Comprehensive prognostic and immune analysis of sterol Oacyltransferase 1 in patients with hepatocellular carcinoma

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.

The role of cholesterol in modifying the lipid-lowering effects of Fuzhuan brick-tea in Caenorhabditis elegans via SBP-1/SREBP

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.

Kuroshio Intrusion Combined with Coastal Currents Affects Phytoplankton in the Northern South China Sea Revealed by Lipid Biomarkers

The northern South China Sea(NSCS)is significantly influenced by the Kuroshio intrusion and the coastal currents.Our knowledge on the roles of both currents on phytoplankton spatial variations is still inadequate.Here,we investigated the concentrations of phytoplankton biomarkers and their proportions in surface suspended particles from 47 sites of the NSCS during summer of 2017 and 2019.Brassicasterol/epi-brassicasterol,dinosterol,and C37 alkenones were used as proxies of biomass for diatoms,dinoflagellates,and haptophytes,respectively,and their sum indicating total phytoplankton biomass.A three end-member mixing model was applied to quantitatively assess the influence extent of the Kuroshio intrusion and the coastal currents.Our results showed that the Kuroshio intrusion and the coastal currents contributed equally to the overall surface water masses in the study area;however,the two currents had distinct effects on the spatial distribution of phytoplankton.For phytoplankton biomass,the eutrophic coastal currents were likely to be the main controlling factors,while the impact of the Kuroshio intrusion was weak and stimulated significant increases in phytoplankton biomass only at certain boundary sites.For phytoplankton community structures,the Kuroshio and its intrusion were the main factors,resulting in an increase in the proportions of dinoflagellates and haptophytes.The proportion of diatoms slightly increased due to the influence of the coastal currents.Our study quantifies the effects of the Kuroshio and the coastal currents on phytoplankton in the NSCS in terms of hydrological parameters,providing an important basis for the understanding of ecological functions and biogeochemical cycles in marginal sea-open ocean boundary regions.

PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A

Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lipid,glucose,and energy metabolism.PPARαreportedly functions as a tumor suppressor through its effects on lipid metabolism;however,the involvement of PPARαin the development of EMC remains unclear.The present study demonstrated that the immunohistochemical expression of nuclear PPARαwas lower in EMC than in normal endometrial tissues,suggesting the tumor suppressive nature of PPARα.A treatment with the PPARαactivator,irbesartan,inhibited the EMC cell lines,Ishikawa and HEC1A,by down-regulating sterol regulatory element-binding protein 1(SREBP1)and fatty acid synthase(FAS)and up-regulating the tumor suppressor genes p21 and p27,antioxidant enzymes,and AT-rich interaction domain 1A(ARID1A).These results indicate the potential of the activation of PPARαas a novel therapeutic approach against EMC.

Anti-Biofilm, Anti-Quorum Sensing, and Anti-Proliferative Activities of Methanolic and Aqueous Roots Extracts of Carica papaya L. and Cocos nucifera L.

Objective: This study focused on the antibacterial and anti-proliferative activity of extracts from Carica papaya and Cocos nucifera roots. Methodology: The minimum inhibitory concentration and the minimum bactericidal concentration of the extracts on Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans, and Staphylococcus aureus were deduced by the microdilution method. The anti-biofilm activity was determined on all four strains and anti-quorum sensing activity by inhibition of violacein production in Chromobacterium violaceum. Anti-proliferative activity on prostate cultured cancer cells was evaluated by MTT assay. Sterols and triterpenes were also assayed in this study. Results: The methanolic extract of Carica papaya showed the best anti-biofilm effect with a percentage inhibition of 66.10 ± 1.79. The methanolic extract of Cocos nucifera had the strongest inhibition on the production of quorum sensing (61.42 ± 0.28). In addition, the methanolic extract of Cocos nucifera roots showed the best cytotoxic effect on prostate cancer LNCaP cell lines (IC50 = 26.98 ± 2.6 μg/mL) and Carica papaya on the PC-3 lines (IC50 = 127.20 ± 5.99 μg/mL). The extracts were also rich in triterpenes and sterols. Conclusion: This study provides support for the ethnomedical use of Carica papaya and Cocos nucifera roots as an antimicrobial and anticancer.

甾醇TMS衍生物EI源质谱规律研究

The mass spectrometric fragmentation of TMS derivatives of sterols was studied and analyzed based on the mass spectrometry of the TMS derivatives of standards.The double bond numbers and the degree of the methylize,alkylize and the related position in the sterol nucleus and the side chains were confirmed by the characteristic ions.Total lipids were extracted using Bligh-Dyer method.Sterols were isolated by solvent partition with chloroform-hexane(1 ∶4,by volume),derivated by BSTFA,and analyzed by GC-MS.The regular pattern was used for identifying the sterols in a dinoflagellate from the Symbodinium sp.

Sulfated Sterols Isolated from Starfish Asterias amurensis Lutken

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.

