Background: The relationship between serum lipid profile levels and cancer risk remained uncertain. Recently, it had been reported a significant inverse association between high-density lipoprotein cholesterol (HDL) a...Background: The relationship between serum lipid profile levels and cancer risk remained uncertain. Recently, it had been reported a significant inverse association between high-density lipoprotein cholesterol (HDL) and the risk of incident cancer that was independent of low-density lipoprotein cholesterol (LDL), age or sex. Objective: The aim of our study was to evaluate the behavior of HDL in cancer patients and in healthy population. Methods: We created a retrospectively search strategy in the laboratory information system (LIS). We filtered and searched those patients with CEA within 5 - 20 ng/ml and any value of HDL and corroborated the presence of cancer (Group 1 (G1)) or not (Group 2 (G2)). Moreover, we searched a control group (patients in outpatient oncology clinic) to observe the values of HDL. Comparisons and statistical logistic regression models were applied to link the levels of this biomarkers and cancer risk. Results: We examined 852 valid patients, median age 62 (50 - 73) years. Within the search strategy group, G2 showed highest levels of HDL (54 (43 - 67) mg/dl) and lowest CEA levels (6.7 (5.7 - 8.4) ng/ml) comparing with G1: HDL (47 (37 - 60) mg/dl) and the CEA (7.9 (6.2 - 10.9) ng/ml);p p r2: 0.092;p p = 0.001)] and CEA [OR: 1.115 (1.060 - 1.174), (p < 0.001)] and they were confirmed as independent predictors of cancer. Conclusion: Our findings confirmed the inverse association of HDL levels between healthy populations and were diagnosed with cancer. Moreover, in a random population, patients with cancer presented lower HDL values compared to those without cancer. Therefore, it could demonstrate the possible positive predictive value of low HDL related to cancer risk.展开更多
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 an...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.展开更多
It is known that high-cholesterol diet impairs coronary vasodilatation in animal models of athe-rosclerosis irrespective of overt pathology. We evaluated the specific role of LDL and HDL on adenosine-elicited coronary...It is known that high-cholesterol diet impairs coronary vasodilatation in animal models of athe-rosclerosis irrespective of overt pathology. We evaluated the specific role of LDL and HDL on adenosine-elicited coronary vasodilatation after short time (10 weeks) high-cholesterol diet in pigs. Nineteen pigs on standard (C), atherogenic (HF) and alternate standard or atherogenic diet every other week (IHF) underwent left coronary angiography and flow (CFR) measurement during intracoronary adenosine injection. Total cholesterol, HDL, LDL, Apo lipoprotein A-1, IL-6, TNF-α and ICAM-1 were measured and histology of coronary samples was performed. IHF and HF show comparable intimal thickening of lesions, similar cholesterol (598.4 ± 198.2 and 633.2 ± 83.5 mg/dL) and LDL (502.6 ± 193.7 and 576.1 ± 83.2), while HDL is double in IHF group (88.3 ± 6.4 vs 46.4 ± 18.7 p < 0.0001). Vasodilation is reduced in HF (CFR = 1.6 ± 0.2, p < 0.001) as compared to C (2.6 ± 0.4), whilst it is preserved in IHF (2.7 ± 0.4). CFR and HDL values of all hypercholesterolemia cases are positively correlated (r = 0.88, p < 0.001). No relation with cytokines/cell adhesion markers is present. These findings suggest for the first time that elevation of plasma HDL level counteracts LDL related vasodilation impairment during coronary atherogenesis in swine.展开更多
Background: Intracoronary thrombus burden is associated with some adverse events and poor prognosis in patients with Acute Coronary Syndrome. Identifying predictors of the intracoronary thrombus burden may contribute ...Background: Intracoronary thrombus burden is associated with some adverse events and poor prognosis in patients with Acute Coronary Syndrome. Identifying predictors of the intracoronary thrombus burden may contribute to the management of Acute Coronary Syndrome. Objective: To assess the correlation between the Monocyte to HDL Cholesterol ratio with thrombus burden in patients with Acute Coronary Syndrome. Patients and Methods: 138 patients with ACS who were admitted to CCU department in