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[en] Highlights: • Cholesterol treatment promoted the expression of KLF5 and miR-27a. • KLF5 positively regulated the transcription of miR-27a. • FBXW7 was identified as a direct target of miR-27a. • Inhibition of FBXW7 accelerated 786-O cells migration and invasion. Clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype of renal cell carcinoma. Accumulation of cholesterol and cholesterol ester is a remarkable feature of ccRCC. However, the effect of cholesterol on ccRCC remains unknown. Out results showed that cholesterol treatment significantly promoted cells migration and invasion in ccRCC. Mechanism analysis indicated that cholesterol induced KLF5 expression. KLF5 positively regulated the transcription of miR-27a, increasing miR-27a expression. MiR-27a directly targeted FBXW7 by binding to its 3′UTR, reducing FBXW7 expression. FBXW7 silencing further increased the expression of KLF5 and miR-27a, and promoted cells migration and invasion. These results suggested that cholesterol accelerated ccRCC cells migration and invasion by regulating KLF5/miR-27a/FBXW7 axis.
[en] The photoionization of alkylphenothiazines in cationic dioctadecyldimethylammonium chloride (DODAC), neutral dipalmitoylphosphatidylcholine (DPPC), and anionic dihexadecylphosphate (DHP) vesicles of different surface charge, after addition of cholesterol, was studied by electron spin resonance (ESR) and electron spin echo modulation (ESEM) methods. Neutral alkylphenothiazines (PCn, where n - 1,3,6,9,12, and 16) were synthesized and used to study the effects of alkyl chain length. It was found that the photoionization efficiency decreases as a function of alkyl chain length of the alkylphenothiazine until PC16 at which point the photoionization efficiency increases for all three vesicle/alkylphenothiazine systems studied. The magnitude of the photoyields as measured by ESR decreases in the order DODAC > DPPC > DHP. The addition of cholesterol to these three vesicle/alkylphenothiazine systems reduces the photoyields in all cases. The ESEM data on the relative distances from the vesicle interface were consistent with these finding. The results are discussed in terms of the alkyl chain length of the alkylphenothiazine, the vesicle surface charge, and the ordering effect of cholesterol. 32 refs., 13 figs
[en] The technique for the preparation of (131I)-19-Iodocholesterol is described. The identification of the synthesized compound was made by spectroscopic, chemical and radiochemical techniques. Biological distribution studies in mice demonstrate that the compound can be used for the diagnosis of tumours and hyperplasia of suprarenal glands
[en] Highlights: • Stard3 regulated adipogenesis in 3T3-L1 cells. • Suppression of Stard3 downregulated the expression of adipogenic gene. • Mtiochondrial ROS was downregulated in Stard3-knockdown 3T3-L1 cells. Start domain-containing protein 3 (Stard3) plays roles in intracellular cholesterol distribution, however, the role of Stard3 in the adipogenesis of 3T3-L1 preadipocytes remains unclear. We demonstrated that Stard3 expression was significantly increased during the adipogenesis of 3T3-L1 preadipocytes, accompanied by an increase of mitochondrial Reactive oxygen species (ROS). Stard3 knocking-down inhibited 3T3-L1 preadipocyte adipogenesis with decreased mitochondrial ROS levels, while ROS inducer rescued the stard3 silencing 3T3 cells with increased ROS. Moreover, Stard3 silencing reduced the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein (C/EBP)α in 3T3- L1 cells. In conclusion, Stard3 enhanced the adipogenesis of preadipocytes by enhancement of cholesterol redistribution to the mitochondrial, increasing mitochondrial ROS production. These results suggest that Stard3 is an essential factor for the 3T3-L1 cells' differentiation.
