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Lipidomic and sterolomic profiles of different brain regions in the mouse model of Alzheimer’s disease 认领 引用
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作者 Xingsen Zhao Liqun Chen +4 位作者 Liangjian Ma Xiaohui Liu Zhongkai Cao Xiangjun Chen Lidan Hu 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第6期2543-2552,共10页
Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol chan... Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease. 展开更多
关键词 Alzheimer’s disease Alzheimer’s disease mouse model brain lipids dyslipidemias lipidomic metabolism neurodegenerative disease sterol
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First discovery of triterpenoids and sterols from Cotinus coggygria var.cinereus Engl.with anti-inflammatory and antibacterial activities 认领 引用
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作者 Yue-Tong Zhu Ze-Rui Li +5 位作者 Ren-Hao Chen Jin-Hao Li Wei Wang Yu-Qi Gao Chun-Huan Li Jin-Ming Gao 《Natural Products and Bioprospecting》 CSCD 2026年第1期1-18,共18页
This study led to the isolation of 17 triterpenoids,including two lanostane-type(1 and 2),two dammarane-type(3 and 7),ten tirucallane-type(4 and 8-16),and three oleanane-type(17-19)triterpenoids,as well as nine sterol... This study led to the isolation of 17 triterpenoids,including two lanostane-type(1 and 2),two dammarane-type(3 and 7),ten tirucallane-type(4 and 8-16),and three oleanane-type(17-19)triterpenoids,as well as nine sterols(5,6,and 20-26)from Cotinus coggygria var.cinereus Engl,which were first discovered from the genus Cotinus.Among them,coggygrenoids A-D(1-4),coggygrerol A(5),and coggygrerol B(6)are undescribed compounds.Addition-ally,seven flavonoids(27-33)were also isolated from this plant.Compound 15 displayed inhibitory activities in LPS-induced RAW 264.7 cells with an IC50 value 6.81±0.15 μM.Molecular docking demonstrated that 15 exhibited favorable affinity for NLRP3 and iNOS.In vitro and in vivo antibacterial evaluations indicated that coggygrnoid C(3)exhibited significant inhibitory activity against methicillin-resistant Staphylococcus aureus ATCC BAA-1717(USA300),with An MIC of 8 μg/mL.Further mechanistic investigations demonstrated that 3 exerted antibacterial activity by compromising the integrity of the cell wall and membrane.Notably,the combination of 3 with ampicillin exhibited an additive antibacterial effect.In the Galleria mellonella infection model,compound 3 exhibited comparable activ-ity to that of the positive control at 20 mg/kg.These findings suggest that triterpenoids of C.coggygria are potential antibacterial lead agents. 展开更多
关键词 Cotinus coggygria var.cinereus Engl. Triterpenoids Sterols Anti-inflammatory activity Antibacterial activity
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Finding the balance: Modifying the cholesterol and steroidal glycoalkaloid synthesis pathway in tomato(Solanum lycopersicum L.) for human health, fruit flavor, and plant defense 认领 引用 被引量：3
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作者 Vincenzo Averello IV Adrian D.Hegeman Changbin Chen 《Horticultural Plant Journal》 SCIE CAS CSCD 2025年第1期42-56,共15页
Unlike most plants, members of the genus Solanum produce cholesterol and use this as a precursor for steroidal glycoalkaloids. The production of the compounds begins as a branch from brassinosteroid biosynthesis, whic... Unlike most plants, members of the genus Solanum produce cholesterol and use this as a precursor for steroidal glycoalkaloids. The production of the compounds begins as a branch from brassinosteroid biosynthesis, which produces cholesterol that is further modified to produce steroidal glycoalkaloids. During the cholesterol biosynthesis pathway, genetic engineering could alter the formation of cholesterol from provitamin D3(7-dehydrocholesterol) and produce vitamin D3. Cholesterol is a precursor for many steroidal glycoalkaloids, including a-tomatine and esculeoside A. Alpha-tomatine is consumed by mammals and it can reduce cholesterol content and improve LDL:HDL ratio. When there is a high a-tomatine content, the fruit will have a bitter flavor, which together with other steroidal glycoalkaloids serving as protective and defensive compounds for tomato against insect, fungal, and bacterial pests. These compounds also affect the rhizosphere bacteria by recruiting beneficial bacteria. One of the steroidal glycoalkaloids, esculeoside A increases while fruit ripening. This review focuses on recent studies that uncovered key reactions of the production of cholesterol and steroidal glycoalkaloids in tomato connecting to human health, fruit flavor, and plant defense and the potential application for tomato crop improvement. 展开更多