National Heart Institute Cairoand Menoufia University Hospitals, Menoufia, underwent primary percutaneous coronary intervention (PCI).Angiographic thrombus burden was classified based on thrombolysis in myocardial infarction (TIMI) thrombus grades. The patients were grouped into 2 categories of low thrombus burden (grades 0 - 3) (49.7%) and high thrombus burden (grades 4 and 5) (50.3%). Results: On analysis we found that the MHR was significantly higher in the high thrombus burden group compared with the low thrombus (0.052 ± 0.019 vs 0.014 ± 0.008);P 0.001. Conclusion: Among Acute Coronary Syndrome patients underwent Primary PCI, MHR was independent predictor of high thrombus burden in patients with Acute Coronary Syndrome.展开更多
Objective Insulin has been reported to influence cholesterol removal from different cells,but the Results have been controversial.Based on our previous study,which we found that insulin promote cholesterol efflux from...Objective Insulin has been reported to influence cholesterol removal from different cells,but the Results have been controversial.Based on our previous study,which we found that insulin promote cholesterol efflux from HepG2 cells and can reverse the decreased cholesterol efflux to HDL though PI3K-Akt pathway,we further investigate the effects of insulin on damaged cholesterol efflux by MCP-1 in this report.展开更多
Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol ...Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.展开更多
Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an impo...Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.展开更多
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 primar...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.展开更多
β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
Objective: To study the correlation between TG/HDL-C ratio and sarcopenia in middle-aged and elderly people in southwest China. Methods: Body mass index (BMI) and serum of middle-aged and elderly people aged 50 - 70 y...Objective: To study the correlation between TG/HDL-C ratio and sarcopenia in middle-aged and elderly people in southwest China. Methods: Body mass index (BMI) and serum of middle-aged and elderly people aged 50 - 70 years in Southwest China were collected, grip strength was measured by grip strength meter, muscle mass and fat mass of upper, lower limbs and trunk were measured by body composition analyzer based on bioelectrical impedance method, and TG and HDL-C in serum were determined by enzymatic method. Results: Pearson correlation analysis showed that TG/HDL-C ratio (r = 0.246, p p p > 0.05). Conclusion: TG/HDL-C ratio is a predictor of skeletal muscle mass, and TG/HDL-C ratio is a protective factor for sarcopenia in middle-aged and elderly people in southwest China, and it can be used as a potential evaluation indicator for sarcopenia.展开更多
目的探究甘油三酯与高密度脂蛋白胆固醇比值(TG/HDL-C)对原发性肝癌发病的影响。方法采用前瞻性队列研究的方式,收集2006年7月—2007年12月参加开滦集团健康体检的99750例在职及离退休职工的体检资料,并对其原发性肝癌的发病情况进行随...目的探究甘油三酯与高密度脂蛋白胆固醇比值(TG/HDL-C)对原发性肝癌发病的影响。方法采用前瞻性队列研究的方式,收集2006年7月—2007年12月参加开滦集团健康体检的99750例在职及离退休职工的体检资料,并对其原发性肝癌的发病情况进行随访,随访截止时间为2021年12月31日。根据TG/HDL-C三分位水平将受试者分成3组,分别为Q1组(TC/HDL-C<0.66,n=33229)、Q2组(0.66≤TC/HDL-C<1.14,n=33302)、Q3组(TC/HDL-C≥1.14,n=33219)。计算各组原发性肝癌的发病密度。符合正态分布的计量资料多组间比较采用单因素方差分析;符合偏态分布的计量资料多组间比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。采用Kaplan⁃Meier法计算各组原发性肝癌的累积发病率,以Logrank检验比较各组间累积发病率的差异。采用Cox比例风险模型分析不同TG/HDL-C水平分组对原发性肝癌发病的影响。结果3组受试者年龄、男性比例、腰围、BMI、空腹血糖、收缩压、舒张压、TG、TC、HDL-C、LDL-C、ALT、超敏C-反应蛋白、慢性肝病、高血压病、糖尿病、恶性肿瘤家族史、饮酒、吸烟、体育锻炼、受教育程度组间对比差异均有统计学意义(P值均<0.05)。在平均(14.06±2.71)年的随访过程中,新发肝癌共计484例,其中男446例,女38例。Q1组、Q2组、Q3组原发性肝癌的发病密度分别是0.39/千人年、0.35/千人年、0.30/千人年。3组受试者的原发性肝癌累积发病率分别是6.03‰、5.28‰和4.49‰,经Log-rank检验,差异有统计学意义(χ^(2)=6.06,P=0.048)。校正了考虑到的混杂因素后,Cox比例风险模型结果显示,以Q3组为对照,Q1、Q2组的风险比及95%可信区间分别为2.04(1.61~2.58)、1.53(1.21~1.92)(P for trend<0.05)。结论TG/HDL-C水平降低与原发性肝癌发病风险升高有关,特别是在慢性肝病的人群中这种关联更加明显。展开更多
