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
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
Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate...Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate liver damage caused by a high cholesterol diet.Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks,and given CTs treatment at a dosage of 200 mg/(kg·day)at the same time.The results indicated that compared with mice fed a normal diet,a high cholesterol diet group resulted in significant weight loss,dysregulation of lipid metabolism in blood and liver,and oxidative stress in the liver,but CTs treatment dramatically reversed these negative effects.Hematoxylin and eosin(H&E)staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake.CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation.Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.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 Dyslipidemia is frequently present in patients with diabetes.The associations of remnant cholesterol and mortality remains unclear in patients with diabetes.AIM To explore the associations of remnant choles...BACKGROUND Dyslipidemia is frequently present in patients with diabetes.The associations of remnant cholesterol and mortality remains unclear in patients with diabetes.AIM To explore the associations of remnant cholesterol with all-cause and cardiovas-cular mortality in patients with diabetes.METHODS This prospective cohort study included 4740 patients with diabetes who par-ticipated in the National Health and Nutrition Examination Survey from 1999 through 2018.Remnant cholesterol was used as the exposure variable,and all-cause and cardiovascular mortality were considered outcome events.Outcome data were obtained from the National Death Index,and all participants were followed from the interview date until death or December 31,2019.Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes,in which remnant cholesterol was modeled as both a categorical and a continuous variable.Restricted cubic splines(RCSs)were calculated to assess the nonlinearity of associations.Subgroup(stratified by sex,age,body mass index,and duration of diabetes)and a series of sensitivity analyses were performed to evaluate the robustness of the associations.RESULTS During a median follow-up duration of 83 months,1370 all-cause deaths and 389 cardiovascular deaths were documented.Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality[hazard ratio(HR)95%confidence interval(CI):0.66(0.52-0.85)];however,when remnant cholesterol was modeled as a continuous variable,it was associated with increased risks of all-cause[HR(95%CI):1.12(1.02-1.21)per SD]and cardiovascular[HR(95%CI):1.16(1.01-1.32),per SD]mortality.The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality.Subgroup and sensitivity analyses did not reveal significant differences from the above results.CONCLUSION In patients with diabetes,higher remnant cholesterol was associated with increased risks of all-cause and cardiovascular mortality,and diabetes patients with slightly higher remnant cholesterol(0.68-1.04 mmol/L)had a lower risk of all-cause mortality.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
Astrocytes are important cellular centers of cholesterol synthesis and metabolism that help maintain normal physiological function at the organism level.Spinal cord injury results in aberrant cholesterol metabolism by...Astrocytes are important cellular centers of cholesterol synthesis and metabolism that help maintain normal physiological function at the organism level.Spinal cord injury results in aberrant cholesterol metabolism by astrocytes and excessive production of oxysterols,which have profound effects on neuropathology.25-Hydroxycholesterol(25-HC),the main product of the membrane-associated enzyme cholesterol-25-hydroxylase(CH25H),plays important roles in mediating neuroinflammation.However,whether the abnormal astrocyte cholesterol metabolism induced by spinal cord injury contributes to the production of 25-HC,as well as the resulting pathological effects,remain unclear.In the present study,spinal cord injury-induced activation of thrombin was found to increase astrocyte CH25H expression.A protease-activated receptor 1 inhibitor was able to attenuate this effect in vitro and in vivo.In cultured primary astrocytes,thrombin interacted with protease-activated receptor 1,mainly through activation of the mitogen-activated protein kinase/nuclear factor-kappa B signaling pathway.Conditioned culture medium from astrocytes in which ch25h expression had been knocked down by siRNA reduced macrophage migration.Finally,injection of the protease activated receptor 1 inhibitor SCH79797 into rat neural sheaths following spinal cord injury reduced migration of microglia/macrophages to the injured site and largely restored motor function.Our results demonstrate a novel regulatory mechanism for thrombin-regulated cholesterol metabolism in astrocytes that could be used to develop anti-inflammatory drugs to treat patients with spinal cord injury.展开更多
Ancestors of human species have been living on the planet earth for about six million years while the modern form of humans only evolved about 200,000 years ago. Civilization is only about 6000 years old, and industri...Ancestors of human species have been living on the planet earth for about six million years while the modern form of humans only evolved about 200,000 years ago. Civilization is only about 6000 years old, and industrialization started in the 1800s. World population interconnectedness is enhanced with love and mercy but disrupted with dishonest, lies and wars. Human species has been feeding on animal fat as the finest and prime source of energy for all human history. In 1953 Ancel Keys and collaborates illusionized human kind that their historical source of energy is toxic. Massive health, behavioral as well as economic consequences followed. Human hearts known historically to be the seat of spirit, soul and emotions is proven by our group to orchestrate with global energetic fields. Global consciousness as represented by the planetary electromagnetic fields is in critical need to be feed with awakening merciful information. Documents refuting Ancek Keys dogma and reverting humanity to the truth in their energy source is presented in this review. The harmony we expect is not only physiological but will affect our global planetary environment for the wellbeing of human species in earth.展开更多
Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. ...Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. This study aimed to examine whether the “cholesterol paradox” also exists in the Chinese population.Methods A total of 2,056 patients who underwent the first percutaneous coronary intervention(PCI)between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L(100 mg/d L). The outcomes of interest included major adverse cardiovascular events(MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.Results All-cause mortality occurred in 8 patients(0.7%) from the low-LDL-C group and 12 patients(2.4%) in the high-LDL-C group, with a significant difference between the two groups(adjusted hazard ratio: 4.030, 95% confidence interval: 1.088–14.934;P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.Conclusion In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the “cholesterol paradox” may be inapplicable to Chinese populations.展开更多
Fuzhuan brick-tea(FZT)has long been consumed for its supposed weight loss and lipid-lowering benefi ts.In this study,we show that the regulation of fat storage in Caenorhabditis elegans from a water extract of FZT was...Fuzhuan brick-tea(FZT)has long been consumed for its supposed weight loss and lipid-lowering benefi ts.In this study,we show that the regulation of fat storage in Caenorhabditis elegans from a water extract of FZT was affected by cholesterol levels.We found that FZT signifi cantly decreased fat storage under normal cholesterol levels or in a cholesterol-free diet,while lipid accumulation was increased for a high cholesterol diet.Moreover,this mechanism may involve the conserved sterol regulatory element-binding protein(SREBP)/mediator-15(MDT-15)signaling pathway and the nuclear hormone receptor NHR-80.In addition,lipid synthesis-related genes inhibited by FZT were partially affected by a cholesterol-free diet.Thus,our fi ndings suggested that the potential lipid-lowering effects of FZT may depend on the cholesterol level,which may help to improve the consumption of FZT.展开更多
Background:Cholesterol is an essential component of lipid rafts in cell plasma membrane,which exerts a hepatoprotective role against mycotoxin exposure in pigs,and cholesterol metabolism is vulnerable to epigenetic hi...Background:Cholesterol is an essential component of lipid rafts in cell plasma membrane,which exerts a hepatoprotective role against mycotoxin exposure in pigs,and cholesterol metabolism is vulnerable to epigenetic histone acetylation.Therefore,our present study aimed to investigate whether a histone deacetylase inhibitor(sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol(DON) exposure by modulating cholesterol metabolism.Herein,we randomly divided 28 pigs into four groups,which were fed an uncontaminated basal diet,contaminated diet(4 mg DON/kg),uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet(4 mg DON/kg) supplemented with 0.2% NaBu for 28 d.Results:We found that the serum alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP) were all increased in pigs exposed to DON,indicative of significant liver injury.Furthermore,the cholesterol content in the serum of DON-exposed pigs was significantly reduced,compared to the healthy Vehicle group.Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure.In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated.Importantly,NaBu effectively restored parameters associated with liver injury,along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway.Mechanistically,we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment.We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu,as determined by ChIP-qPCR analysis.Notably,nuclear receptor RORγ,a novel regulator of cholesterol biosynthesis,was found in the hyperacetylated regions.Again,a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu.Consistent with RORγ expression,NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR,SQLE,and DHCR24.Furthermore,we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bonds to the promoters of the above target genes.Conclusions:Collectively,our results demonstrate the utility of the natural product Na Bu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification.展开更多
Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Method...Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Methods In the present research work, the homologous structures and binding potentials were identified between plant/mammalian lipocalins and plant DUF538 protein by using bioinformatics and experimental tools including molecular dynamics simulation, molecular docking and recombinant technology-based techniques. Results Molecular docking analysis of their interactions with lipidic ligands including cholesterol and palmitic acid revealed the similar and comparable binding potentials between DUF538 and lipocalin proteins. Both the test proteins were found to have more affinity to cholesterol molecule in compare to palmitic acid. By using recombinant technology-based experiments, the heterologously expressed and purified fused product of DUF538 protein exhibited about 61% cholesterol binding ability. Conclusion As a conclusion, plants DUF538 protein family was predicted to be the structural and may be the functional homologues of plants/animals lipocalin superfamily.展开更多