关键词 Cholesterol Steroidal glycoalkaloids Tomato Biosynthesis a-tomatine Sterols Terpenoids Plant defense
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Chaeglobol A,an unusual octocyclic sterol with antifungal activity from the marine-derived fungus Chaetomium globosum HBU-45 认领 引用 被引量：3
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作者 Yun-Feng Liu Hui-Fang Du +4 位作者 Ya-Hui Zhang Zhi-Qin Liu Xiao-Qian Qi Du-Qiang Luo Fei Cao 《Chinese Chemical Letters》 SCIE CAS CSCD 2025年第3期407-410,共4页
Chemical investigation of the marine-derived fungus Chaetomium globosum HBU-45 led to the discovery of chaeglobol A(1).Its structure was determined by spectroscopic analysis,computational electronic circular dichroism... Chemical investigation of the marine-derived fungus Chaetomium globosum HBU-45 led to the discovery of chaeglobol A(1).Its structure was determined by spectroscopic analysis,computational electronic circular dichroism(ECD)/optical rotatory dispersion(ORD)methods,and X-ray crystallography.Compound 1 represents a new skeleton with an uncommon 6/6/6/5/6/5/6/5 octacyclic system,which is presumably biosynthesized via a[4+2]cycloaddition and an enzymatic cyclization.Chaeglobol A(1)exhibited inhibitory activity against B.dothidea by destroying cell membrane integrity and causing oxidative damage within the cells. 展开更多
关键词 Marine-derived fungus Chaetomium globosum Octocyclic sterol Antifungal activity Single-crystal X-ray diffraction
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Sea cucumber derived sulfated sterols alter glucose metabolism by promoting gluconeogenesis and reducing glycogenesis in healthy mice 认领 引用
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作者 Shanyun Yu Teng Wang +4 位作者 Yingcai Zhao Xiaoyue Li Changhu Xue Yuming Wang Tiantian Zhang 《Food Science and Human Wellness》 SCIE CAS CSCD 2025年第2期719-728,共10页
Sea cucumber derived sulfated sterols significantly ameliorated insulin resistance and decreased lipid accumulation compared to plant sterols.Interestingly,our recent study found that intervention with sea cucumber su... Sea cucumber derived sulfated sterols significantly ameliorated insulin resistance and decreased lipid accumulation compared to plant sterols.Interestingly,our recent study found that intervention with sea cucumber sulfated sterols could significantly increase blood glucose levels of healthy mice in the presence of glucose,while cholesterol sulfate,as one of sulfated sterols,did not have the same effect.However,the exact mechanism of sulfated sterols on glucose metabolism is still unknown.In the present study,we investigated the potential mechanism by which sulfated sterols influenced blood glucose homeostasis in healthy mice.Results showed that intervention with sea cucumber sulfated sterols did not affect the levels of hormones related to glucose metabolism,while led to a significant decrease in the synthesis of liver glycogen and muscle glycogen.Besides,the expression of proteins associated with the promotion of gluconeogenesis dramatically increased in the mice intervened with sea cucumber sulfated sterols.These findings suggested that sea cucumber sulfated sterols might change blood glucose metabolism in healthy mice by reducing glycogenesis and promoting gluconeogenesis. 展开更多
关键词 Sea cucumber Sulfated sterols Cholesterol sulfate Blood glucose Metabolism
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Cloning and expression of two sterol C-24 methyltransferase genes from upland cotton(Gossypium hirsuturm L.) 认领 引用 被引量：8
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作者 Ming Luo Kuning Tan +3 位作者 Zhongyi Xiao Mingyu Hu Peng Liao Kuijun Chen 《Journal of Genetics and Genomics》 SCIE CAS 北大核心 2008年第6期357-363,共7页
Brassinosteroids(BRs)are an important class of plant steroidal hormones that are essential in a wide variety of physiological processes.Two kinds of intermediates,sitosterol and campesterol,play a crucial role in cell... Brassinosteroids(BRs)are an important class of plant steroidal hormones that are essential in a wide variety of physiological processes.Two kinds of intermediates,sitosterol and campesterol,play a crucial role in cell elongation,cellulose biosynthesis,and accumulation.To illuminate the effects of sitosterol and campesterol on the development of cotton(Gossypiurn hirsuturm L.)fibers through screening cotton fiber EST database and contigging the candidate ESTs,two key genes GhSMT2-1 and GhSMT2-2 controlling the sitosterol biosynthesis were cloned from developing fibers of upland cotton cv.Xuzhou 142.The full length of GhSMT2-1 was 1,151 bp,including an 8 bp 5'-untranslated region(UTR),a 1,086 bp open reading frame(ORF),and a 57 bp 3'-UTR.GhSMT2-1 gene encoded a polypeptide of 361 amino acid residues with a predicted molecular mass of 40 kDa.The full length of