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.

Association between Low-density Lipoprotein Receptor-related Protein 5 Polymorphisms and Type 2 Diabetes Mellitus in Han Chinese:a Case-control Study

Objective To investigate the association between low-density lipoprotein receptor-related protein 5 （LRPS） variants （rs12363572 and rs4930588） and type 2 diabetes mellitus （T2DM） in Han Chinese. Methods A total of 1842 T2DM cases （507 newly diagnosed cases and 1335 previously diagnosed cases） and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms （SNPs）. Odds ratios （ORs） and 95% confidence intervals （95% CIs） were calculated to describe the strength of the association by logistic regression. Results In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index （BMI）, the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype ~ was associated with reduced risk of T2DM （OR 0.820, 95% CI 0.732-0.919）. In addition, rs12363572 was associated with BMI （P〈0.001） and rs4930588 was associated with triglyceride levels （P=0.043） in 507 newly diagnosed T2DM cases but not in healthy controls. Conclusion No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM.

Low-density lipoprotein receptor-related protein 1 is a CROPs-associated receptor for Clostridioides infection toxin B

As the leading cause of worldwide hospital-acquired infection,Clostridioides difficile(C.difficile)infection has caused heavy economic and hospitalized burden,while its pathogenesis is not fully understood.Toxin B(Tcd B)is one of the major virulent factors of C.difficile.Recently,CSPG4 and FZD2 were reported to be the receptors that mediate Tcd B cellular entry.However,genetic ablation of genes encoding these receptors failed to completely block Tcd B entry,implicating the existence of alternative receptor(s)for this toxin.Here,by employing the CRISPR-Cas9 screen in CSPG4-deficient He La cells,we identified LDL receptor-related protein-1(LRP1)as a novel receptor for Tcd B.Knockout of LRP1 in both CSPG4-deficient He La cells and colonic epithelium Caco2 cells conferred cells with increased Tcd B resistance,while LRP1 overexpression sensitized cells to Tcd B at a low concentration.Co-immunoprecipitation assay showed that LRP1 interacts with full-length Tcd B.Moreover,CROPs domain,which is dispensable for Tcd B’s interaction with CSPG4 and FZD2,is sufficient for binding to LRP1.As such,our study provided evidence for a novel mechanism of Tcd B entry and suggested potential therapeutic targets for treating C.difficile infection.

C1q/TNF-related protein 5 promotes atherogenesis by enhancing transcytosis and oxidative modification of low-density lipoprotein through increasing 12/15-lipoxygenase

Objective Increased transcytosis of low-density lipoprotein (LDL)across the endothelium and oxidation of LDL deposited within the subendothelial space are crucial early events in atherogenesis. C1q/TNF-related protein (CTRP) 5 is a novel secreted glycoprotein and its biological functions are largely undefined.

Roles of low?density lipoproteinreceptor?related protein 1 in tumors

Low-density lipoprotein receptor-related protein 1(LRP1,also known as CD91),a multifunctional endocytic and cell signaling receptor,is widely expressed on the surface of multiple cell types such as hepatocytes,fibroblasts,neurons,astrocytes,macrophages,smooth muscle cells,and malignant cells.Emerging in vitro and in vivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression.For example,LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase(MMP)-2and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor,the serine/threonine protein kinase signaling pathway,and the expression of Caspase-3.LRPI-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion.In addition,LRP1 has been shown to be down-regulated by microRNA-205 and methylation of LRP1CpG islands.Furthermore,a novel fusion gene,LRP1-SNRNP25,promotes osteosarcoma cell invasion and migration.Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.

Lipoprotein in cholesterol transport: Highlights and recent insights into its structural basis and functional mechanism

Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease （CVD）. The highly dynamic lipoprotein molecules are capable of adopting an array of conformations that is crucial to lipid transport along the cholesterol transport pathway, among which high-density lipopro- tein （HDL） and low-density lipoprotein （LDL） are major players in plasma cholesterol metabolism. For a more detailed illustration of cholesterol transport process, as well as the development of therapies to prevent CVD, here we review the functional mechanism and structural basis of lipoproteins in cholesterol transport, as well as their structural dynamics in the plasma lipoprotein （HDL and LDL） elevations, in order to obtain better quantitative understandings on structure-function relationship of lipoproteins. Finally, we also provide an approach for further research on the lipoprotein in cholesterol transport.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Mechanisms of dysregulation of low-density lipoprotein receptor expression in HepG2 cells induced by inflammatory cytokines