Background:Nonalcoholic fatty liver disease(NAFLD)is an independent risk factor for severe acute pancreatitis(AP).The underlying mechanism remains unclear.We sought to determine how bacterial translocation and cholest...Background:Nonalcoholic fatty liver disease(NAFLD)is an independent risk factor for severe acute pancreatitis(AP).The underlying mechanism remains unclear.We sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD mice.Methods:C57BL/6N mice were fed on a high-fat diet(HFD)to generate the NAFLD model,and mice in the control group were provided with a normal diet(ND).After being anesthetized with ketamine/xylazine,mice got a retrograde infusion of taurocholic acid sodium into the pancreatic duct to induce AP,and sham operation(SO)was used as control.Serum amylase and Schmidt’s pathological score system were used to evaluate AP severity.Bacterial loads,total cholesterol level,and cholesterol metabolic-associated molecules[low-density lipoprotein receptor(LDLR)and ATP-binding cassette transporter A1(ABCA1)]were analyzed in the liver and pancreas.Results:Compared with the ND-AP group,mice in the HFD-AP group had severer pancreatitis,manifested with higher serum amylase levels and higher AP pathologic scores,especially the inflammation and hemorrhage scores.Compared with the HFD-SO group and ND-AP group,bacterial loads in the liver and pancreas were significantly higher in the HFD-AP group.Mice in the HFD-AP group showed a decreased LDLR expression and an increased ABCA1 expression in the pancreas,although there was no significant difference in pancreas total cholesterol between the HFD-AP group and the ND-AP group.Conclusions:NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.展开更多
OBJECTIVE To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.METHODS A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Co...OBJECTIVE To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.METHODS A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 com-munity older adults.After the baseline survey,the last follow-up was March 31,2021 with an average 8.13 years of follow-up.Cox proportional hazard model was used to estimate the hazard ratios(HR)with 95%CI for cardiovascular disease(CVD)death and all-cause death in associations with baseline lipid indicators.RESULTS A total of 4499 participants were recruited,and the mean levels of uric acid,body mass index,systolic blood pres-sure,diastolic blood pressure,fasting plasma glucose,total cholesterol(TC),triglyceride,and low-density lipoprotein cholesterol(LDL-C)showed an upward trend with the increasing remnant cholesterol(RC)quarters(Ptrend<0.05),while the downward tr-end was found in high-density lipoprotein cholesterol(HDL-C).During the total 36,596 person-years follow-up,the CVD mortal-ity and all-cause mortality during an average 8.13 years of follow-up was 3.87%(95%CI:3.30%-4.43%)and 14.83%(95%CI:13.79%-15.86%)with 174 CVD death participants and 667 all-cause death participants.After adjusting for confounders,the higher level of TC(HR=0.854,95%CI:0.730-0.997),LDL-C(HR=0.817,95%CI:0.680-0.982)and HDL-C(HR=0.443,95%CI:0.271-0.724)were associated with lower risk of CVD death,and the higher level of HDL-C(HR=0.637,95%CI:0.501-0.810)were associated with lower risk of all-cause death.The higher level of RC(HR=1.276,95%CI:1.010-1.613)increase the risk of CVD death.Com-pared with the normal lipid group,TC≥6.20 mmol/L group and LDL-C≥4.10 mmol/L group were no longer associated with lower risk of CVD death,while RC≥0.80 mmol/L group was still associated with higher risk of CVD death.In normal lipid gr-oup,the higher levels of TC,LDL-C and HDL-C were related with lower CVD death.CONCLUSIONS In community older adults,higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range.Higher RC was associated with higher CVD mortality,which may be a better lipid indicator for es-timating the CVD death risk in older adults.展开更多
Niacin or nicotinic acid is a form of B3 vitamin prescribed at higher concentrations for the suppression of cholesterol levels. Supplemental doses may cause very little or no side effects. However, higher concentratio...Niacin or nicotinic acid is a form of B3 vitamin prescribed at higher concentrations for the suppression of cholesterol levels. Supplemental doses may cause very little or no side effects. However, higher concentrations of niacin cause hot flushes for most people. Here we propose a biochemical mechanism of niacin induced hot flushes. Orally taken prescription doses of niacin are converted to NAD with the liberation of excess pyrophosphate which in turn releases energy in the form of heat (hot flushes through capsaicin receptor) by the action of pyrophosphatases. The excess pyrophosphate may suppress cholesterol biosynthesis through feedback mechanism. The pathways of NAD and cholesterol biosynthesis were discussed with refence to the production and function of pyrophosphate.展开更多
The thought of using branched-chain amino acids (BCAA) in the prevention and treatment of certain disorders is becoming increasingly popular. Individual BCAA use has been associated with improving glucose tolerance an...The thought of using branched-chain amino acids (BCAA) in the prevention and treatment of certain disorders is becoming increasingly popular. Individual BCAA use has been associated with improving glucose tolerance and liver disease. Previous studies have cited improvements in glucose metabolism with a single dose of L-isoleucine (ILE). However, it is still unclear whether chronic consumption of ILE has any direct benefit. The objective of this study was to examine the influence of chronic ILE supplementation alone or in combination with exercise on fasting serum glucose, insulin, lipids, and lipoprotein cholesterol levels;glucose tolerance;and hepatic lipids in rats. Male Sprague-Dawley rats (n = 40) were divided into Control (low fructose diet);High Fructose diet (HF);HF plus 1.5% ILE (HF + ILE);HF plus exercise (HF + EX);and HF plus 1.5% ILE and exercise (HF + ILE + EX). The HF diets consisted of 70% kcalories from fructose. After 6 weeks of treatment, no significant differences were observed between groups for changes in fasting serum glucose, insulin, lipids, or lipoprotein cholesterol levels. However, hepatic total cholesterol was significantly lower in the HF + ILE + EX compared to the Control and HF, while, the HF + ILE had significantly lower hepatic free cholesterol compared to the HF. We also found no differences between groups for serum glucose response following an oral glucose tolerance test. In conclusion, our study shows that ILE supplementation in rats does not influence serum glucose and lipid biomarkers but may have an influence on lipid metabolic pathways within the liver.展开更多
