Alimentary proteins, amino acids and cholesterolemia

Numerous data from both epidemiological and experimental origins indicate that some alimentary proteins and amino acids in supplements can modify the blood LDL cholesterol, HDL cholesterol and total cholesterol. After an initial approval of the health claim for soy protein consumption for the prevention of coronary heart disease, more recently it has been concluded from an overall analysis of literature that isolated soy protein with isoflavones only slightly decrease LDL and total cholesterol. Other plant extracts and also some proteins from animal origin have been reported to exert a lowering effect on blood cholesterol when compared with a reference protein (often casein). The underlying mechanisms are still little understood. Individual amino acids and mixture of amino acids have also been tested (mostly in animal studies) for their effects on cholesterol parameters and on cholesterol metabolism. Methionine, lysine, cystine, leucine, aspartate and glutamate have been tested individually and in combination in different models of either normo or hypercholesterolemic animals and found to be able to modify blood cholesterol and/or LDL cholesterol and/or HDL cholesterol. It is however not known if these results are relevant to human nutrition.     

Pharmacological properties of plant sterols in vivo and in vitro observations

Plant sterols have been investigated as one of the safe potential alternative methods in lowering plasma cholesterol levels. Several human studies have shown that plant sterols/stanols significantly reduce plasma total and LDL cholesterol. In this article, pharmacological characteristics of plant sterols/stanols have been summarized and discussed. In particular, experimental data that demonstrate the effects of dietary phytosterols on lipid metabolism and development of atherosclerotic lesions have been critically reviewed. Despite their similar chemical structures, phytosterols and cholesterol differ markedly from each other in regard to their pharmacological characteristics including intestinal absorption and metabolic fate. Compared to cholesterol, plant sterols have poor intestinal absorption. The most and best studied effects of plant sterols are their inhibition of intestinal cholesterol absorption. Other biological activities of phytosterols such as effects on lecithin:cholesterol acyltransferase activity, bile acid synthesis, oxidation and uptake of lipoproteins, hepatic and lipoprotein lipase activities and coagulation system have been linked to their anti-atherogenic properties. Moreover, evidence for beneficial effects of plant sterols on disorders such as cutaneous xanthomatosis, colon cancer and prostate hyperplasia has been discussed. Finally, the potential adverse effects of plant sterols as well as pathophysiology of hereditary sitosterolemia are also reviewed. In conclusion, more pharmacokinetic data are needed to better understand metabolic fate of plant sterols/stanols and their fatty acid esters as well as their interactions with other nutraceutical/pharmaceutical agents.     

Effects of antinutritional factors on plasma lipoprotein levels in Japanese flounder Paralichthys olivaceus

This study examined the effects of four types of antinutritional factor (phytic acid, stachyose, soy saponins and soy isoflavones) on lipoprotein levels in plasma of Japanese flounder Paralichthys olivaceus. A basal diet was prepared with fish meal as primary protein source, the other diets were supplemented with 0·2, 0·4 or 0·8% phytic acid, 0·4, 0·8 or 1·5% stachyose, 0·1, 0·35 or 0·7% soy saponins and 0·10, 0·35 or 0·70% soy isoflavones, by dry mass, in place of white flour in the basal diet. Total cholesterol (TC) and triglyceride (TG) levels in plasma of P. olivaceus were not affected by phytic acid or stachyose. In general, addition of 0·2-0·8% phytic acid or 0·4-1·5% stachyose decreased plasma high-density lipoprotein cholesterol (HDL-C) levels, increased plasma low-density lipoprotein cholesterol (LDL-C) levels, thereby increasing the LDL-C:HDL-C ratio. By contrast, supplementation with 0·35-0·7% soy saponins generally depressed plasma TC levels and the LDL-C:HDL-C ratio. Supplementation with 0·35-0·7% soy isoflavones, however, increased plasma TC and TG levels. These results indicate that soy saponins may be partly responsible for the cholesterol-lowering effects of soybean meal.     