Background Low-density lipoprotein （LDL） receptor is normally regulated via a feedback system that is dependent on intracellular cholesterol levels. We have demonstrated that cytokines disrupt cholesterol-mediated LDL receptor feedback regulation causing intracellular accumulation of unmodified LDL in peripheral cells. Liver is the central organ for lipid homeostasis. The aim of this study was to investigate the regulation of cholesterol exogenous uptake via LDL receptor and its underlying mechanisms in human hepatic cell line （HepG2） cells under physiological and inflammatory conditions. Methods Intracellular total cholesterol （TC）, free cholesterol （FC） and cholesterol ester （CE） were measured by an enzymic assay. Oil Red O staining was used to visualize lipid droplet accumulation in cells. Total cellular RNA was isolated from cells for detecting LDL receptor, sterol regulatory element binding protein （SREBP）-2 and SREBP cleavage-activating protein （SCAP） mRNA levels using real-time quantitative PCR. LDL receptor and SREBP-2 protein expression were examined by Western blotting. Confocal microscopy was used to investigate the translocation of SCAP-SREBP complex from the endoplasmic reticulum （ER） to the Golgi by dual staining with anti-human SCAP and anti-Golgin antibodies. Results LDL loading increased intracellular cholesterol level, thereby reduced LDL receptor mRNA and protein expression in HepG2 cells under physiological conditions. However, interleukin 1β （IL-1β） further increased intracellular cholesterol level in the presence of LDL by increasing both LDL receptor mRNA and protein expression in HepG2. LDL also reduced the SREBP and SCAP mRNA level under physiological conditions. Exposure to IL-1β caused over-expression of SREBP-2 and also disrupted normal distribution of SCAP-SREBP complex in HepG2 by enhancing translocation of SCAP-SREBP from the ER to the Golgi despite a high concentration of LDL in the culture medium. Conclusions IL-1β disrupts cholesterol-mediated LDL receptor feedback regulation by enhancing SCAP-SREBP complex translocation from the ER to the Golgi, thereby increasing SREBP-2 mediated LDL receptor expression even in the presence of high concentration of LDL. This results in LDL cholesterol accumulation in hepatic cells via LDL receptor pathway under inflammatory stress.

Therapeutic approach targeting apolipoprotein E binding region and low-density lipoprotein receptor for Alzheimer's disease

Approximately 13% of the population over the age of 65 years is estimated to have AD. The total number of cases is expected to increase over the coming decades. The apolipoprotein E (ApoE) genotype is the greatest genetic deter-minant for Alzheimer's disease (AD) development. The ApoE4 allele increases the risk of AD by 4 to 14 fold while the ApoE2 allele has an opposing effect;decreasing risk. Indeed many studies have demonstrated that carriers of the ApoE2 allele are associated with greater likelihood of survival to advanced age, superior verbal learning ability in advanced age, and reduced accumulation of amyloid pathology in the aged brain. In addition, it is known that ApoE proteins have different affinities for the low-density lipoprotein receptor (LDLR), with ApoE2 having the weakest binding to the LDL receptor at < 2% relative to ApoE3 and E4. Because ApoE2 has shown protective effects in re-gard to AD, a novel approach for ApoE4 carriers may be to create a peptide antagonist that blocks the ApoE inter-actions with LDLR at its 135-150 N-terminal binding domain. This peptide may create a more ApoE2-like structure by decreasing the affinity of ApoE4 for LDLR thereby reducing AD onset, memory impairment, and amyloid plaque formation. In this review, we will discuss the different detrimental effects that ApoE4 can cause. Most importantly, we will review how ApoE4 binding to LDLR promotes AD pathogenesis and how blocking ApoE4 binding may be a promising novel therapeutic approach for AD.

LRP6 Bidirectionally Regulates Insulin Sensitivity through Insulin Receptor and S6K Signaling in Rats with CG-IUGR

Objective Intrauterine growth restriction followed by postnatal catch-up growth(CG-IUGR)increases the risk of insulin resistance-related diseases.Low-density lipoprotein receptor-related protein 6(LRP6)plays a substantial role in glucose metabolism.However,whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear.This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR.Methods The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction.The mRNA and protein expression of the components in the insulin pathway,LRP6/β-catenin and mammalian target of rapamycin(mTOR)/S6 kinase(S6K)signaling,was determined.Liver tissues were immunostained for the expression of LRP6 andβ-catenin.LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling.Results Compared with the control rats,CG-IUGR rats showed higher homeostasis model assessment for insulin resistance(HOMA-IR)index and fasting insulin level,decreased insulin signaling,reduced mTOR/S6K/insulin receptor substrate-1(IRS-1)serine307 activity,and decreased LRP6/β-catenin in the liver tissue.The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age(AGA)rats led to reductions in insulin receptor(IR)signaling and mTOR/S6K/IRS-1 serine307 activity.In contrast,LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity.Conclusion LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways,IR and mTOR-S6K signaling.LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.

