative RT-PCR 24,48 and 72 h after glucose treatment.The results showed that ABCA1 mRNA expression in the 16.7 mmol/L glucose group was not significantly different from that in the control group at all testing time points(P>0.05 for each).In the 30 mmol/L glucose group,macrophage ABCA1 mRNA expression was not changed significantly at 24 h(P=0.14),but was substantially decreased by 40.4% at 48 h(P=0.009) and by 48.1% at 72 h(P=0.015) as compared with that in the control group.It was concluded that ABCA1 is of vital importance for HDL-C biogenesis.High glucose may hamper HDL-C biogenesis by decreasing ABCA1 expression,which contributes to low HDL-C level in diabetes.
基金supported by the Natural Science Foundation of Zhejiang Province(No.LY22H050001)the Key Project of Provincial Ministry Construction,Health Science and Technology Project Plan of Zhejiang Province(No.WKJ-ZJ-2128)+2 种基金Key Laboratory of Women’s Reproductive Health Research of Zhejiang Province(No.ZDFY2020-RH-0006)the National Natural Science Foundation of China(No.U20A20351)Key Research and Development Plan of Zhejiang Province(No.2021C03079).
文摘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.
基金Supported by the Special Fund for Clinical Research of Nanjing Drum Tower Hospital(No.2023-LCYJPY-37).
文摘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.
文摘BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.