7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigat...7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigate the absorption mechanism of 7-ketophytosterols and their effects on the cholesterol transport using Caco-2 cell model. The absorption percentage of 7-ketositosterol and 7-ketocampesterol was 1.16%-1.68% and 1.18%-2.23% respectively in the Caco-2 model, which is higher than that of their parent phytosterols, but lower than cholesterol-d7. The apparent permeability of 7-ketositosterol and 7-ketocampesterol at 30 μmol/L in the basolateral(BL)-to-apical(AP)direction were 0.42-and 0.55-fold of that in the AP-to-BL direction, indicating an active intake in the permeation mechanism of 7-ketophytosterols. Ezetimibe could significantly inhibit the transport of 7-ketophytosterols(P < 0.05), which means that their transport depends on niemann-pick c1-like 1(NPC1L1)protein. The transport of cholesterol-d7 was significantly inhibited by 7-ketophytosterols(P < 0.05). Taken together, this study deepened our understanding of the absorption mechanism of common food-born 7-ketophytosterols and provides useful information on the inhibition of 7-ketophytosterols absorption.展开更多
Cholesterol and cholesterol oxides impact on the functional properties of cells, in respect of the intracellular and extracellular distribution of compounds across cell membranes, carcinogenesis and drug resistance. A...Cholesterol and cholesterol oxides impact on the functional properties of cells, in respect of the intracellular and extracellular distribution of compounds across cell membranes, carcinogenesis and drug resistance. Abnormal levels of cholesterol oxides and steroids in cancerous tissues promote interest in steroid receptor cross-talk during cell-signalling and the steroid metabolome of cancer patients. The research literature links the cytotoxic properties of oxysterols to interference with the NO/cGMP pathway. cGMP participates in cell-signalling and has a molecular structure that relates to cancer-inducing and cancer-preventing agents. This study uses a molecular modelling approach to compare the structures of cholesterol oxides to cGMP. Cholesterol and cholesterol oxide structures fit to a cGMP structural template in several ways, some of which are replicated by corticosteroids and gonadal steroid hormones. The results of this study support the concept that cholesterol oxides modulate cell apoptosis and autophagy via the NO/cGMP pathway and in conjunction with steroid hormones participate in modulating regulation of cell function by cGMP.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
BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which ...BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.展开更多
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.
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.
基金supported by the National Basic Research Program of China(2013CB127106)。
文摘Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate liver damage caused by a high cholesterol diet.Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks,and given CTs treatment at a dosage of 200 mg/(kg·day)at the same time.The results indicated that compared with mice fed a normal diet,a high cholesterol diet group resulted in significant weight loss,dysregulation of lipid metabolism in blood and liver,and oxidative stress in the liver,but CTs treatment dramatically reversed these negative effects.Hematoxylin and eosin(H&E)staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake.CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation.Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.
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Supported by Project of National Natural Science Foundation of China,No.82274345 and No.82104907Fundamental Research Funds for the Central public welfare research institutes Grant,No.ZZ13-YQ-016 and No.ZZ13-YQ-016-C1.
文摘BACKGROUND Dyslipidemia is frequently present in patients with diabetes.The associations of remnant cholesterol and mortality remains unclear in patients with diabetes.AIM To explore the associations of remnant cholesterol with all-cause and cardiovas-cular mortality in patients with diabetes.METHODS This prospective cohort study included 4740 patients with diabetes who par-ticipated in the National Health and Nutrition Examination Survey from 1999 through 2018.Remnant cholesterol was used as the exposure variable,and all-cause and cardiovascular mortality were considered outcome events.Outcome data were obtained from the National Death Index,and all participants were followed from the interview date until death or December 31,2019.Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes,in which remnant cholesterol was modeled as both a categorical and a continuous variable.Restricted cubic splines(RCSs)were calculated to assess the nonlinearity of associations.Subgroup(stratified by sex,age,body mass index,and duration of diabetes)and a series of sensitivity analyses were performed to evaluate the robustness of the associations.RESULTS During a median follow-up duration of 83 months,1370 all-cause deaths and 389 cardiovascular deaths were documented.Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality[hazard ratio(HR)95%confidence interval(CI):0.66(0.52-0.85)];however,when remnant cholesterol was modeled as a continuous variable,it was associated with increased risks of all-cause[HR(95%CI):1.12(1.02-1.21)per SD]and cardiovascular[HR(95%CI):1.16(1.01-1.32),per SD]mortality.The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality.Subgroup and sensitivity analyses did not reveal significant differences from the above results.CONCLUSION In patients with diabetes,higher remnant cholesterol was associated with increased risks of all-cause and cardiovascular mortality,and diabetes patients with slightly higher remnant cholesterol(0.68-1.04 mmol/L)had a lower risk of all-cause mortality.