Effects of soybean isoflavones, probiotics, and their interactions on lipid metabolism and endocrine system in an animal model of obesity and diabetes

The effects of soybean isoflavones with or without probiotics on tissue fat deposition, plasma cholesterol, and steroid and thyroid hormones were studied in SHR/N-cp rats, an animal model of obesity, and were compared to lean phenotype. We tested the hypothesis that probiotics by promoting the conversion of isoflavone glycosides to their metabolically active aglycone form will have a synergistic effect on body fat, cholesterol metabolism, and the endocrine system. Obese and lean SHR/N-cp rats were fed AIN-93 diets containing 0.1% soy isoflavone mixture, 0.1% probiotic mixture, or both together. Different fat tissues were teased and weighed. Plasma was analyzed for cholesterol and steroid and thyroid hormones. In both phenotypes, isoflavones lowered fat deposition in several fat depots. Probiotics alone had no significant effect on fat depots. Isoflavones lowered total, LDL, and HDL cholesterol in lean rats, but in obese rats isoflavones lowered only total and LDL cholesterol. Isoflavones also lowered many of the steroid hormones involved in lipid metabolism but had no significant effect on thyroid hormones. Probiotics had no significant effect on cholesterol or hormones. Thus, our data show that soy isoflavones also lower plasma cholesterol and that this hypocholesterolemic effect appears to be due in part to the modulation of steroid hormones. Probiotics do not seem to enhance the effect of isoflavones.     

Activity of isoflavones and berberine on vasomotor symptoms and lipid profile in menopausal women

The aim of this study was to evaluate the efficacy of a food supplement combination based on isoflavones and berberine (ISB) in the treatment of menopausal symptoms and dyslipidaemia. Isoflavones are extracted from soy and absorbed in the body after being activated by lactobacillus. Berberine, extracted from the plant Berberis aristata, lowers plasma cholesterol and triglycerides (TG) by increasing low-density lipoprotein (LDL) receptors and reducing hepatic synthesis of TG. One hundred twenty women with a mean age of 54.8?±?0.6 years were enrolled and randomized to treatment with ISB (estromineral lipid [EL]?=?60 cases) or calcium and vitamin D(3) (CaD?=?60 cases). Menopausal symptoms, plasma cholesterol, and TG were evaluated at baseline, and after 4 and 12 weeks. EL treatment significantly lowered plasma total cholesterol (-13.5% ± 0.7 vs -0.2% ± 0.5), LDL cholesterol (-12.4% ± 1.5 vs + 0.8 % ± 0.7) and TG (-18.9% ± 2.5 vs -1.3% ± 1.2) and improved menopausal symptoms compared with CaD treatment. Safety parameters were unchanged during the study. The combination of berberine and isoflavones was effective in lowering cardiovascular (CV) risk factors in menopausal women with moderate dyslipidaemia and in improving their quality of life.     

Molecular mechanisms of action of the soy isoflavones includes activation of promiscuous nuclear receptors. A review

Consumption of soy has been demonstrated to reduce circulating cholesterol levels, most notably reducing low-density lipoprotein (LDL) cholesterol levels in hypercholesterolemic individuals. The component or components that might be responsible for this effect is still a matter of debate or controversy among many researchers. Candidate agents include an activity of soy protein itself, bioactive peptides produced during the digestive process, or the soy isoflavones. Although soy intake may provide other health benefits including preventative or remediative effects on cancer, osteoporosis and symptoms of menopause, this review will focus on isoflavones as agents affecting lipid metabolism. Isoflavones were first discovered as a bioactive agent disrupting estrogen action in female sheep, thereby earning the often-used term 'phytoestrogens'. Subsequent work confirmed the ability of isoflavones to bind to estrogen receptors. Along with the cholesterol-lowering effect of soy intake, research that is more recent has pointed to a beneficial antidiabetic effect of soy intake, perhaps mediated by soy isoflavones. The two common categories of antidiabetic drugs acting on nuclear receptors known as peroxisome proliferator activated receptors (PPARs) are the fibrates and glitazones. We and others have recently asked the research question 'do the soy isoflavones have activities as either "phytofibrates" or "phytoglitazones"?' Such an activity should be able to be confirmed both in vivo and in vitro. In both the in vivo and in vitro cases, this action has indeed been confirmed. Further work suggests a possible action of isoflavones similar to the nonestrogenic ligands that bind the estrogen-related receptors (ERRs). Recently, these receptors have been demonstrated to contribute to lipolytic processes. Finally, evaluation of receptor activation studies suggests that thyroid receptor activation may provide additional clues explaining the metabolic action of isoflavones. The recent advances in the discovery and evaluation of the promiscuous nuclear receptors that bind many different chemical ligands should prove to help explain some of the biological effects of soy isoflavones and other phytochemicals.     

