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.

EFFECT OF HERB-MEDICINE-CAKE-SEPARATED MOXIBUSTION ON SERUM LIPOPROTEIN CONTENTS AND RATIO OF HDL-Ch AND LDL-Ch IN HYPERLIPEMIA RABBITS

Objective: To observe the effect of herb-medicine-cake-separated moxibustion on serum lipoprotein in hyperlipemia rabbits. Methods: 55 New-Zealand rabbits were randomly divided into control group (n=13), model group (n=14), direct moxibustion group (n=14) and herb-medicine-cake-separated moxibustion (indirect moxibustion) group (n=14). Hyperlipemia model was established by feeding the animals with specialized forage (15% vitellus powder, 5% lard, 0.5% cholesterol and common forage) for 6 weeks. Moxibustion was applied to “Juque”(CV 14), “Tianshu”(ST 25), “Fenglong”(ST 40), etc., 4 moxa-cones for every acupoint, once daily and continuously for 40 days. Serum high density lipoprotein-cholesterol (HDL-Ch), low density lipoprotein-cholesterol (LDL-Ch) and total cholesterol (TCh) contents were assayed with colorimetric method. Results: Compared with control group, serum LDL-Ch content, HDL-Ch/LDL-Ch and HDL-Ch/TCh of model group were significantly higher (P<0.05～0.01), while compared with model group, LDL-Ch contents of two moxibustion groups were strikingly lower (P<0.01). No significant differences were found between two moxibustion groups in all the 4 indexes. Conclusion: Both direct and indirect moxibustion can effectively lower serum LDL-Ch, raise HDL-Ch, HDL-Ch/LDL-Ch and HDL-Ch/TCh, and regulate lipoprotein metabolism in hyperlipemia rabbits.

Low-density lipoprotein receptor-related protein 2(LRP2)is required for lipid export in the midgut of the migratory locust,Locusta migratoria

Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.

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.

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.

基于Verilog HDL语言的调频备份发射机控制系统设计与实现

随着调频广播事业的发展,发射台的发射频率日益增多,为了降低运维成本并减少各频点备份发射机的数量,本文介绍了一种基于Verilog HDL语言设计的调频发射机备机控制系统。该系统能够控制宽带调频发射机的频率切换、音频源选择以及开关机操作,从而实现单台发射机备份多个频点的功能。这一方案不仅简化了设备配置,还提高了系统的灵活性和可靠性。

Initial decrease in the lipoprotein(a)level is a novel prognostic biomarker in patients with acute coronary syndrome

BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains unclear.AIM To investigate the hypothesis that the Lp(a)levels are altered by various conditions during the acute phase of ACS,resulting in subsequent cardiovascular events.METHODS From September 2009 to May 2016,377 patients with ACS who underwent emergent coronary angiography,and 249 who completed≥1000 d of follow-up were enrolled.Lp(a)levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention(PCI)to 48 h after PCI.The primary endpoint was the occurrence of major adverse cardiac events(MACE;cardiac death,other vascular death,ACS,and non-cardiac vascular events).RESULTS The mean circulating Lp(a)level decreased significantly from pre-PCI(0 h)to 12 h after(19.0 mg/dL to 17.8 mg/dL,P<0.001),and then increased significantly up to 48 h after(19.3 mg/dL,P<0.001).The changes from 0 to 12 h[Lp(a)Δ0-12]significantly correlated with the basal levels of creatinine[Spearman’s rank correlation coefficient(SRCC):-0.181,P<0.01]and Lp(a)(SRCC:-0.306,P<0.05).Among the tertiles classified according to Lp(a)Δ0-12,MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups(66.2%vs 53.6%,P=0.034).A multivariate analysis revealed that Lp(a)Δ0-12[hazard ratio(HR):0.96,95%confidence interval(95%CI):0.92-0.99]and basal creatinine(HR:1.13,95%CI:1.05-1.22)were independent determinants of subsequent MACE.CONCLUSION Circulating Lp(a)levels in patients with ACS decreased significantly after emergent PCI,and a greater decrease was independently associated with a worse prognosis.