GhSMT2-2 was 1,166 bp,including an 18 bp 5'-UTR,a 1,086 bp ORF,and a 62 bp 3'-UTR.GhSMT2-2 gene encoded a polypeptide of 361 amino acid residues with a predicted molecular mass of 40 kDa.The two deduced amino acid sequences had high homology with the SMT2 from Arabidopsis thaliana and Nicotiana tabacurn.Furthermore,the typical conserved structures characterized by the sterol C-24 methyltransferase,such as region I(LDVGCGVGGPMRAI),region II(IEATCHAP),and region III(YEWGWGQSFHF),were present in both deduced proteins.Southern blotting analysis indicated that GhSMT2-1 or GhSMT2-2 was a single copy in upland cotton genome.Quantitative real-time RT-PCR analysis revealed that the highest expression levels of both genes were detected in 10 DPA(day post anthesis)fibers,while the lowest levels were observed in cotyledon and leaves.The expression level of GhSMT2-1 was 10 times higher than that of GhSMT2-2 in all the organs and tissues detected.These results indicate that the homologue of sterol C-24 methyltransferase gene was cloned from upland cotton and both GhSMT2 genes play a crucial role in fiber elongation.The role of GhSMT2-1 may be more important than that of GhSMT2-2. 展开更多
关键词 cotton fiber sitosterol campesterol sterol C-24 methyltransferase GhSMT2-1 GhSMT2-2
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New insights into the regulation of cholesterol eft from the sperm membrane 认领 引用 被引量：6
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作者 Tamara Leahy Bart M Gadella 《Asian Journal of Andrology》 SCIE CAS CSCD 2015年第4期561-567,共7页
Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly co... Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon＇s preparation for fertilization. Some factors that regulate these events are described （e.g., bicarbonate, calcium） but the mechanisms underlying cholesterol export are poorly understood. How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings？ This review will provide an overview of knowledge in this area and highlight our gaps in understanding. The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors. Armed with such knowledlze, sl）erm handlin~ techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization. 展开更多
关键词 ATP binding cassette transporters albumin high-density lipoprotein lipid rafts membrane fluidity membranemicrodomains membrane packing oxysterols reverse cholesterol transport sterol transporters
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Maintaining cholesterol homeostasis: Sterol regulatory element-binding proteins 认领 引用 被引量：19
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作者 LutzW.Weber MeinradBoll AndreasStampfl 《World Journal of Gastroenterology》 SCIE CAS 2004年第21期3081-3087,共7页
The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane pr... The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane proteins aremembers of the basic helix-loop-helix-leucine zipper (bHLHZip) family of transcription factors. They activate the expression of at least 30 genes involved in the synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum (ER), where they form a complex with another protein, SREBP cleavage activating protein (SCAP). The SCAP molecule contains a sterol sensory domain. In the presence of high cellular sterol concentrations SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage steps to release the mature, biologically active transcription factor, nuclear SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response elements (SRE) in the promoter/enhancer regions of target genes. Additional transcription factors are required to activate transcription of these genes. Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are isoforms produced from a single gene by alternate splicing. SREBP-2 is encoded by a different gene and does not display any isoforms. It appears that SREBPs alone, in the sequence described above, can exert complete control over cholesterol synthesis, whereas many additional factors (hormones, cytokines, etc.) are required for complete control of lipid metabolism. Medicinal manipulation of the SREBP/SCAP system is expected to prove highly beneficial in the management of cholesterol-related disease. 展开更多
关键词 Animals CCAAT-Enhancer-Binding Proteins Cholesterol DNA-Binding Proteins Homeostasis Humans Sterol Regulatory Element Binding Protein 1 Sterol Regulatory Element Binding Protein 2 Transcription Factors
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UPLC/MS-MS-based pharmacokinetics of phytosterol magnetic targeted drug delivery system in rat and tissue distribution in mouse 认领 引用
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作者 Xiao-Yu Wang Wen-Jing Chen +7 位作者 Yi-Fan Mao Jun-Li Zhang Hai-Ting Zhu Hui-Nan Wang Ming-Rui Jiang Xin-Ning Zhang Peng Xu Ying-Zi Wang 《Integrative Medicine Discovery》 2025年第16期1-9,共9页
Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation... Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation into its in vivo pharmacokinetics and tissue distribution is warranted despite its demonstrated biocompatibility and safety.Methods:A UPLC-MS/MS method was established to determine the concentration of euphorbia sterol in rat plasma and mouse tissue homogenates,healthy male SD rats and KM mice were administered in groups,drug concentrations at different time points were determined,pharmacokinetic parameters were analyzed by DAS software,and data were processed by SAS software.Results:The proposed method met the requirements of biological sample detection.The plasma pharmacokinetics of rats showed that the drug concentration in the microsphere group was lower than that in the injection group,and the parameters such as mean residence time(MRT(0–t)),half-life(T1/2z)and apparent volume of distribution(Vz)were significantly different from those in the solution group.The distribution of mouse tissues showed that the drug concentrations in the liver and lung tissues of the microsphere preparation group were higher than those in the injection group,and the drug concentrations in the lung and liver tissues were more distributed.Conclusion:The targeted drug delivery system changed the pharmacokinetic behavior and tissue distribution of euphorbia sterol,slowed down plasma elimination,prolonged the half-life,and improved the targeting of drugs in lung and liver tissues and the magnetic targeting effect of lungs. 展开更多
关键词 euphorbia sterol magnetic targeted drug delivery system pharmacokinetics tissue distribution
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The role of cholesterol in modifying the lipid-lowering effects of Fuzhuan brick-tea in Caenorhabditis elegans via SBP-1/SREBP 认领 引用 被引量：8
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作者 Lianyun Pan Yan Lu +4 位作者 Shen Dai Xiangyue Tang Ligui Xiong Zhonghua Liu Yushun Gong 《Food Science and Human Wellness》 SCIE CAS CSCD 2023年第6期2297-2305,共9页
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
关键词 Fuzhuan brick tea Cholesterol Fat storage Sterol regulatory element-binding protein
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Effect of Daxx on cholesterol accumulation in hepatic cells 认领 引用 被引量：6
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作者 Qin-Hui Tuo Lei Liang +2 位作者 Bing-Yang Zhu Xuan Cao Duan-Fang Liao 《World Journal of Gastroenterology》 SCIE CAS 2008年第3期435-440,共6页
AIM： To study the effect of Daxx on cholesterol accumulation in hepatic cells. METHODS： Sprague Dawley （SD） rats were fed a normal or high fat diet for 6 wk, and serum lipids and Daxx expression of hepatic tissues... AIM： To study the effect of Daxx on cholesterol accumulation in hepatic cells. METHODS： Sprague Dawley （SD） rats were fed a normal or high fat diet for 6 wk, and serum lipids and Daxx expression of hepatic tissues were measured by immunoblot assays. HepG2 cells were transfected with the pEGFP-C1/Daxx or pEGFP-C1 plasmid. Cells stably transfected with Daxx were identified by RTPCR analysis. Total cholesterol levels were determined by high performance liquid chromatography. Activated- SREBP and caveolin-1 were assayed by western blotting. RESULTS： Hepatic Daxx protein was higher in normal rats than in high fat diet-fed rats. Noticeable negative correlations were seen between Daxx and LDL-C （γ=-7.56, ρ=0.018）, and between Daxx and TC （γ=-9.07, ρ= 0.01）, respectively. The total cholesterol of HepG2/GFP-Daxx cells was lower than that of control cells or HepG2/GFP cells （9.28±0.19 vs 14.36± 4.45 or 13.94±2.62, both P 〈 0.05）. Furthermore, in HepG2/GFP cells, the expression of activated SREBP was lower than that of control cells, whereas caveolin-1 expression was higher. CONCLUSION： Overexpression of Daxx in HepG2 cells decreased intracellular cholesterol accumulation, which might be associated with inhibition of SREBP activity and an increase in caveolin-1 expression. 展开更多
关键词 Daxx Cholesterol Hepatic cells Sterol regulatory element-binding protein Caveolin-1
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Extracts of Zanthoxylum bungeanum regulate cholesterol accumulation induced by sterols and LPS in vitro and in vivo 认领 引用 被引量：4
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作者 吴婷婷 侯爱君 +1 位作者 洪臻怡 朱依谆 《Journal of Chinese Pharmaceutical Sciences》 CAS 2012年第6期582-590,共9页