Clinical pharmacology of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

In this article, de novo cholesterol synthesis, its inhibition by HMG-CoA reductase inhibitors (statins) and clinical pharmacology aspects of the statins have been reviewed. Statins are available in both active and pro-drug forms. Their affinity to bind and subsequently to inhibit HMG-CoA reductase activity is approximately 3 orders of magnitude higher than that of natural substrate (HMG-CoA). All members of this group of lipid-lowering agents are, to a varying degree, absorbed from the gut. However, their bioavailability depends on their lipophobicity and their concomitant use with meals. The interaction between HMG-CoA reductase inhibitors and other lipid-lowering agents has been reviewed in more detail. One major side-effect of lipid-lowering combination therapy is myopathy with or without rhabdomyolysis. Combination of statins with gemfibrozil seems to increase risk of this adverse event, particularly in patients with renal impairment, more than combination with other lipid-lowering agents. Combination therapy with other agents including anticoagulants, antihypertensive, anti-inflammatory, oral hypoglycemic and antifungal agents as well as beta-blockers, H2 blockers, cyclosporine and digoxin has been also reviewed. The pleiotropic non-lipid lowering properties of statins and their effects on the quality of lipoprotein particles, the activities of cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase as well as their possible synergistic effects with n-3 fatty acids, phytosterols, vitamin E and aspirin in reducing cardiovascular events warrant further investigation.     

Synthetic peptides: managing lipid disorders

PURPOSE OF REVIEW: Recent publications related to the potential use of synthetic peptides for the management of lipid disorders and their vascular complications are reviewed. RECENT FINDINGS: The potential use of synthetic peptides for the management of lipid disorders and their vascular complications has emerged in recent years. These peptides are models of apolipoproteins, but are much smaller in size than the apolipoproteins. Oral peptides that improve the antiinflammatory properties of HDLs have been shown to potently inhibit atherosclerosis in mouse models. Injection of a peptide with a class A amphipathic helix in a rat model of diabetes dramatically reduced endothelial sloughing and improved vasoreactivity. Injected synthetic peptides have also been described that dramatically lower plasma cholesterol and restore endothelial function in a rabbit model of familial hypercholesterolemia. These studies suggest the therapeutic potential for synthetic peptides in the management of lipid disorders and their vascular complications. SUMMARY: Synthetic peptides much smaller than exchangeable human plasma apolipoproteins but with physical and chemical characteristics similar to the plasma apolipoproteins have shown promise in the management of lipid disorders and their vascular complications in animal models. The initial success of these animal studies suggests that synthetic peptides have the potential to emerge as a new therapeutic class of agents in the management of patients with lipid disorders.     