Difference analysis of the influence of smoking on LDL,Cys-C,and hs-CRP in patients with cerebral infarction

Objective:To compare the effects of smoking on low-density lipoprotein(LDL),cystatin C(Cys-C)and C-reactive protein(hs-CRP)in patients with cerebral infarction.Methods:The clinical data of acute stroke patients classified as large atherosclerosis by the trial of Org 10172 in acute stroke treatment(TOAST)classification were collected,and the differences of gener-al data and results of LDL,Cys-C and hs-CRP in smoking and nonsmoking patients were compared to search for rel-evant clinical data with statistical significance.Results:A total of 116 patients with acute stroke classified as large atherosclerotic by TOAST were collected and divid-ed into groups according to smoking status.Among the smoking patients,gender,age,occupation,drinking,hy-pertension,and diabetes were used as influencing factors to compare whether LDL was greater than or equal to 1.3 mmol/L,Cys-C≥0.8 mg/L and hs-CRP≥4 mg/L,with P values greater than 0.05.There was no statistical differ-ence.Among non-smoking patients,occupation,alcohol consumption,and high blood pressure had statistical sig-nificance for whether LDL was greater than 1.3 mmol/L.Age,occupation,and diabetes had statistical significance for whether Cys-C was greater than 0.8 mg/L.Conclu-sion:In this study,there was no statistically significant impact on the test results of LDL,Cys-C,and CRP whether the patients with ischemic stroke were smokers or nonsmokers.

Lack of Association of Common Polymorphism of LRP1 Gene with Myocardial Infarction in a Chinese Han Population

This study examined the association of a common polymorphic allele（25G） of the low-density lipoprotein receptor-related protein1（LRP1） gene with myocardial infarction（MI）.The genotypes of LRP1 25CG（rs35282763） were determined in 347 MI patients and 347 age-and sex-frequency-matched controls from an unrelated Chinese Han population.Factor Ⅷ（FⅧ） levels were measured in the MI patients and controls by chromogenic assay and enzyme-linked immunosor-bent assay（ELISA）.The results showed that LRP1 25CG（rs35282763） genotype distribution did not differ significantly between patients（n=206 for 25CC,n=122 for 25CG） and controls（n=191 for 25CC,n=126 for 25CG;P0.05）.The 25G allele was not associated with a reduced risk of MI（P0.05）.Further stratifications for age,sex,and other cardiovascular risk factors did not affect the negative findings.It was concluded that the presence of the G allele at the 25CG（rs35282763） polymorphism of the LRP1 is not associated with a reduced risk of MI,and genotyping for LRP1 25CG（rs35282763） polymor-phism is not useful in assessing the individual risk of MI.

Dynamics of hepatic and intestinal cholesterol and bile acid pathways: The impact of the animal model of estrogen deficiency and exercise training

Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative.

APOE and APOC1 gene polymorphisms are associated with cognitive impairment progression in Chinese patients with late-onset Alzheimer's disease

Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer＇s disease patients. We performed a 30-month longitudi- nal cohort study to investigate the relationship between Alzheimer＇s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer＇s disease were recruit- ed form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess pa- tients＇ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE 4 carriers compared with non-carriers. In addition, the APOE 4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive im- pairment progression group. In conclusion, APOE e4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ~4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer＇s disease.

Oxidized phospholipids are ligands for LRP6

Low-density lipoprotein receptor–related protein 6(LRP6) is a co-receptor for Wnt signaling and can be recruited by multiple growth factors/hormones to their receptors facilitating intracellular signaling activation. The ligands that bind directly to LRP6 have not been identified. Here, we report that bioactive oxidized phospholipids(oxPLs) are native ligands of LRP6, but not the closely related LRP5. oxPLs are products of lipid oxidation involving in pathological conditions such as hyperlipidemia, atherosclerosis, and inflammation. We found that cell surface LRP6 in bone marrow mesenchymal stromal cells(MSCs) decreased rapidly in response to increased oxPLs in marrow microenvironment. LRP6 directly bound and mediated the uptake of oxPLs by MSCs. oxPL-LRP6 binding induced LRP6 endocytosis through a clathrin-mediated pathway, decreasing responses of MSCs to osteogenic factors and diminishing osteoblast differentiation ability. Thus, LRP6 functions as a receptor and molecular target of oxPLs for their adverse effect on MSCs, revealing a potential mechanism underlying atherosclerosis-associated bone loss.