In this investigation,the effects of PE,EtOAc,and BuOH fractions from Zanthoxylum bungeanum on cholesterol accumulation induced by sterols and LPS were determined in vitro and in vivo.HepG2 cells induced by 25-hydroxy... In this investigation,the effects of PE,EtOAc,and BuOH fractions from Zanthoxylum bungeanum on cholesterol accumulation induced by sterols and LPS were determined in vitro and in vivo.HepG2 cells induced by 25-hydroxychoelsterol and cholesterol were employed as cell model.After treatment with PE,EtOAC,or BuOH fractions,cellular total cholesterol and apolipoprotein B secretion were significantly reduced.In addition,compared with control group,expressions of SREBP2,HMGCR,and ACAT decreased,while CYP27A1,ABCA1,and LDLR levels increased.Cholesterol accumulation was also induced in C57BL/6 mice by LPS and the mice were used as the animal model.Determination of serum TNF-α level and hepatic mRNA expression of TNF-α,IL-6,iNOS,COX-2 revealed that EtOAc and BuOH fractions had anti-inflammatory effects.Furthermore,hepatic total cholesterol was reduced,accompanied by the elevation of LXR-α and ABCA1 gene expression in BuOH fraction treated mice.Since EtOAc and BuOH fractions were found active,bioassay-guided isolation was performed and β-sitosterol,eudesmin,sesamin and syringaresinol-β-D-glucoside were isolated from the fractions. 展开更多
关键词 Zanthoxylum bungeanum Cholesterol metabolism Sterols LPS HepG2 C57BL/6
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Dietary Calcium Decreases Plasma Cholesterol Level only in Female but not in Male Hamster Fed a High Cholesterol Diet 认领 引用 被引量：1
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作者 MA Ka Ying LIANG Yin Tong +7 位作者 CHEN Jing Nan JIANG Yue KWAN Kin Ming PENG Cheng JIAO Rui ZUO Yuan Yuan HUANG Yu CHEN Zhen Yu 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2012年第4期392-398,共7页
Objective To investigate the effect of dietary calcium on plasma lipoprotein profile in castrated and ovariectomized hamsters. Methods Male, castrated, female and ovariectomized hamsters （n=36 each group） were rando... Objective To investigate the effect of dietary calcium on plasma lipoprotein profile in castrated and ovariectomized hamsters. Methods Male, castrated, female and ovariectomized hamsters （n=36 each group） were randomly divided into three sub-groups （n=12） and fed one of the three diets containing O, 2, and B g calcium per kg diet for a period of six weeks. Changes in plasma lipoprotein profile were monitored at the end of week O, 3 and 6. Results Plasma total cholesterol （TC）, non-high density lipoprotein cholesterol （non-HDL-C）, triacylglycerols （TG） and TC/HDL-C were decreased only in intact female and ovariectomized hamsters. In contrast, three levels of dietary calcium had no effect on lipoprotein profiles in both intact male and castrated hamsters. Conclusion Beneficial modification of lipoprotein profile by dietary calcium was gender-dependent at least in hamsters. 展开更多
关键词 Calcium Cholesterol Triacylglycerols Fecal sterols
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Mitochondrial function and regulation of macrophage sterol metabolism and inflammatory responses 认领 引用 被引量：9
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作者 Annette Graham Anne-Marie Allen 《World Journal of Cardiology》 2015年第5期277-286,共10页
The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activator... The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis.Macrophage generation of oxysterol activators of liver X receptors(LXRs),via sterol 27-hydroxylase,is regulated by the rate of flux of cholesterolto the inner mitochondrial membrane,via a complex of cholesterol trafficking proteins.Oxysterols are key signalling molecules,regulating the transcriptional activity of LXRs which coordinate macrophage sterol metabolism and cytokine production,key features influencing the impact of these cells within atherosclerotic lesions.The precise identity of the complex of proteins mediating mitochondrial cholesterol trafficking in macrophages remains a matter of debate,but may include steroidogenic acute regulatory protein and translocator protein.There is clear evidence that targeting either of these proteins enhances removal of cholesterol via LXRα-dependent induction of ATP binding cassette transporters(ABCA1,ABCG1)and limits the production of inflammatory cytokines;interventions which influence mitochondrial structure and bioenergetics also impact on removal of cholesterol from macrophages.Thus,molecules which can sustain or improve mitochondrial structure,the function of the electron transport chain,or increase the activity of components of the protein complex involved in cholesterol transfer,may therefore have utility in limiting or regressing atheroma development,reducing the incidence of coronary heart disease and myocardial infarction. 展开更多
关键词 Atherosclerosis Macrophage Cholesterol High density lipoproteins Apolipoproteins ATP binding cassette transporters Scavenger receptor B1 Mitochondria(dys)function Sterol 27-hydroxylase Liver X receptors