血浆同型半胱氨酸水平升高与动脉粥样硬化

心血管疾病已成为当今全球性致残与致死的最重要原因之一。目前确定的冠心病的危险因素主要包括高龄、血脂异常、高血压、糖尿病、吸烟、肥胖症。大量的临床试验及流行病学研究已经证实血浆同型半胱氨酸水平升高是心血管疾病的一个独立的危险因素。健康人的血浆同型半胱氨酸水平为5～10μmol／L。血浆同型半胱氨酸水平严重升高的主要原因是胱硫醚-β-合成酶(cystathionine-β-synthase,CBS)基因的缺陷。CBS基因缺陷的纯合体可导致血浆同型半胱氨酸水平升高至100～500μmol／L。血浆同型半胱氨酸水平严重升高的病人通常伴随神经系统异常、早发性的动脉粥样硬化。叶酸、维生素B6和B12治疗能降低血浆同型半胱氨酸的水平并改善血管内皮功能、减少经皮冠状动脉腔内成形术(percutaneou stransluminal coronary angioplasty,PTCA)术后并发症。迄今为止,血浆同型半胱氨酸水平升高引起心血管疾病的发病机制并未完全明了,目前认为主要与以下几个方面有关：(1)内皮细胞损伤及功能障碍。我们实验室在CBS基因敲除的小鼠模型上证实血浆同型半胱氨酸水平升高能抑制eNOS的活性,导致主动脉内皮功能的障碍。我们还在细胞模型上证实了同型半胱氨酸能显著抑制内皮细胞的增殖。(2)KH固醇和甘油三脂生物合成代谢异常。我们实验室在apoE、CBS双基因敲除的小鼠模型上证实血浆同型半胱氨酸水平升高能改变肝脏的脂肪代谢,增加巨噬细胞对修饰LDL的摄取,从而导致胆固醇脂和甘油三脂在血管壁的堆积,促进主动脉粥样斑块的形成。(3)刺激血管平滑肌细胞增殖。此外还发现同型半胱氨酸能激活蛋白激酶C信号途径,促进胶原蛋白的合成,抑制弹性蛋白和胶原蛋白的交联。(4)激活血栓形成。(5)激活单核细胞。目前认为同型半胱氦酸主要通过以下几个化学机制致病;(1)自氧化产生活性氧。同型半胱氨酸在自氧化的过程中能产生大量的活性氧,从而引起血液中脂蛋白和细胞膜脂质的过氧化损伤,并进一步引起内皮功能的障碍。(2)在腺苷的参与下形成SAH,一种甲基转移抑制剂,导致细胞内的低甲基化。(3)与一氧化氮结合形成亚硝酰物。(4)参与蛋白质的合成。总之,我们和其他实验室的研究结果均表明同型半胱氨酸不仅与动脉粥样硬化相关,而且具有致病效应。尽管补充叶酸、维生素B6和B12等治疗能降低血浆同型半胱氨酸的水平,但是否能降低心血管疾病的风险仍有待于大量的动物研究及临床试验。     

The plasma lecithins:cholesterol acyltransferase reaction

Evidence for the existence of a plasma lecithin : cholesterol acyltransferase is reviewed with emphasis not only on the lipid reactants, but also on the lipoprotein "substrates" and "products." The cholesteryl esters of all major lipoprotein classes become labeled when plasma is incubated with cholesterol-(14)C. However, the smaller, lecithin-rich high density lipoproteins appear to be preferred substrates. Most studies of factors that influence the acyltransferase reaction have not adequately distinguished between effects on the enzyme and effects on the lipoprotein substrates. However, the fact that cholesterol esterification is diminished in plasma from eviscerated animals or from patients with reduced liver function suggests that the liver may regulate both the level of the enzyme and that of the substrates. Several indications exist that the acyltransferase reaction is the major source of plasma esterified cholesterol in man. Furthermore, the reaction may have a broader, extracellular function. One possibility is that it plays a role in the transport of cholesterol from peripheral tissues to the liver.     