This study was aimed to analyze the effect of procyanidin B2(PC)and tannin acid(TA)on the activities of cholesterol esterase(CEase)and the inhibitory mechanisms of enzymatic activity.The interaction mechanisms were in...This study was aimed to analyze the effect of procyanidin B2(PC)and tannin acid(TA)on the activities of cholesterol esterase(CEase)and the inhibitory mechanisms of enzymatic activity.The interaction mechanisms were investigated by enzymatic kinetics,multi-spectroscopy methods,thermodynamics analysis,molecular docking,and dynamic simulations.PC and TA could bind with CEase and inhibit the activity of enzyme in a mixed-competitive manner and non-competitive manner,which was verified by molecular docking simulations and dynamics simulations.Also,PC and TA showed the synergistic inhibition with orlistat.Fluorescence,UVvis and the thermodynamic analysis revealed that the complexes were formed from CEase and inhibitors by noncovalent interaction.As revealed by the circular dichroism results,both PC and TA decreased enzymatic activities by altering the conformations of CEase.The inhibition of PC and TA on CEase might be one mechanism for its cholesterol-lowering effect.展开更多
Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed...Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.展开更多
Cells are surrounded by a double-layered phospholipid cell membrane responsible for the isolation of intracellular contents, active regulation of uptake from the extracellular environment, and intercellular connection...Cells are surrounded by a double-layered phospholipid cell membrane responsible for the isolation of intracellular contents, active regulation of uptake from the extracellular environment, and intercellular connection and communication. These cell membranes must be intact and functionally active for cell survival and biological functioning. Compromised damage repair mechanisms usually result in impaired cellular homeostasis, leading to early or late problems. Chronic myopathies, certain myocardial diseases, aging, and acute or chronic neurodegenerative diseases (like Parkinson and Alzheimer) are directly related to cell membrane damage. This study examined the effect of a cholesterol-loaded nanoparticle (methyl-beta cyclodextrin) or the silk protein sericin on cell membrane and DNA integrity and cell viability in an in vitro cell damage model (frozen-thawed rabbit sperm cells). The cells were stored in liquid nitrogen (-196°C), thawed in small batches, and treated with cholesterol-loaded cyclodextrin or sericin before incubation at 35°C for 4 hours. Cell membrane integrity, DNA damage, and viability rates were assessed immediately after thawing and after the incubation period. The administration of sericin and cholesterol in a cell damage model increased cell survival and reduced DNA damage over a 4-hour post-thaw incubation period, suggesting their potential use as a “first aid” intervention at the cellular level.展开更多
文摘Background: The relationship between serum lipid profile levels and cancer risk remained uncertain. Recently, it had been reported a significant inverse association between high-density lipoprotein cholesterol (HDL) and the risk of incident cancer that was independent of low-density lipoprotein cholesterol (LDL), age or sex. Objective: The aim of our study was to evaluate the behavior of HDL in cancer patients and in healthy population. Methods: We created a retrospectively search strategy in the laboratory information system (LIS). We filtered and searched those patients with CEA within 5 - 20 ng/ml and any value of HDL and corroborated the presence of cancer (Group 1 (G1)) or not (Group 2 (G2)). Moreover, we searched a control group (patients in outpatient oncology clinic) to observe the values of HDL. Comparisons and statistical logistic regression models were applied to link the levels of this biomarkers and cancer risk. Results: We examined 852 valid patients, median age 62 (50 - 73) years. Within the search strategy group, G2 showed highest levels of HDL (54 (43 - 67) mg/dl) and lowest CEA levels (6.7 (5.7 - 8.4) ng/ml) comparing with G1: HDL (47 (37 - 60) mg/dl) and the CEA (7.9 (6.2 - 10.9) ng/ml);p p r2: 0.092;p p = 0.001)] and CEA [OR: 1.115 (1.060 - 1.174), (p < 0.001)] and they were confirmed as independent predictors of cancer. Conclusion: Our findings confirmed the inverse association of HDL levels between healthy populations and were diagnosed with cancer. Moreover, in a random population, patients with cancer presented lower HDL values compared to those without cancer. Therefore, it could demonstrate the possible positive predictive value of low HDL related to cancer risk.
文摘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.
