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
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
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
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
BACKGROUND Sterol O-acyltransferase 1(SOAT1)is an important target in the diagnosis and treatment of liver cancer.However,the prognostic value of SOAT1 in patients with hepatocellular carcinoma(HCC)is still not clear....BACKGROUND Sterol O-acyltransferase 1(SOAT1)is an important target in the diagnosis and treatment of liver cancer.However,the prognostic value of SOAT1 in patients with hepatocellular carcinoma(HCC)is still not clear.AIM To investigate the correlation of SOAT1 expression with HCC,using RNA-seq and gene expression data of The Cancer Genome Atlas(TCGA)-liver hepatocellular carcinoma(LIHC)and pan-cancer.METHODS The correlation between SOAT1 expression and HCC was analyzed.Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC.Overall survival and disease-specific survival were explored based on TCGA-LIHC data.Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology(GO)analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of differentially expressed genes.In addition,the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy.RESULTS SOAT1 and SOAT2 were highly expressed in unpaired samples,while only SOAT1 was highly expressed in paired samples.The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748,while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676.Patients with higher SOAT1 expression had lower survival rates.Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway,the IL-18 signaling pathway,the calcium signaling pathway,secreted factors,the Wnt signaling pathway,the Jak/STAT signaling pathway,the MAPK family signaling pathway,and cell–cell communication were involved in such association.SOAT1 expression was positively associated with the abundance of macrophages,Th2 cells,T helper cells,CD56bright natural killer cells,and Th1 cells,and negatively linked to the abundance of Th17 cells,dendritic cells,and cytotoxic cells.CONCLUSION Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment,which is helpful for the development of new strategies for immunotherapy and metabolic therapy.展开更多
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
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 ...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
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
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
Aim To study the chemical constituents of starfish Asterias amurensis. Methods The constituents were separated and purified by different chromatographic methods, and their structures were elucidated by MS and NMR. Res...Aim To study the chemical constituents of starfish Asterias amurensis. Methods The constituents were separated and purified by different chromatographic methods, and their structures were elucidated by MS and NMR. Results Six compounds were isolated from Asterias amurensis Lutken. Their structures were identified as 3β-O-sulfated-cholest-5-en sodium salt （1）, 3β-O-sulfated-6α-ol- pregn-9（ 11 ） -en-20-one sodium salt （ 2 ）, 3β-O-sulfated-6α-ol-cholest-9 （ 11 ） -en-23-one sodium salt （3）, 3β-O-sulfated-6α, 20β-diol-cholest-9 （ 11 ）-en-23-one sodium salt （ 4 ）, 3β-O-sulfated-6α-ol- cholesta-9 （ 11 ）, 20 （ 22 ） -dien-23-one sodium salt （ 5 ）, and 3β-O-sulfated-6ct-ol-ergost-9 （ 11 ） -en-23- one sodium salt （6）. Conclusion Compounds 1 - 6 were obtained from this species for the first time.展开更多
Syntheses of 3 ketolanosterol, 3 acetolanosterol, 3 oximolanosterol, 3α and 3β aminolanosterol were described The products have been fully characterized on the basis of their chromatographic (TLC R f, GLC R...Syntheses of 3 ketolanosterol, 3 acetolanosterol, 3 oximolanosterol, 3α and 3β aminolanosterol were described The products have been fully characterized on the basis of their chromatographic (TLC R f, GLC RRTc) and spectral (IR, MS, 1 H NMR, 13 C NMR) properties展开更多
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
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
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
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
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
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
The effects of low ratio of n-6/n-3 polyunsaturated fatty acids(PUFA)have been clarified against atherosclerosis.Increasing evidence indicated that plant sterols(PS)have a significant cholesterol-lowering effect.This ...The effects of low ratio of n-6/n-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/n-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/n-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/n-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
文摘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.
基金supported by National Natural Science Foundation of China(32072145)。
文摘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.
基金funded by the S&T Program of Hebei(No.21323202D)the Natural Science Interdisciplinary Research Program of Hebei University(No.DXK201913)+4 种基金the Natural Sci-ence Foundation of Hebei Province of China(Nos.H2024201028,H2020201029)the Excellent Youth Research Innovation Team of Hebei University(No.QNTD202406)the Hebei University Research and Innovation Team(No.IT2023C1)the Innovation Capacity Improvement Plan of Hebei Province(No.20567605H)the National Training Program of Innovation and Entrepreneurship for Undergraduates(No.DC2024177)。
文摘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.
基金sponsored by the Fundamental Research Funds forthe Central Universities(No.2024-JYB-JBZD-047)High Level Key Discipline Construction of Traditional Chinese Medicine(zyyzdxk-2023272).
