[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 (PC_n, 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

No abstract available

[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] Highlights: • An NMR assignment of Lam4S2 identified significant conformational exchange. • Lam4S2 binding to sterol confirms the StART-like cavity as its binding site. • Using MβCD as cholesterol donor/acceptor, the upper limit of sterol exchange is ∼6 s⁻¹. Sterols are essential components of cellular membranes and shape their biophysical properties. The recently discovered family of Lipid transfer proteins Anchored at Membrane contact sites (LAMs) has been suggested to carry out intracellular sterol traffic using StART-like domains. Here, we studied the second StART-like domain of Lam4p from S. cerevisiae by NMR. We show that NMR data are consistent with the StART-like domain structure, and that several functionally important regions within the domain exhibit significant conformational dynamics. NMR titration experiments confirm sterol binding to the canonical sterol-binding site and suggest a role of membrane interactions on the thermodynamics and kinetics of sterol binding.

[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] 

Introduction

The apolipoprotein A1 (apoA1) remnant ratio has been identified as an independent cardiovascular (CV) risk factor. Higher apoA1 remnant ratios may predict lower CV risk in some patients. This analysis aimed to evaluate the effects of evolocumab on the change from baseline in the apoA1 remnant ratio compared with placebo.

Methods

This pooled post hoc analysis included 2464 patients with mixed dyslipidemia treated with evolocumab 140 mg every 2 weeks (Q2W) or 420 mg once monthly (QM) in three phase 3 evolocumab trials. The apoA1 remnant ratio was calculated by dividing apoA1 by the difference between non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C). ApoA1 remnant ratio strata were generated using previously published tertile (< 4.7, 4.7–6.8, and > 6.8) and partitioning categories (< 3.6, 3.6–6.0, and > 6.0).

Results

The baseline apoA1 remnant ratio in evolocumab and placebo treatment arms was 7.1 and 7.3, respectively. At week 12, evolocumab 140 mg Q2W and 420 mg QM increased the apoA1 remnant ratio by 25.0% and 33.6%, respectively, versus placebo (p < 0.0001 for both groups). When patients were categorized by week 12 apoA1 remnant ratio thresholds (< 3.6 vs. > 3.6, and < 4.7 vs. > 4.7), those with higher week 12 apoA1 remnant ratios were significantly more likely to have also achieved a target non-HDL-C level of < 100 mg/dl. In the subset of women > 50 years of age, the proportion of patients at apoA1 remnant ratio thresholds < 3.6, 3.6–6.0, and > 6.0 at baseline shifted toward or remained at higher thresholds at week 12.

Conclusions

This post hoc analysis suggests that evolocumab increases the apoA1 remnant ratio. Funding:

Amgen Inc.

Plain Language Summary

Plain language summary available for this article.

[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] Highlights: • Triol binds to the indole ring of Trp122 of voltage-gated sodium channel with a high affinity. • Triol negatively modulates action potential bursts of hippocampal neurons. • Triol inhibits low Mg²⁺–induced hyperexcitability in acute preparation of hippocampal slices. • Triol attenuates PTZ-induced epileptic seizures. Neuronal hyperexcitability is identified as a critical pathological basis of epileptic seizures. Cholestane-3β, 5α, 6β-triol (Triol) is a major metabolic oxysterol of cholesterol. Although its neuroprotective effect on ischemia-induced neuronal injury and negative modulation of voltage-gated sodium (Nav) channels were well established, the physical binding site of triol to sodium channels and its effects on neuronal hyperexcitability have not yet been explored. In this study, we utilized molecular docking and molecular dynamics simulation to investigate the interaction between triol and Nav Channels. Our results demonstrated that triol binds to the indole ring of Trp122 of the Nav Channel in silico with a high biological affinity. We further found that triol negatively modulates the action potentials bursts of hippocampal neurons by cell-attached patch recording. Moreover, triol significantly inhibits low Mg²⁺-induced hyperexcitability in vitro. In addition, triol attenuates pentylenetetrazole (PTZ)-induced convulsive-form behavioral deficits in vivo. Together, our results suggest that triol suppresses neuronal hyperexcitability via binding to Nav channel, indicating that triol might be an attractive lead compound for the treatment of neuronal hyperexcitability-related neurological disorders, especially epileptic seizures.