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Development of a novel electrospun nanofibrous delivery system for poorly water-soluble β-sitosterol 认领 引用 被引量：1
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作者 Urve Paaver Ivo Laidmae +4 位作者 Hélder A.Santos Jouko Yliruusi Jaan Aruvali Karin Kogermann Jyrki Heinamaki 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2016年第4期500-506,共7页
Electrospinning was used as a novel technique for fabricating polymeric nanofibers of a serum cholesterol lowering and poorly water-soluble plant sterol, β-sitosterol. Chitosan was used as a stabilizer/carrier polyme... Electrospinning was used as a novel technique for fabricating polymeric nanofibers of a serum cholesterol lowering and poorly water-soluble plant sterol, β-sitosterol. Chitosan was used as a stabilizer/carrier polymer. The mean diameters of nanofibers ranged from 150 nm to218 nm. β-sitosterol was in an amorphous form and homogeneously dispersed in the nanofibers. The β-sitosterol-loaded nanofibers were freely water-soluble and exhibited very short lag-time in releasing the plant sterol. The dissolution was associated with an immediate recrystallization of β-sitosterol in submicron level. In conclusion, electrospinning is a promising future technology for the formulation of poorly water-soluble plant sterols. 展开更多
关键词 Electrospinning Plant sterol β-sitosterol Nanofibers Solid-state properties Dissolution
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Combined Effects of Plant Sterols with Low Ratio of n-6/n-3 Polyunsaturated Fatty Acids against Atherosclerosis in ApoE–/–Mice 认领 引用
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作者 Chen CHEN Li LU +3 位作者 Ya-ting QIN Chao LV Xiao-ning WAN Xiao-mei GUO 《Current Medical Science》 SCIE CAS 2020年第6期1099-1106,共8页
The effects of low ratio of n-6-3 polyunsaturated fatty acids(PUFA)have been clarified against atherosclerosis.Increasing evidence indicated that plant sterols(PS)have a significant cholesterol-lowering effect.This st... The effects of low ratio of n-6-3 polyunsaturated fatty acids(PUFA)have been clarified against atherosclerosis.Increasing evidence indicated that plant sterols(PS)have a significant cholesterol-lowering effect.This study explored the effects of PS combined with n-6-3(2:1)PUFA on atherosclerosis and investigated the possible mechanism.In ApoE−/−mice,the milk fat in high fat diets was replaced with n-6-3(2:1)PUFA alone or supplemented with 6%PS for 16 weeks.Results demonstrated that PS combined with PUFA exerted commentary and synergistic effects on ameliorating atherosclerosis,improving lipid metabolism and lipid deposition in liver,and alleviating inflammatory response.These changes were accompanied with decreased serum TC,TG,LDL-C and increased fecal cholesterol efflux,as well as the lower inflammatory cytokine CRP,IL-6,TNF-α.It is suggested that the underlying mechanism of PS combined with n-6-3(2:1)PUFA promoting the fecal cholesterol efflux may be mediated by liver X receptorα/ATP-binding cassette transporter A1 pathway. 展开更多
关键词 plant sterols polyunsaturated fatty acids atherosclerosis lipid metabolism fecal cholesterol inflammatory response
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Cholesterol metabolism in cholestatic liver disease and liver transplantation:From molecular mechanisms to clinical implications 认领 引用 被引量：13
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作者 Katriina Nemes Fredrik Aberg +1 位作者 Helena Gylling Helena Isoniemi 《World Journal of Hepatology》 2016年第22期924-932,共9页
The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that aff... The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. 展开更多
关键词 Cholesterol metabolism Cholestasis Liver transplantation Non-cholesterol sterols Cholestanol Donor Low density lipoprotein receptor mutation Apolipoprotein B-100 Lipoprotein-X
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An Abietane Diterpene and a Sterol from Fungus Phellinus igniarius 认领 引用 被引量：13
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作者 Ying WANG Su Juan WANG +3 位作者 Shun Yan MO Shuai LI Yong Chun YANG Jian Gong SHI 《Chinese Chemical Letters》 SCIE CAS 2006年第4期481-484,共4页
A new abietane diterpene 12-hydroxy-7-oxo-5, 8, 11, 13-tetraene-18, 6-abietanolide, together with a new natural sterol stigmasta-7, 22-diene-3β, 5α 6α-triol have been isolated from the fruiting body of the fungus P... A new abietane diterpene 12-hydroxy-7-oxo-5, 8, 11, 13-tetraene-18, 6-abietanolide, together with a new natural sterol stigmasta-7, 22-diene-3β, 5α 6α-triol have been isolated from the fruiting body of the fungus Phellinus igniarius. Their structures were elucidated by spectroscopic methods including 2D NMR techniques. 展开更多
关键词 Phellinus igniarius Polyporaceae fungus diterpene sterol.