文摘It is known that high-cholesterol diet impairs coronary vasodilatation in animal models of athe-rosclerosis irrespective of overt pathology. We evaluated the specific role of LDL and HDL on adenosine-elicited coronary vasodilatation after short time (10 weeks) high-cholesterol diet in pigs. Nineteen pigs on standard (C), atherogenic (HF) and alternate standard or atherogenic diet every other week (IHF) underwent left coronary angiography and flow (CFR) measurement during intracoronary adenosine injection. Total cholesterol, HDL, LDL, Apo lipoprotein A-1, IL-6, TNF-α and ICAM-1 were measured and histology of coronary samples was performed. IHF and HF show comparable intimal thickening of lesions, similar cholesterol (598.4 ± 198.2 and 633.2 ± 83.5 mg/dL) and LDL (502.6 ± 193.7 and 576.1 ± 83.2), while HDL is double in IHF group (88.3 ± 6.4 vs 46.4 ± 18.7 p < 0.0001). Vasodilation is reduced in HF (CFR = 1.6 ± 0.2, p < 0.001) as compared to C (2.6 ± 0.4), whilst it is preserved in IHF (2.7 ± 0.4). CFR and HDL values of all hypercholesterolemia cases are positively correlated (r = 0.88, p < 0.001). No relation with cytokines/cell adhesion markers is present. These findings suggest for the first time that elevation of plasma HDL level counteracts LDL related vasodilation impairment during coronary atherogenesis in swine.
文摘Background: Intracoronary thrombus burden is associated with some adverse events and poor prognosis in patients with Acute Coronary Syndrome. Identifying predictors of the intracoronary thrombus burden may contribute to the management of Acute Coronary Syndrome. Objective: To assess the correlation between the Monocyte to HDL Cholesterol ratio with thrombus burden in patients with Acute Coronary Syndrome. Patients and Methods: 138 patients with ACS who were admitted to CCU department in National Heart Institute Cairoand Menoufia University Hospitals, Menoufia, underwent primary percutaneous coronary intervention (PCI).Angiographic thrombus burden was classified based on thrombolysis in myocardial infarction (TIMI) thrombus grades. The patients were grouped into 2 categories of low thrombus burden (grades 0 - 3) (49.7%) and high thrombus burden (grades 4 and 5) (50.3%). Results: On analysis we found that the MHR was significantly higher in the high thrombus burden group compared with the low thrombus (0.052 ± 0.019 vs 0.014 ± 0.008);P 0.001. Conclusion: Among Acute Coronary Syndrome patients underwent Primary PCI, MHR was independent predictor of high thrombus burden in patients with Acute Coronary Syndrome.
文摘Objective Insulin has been reported to influence cholesterol removal from different cells,but the Results have been controversial.Based on our previous study,which we found that insulin promote cholesterol efflux from HepG2 cells and can reverse the decreased cholesterol efflux to HDL though PI3K-Akt pathway,we further investigate the effects of insulin on damaged cholesterol efflux by MCP-1 in this report.
基金supported by the National Natural Science Foundation of China,No.82072110Suzhou Municipal Science and Technology Bureau,No.SKJY2021046+1 种基金Shanghai Key Lab of Forensic Medicine&Key Lab of Forensic Science,Ministry of Justice,China(Academy of Forensic Science),No.KF202201a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(all to TW).
文摘Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.
基金Supported by Hebei Natural Science Foundation,No.H2022206539Hebei Provincial Government Funded Clinical Talents Training Project,No.ZF2023143.
文摘Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.
基金financially supported by the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP)China Postdoctoral Science Foundation,No.2022M711733(to ZZ)+2 种基金the National Natural Science Foundation of China,No.82160920(to ZZ)Hebei Postdoctoral Scientific Research Project,No.B2022003040(to ZZ)Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine(to WP)。
文摘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.
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
文摘Objective: To study the correlation between TG/HDL-C ratio and sarcopenia in middle-aged and elderly people in southwest China. Methods: Body mass index (BMI) and serum of middle-aged and elderly people aged 50 - 70 years in Southwest China were collected, grip strength was measured by grip strength meter, muscle mass and fat mass of upper, lower limbs and trunk were measured by body composition analyzer based on bioelectrical impedance method, and TG and HDL-C in serum were determined by enzymatic method. Results: Pearson correlation analysis showed that TG/HDL-C ratio (r = 0.246, p p p > 0.05). Conclusion: TG/HDL-C ratio is a predictor of skeletal muscle mass, and TG/HDL-C ratio is a protective factor for sarcopenia in middle-aged and elderly people in southwest China, and it can be used as a potential evaluation indicator for sarcopenia.