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.
基金supported by the National Natural Science Foundation of ChinaNo.81971826 (to AG)+5 种基金the China Postdoctoral Science FoundationNo.2020M681 689 (to YH)the Scientific Research Project of The Health Commission of Jiangsu ProvinceNo.ZDB2020003 (to AG)the Basic Scientific Research Projects of NantongNo.JC2020041 (to YH)
文摘Astrocytes are important cellular centers of cholesterol synthesis and metabolism that help maintain normal physiological function at the organism level.Spinal cord injury results in aberrant cholesterol metabolism by astrocytes and excessive production of oxysterols,which have profound effects on neuropathology.25-Hydroxycholesterol(25-HC),the main product of the membrane-associated enzyme cholesterol-25-hydroxylase(CH25H),plays important roles in mediating neuroinflammation.However,whether the abnormal astrocyte cholesterol metabolism induced by spinal cord injury contributes to the production of 25-HC,as well as the resulting pathological effects,remain unclear.In the present study,spinal cord injury-induced activation of thrombin was found to increase astrocyte CH25H expression.A protease-activated receptor 1 inhibitor was able to attenuate this effect in vitro and in vivo.In cultured primary astrocytes,thrombin interacted with protease-activated receptor 1,mainly through activation of the mitogen-activated protein kinase/nuclear factor-kappa B signaling pathway.Conditioned culture medium from astrocytes in which ch25h expression had been knocked down by siRNA reduced macrophage migration.Finally,injection of the protease activated receptor 1 inhibitor SCH79797 into rat neural sheaths following spinal cord injury reduced migration of microglia/macrophages to the injured site and largely restored motor function.Our results demonstrate a novel regulatory mechanism for thrombin-regulated cholesterol metabolism in astrocytes that could be used to develop anti-inflammatory drugs to treat patients with spinal cord injury.
文摘Ancestors of human species have been living on the planet earth for about six million years while the modern form of humans only evolved about 200,000 years ago. Civilization is only about 6000 years old, and industrialization started in the 1800s. World population interconnectedness is enhanced with love and mercy but disrupted with dishonest, lies and wars. Human species has been feeding on animal fat as the finest and prime source of energy for all human history. In 1953 Ancel Keys and collaborates illusionized human kind that their historical source of energy is toxic. Massive health, behavioral as well as economic consequences followed. Human hearts known historically to be the seat of spirit, soul and emotions is proven by our group to orchestrate with global energetic fields. Global consciousness as represented by the planetary electromagnetic fields is in critical need to be feed with awakening merciful information. Documents refuting Ancek Keys dogma and reverting humanity to the truth in their energy source is presented in this review. The harmony we expect is not only physiological but will affect our global planetary environment for the wellbeing of human species in earth.
基金supported by the Ethics Committee of Sir Run Run Shaw Hospital of Zhejiang University [NO.20200224-33]Key Project of Medical and Health Science and Technology of Zhejiang Province [NO. WKJ-ZJ-1715]+7 种基金Zhejiang Province Traditional Chinese Medicine Science and Technology Project [NO. 2017ZA006]Natural Science Foundation of Zhejiang Province [NO. LQ17H020006]Medical health Science and Technology project of Zhejiang Province [NO. 2017KY207]National Natural Science Foundation of China [82070408]Medical and health project [2021RC014]Hangzhou Medical Health Science and Technology Project [B20200116]“Pioneer” and “Leading Goose” R&D Program of Zhejiang[2023C04013]Administration of Traditional Chinese Medicine of Zhejiang Province [GZY-ZJ-KJ-23001]。
文摘Objective Foreign studies have reported that coronary artery disease(CAD) patients with high baseline low-density lipoprotein cholesterol(LDL-C) may have a good prognosis, which is called the “cholesterol paradox”. This study aimed to examine whether the “cholesterol paradox” also exists in the Chinese population.Methods A total of 2,056 patients who underwent the first percutaneous coronary intervention(PCI)between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L(100 mg/d L). The outcomes of interest included major adverse cardiovascular events(MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.Results All-cause mortality occurred in 8 patients(0.7%) from the low-LDL-C group and 12 patients(2.4%) in the high-LDL-C group, with a significant difference between the two groups(adjusted hazard ratio: 4.030, 95% confidence interval: 1.088–14.934;P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.Conclusion In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the “cholesterol paradox” may be inapplicable to Chinese populations.