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Occurrence of Different Forms and Implications of Compound Specific Sterols in Continental Sediments of the Northeast South China Sea 认领 引用 被引量：6
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作者 QIU Hong ZOU Li +2 位作者 ZHANG Minsheng ZHU Chaoqi JIA Yonggang 《Acta Geologica Sinica(English Edition)》 SCIE CAS CSCD 2019年第2期420-429,共10页
The South China Sea(SCS) is one of the most productive and accumulative marginal shelves of organic carbon in the world. To expound the transformation and preservation of organic carbon in the Northeast SCS, where abu... The South China Sea(SCS) is one of the most productive and accumulative marginal shelves of organic carbon in the world. To expound the transformation and preservation of organic carbon in the Northeast SCS, where abundant oil and gas resources have been reported, compound specific sterols in free(FR), base hydrolytic(BH), and acid hydrolytic(AH) forms were analyzed in surface and columnar sediments in May, 2016. The results showed that the total contents of sterols detected ranged from 0.15 to 3.74 ppm dry weight in the surface sediments, and gradually decreased from 3.41 to0.17 ppm dry weight from surface to deep sediments, in which cholesterol(27△5) was the most abundant component. Sterols mainly existed in the BH form(54.51%-74.20%), followed by the FR form(25.50%-45.49%) and then the AH form(0-3.77%) in turn, in the surface sediments. BH and FR sterols accounted for 0-49.08% and 50.92%-100% in the columnar sediments, while AH sterols were undetectable. The contents of specific sterols indicated that, the primary source of marine organic carbon was about 5 times as much as that from terrestrial input. More and more FR sterols transformed into BH sterols with increasing sedimentary depth, and BH sterols absolutely dominated in sediment depths under 25 cm. The forms of Sterols C27 were maintained at a relative consistence state, but Sterols C28 to C30 degraded gradually during the sedimentation process. It was suggested that the stability of sterols, based on the chemical structures, might be the primary factor controlling their degradation and preservation in deeper sediments. These results would help to understand the organic carbon(OC) transformation in a hydrate formation area in a marginal sea. 展开更多
关键词 sterols sediments occurrence forms transformation northeast South China Sea
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Metabolic engineering strategies for de novo biosynthesis of sterols and steroids in yeast 认领 引用 被引量：11
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作者 Yuehao Gu Xue Jiao +1 位作者 Lidan Ye Hongwei Yu 《Bioresources and Bioprocessing》 SCIE EI 2021年第1期380-393,共14页
Steroidal compounds are of great interest in the pharmaceutical field,with steroidal drugs as the second largest category of medicine in the world.Advances in synthetic biology and metabolic engineering have enabled d... Steroidal compounds are of great interest in the pharmaceutical field,with steroidal drugs as the second largest category of medicine in the world.Advances in synthetic biology and metabolic engineering have enabled de novo biosynthesis of sterols and steroids in yeast,which is a green and safe production route for these valuable steroidal compounds.In this review,we summarize the metabolic engineering strategies developed and employed for improving the de novo biosynthesis of sterols and steroids in yeast based on the regulation mechanisms,and introduce the recent progresses in de novo synthesis of some typical sterols and steroids in yeast.The remaining challenges and future perspectives are also discussed. 展开更多
关键词 Sterols and steroids De novo biosynthesis Yeast Metabolic engineering
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