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

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

Association between sensitivity to thyroid hormones and non-highdensity lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

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.

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.

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.

The pleiotropic vasoprotective functions of high density lipoproteins(HDL)

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

Lipoprotein(a)and Benefit of PCSK9 Inhibition in Emergency Complex Higher-risk and Indicated Patients

Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.

An Analysis of Health Factors Affecting Employees’ Absenteeism: Influences of HDL Cholesterol and Blood Sugar Levels

Background: Workers’ health condition is an important issue. It affects not only the well-being of workers but also the firms and society as a whole through medical costs and productivity losses due to absenteeism and presenteeism. Data and Methods: Data were obtained from 1136 employees at an operational site of a large corporation. The dataset contained both medical checkups and working record information. Health factors affecting long-term absence (over three days in three months) were analyzed. Logistic regression models and the procedure for selecting proper covariates based on likelihood test statistics and the Akaike information criterion were used. Results: Among health factors, high-density lipoprotein cholesterol (HDL-C) and blood sugar levels were important in the selected model. For HDL-C, the odds ratio (OR) based on one standard deviation difference was 0.75 with a 95% confidence interval (CI) of 0.59 - 0.95. For blood sugar, the OR was 1.20 with a 95% CI of 1.01 - 1.42. Improving HDL-C and blood sugar levels would reduce long-term absence by 25% and 20%, respectively. Conclusion: Controlling HDL-C and blood sugar levels is important to reduce long-term absenteeism. These factors can be improved by modifying eating habits. Since the operational site has its own company cafeterias, which most employees use, nutritional intervention is relatively easy with little or no cost. It may be worthwhile to implement nutritional intervention, especially for patients with low HDL-C or high blood sugar levels. Limitations: The results of this study were based on one operational site of a corporation. The employees were mainly operators working inside the building. The results may be different from other types of jobs and working conditions, such as fieldwork. Analyses of different types of jobs and working conditions are necessary.

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.

Comparison of the effects of 3 kinds of oils rich in omega-3 polyunsaturated fatty acids on glycolipid metabolism and lipoprotein subfractions

Dietary omega-3 polyunsaturated fatty acids(ω-3 PUFAs)can be classifi ed into animal-and plant-derivedω-3 PUFAs.Patients with type 2 diabetes(T2DM)are frequently accompanied by dyslipidemia,which is closely related to the high-density lipoprotein(HDL-C)subfractions change.This study aimed to determine the effects of different sourcesω-3 PUFAs on glucolipid metabolism and lipoprotein subfractions in T2DM with dyslipidemia.Ninety T2DM patients with dyslipidemia were randomly assigned to take 3 g/day fi sh oil(FO,containing eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)),3 g/day perilla oil(PO,containingα-linolenic acid(ALA)),or 3 g/day blend oil(BO,containing EPA,DHA and ALA)for 3 months.90 patients completed the intervention.There was a significant reduction of glycated hemoglobin(HbA1c)in all the groups.The triglycerides(TG)in the FO group were signifi cantly different with a group×time interaction(P=0.043),which was higher compared with the other two groups.The serum small HDL-C subfractions in the PO group was higher and the serum large HDL-C subfractions in the PO group was lower than those in the BO and FO groups.Plant-derivedω-3 PUFAs are more effective at controlling blood glucose than animal-derivedω-3 PUFAs.However,animal-derivedω-3 PUFAs have a signifi cant lowering effect on TG compared with plant-derivedω-3 PUFAs.Particularly,large HDL-C subfractions after animal-derivedω-3 PUFAs intake were higher than plant-derivedω-3 PUFAs intake;while small HDL-C subfractions were lower.Both the animal-and plant-derivedω-3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