基金supported by the National Natural Science Foundation of China(31801547)Some C.elegans strains were provided by CGC,which is funded by the NIH Office of Research Infrastructure Programs.
文摘Fuzhuan brick-tea(FZT)has long been consumed for its supposed weight loss and lipid-lowering benefi ts.In this study,we show that the regulation of fat storage in Caenorhabditis elegans from a water extract of FZT was affected by cholesterol levels.We found that FZT signifi cantly decreased fat storage under normal cholesterol levels or in a cholesterol-free diet,while lipid accumulation was increased for a high cholesterol diet.Moreover,this mechanism may involve the conserved sterol regulatory element-binding protein(SREBP)/mediator-15(MDT-15)signaling pathway and the nuclear hormone receptor NHR-80.In addition,lipid synthesis-related genes inhibited by FZT were partially affected by a cholesterol-free diet.Thus,our fi ndings suggested that the potential lipid-lowering effects of FZT may depend on the cholesterol level,which may help to improve the consumption of FZT.
基金supported by Key Research and Development Project(Modern Agriculture)of Jiangsu Province(BE2019341)Jiangsu Agricultural Science and Technology Innovation Fund(CX[20]2003)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Background:Cholesterol is an essential component of lipid rafts in cell plasma membrane,which exerts a hepatoprotective role against mycotoxin exposure in pigs,and cholesterol metabolism is vulnerable to epigenetic histone acetylation.Therefore,our present study aimed to investigate whether a histone deacetylase inhibitor(sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol(DON) exposure by modulating cholesterol metabolism.Herein,we randomly divided 28 pigs into four groups,which were fed an uncontaminated basal diet,contaminated diet(4 mg DON/kg),uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet(4 mg DON/kg) supplemented with 0.2% NaBu for 28 d.Results:We found that the serum alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP) were all increased in pigs exposed to DON,indicative of significant liver injury.Furthermore,the cholesterol content in the serum of DON-exposed pigs was significantly reduced,compared to the healthy Vehicle group.Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure.In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated.Importantly,NaBu effectively restored parameters associated with liver injury,along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway.Mechanistically,we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment.We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu,as determined by ChIP-qPCR analysis.Notably,nuclear receptor RORγ,a novel regulator of cholesterol biosynthesis,was found in the hyperacetylated regions.Again,a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu.Consistent with RORγ expression,NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR,SQLE,and DHCR24.Furthermore,we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bonds to the promoters of the above target genes.Conclusions:Collectively,our results demonstrate the utility of the natural product Na Bu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification.
基金supported by a grant from Department of Animal Biology and Research Center for Bioscience and Biotechnology(RCBB),University of Tabriz(6906).
文摘Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Methods In the present research work, the homologous structures and binding potentials were identified between plant/mammalian lipocalins and plant DUF538 protein by using bioinformatics and experimental tools including molecular dynamics simulation, molecular docking and recombinant technology-based techniques. Results Molecular docking analysis of their interactions with lipidic ligands including cholesterol and palmitic acid revealed the similar and comparable binding potentials between DUF538 and lipocalin proteins. Both the test proteins were found to have more affinity to cholesterol molecule in compare to palmitic acid. By using recombinant technology-based experiments, the heterologously expressed and purified fused product of DUF538 protein exhibited about 61% cholesterol binding ability. Conclusion As a conclusion, plants DUF538 protein family was predicted to be the structural and may be the functional homologues of plants/animals lipocalin superfamily.
基金This study was supported by grants from the National Nat-ural Science Foundation of China(82070539 and 81873549)the Youth Innovation Foundation of Aerospace Center Hospital(2021QN02).
文摘Background:Nonalcoholic fatty liver disease(NAFLD)is an independent risk factor for severe acute pancreatitis(AP).The underlying mechanism remains unclear.We sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD mice.Methods:C57BL/6N mice were fed on a high-fat diet(HFD)to generate the NAFLD model,and mice in the control group were provided with a normal diet(ND).After being anesthetized with ketamine/xylazine,mice got a retrograde infusion of taurocholic acid sodium into the pancreatic duct to induce AP,and sham operation(SO)was used as control.Serum amylase and Schmidt’s pathological score system were used to evaluate AP severity.Bacterial loads,total cholesterol level,and cholesterol metabolic-associated molecules[low-density lipoprotein receptor(LDLR)and ATP-binding cassette transporter A1(ABCA1)]were analyzed in the liver and pancreas.Results:Compared with the ND-AP group,mice in the HFD-AP group had severer pancreatitis,manifested with higher serum amylase levels and higher AP pathologic scores,especially the inflammation and hemorrhage scores.Compared with the HFD-SO group and ND-AP group,bacterial loads in the liver and pancreas were significantly higher in the HFD-AP group.Mice in the HFD-AP group showed a decreased LDLR expression and an increased ABCA1 expression in the pancreas,although there was no significant difference in pancreas total cholesterol between the HFD-AP group and the ND-AP group.Conclusions:NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.