Steroids from the Fungus Pleurotus ostreatus

Twelve steroids, including eight ergostane-type sterols and four mono-glucosides of ergostane-type sterols, were isolated from the ethyl acetate soluble fraction of the fungus Pleurotus ostreatus ( Jacq. : Fr.) Kummer. A new compound 3-O-beta-D-glucopyranosyl-22E, 24R-ergosta-7, 22-diene-5alpha, 6beta, 9alpha-triol, was structurally elucidated by spectroscopic and chemical methods. The eleven known compounds were 22E, 24R-ergosta-7, 22-diene-3beta, 5alpha, 6beta, 9alpha-tetraol; 3-O-beta-D-glucopyranosyl-22E, 24R-ergosta-7, 22-diene-5alpha, 6beta-diol; 22E, 24R-ergosta-7, 22-diene-3beta, 5alpha, 6beta-triol; 22E, 24R-ergosta-5, 7, 22-trien-3beta-ol 3-O-beta-D-glucopyranoside; ergosterol; 22E, 24R-ergosta-7, 22-dien-3beta-ol 3-O-beta-D-glucopyranoside; 22E, 24R-ergosta-7, 22-diene-3beta-ol; 22E, 24R-ergosta-4, 6, 8, 22-tetraen-3-one; 22E, 24R-ergosta-7, 22-diene-3beta, 5alpha, 6alpha-triol; ergosterol peroxide; 22E, 24R-ergosta-7, 22-diene-3beta, 5alpha-diol-6-one.

固醇调节元件结合蛋白在肿瘤代谢与肿瘤进展中的作用

肿瘤细胞中的脂质代谢改变是肿瘤细胞重要特征。肿瘤细胞中脂肪酸从头合成途径的增加为肿瘤细胞的增殖提供了生物膜合成所需要的基质、信号脂质等,进而促进肿瘤的侵袭和转移。固醇调节元件结合蛋白（sterol regulatory element-binding proteins,SREBPs）是一种核转录因子,能直接激活参与脂肪酸、三酰甘油、胆固醇合成及磷酸脂合成与摄取等30多个基因的表达。

Synthesis of 3 Nitrogen containing Function Substituted Lanosterol Derivatives Inhibitors of (S) Adenosyl L Me thionine:Δ 24(25) Sterol Methyltransferase

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

Maintaining cholesterol homeostasis: Sterol regulatory element-binding proteins

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.

An Abietane Diterpene and a Sterol from Fungus Phellinus igniarius

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.

Tracing the settlement region of massive floating green algae in the Yellow Sea

Outbreaks of large-scale green tides formed by Ulva prolifera in the Yellow Sea (YS) cause heavy ecological damages and huge economic losses. However, the ecological consequences of green tides remain poorly understood due to the lack of knowledge on the settlement region of massive green algae floating in the YS. In this study, we established a method to trace the settlement region of floating green algae, using 28-isofucosterol preserved in sediment as the specific biomarker for green algae. Sterols including 28-isofucosterol in surface sediment samples collected during an investigation in the YS and the Bohai Sea (BS) in August 2015 were analyzed using gas chromatography coupled with a mass spectrometer (GC-MS). Based on the content of 28-isofucosterol in sediment samples, the potential settlement region of fl oating green algae was identifi ed in the sea area southeast to the Shandong Peninsula around the sampling site H06 (122.66°E, 36.00°N). This paper presents a first result on the settlement region of floating green algae in the YS for providing a solid basis to elucidate the ecological consequences of green tides in the area.

MicroRNA-185-5p mediates regulation of SREBP2 expression by hepatitis C virus core protein

AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGCR) was measured by quantitative real-time PCR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi RNA.RESULTS: HCV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGCR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HCV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HCV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HCV core protein. CONCLUSION: HCV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein.

Occurrence of Different Forms and Implications of Compound Specific Sterols in Continental Sediments of the Northeast South China Sea

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.

Chemical Constituents from Bletilla ochracea Schltr.

To study the chemical constituents in Bletilla ochracea Schltr. , repeated column chromatographies and preparative TLC were used for the isolation of compounds, and spectroscopic techniques （NMR, IR, UV and MS） were used for their structural identification. Seven compounds, 2,7-bis （ allyloxy ） -5-methoxy-3-methyl-9, 10-dihydrophenanthrene（1）, gastrodin（2）, gastrodigenin（3）, β-sitosterol（4）, stigmasterol（5）, 4-hydroxybernzaldehyde（6）, and daucosterol（7） were obtained from the roots of B. ochracea Schltr. Compound 1 is structurally illustrated as a novel compound, and the others are isolated from the title plant for the first time.

Cloning and expression of two sterol C-24 methyltransferase genes from upland cotton(Gossypium hirsuturm L.)

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.

Mitochondrial function and regulation of macrophage sterol metabolism and inflammatory responses

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.