The uPA/uPAR system in astrocytic wound healing

The repair of injured tissue is a highly complex process that involves cell prolife ration,differentiation,and migration.Cell migration requires the dismantling of intercellular contacts in the injured zone and their subsequent reconstitution in the wounded area.Urokinase-type plasminogen activator(u PA)is a serine proteinase found in multiple cell types including endothelial cells,smooth muscle cells,monocytes,and macrophages.A substantial body of experimental evidence with different cell types outside the central nervous system indicates that the binding of uPA to its receptor(uPAR)on the cell surface prompts cell migration by inducing plasmin-mediated degradation of the extracellular matrix.In contrast,although uPA and uPAR are abundantly found in astrocytes and u PA binding to uPAR triggers astrocytic activation,it is unknown if uPA also plays a role in astrocytic migration.Neuronal cadherin is a member of cell adhesion proteins pivotal for the formation of cell-cell conta cts between astrocytes.More specifically,while the extracellular domain of neuronal cadherin interacts with the extracellular domain of neuronal cadherin in neighboring cells,its intracellular domain binds toβ-catenin,which in turn links the complex to the actin cytos keleton.Glycogen synthase kinase 3βis a serine-threonine kinase that prevents the cytoplasmic accumulation ofβ-catenin by inducing its phosphorylation at Ser33,Ser37,and Ser41,thus activating a sequence of events that lead to its proteasomal degradation.The data discussed in this perspective indicate that astrocytes release u PA following a mechanical injury,and that binding of this u PA to uPAR on the cell membrane induces the detachment ofβ-catenin from the intracellular domain of neuronal cadherin by triggering its extracellular signal-regulated kinase 1/2-mediated phosphorylation at Tyr650.Remarkably,this is followed by the cytoplasmic accumulation ofβ-catenin because uPA-induced extracellular signalregulated kinase 1/2 activation also phosphorylates lipoprotein receptor-related protein 6 at Ser1490,which in turn,by recruiting glycogen synthase kinase 3βto its intracellular domain abrogates its effect onβ-catenin.The cytoplasmic accumulation ofβ-catenin is followed by its nuclear translocation,where it induces the expression of uPAR,which is required for the migration of astrocytes from the injured edge into the wounded area.

Downregulation of p38 MAPK Involved in Inhibition of LDL-induced Proliferation of Mesangial Cells and Matrix by Curcumin

Curcumin, as a main pharmacological component in the traditional Chinese medicine-- tttrmeric, has shown anti-inflammatory, anti-oxidation, anti-tumor and anti-fibrotic effects. This study aimed to investigate the possible underlying signaling pathway which was involved in the inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin. Rat mesangial cells in vitro were incubated with low-density lipoprotein （LDL） and different concentrations of curcumin （0, 6.25, 12.5, 25.0 9mol/L） or p38 MAPK inhibitor, SB203580 （10 μmol/L）. Under LDL incubation, mesangial cells proliferated, the expression of MMP-2 mRNA and protein was decreased, the expression of COX-2 mRNA and protein was increased, reactive oxygen species （ROS） generation was increased and p38 MAPK was activated significantly （P〈0.05）. When LDL-induced cells were treated with curcumin in the concentration of 12.5 or 25.0 μmol/L, LDL-induced proliferation ofmesangial cells was suppressed, the expression of MMP-2 mRNA and protein increased, the expression of COX-2 mRNA and protein downregulated, the production of ROS inhibited and p38 MAPK inactivated （P〈0.05）. In conclusion, curcumin can inhibit the LDL-induced proliferation of mesangial cells and up-regulate the expression of MMP-2, which may be related with the inhibitory effect of curcumin on COX-2 expression, ROS pro- duction and p38 MAPK.