基金supported by the National Natural Science Foundation of China(No.82173589&No.82173590)the National Key Research and Development Program of China(2022YFC2503605)+1 种基金the Capital’s Funds for Health Improvement and Research(2022-2G-5031),the Beijing Nova Program(No.20220484020)the Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province(2-6-2020E10004).
文摘OBJECTIVE To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.METHODS A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 com-munity older adults.After the baseline survey,the last follow-up was March 31,2021 with an average 8.13 years of follow-up.Cox proportional hazard model was used to estimate the hazard ratios(HR)with 95%CI for cardiovascular disease(CVD)death and all-cause death in associations with baseline lipid indicators.RESULTS A total of 4499 participants were recruited,and the mean levels of uric acid,body mass index,systolic blood pres-sure,diastolic blood pressure,fasting plasma glucose,total cholesterol(TC),triglyceride,and low-density lipoprotein cholesterol(LDL-C)showed an upward trend with the increasing remnant cholesterol(RC)quarters(Ptrend<0.05),while the downward tr-end was found in high-density lipoprotein cholesterol(HDL-C).During the total 36,596 person-years follow-up,the CVD mortal-ity and all-cause mortality during an average 8.13 years of follow-up was 3.87%(95%CI:3.30%-4.43%)and 14.83%(95%CI:13.79%-15.86%)with 174 CVD death participants and 667 all-cause death participants.After adjusting for confounders,the higher level of TC(HR=0.854,95%CI:0.730-0.997),LDL-C(HR=0.817,95%CI:0.680-0.982)and HDL-C(HR=0.443,95%CI:0.271-0.724)were associated with lower risk of CVD death,and the higher level of HDL-C(HR=0.637,95%CI:0.501-0.810)were associated with lower risk of all-cause death.The higher level of RC(HR=1.276,95%CI:1.010-1.613)increase the risk of CVD death.Com-pared with the normal lipid group,TC≥6.20 mmol/L group and LDL-C≥4.10 mmol/L group were no longer associated with lower risk of CVD death,while RC≥0.80 mmol/L group was still associated with higher risk of CVD death.In normal lipid gr-oup,the higher levels of TC,LDL-C and HDL-C were related with lower CVD death.CONCLUSIONS In community older adults,higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range.Higher RC was associated with higher CVD mortality,which may be a better lipid indicator for es-timating the CVD death risk in older adults.
文摘Niacin or nicotinic acid is a form of B3 vitamin prescribed at higher concentrations for the suppression of cholesterol levels. Supplemental doses may cause very little or no side effects. However, higher concentrations of niacin cause hot flushes for most people. Here we propose a biochemical mechanism of niacin induced hot flushes. Orally taken prescription doses of niacin are converted to NAD with the liberation of excess pyrophosphate which in turn releases energy in the form of heat (hot flushes through capsaicin receptor) by the action of pyrophosphatases. The excess pyrophosphate may suppress cholesterol biosynthesis through feedback mechanism. The pathways of NAD and cholesterol biosynthesis were discussed with refence to the production and function of pyrophosphate.
文摘The thought of using branched-chain amino acids (BCAA) in the prevention and treatment of certain disorders is becoming increasingly popular. Individual BCAA use has been associated with improving glucose tolerance and liver disease. Previous studies have cited improvements in glucose metabolism with a single dose of L-isoleucine (ILE). However, it is still unclear whether chronic consumption of ILE has any direct benefit. The objective of this study was to examine the influence of chronic ILE supplementation alone or in combination with exercise on fasting serum glucose, insulin, lipids, and lipoprotein cholesterol levels;glucose tolerance;and hepatic lipids in rats. Male Sprague-Dawley rats (n = 40) were divided into Control (low fructose diet);High Fructose diet (HF);HF plus 1.5% ILE (HF + ILE);HF plus exercise (HF + EX);and HF plus 1.5% ILE and exercise (HF + ILE + EX). The HF diets consisted of 70% kcalories from fructose. After 6 weeks of treatment, no significant differences were observed between groups for changes in fasting serum glucose, insulin, lipids, or lipoprotein cholesterol levels. However, hepatic total cholesterol was significantly lower in the HF + ILE + EX compared to the Control and HF, while, the HF + ILE had significantly lower hepatic free cholesterol compared to the HF. We also found no differences between groups for serum glucose response following an oral glucose tolerance test. In conclusion, our study shows that ILE supplementation in rats does not influence serum glucose and lipid biomarkers but may have an influence on lipid metabolic pathways within the liver.