文摘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.
基金Supported by the Tianjin Municipal Project of Science and Technology,No.21ZXGWSY00040and the Tianjin Health Research Project,No.TJWJ2022QN043.
文摘BACKGROUND Sterol O-acyltransferase 1(SOAT1)is an important target in the diagnosis and treatment of liver cancer.However,the prognostic value of SOAT1 in patients with hepatocellular carcinoma(HCC)is still not clear.AIM To investigate the correlation of SOAT1 expression with HCC,using RNA-seq and gene expression data of The Cancer Genome Atlas(TCGA)-liver hepatocellular carcinoma(LIHC)and pan-cancer.METHODS The correlation between SOAT1 expression and HCC was analyzed.Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC.Overall survival and disease-specific survival were explored based on TCGA-LIHC data.Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology(GO)analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of differentially expressed genes.In addition,the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy.RESULTS SOAT1 and SOAT2 were highly expressed in unpaired samples,while only SOAT1 was highly expressed in paired samples.The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748,while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676.Patients with higher SOAT1 expression had lower survival rates.Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway,the IL-18 signaling pathway,the calcium signaling pathway,secreted factors,the Wnt signaling pathway,the Jak/STAT signaling pathway,the MAPK family signaling pathway,and cell–cell communication were involved in such association.SOAT1 expression was positively associated with the abundance of macrophages,Th2 cells,T helper cells,CD56bright natural killer cells,and Th1 cells,and negatively linked to the abundance of Th17 cells,dendritic cells,and cytotoxic cells.CONCLUSION Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment,which is helpful for the development of new strategies for immunotherapy and metabolic therapy.
文摘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.
基金supported by the National Natural Science Foundation of China(No.30370904 and 30671258)the National High Technology Research and Development Program(863 Project)of China(No.2006AA10Z121)the Program for New Century Excellent Talents in University(No.NCET-07-0712).
文摘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.
文摘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.
基金National Science and Technology Major Project(Grant No. 2012ZX09501001-003)
文摘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.
文摘Aim To study the chemical constituents of starfish Asterias amurensis. Methods The constituents were separated and purified by different chromatographic methods, and their structures were elucidated by MS and NMR. Results Six compounds were isolated from Asterias amurensis Lutken. Their structures were identified as 3β-O-sulfated-cholest-5-en sodium salt （1）, 3β-O-sulfated-6α-ol- pregn-9（ 11 ） -en-20-one sodium salt （ 2 ）, 3β-O-sulfated-6α-ol-cholest-9 （ 11 ） -en-23-one sodium salt （3）, 3β-O-sulfated-6α, 20β-diol-cholest-9 （ 11 ）-en-23-one sodium salt （ 4 ）, 3β-O-sulfated-6α-ol- cholesta-9 （ 11 ）, 20 （ 22 ） -dien-23-one sodium salt （ 5 ）, and 3β-O-sulfated-6ct-ol-ergost-9 （ 11 ） -en-23- one sodium salt （6）. Conclusion Compounds 1 - 6 were obtained from this species for the first time.
文摘Syntheses of 3 ketolanosterol, 3 acetolanosterol, 3 oximolanosterol, 3α and 3β aminolanosterol were described The products have been fully characterized on the basis of their chromatographic (TLC R f, GLC RRTc) and spectral (IR, MS, 1 H NMR, 13 C NMR) properties
文摘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.
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The National Natural Science Foundation of China, No. 30470719 and 30600249The National Major Basic Research Program of China (973), No. 2006CB503808The Sanitarian Research Foundation of Hunan province, No. B2004-078
文摘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.
基金supported by a grant from Hong Kong Research Grant Council(CUHK4622/08M)
文摘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.
文摘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.
基金This study is supported by the European Social Fund’s Doctoral Studies and Internationalisation Programme DoRa.The work is part of the ETF Grant Project No.ETF7980 and IUT-34-18 Project.Kerly Kustavus is kindly acknowledged for drawing the chemical structures of plant sterols.Dr.Korbinian Löbmann is kindly acknowledged for providing the Mercury files for the theoretical XRPD pattern calculations.Dr.H.A.Santos acknowledges financial support from the Academy of Finland(Decision No.252215).
文摘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.
基金This study was supported by the National Natural Science Foundation of China(No.81873518).
文摘The effects of low ratio of n-6/n-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/n-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/n-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/n-3(2:1)PUFA promoting the fecal cholesterol efflux may be mediated by liver X receptorα/ATP-binding cassette transporter A1 pathway.