How isoflavone levels in common rodent diets can interfere with the value of animal models and with experimental results

Phytoestrogens are a diverse group of plant-derived compounds structurally or functionally mimicking mammalian oestrogens. A variety of effects, in vitro, in animal models and in humans, have been attributed to these compounds. It is generally not appreciated that many commercial rodent diets are formulated with soy as a source of protein and thus large daily doses of phytoestrogens in the form of isoflavones are delivered to the animals. The content of isoflavones in laboratory diets depends on a number of factors and, therefore, varies considerably, both between different formulations, and also from batch to batch of the same formulation. Dietary isoflavones can influence a number of different endpoints, rendering the dietary levels of such compounds an important experimental factor to consider. The levels of isoflavones in common laboratory diets are reviewed in relation to the dietary levels influencing different endpoints.     

Soy protein with or without isoflavones, soy germ and soy germ extract, and daidzein lessen plasma cholesterol levels in golden Syrian hamsters

Dietary isolated soy protein (ISP, containing approximately equal amounts of daidzein and genistein), ethanol-extracted ISP (ISP (-)), soygerm or soygerm extract (containing large amounts of daidzein and glycitein and little genistein) and the isoflavone, daidzein, were hypothesized to lessen plasma cholesterol in comparison with casein. Sixty male and 60 female golden Syrian hamsters (6-8 weeks of age) were randomly assigned to six treatments fed for 10 weeks. Four of the experimental diets (ISP, daidzein, soygerm, and soygerm extract) contained 1.3 mmol total isoflavones/kg. The ISP (-) diet contained 0.013 mmol isoflavone/kg, whereas the casein diet contained no isoflavones. Hamsters fed ISP, ISP (-), daidzein, soygerm, and soygerm extract had significantly less plasma total cholesterol (by 16%-28%), less non-HDL cholesterol (by 15%-50%) and less non-HDL/HDL cholesterol ratios compared with hamsters fed casein (P < 0.01). For male hamsters, there were no differences among treatments in plasma HDL concentrations. Female hamsters fed ISP (-) had significantly greater HDL levels (P < 0.01) than females fed casein or daidzein. Triglyceride concentration was significantly less in hamsters fed ISP (-) compared with the casein-fed females. Because soy protein with or without isoflavones, soygerm and soygerm extract, and daidzein lessened plasma cholesterol to an approximately equal extent, soy protein alone, varying mixtures of isoflavones, and other extractable components of soy are responsible for cholesterol-lessening effects of soy foods, mainly due to their effects to lessen LDL cholesterol.     

A comprehensive review on the lipid and pleiotropic effects of pitavastatin

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are administered as first line therapy for hypercholesterolemia, both in primary and secondary prevention. There is a growing body of evidence showing that beyond their lipid-lowering effect, statins have a number of additional beneficial properties. Pitavastatin is a unique lipophilic statin with a strong effect on lowering plasma total cholesterol and triacylglycerol. It has been reported to have pleiotropic effects such as decreasing inflammation and oxidative stress, regulating angiogenesis and osteogenesis, improving endothelial function and arterial stiffness, and reducing tumor progression. Based on the available studies considering the risk of statin-associated muscle symptoms it seems to be also the safest statin. The unique lipid and non-lipid effects of pitavastatin make this molecule a particularly interesting option for the management of different human diseases. In this review, we first summarized the lipid effects of pitavastatin and then strive to unravel the diverse pleiotropic effects of this molecule.     

The effects of soy protein in women and men with elevated plasma lipids

Fifty four postmenopausal women with elevated cholesterol were recruited for a randomised, double-blind controlled trial of soy protein containing isoflavones. (ISP+) or a soy protein with a low isoflavone content (ISP-), taken daily for 12 weeks. There was an overall reduction after 12 weeks in total cholesterol (TC), LDL cholesterol (LDL-C), sex hormone binding globulin (SHBG), and luteinizing hormone (LH). There were no significant differences between treatment groups. In a separate study 27 male subjects with a TC > 5.5 mmol/l were given ISP+ for 12 weeks. In this male study there was a significant increase in HDL cholesterol (HDL-C) and SHBG. Soy protein has a cholesterol lowering effect in both women and men. These studies suggest that this effect is independent of isoflavones. Soy protein also reduces SHBG levels in both sexes.     