基金supported by the National Natural Science Foundation of China (32072179)Zhejiang Provincial Natural Science Foundation of China (LD21C200001)。
文摘7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigate the absorption mechanism of 7-ketophytosterols and their effects on the cholesterol transport using Caco-2 cell model. The absorption percentage of 7-ketositosterol and 7-ketocampesterol was 1.16%-1.68% and 1.18%-2.23% respectively in the Caco-2 model, which is higher than that of their parent phytosterols, but lower than cholesterol-d7. The apparent permeability of 7-ketositosterol and 7-ketocampesterol at 30 μmol/L in the basolateral(BL)-to-apical(AP)direction were 0.42-and 0.55-fold of that in the AP-to-BL direction, indicating an active intake in the permeation mechanism of 7-ketophytosterols. Ezetimibe could significantly inhibit the transport of 7-ketophytosterols(P < 0.05), which means that their transport depends on niemann-pick c1-like 1(NPC1L1)protein. The transport of cholesterol-d7 was significantly inhibited by 7-ketophytosterols(P < 0.05). Taken together, this study deepened our understanding of the absorption mechanism of common food-born 7-ketophytosterols and provides useful information on the inhibition of 7-ketophytosterols absorption.
文摘Cholesterol and cholesterol oxides impact on the functional properties of cells, in respect of the intracellular and extracellular distribution of compounds across cell membranes, carcinogenesis and drug resistance. Abnormal levels of cholesterol oxides and steroids in cancerous tissues promote interest in steroid receptor cross-talk during cell-signalling and the steroid metabolome of cancer patients. The research literature links the cytotoxic properties of oxysterols to interference with the NO/cGMP pathway. cGMP participates in cell-signalling and has a molecular structure that relates to cancer-inducing and cancer-preventing agents. This study uses a molecular modelling approach to compare the structures of cholesterol oxides to cGMP. Cholesterol and cholesterol oxide structures fit to a cGMP structural template in several ways, some of which are replicated by corticosteroids and gonadal steroid hormones. The results of this study support the concept that cholesterol oxides modulate cell apoptosis and autophagy via the NO/cGMP pathway and in conjunction with steroid hormones participate in modulating regulation of cell function by cGMP.
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.
基金The study was reviewed and approved by the Institutional Review Board of Chaohu Hospital Affiliated to AnhuiMedical University,Approval No.KYXM-202208-011.
文摘BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the thalamus.Most patients with thalamic infarction have an adverse prognosis,which seriously affects their safety.Therefore,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive measures.AIM To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic infarction.METHODS From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score<26;35 patients]and a group with normal cognitive function(MoCA score of 26-30;45 patients)according to the MoCA score.In addition,50 healthy people in the same period were selected as the control group.A correlation between the non-HDL-C and Hcy levels and the MoCA score and receiver operating characteristic curve was observed,and the serum non-HDL-C and Hcy levels were analyzed for the diagnosis of cognitive impairment in patients with thalamic infarction.According to the Modified Rankin Scale(MRS)score,80 patients with thalamic infarction were divided into a good prognosis group(MRS score≤2)and a poor prognosis group(MRS score>2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P<0.05).There was no significant difference in the non-HDL-C level between the control group and the group with normal cognitive function(P>0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were correlated with the MoCA score(P<0.05),cognitive impairment[areas under the curve(AUC)=0.709,95%confidence interval(95%CI):0.599-0.816],the non-HDL-C level,and could predict cognitive impairment in patients with thalamic infarction(AUC=0.738,95%CI:0.618-0.859).Hcy combined with non-HDL-C levels can predict cognitive impairment in patients with thalamic infarction(AUC=0.769,95%CI:0.721-0.895).RESULTS There were 50 patients in the good prognosis group and 30 patients in the poor prognosis group.Compared with the good prognosis group,in the poor prognosis group,the National Institutes of Health Stroke Scale(NIHSS)score,non-HDL-C level,Hcy level,large-area cerebral infarction,atrial fibrillation,and activated partial prothrombin time were statistically significant(P<0.05).The non-HDL-C level,the Hcy level,the NIHSS score,extensive cerebral serum,and atrial fibrillation may all be independent risk factors for poor prognosis in patients with thalamic infarction(P<0.05).CONCLUSION Non-HDL-C and Hcy levels are positively correlated with cognitive impairment in patients with thalamic infarction.Non-HDL-C and Hcy levels can be used in the diagnosis of cognitive impairment in patients with thalamic infarction,and the combined detection effect is better.The main factors affecting the prognosis of patients with thalamic infarction are the non-HDL-C level,the Hcy level,the NIHSS score,large-area cerebral infarction,and atrial fibrillation.Clinically,corresponding preventive measures can be formulated based on the above factors to prevent poor prognosis and reduce mortality.