文摘目的探究甘油三酯与高密度脂蛋白胆固醇比值(TG/HDL-C)对原发性肝癌发病的影响。方法采用前瞻性队列研究的方式,收集2006年7月—2007年12月参加开滦集团健康体检的99750例在职及离退休职工的体检资料,并对其原发性肝癌的发病情况进行随访,随访截止时间为2021年12月31日。根据TG/HDL-C三分位水平将受试者分成3组,分别为Q1组(TC/HDL-C<0.66,n=33229)、Q2组(0.66≤TC/HDL-C<1.14,n=33302)、Q3组(TC/HDL-C≥1.14,n=33219)。计算各组原发性肝癌的发病密度。符合正态分布的计量资料多组间比较采用单因素方差分析;符合偏态分布的计量资料多组间比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。采用Kaplan⁃Meier法计算各组原发性肝癌的累积发病率,以Logrank检验比较各组间累积发病率的差异。采用Cox比例风险模型分析不同TG/HDL-C水平分组对原发性肝癌发病的影响。结果3组受试者年龄、男性比例、腰围、BMI、空腹血糖、收缩压、舒张压、TG、TC、HDL-C、LDL-C、ALT、超敏C-反应蛋白、慢性肝病、高血压病、糖尿病、恶性肿瘤家族史、饮酒、吸烟、体育锻炼、受教育程度组间对比差异均有统计学意义(P值均<0.05)。在平均(14.06±2.71)年的随访过程中,新发肝癌共计484例,其中男446例,女38例。Q1组、Q2组、Q3组原发性肝癌的发病密度分别是0.39/千人年、0.35/千人年、0.30/千人年。3组受试者的原发性肝癌累积发病率分别是6.03‰、5.28‰和4.49‰,经Log-rank检验,差异有统计学意义(χ^(2)=6.06,P=0.048)。校正了考虑到的混杂因素后,Cox比例风险模型结果显示,以Q3组为对照,Q1、Q2组的风险比及95%可信区间分别为2.04(1.61~2.58)、1.53(1.21~1.92)(P for trend<0.05)。结论TG/HDL-C水平降低与原发性肝癌发病风险升高有关,特别是在慢性肝病的人群中这种关联更加明显。
基金supported by the National Basic Research Program of China(‘973’program,2013CB127106)。
文摘This study was aimed to analyze the effect of procyanidin B2(PC)and tannin acid(TA)on the activities of cholesterol esterase(CEase)and the inhibitory mechanisms of enzymatic activity.The interaction mechanisms were investigated by enzymatic kinetics,multi-spectroscopy methods,thermodynamics analysis,molecular docking,and dynamic simulations.PC and TA could bind with CEase and inhibit the activity of enzyme in a mixed-competitive manner and non-competitive manner,which was verified by molecular docking simulations and dynamics simulations.Also,PC and TA showed the synergistic inhibition with orlistat.Fluorescence,UVvis and the thermodynamic analysis revealed that the complexes were formed from CEase and inhibitors by noncovalent interaction.As revealed by the circular dichroism results,both PC and TA decreased enzymatic activities by altering the conformations of CEase.The inhibition of PC and TA on CEase might be one mechanism for its cholesterol-lowering effect.
基金funded in part by grants from the National Natural Science Foundation of China (No.31930105)National Key Research and Development Program of China (2022YFF1000204)China Agriculture Research Systems (CARS-40)。
文摘Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.
文摘Cells are surrounded by a double-layered phospholipid cell membrane responsible for the isolation of intracellular contents, active regulation of uptake from the extracellular environment, and intercellular connection and communication. These cell membranes must be intact and functionally active for cell survival and biological functioning. Compromised damage repair mechanisms usually result in impaired cellular homeostasis, leading to early or late problems. Chronic myopathies, certain myocardial diseases, aging, and acute or chronic neurodegenerative diseases (like Parkinson and Alzheimer) are directly related to cell membrane damage. This study examined the effect of a cholesterol-loaded nanoparticle (methyl-beta cyclodextrin) or the silk protein sericin on cell membrane and DNA integrity and cell viability in an in vitro cell damage model (frozen-thawed rabbit sperm cells). The cells were stored in liquid nitrogen (-196°C), thawed in small batches, and treated with cholesterol-loaded cyclodextrin or sericin before incubation at 35°C for 4 hours. Cell membrane integrity, DNA damage, and viability rates were assessed immediately after thawing and after the incubation period. The administration of sericin and cholesterol in a cell damage model increased cell survival and reduced DNA damage over a 4-hour post-thaw incubation period, suggesting their potential use as a “first aid” intervention at the cellular level.