Role of soy isoflavones in the hypotriglyceridemic effect of soy protein in the rat

The present study was undertaken to determine whether isoflavones present in soy protein isolate contribute to the triglyceride-lowering effect of the protein relative to casein. Plasma triglyceride concentrations, their secretion rate into blood circulation, and post-heparin plasma lipoprotein lipase activity (a major determinant of intravascular catabolism of triglycerides) were measured in the fasted state in male Sprague-Dawley rats fed for 21 days one of three experimental diets varying in protein source (20% weight/weight): soy protein isolate, casein or casein to which 1.82 mg/g isoflavones (genistein and daidzein) were added to match the isoflavone content of soy protein isolate. Body weight gain was slightly lower in soy protein fed rats than in casein fed rats, but this effect was not statistically significant (P = 0.22). Casein plus isoflavones diet induced intermediary weight gain. A decrease in plasma total triglycerides was observed in rats fed soy protein and casein plus isoflavones compared with casein (P < 0.05), and there was a tendency to a positive correlation between weight gain and plasma triglyceride concentrations (r = 0.35, P = 0.06). However, no significant effect was observed on hepatic triglyceride concentrations, triglyceride secretion rate by the liver and post-heparin plasma lipoprotein lipase activity. These results show that soy protein isolate, in comparison with casein, has a hypotriglyceridemic effect in the rat and suggest that isoflavones may be responsible, at least in part, for this effect. The lowering effect of soy protein isolate and isoflavones on plasma triglyceride concentrations may be mediated by an alteration in energy balance, and possibly by the hepatic production of lipoproteins more susceptible to intravascular hydrolysis. Subtle but sustained changes in triglyceride secretion and post-heparin plasma lipoprotein lipase activity may also be implicated.     

Pyroglutamyl apelin-13 identified as the major apelin isoform in human plasma

Apelin is emerging as an important hormone regulator of cardiovascular homoeostasis and an important biomarker for heart failure. Apelin concentrations have historically been measured by immunoassays; however, reported apelin concentrations measured in healthy volunteers show a large disparity from a few picograms per milliliter (pg/ml) to several nanograms per milliliter (ng/ml). Apelin exists in several isoforms ranging in size from 12 to 36 residues, and immunoassays generally cannot distinguish the specific forms present. In this study, an optimized method for enriching apelin peptides with cation-exchange beads followed with mass spectrometry analysis is presented. Apelin peptides are labile in plasma at physiological conditions; however, by lowering the plasma pH to 4.5, the recovery of apelin peptides can be increased significantly. Through optimizing the cation-exchange extraction process, we improved the lower limit of detection for most of the apelin peptides monitored to a few pg/ml. Using the improved method, we detected pyroglutamyl apelin-13 [(pyr)apelin-13] as the major apelin isoform present in plasma from several healthy volunteers at concentrations ranging from 7.7 to 23.3 pg/ml.     

Phytoestrogens and breast cancer

The role of phytoestrogens and consumption of phytoestrogen-rich foods such as soy containing isoflavones and whole grain products with lignans for the prevention of breast cancer is reviewed. It is concluded that soy-containing diet in adult women is not or only slightly protective with regard to breast cancer, but that it may be beneficial if consumed in early life before puberty or during adolescence supporting results of immigrant and epidemiological studies. No negative effects of soy on breast cancer have been observed. On the other hand, a diet low in lignans, resulting in a low plasma enterolactone concentration, increases risk both in a case-control and a prospective study, but some controversial results have also been obtained. Some of these results may be explained by the fact that the determinants of plasma or urinary enterolactone concentration are very different in different countries. In Scandinavia, the main determinants are whole grain cereal food, vegetables and berries. Whether the protective effect is caused by the phytoestrogens in the diet or whether they are only biomarkers of a healthy diet has not been established.     