Lipoprotein (a) Cut-Off in Chronic Kidney Disease Patients with a History of Cardiovascular Disease in Center Hospital University Souro SANOU, Burkina Faso

Patients living with chronic kidney disease (CKD) are at high risk of cardiovascular events. Our aim in this study was to assess the cut-off value for lipoprotein (a) (Lp(a)) in CKD patients with a history of cardiovascular disease (CVD). This was a cross-sectional study. Variables including age, sex, history of CVD, body mass index and CKD stage, were collected during CKD patient’s first admission in the nephrology dialysis department. Blood samples were collected for quantitative determination of Lp(a) by immunoturbidimetric method. They were divided into two groups: CKD patients without history of CVD and CKD patients with history of CVD. Fisher’s exact test was used to assess associations with a significance level of 0.05%. Area under the curve (AUC) and new cut-off value for Lp(a) were identified by drawing Receiver Operating Characteristic (ROC) curve. A total of seventy CKD patients with median age of 43 years [minimum-maximum = 15 - 78 years] were included. Patients with history of CVD were 65.71% (46/70). New Lp(a) cut-off point in CKD patients with history of CVD was 66.50 nmol/L [sensitivity, 87.00%;specificity, 58.30%;AUC = 0.727;p = 0.000]. ROC curve demonstrated good performance of Lp(a) to screen CKD patients with history of CVD. Further research is needed to determine an LPA gene polymorphism’s contribution to increasing risk for CVD at each kidney disease stage.

Diagnostic and prognostic implications of non-high-density lipoprotein cholesterol and homocysteine levels for cognitive impairment in thalamic infarction

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.

Hepatitis C virus G1b infection decreases the number of small low-density lipoprotein particles

AIM: To investigate how hepatitis C virus (HCV) G1b infection influences the particle number of lipoproteins.METHODS: The numbers of lipoprotein particles in fasting sera from 173 Japanese subjects, 82 with active HCV G1b infection (active HCV group) and 91 with cleared HCV infection (SVR group), were examined. Serum lipoprotein was fractionated by high-performance liquid chromatography into twenty fractions. The cholesterol and triglyceride concentrations in each fraction were measured using LipoSEARCH. The number of lipoprotein particles in each fraction was calculated using a newly developed algorithm, and the relationship between chronic HCV G1b infection and the lipoprotein particle number was determined by multiple linear regression analysis.RESULTS: The median number of low-density lipoprotein (LDL) particles was significantly lower in the active HCV group [1182 nmol/L, interquartile range (IQR): 444 nmol/L] than in the SVR group (1363 nmol/L, IQR: 472 nmol/L, P &#x0003c; 0.001), as was that of high-density lipoprotein (HDL) particles (14168 nmol/L vs 15054 nmol/L, IQR: 4114 nmol/L vs 3385 nmol/L, P = 0.042). The number of very low-density lipoprotein (VLDL) particles was similar between the two groups. Among the four LDL sub-fractions, the number of large LDL particles was similar between the two groups. However, the numbers of medium (median: 533.0 nmol/L, IQR: 214.7 nmol/L vs median: 633.5 nmol/L, IQR: 229.6 nmol/L, P &#x0003c; 0.001), small (median: 190.9 nmol/L, IQR: 152.4 nmol/L vs median: 263.2 nmol/L, IQR: 159.9 nmol/L; P &#x0003c; 0.001), and very small LDL particles (median: 103.5 nmol/L, IQR: 66.8 nmol/L vs median: 139.3 nmol/L, IQR: 67.3 nmol/L, P &#x0003c; 0.001) were significantly lower in the active HCV group than in the SVR group, respectively. Multiple linear regression analysis indicated an association between HCV G1b infection and the decreased numbers of medium, small, and very small LDL particles. However, active HCV infection did not affect the number of large LDL particles or any sub-fractions of VLDL and HDL particles.CONCLUSION: HCV G1b infection decreases the numbers of medium, small, and very small LDL particles.