Prospective randomized clinical trial evaluating the impact of vinegar on lipids in non-diabetics

Background: Heart disease is now considered an inflammatory process targeted primarily by medical therapy on lipid levels. Complementary and alternative medicine searches for novel non-pharmacologic therapy, including pursuing various diets. Animal studies and consumer literature suggest benefits of vinegar on lipid levels and diabetes mellitus. Our nonrandomized pilot study from our group suggested a benefit in raising high-density lipoprotein cholesterol (HDL-C). Based on this data, we conducted a randomized placebo controlled clinical trial to determine the effects of apple cider vinegar intake in those without diabetes mellitus on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, HDL-C, Hemoglobin A1C(Hgb-A1C) and measurement of inflammation with high sensitivity CRP levels (HS-CRP). Methods: A prospective randomized, double blind, placebo-controlled clinical trial consisting of 114 participants was conducted. Participants consumed 30 mL of either apple cider vinegar or placebo for two months. Measurements were collected at baseline, eight and sixteen weeks. The primary endpoint was the change in HDL-C from baseline to eight weeks between the vinegar and placebo groups. Secondary endpoints were change from baseline to eight weeks in TC, LDL-C, triglycerides, Hgb-A1cand HS-CRP. Results: Change in serum HDL-C concentration was not significantly different between the vinegar and control groups after eight weeks of supplementation. Secondary endpoints including TC, LDL-C, Hgb-A1cand HS-CRP were not statistically different at the Bonferroni corrected significance level of 0.01. No significant difference was found regardless of baseline HDL-C levels. Conclusions: We found no significant difference in HDL-C, LDL-C, triglycerides, total cholesterol, or HS-CRP levels with use of vinegar but a trend down of Hgb-A1cin this group of non-diabetic participants. Further investigation is required to define the impact of vinegar in those with diabetes mellitus.

Analysis of correlation between carotid atherosclerotic plaques and serum hs-CRP, Apo-B, ox-LDL and MMP-9 levels in patients with atherosclerotic cerebral infarction

ObjectiveTo analyze the correlation between the levels of serum hypersensitive c-reactive protein(hs-CRP),apolipoprotein-B(Apo-B),oxidized low-density lipoprotein(ox-LDL)and matrix metalloproteinase-9(MMP-9)and carotid arteryplaque(CAP)in patients with atherosclerotic cerebral infarction(ASCI).Methods 125 patients with ASCI diagnosed in the Department of Neurology of Panzhihua Central Hospital from January 2018 to December 2018 were selected as the case group,and 125 healthy volunteers in the same period were selected as the control group.Serum levels of hs-CRP,Apo-B,ox-LDL and MMP-9 were compared between the two groups.Carotid ultrasound was performed in patients with ASCI.The correlation between serum levels of hs-CRP,Apo-B,ox-LDL and MMP-9 and the formation of CAP in patients with ASCI was analyzed by SPSS 23.0 statistics.Results Compared with the control group,the levels of serum hs-CRP,Apo-B,ox-LDL and MMP-9 increased significantly in the case group(P<0.01).The serum levels of hs-CRP,Apo-B,ox-LDL and MMP-9 in patients with CAP were significantly higher than those without CAP in the case group(P<0.01).Multivariate logistic regression analysis showed that serum levels of hs-CRP(OR=4.76,95%CI:2.35-9.18),Apo-B(OR=3.16,95%CI:1.59-7.32),ox-LDL(OR=1.48,95%CI:1.15-2.01)and MMP-9(OR=3.86,95%CI:1.63-9.14)were independent risk factors for CAP formation in patients with ASCI(P<0.05).ConclusionsThe contents of serumhs-CRP,Apo-B,ox-LDL and MMP-9 may reflect the serverity of inflammation and instability of carotid atherosclerotic plaque in ASCI patient.The levels of serum hs-CRP,Apo-B,ox-LDL and MMP-9 in patients with ASCI are significantly increased,which are closely related to the formation of CAP in patients with ASCI,so it can be used as important serum biomarkers for clinical diagnosis of ASCI and CAP formation.

Oxidative alterations in sickle cell disease: Possible involvement in disease pathogenesis

Sickle cell disease(SCD) is the first molecular disease in the literature. Although the structural alteration and dysfunction of the sickle hemoglobin(HbS) are well understood, the many factors modifying the clinical signs and symptoms of the disease are under investigation. Besides having an abnormal electrophoretic mobility and solubility, HbS is unstable. The autooxidation rate of the abnormal HbS has been reported to be almost two times of the normal. There are two more components of the oxidative damage in SCD: Free radical induced oxidative damage during vaso-occlusion induced ischemia-reperfusion injury and decreased antioxidant capacity in the erythrocyte and in the circulation. We will discuss the effects of oxidative alterations in the erythrocyte and in the plasma of SCD patients in this review.