Unravelling the functional significance of PCSK9

PURPOSE OF REVIEW: Proprotein convertase subtilisin kexin type 9 (PCSK9) has emerged as a potential target for lowering plasma LDL cholesterol levels. This review summarizes recent studies published in print or online before January 2007 which have investigated the functional significance of this intriguing protease. RECENT FINDINGS: Increasing interest in PCSK9 has given rise to landmark epidemiological studies, the generation of animal models, the discovery of new human mutations, as well as numerous in-vitro studies. These studies have helped to unravel the molecular functions of PCSK9. SUMMARY: Mutations of PCSK9 are associated either with hypercholesterolemia or with hypocholesterolemia. In the latter case, the incidence of coronary heart disease is reduced, thereby demonstrating that low LDL cholesterol levels from birth are highly beneficial. PCSK9 promotes the degradation of the LDL receptor in hepatocytes apparently both intracellularly and by being a secreted protein that can bind the LDL receptor and be internalized. By virtue of its role as a major inhibitor of the LDL receptor, PCSK9 is a promising therapeutic target. Specific PCSK9 pharmacological inhibitors may prove to be useful in amplifying the well documented benefits of statins.     

Interaction of 7-ketocholesterol with two major components of the inner leaflet of the plasma membrane: phosphatidylethanolamine and phosphatidylserine

7-Ketocholesterol is one of the major forms of oxidized cholesterol found in vivo. Several toxic effects of this sterol have been documented, and it is suggested to have a role in atherosclerosis. We have studied how this oxysterol modifies the physical properties of bilayers composed of the major lipid components of the cytoplasmic leaflet of the plasma membrane. 7-Ketocholesterol is much less effective in promoting the formation of the H ii phase in phosphatidylethanolamines than cholesterol. This is likely due to the fact that 7-ketocholesterol is more polar than cholesterol and hence would be located closer to the membrane interface. However, in ternary mixtures of dipalmitoleoylphosphatidylethanolamine with low concentrations of both sterols, the effect of 7-ketocholesterol on lowering T H is enhanced. Both cholesterol and 7-ketocholesterol are very soluble in bilayers of phosphatidylethanolamine, particularly with 1-palmitoyl-2-oleoylphosphatidylethanolamine. There is, however, a much greater solubility of 7-ketocholesterol in bilayers of 1-stearoyl-2-oleoylphosphatidylserine than is the case for cholesterol. In ternary mixtures of 1-stearoyl-2-oleoylphosphatidylserine with both sterols, it appears that the solubility of cholesterol is enhanced by the presence of 7-ketocholesterol. It is thus to be expected that several of the biophysical properties of a membrane would change as a result of the oxidation of cholesterol to 7-ketocholesterol.     

Soy isoflavones and cellular mechanics

Soy isoflavones are diphenolic compounds that are frequently used for alternative treatment of ageing symptoms in both genders. They operate at principally two hierarchical levels of functional organization – cellular and molecular, while these ‘types’ of action appear to have indefinite borders. Soy isoflavone action at the cellular level involves inter alia the effects on cell mechanics. This epigenetic and modular determinant of cell function and fate is defined by: the anchorage to extracellular matrix (ECM) and neighboring cells, cytoskeleton organization, membrane tension and vesicle trafficking. Soy isoflavones have been reported to: (i) generally fashion an inert cell phenotype in some cancers and enhance the cell anchorage in connective tissues, via the effects on ECM proteins, focal adhesion kinases-mediated events and matrix metalloproteinases inhibition; (ii) affect cytoskeleton integrity, the effects being related to Ca²⁺ ions fluxes and involving cell retraction or differentiation/proliferation-related variations in mechanical status; (iii) increase, remain “silent” or decrease membrane tension/fluidity, which depends on polarity and a number and arrangement of functional groups in applied isoflavone; (iv) provoke inhibitory effects on vesicle trafficking and exo-/endocytosis, which are usually followed by changed cell morphology. Here we present and discuss the abundance of effects arising from cells’ “encounter” with soy isoflavones, focusing on different morphofunctional definers of cell mechanics.