[en] Dietary cholesterol should be limited to less than 200 mg/ day. A single large egg yolk contains approximately 275 mg of cholesterol. Thus, consumption of a single egg yolk exceeds the recommended daily intake of cholesterol. This study was focused on determination of the effect of addition of increasing amount of β-cyclodextrin (β-CD) to encapsulate cholesterol in egg yolk. The quality of cholesterol-reduced egg yolk powder was evaluated by determining its nutritional composition and colour analysis. Increasing amount of β-CD (0-15 mM) was added in liquid egg yolk and the encapsulated cholesterol in the form of precipitate was removed. The supernatant was dried and the end product; cholesterol-reduced egg yolk powder (CREYP) was analyzed for moisture content, total lipid, fatty acids content, protein and colour. There were no significant difference (p>0.05) in term of total solid content. However, protein content of CREYP was significantly (p<0.05) reduced up to 7 mM β-CD and no further significant reduction was noticed with further addition of β-cyclodextrin. The appearance of the powder became lighter in colour as validated using chromameter; L*, a*, b*, C* and ho values. The results obtained from this study indicate that cholesterol can be successfully removed from egg yolk. However, slight reduction in protein content was observed. Nutritional composition of CREYP was minimally affected with the removal of encapsulated cholesterol. Therefore, cholesterol-reduced egg yolk powder can be utilized as an essential ingredient in any egg yolk based products. (author)
[en] Background: Oral garlic supplementation may be effective in decreasing serum cholesterol levels as much as 15% to 20%. Garlic indirectly effect atherosclerosis by reduction of hyperlipidaemia, hypertension and probably diabetes mellitus and prevents thrombus formation. This study was undertaken to test the hypothesis that garlic powder with a prolonged mode of action promises potent biological effects into hypercholesterolaemia. Methods: Fifty albino rats were randomly divided into 5 equal groups (n=10). All rats were initially fed normal diet for at least 7 days. Then Group A was control and was fed a normal diet + 0.5% cholesterol, Group B was fed normal diet and 3 mg garlic per 10 g of feed and Group C was fed normal diet and 10 mg garlic per 10 g of feed. The experiment lasted for 12 weeks. Body weight and serum cholesterol were noted before and after giving garlic + cholesterol. Results: Effect of serum cholesterol level was significantly decreased after taking 3 and 10 mg of garlic. However it was observed that the body weight was increased after taking garlic. Conclusion: Garlic consumption although can decrease the level of serum cholesterol but it increases the body weight. Garlic consumption alone can decrease serum cholesterol level, but it cannot be used as the main therapeutic agent for hyperlipidaemia. (author)
[en] B.mori nucleopolyhedrovirus (BmNPV), which produces BV and ODV two virion phenotypes in its life cycle, caused the amount of economic loss in sericulture. But the mechanism of its infection was still unclear. In this study we characterized B.mori nuclear hormone receptor 96 (BmNHR96) as a NHR96 family member, which was localized in the nucleus. We also found BmNHR96 over-expression could enhance the entry of BV as well as cellular cholesterol level. Furthermore, we validated that BmNHR96 increased membrane fusion mediated by GP64, which could probably promote BV-infection. In summary, our study suggested that BmNHR96 plays an important role in BV infection and this function probably actualized by affecting cellular cholesterol level, and our results provided insights to the mechanisms of BV-infection of B.mori. - Highlights: • BmNHR96 localized in cell nucleus. • Over-expression of BmNHR96 could enhance the invasion of BV. • Cellular cholesterol level was increased when BmNHR96 was over-expressed. • BmNHR96 over-expression can improve the membrane-fusion mediated by GP64.
[en] Highlights: •21-Methylpyrenyl-cholesterol specifically and stably associates to lipoproteins. •It is not esterified by LCAT, and thus reliably labels their peripheral hemi-membrane. •HDL vs. LDL are well distinguishable by various fluorescent labelling characteristics. •LDL peripheral hemi-membrane harbors cholesterol-rich ordered lipid (micro)domains. •Cultured cells can be stained by such labelled lipoproteins-mediated delivery. -- Abstract: Lipoproteins are important biological components. However, they have few convenient fluorescent labelling probes currently reported, and their physiological reliability can be questioned. We compared the association of two fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and to purified HDL and LDL. Both lipoproteins could be stably labelled by Pyr-met-Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met-Chol were well distinguishable between HDL and LDL, regarding dializability, associated probe amount and labelling kinetics. We took benefit of the pyrene labelling to approach the structural organization of LDL peripheral hemi-membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence emission of pyrene excimers, indicating that the probe was present in an ordered lipid micro-environment. Since the peripheral membrane of LDL contains more sphingomyelin (SM) than HDL, this excimer formation was consistent with the existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already suggested in model membranes of similar composition and reminiscent to the well-described “lipid rafts” in bilayer membranes. Finally, we showed that Pyr-met-Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a staining pattern well different to that observed with NBD-Chol non-specifically delivered to the cells
[en] Neuroblastoma (NB) is an extra cranial pediatric embryonal tumor most prevalent in children less than 1 year of age. NB accounts for 7% of all pediatric cancers but accounts for 15% of all childhood cancer deaths. Scavenger receptor class B type 1 (SR-B1), a mediator of cellular cholesterol uptake, is overexpressed in and have been linked to the aggressiveness of many cancers. Nevertheless, no studies have so far investigated the relationship between SR-B1 and NB. Elucidation of receptors that promote NB may pave the way for discovery of new therapeutic targets. Here we show that inhibition of SR-B1 reduced cell survival, migration and invasion, and cholesterol content in NB cell lines. Additionally analysis of SR-B1 levels in NB patient biopsies using the R2: Genomics Analysis and Visualization Platform showed that high SR-B1 expression correlated with decreased overall and event-free survival.