High Amounts Of Cholesterol Research Articles

Probing Slipids Force Field for Phase Transitions in SOPC Lipid Bilayers with Various Cholesterol Concentrations

We explore the phase behavior of lipid bilayers containing SOPC (1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine) with various molar concentrations (0 mol%, 10 mol% and 30 mol%) of cholesterol. To this end, we performed extensive atomistic molecular dynamics simulations in conjunction with the Slipids force field with optimized parameters for the headgroups of phospholipids. We computed thermodynamic and structural quantities describing the ordering of the tails, the mobility of the heads and the arrangement of the lipids in the bilayers. We analyzed the behavior of the named quantities over the temperature range between 271 K and 283 K, where the experimentally determined melting temperature, Tm=279 K, lies, as well as at 400 K, which is used as a reference temperature. The obtained results are compared to available experimental data along with the outcome from molecular dynamics simulations of similar phospholipids containing different amounts of cholesterol. In the temperature interval of interest, we found evidence of the occurrence of a thermal-driven phase transition (melting) in both the pure system and the one with the lower concentration of cholesterol, while in the remaining system, the higher amount of cholesterol in the bilayer smears out the transitional behavior. Thus, we demonstrate the ability of the Slipids force field to predict the phase behavior of bilayers of SOPC and SOPC mixed with cholesterol.

Sticholysin recognition of ceramide-phosphoethanolamine

Actinoporins are pore-forming toxins produced by sea anemones. They exert their activity by binding to the membranes of target cells. There, they oligomerize, forming cation-selective pores, and inducing cell death by osmotic shock. In the early days of the field, it was shown that accessible sphingomyelin (SM) in the bilayer is required for the activity of actinoporins. While these toxins can also act on membranes composed solely of phosphatidylcholine (PC) with a high amount of cholesterol (Chol), consensus is that SM acts as a lipid receptor for actinoporins. It has been shown that the 2NH and 3OH moieties of SM are essential for actinoporin recognition. Hence, we wondered if ceramide-phosphoethanolamine (CPE) could also be recognized. Like SM, CPE has the 2NH and 3OH groups, and a positively charged headgroup. While actinoporins have been observed to affect membranes containing CPE, Chol was always also present, with the recognition of CPE remaining unclear. To test this possibility, we used sticholysins, produced by the Caribbean Sea anemone Stichodactyla helianthus. Our results show that sticholysins can induce calcein release on vesicles composed only of PC and CPE, in absence of Chol, in a way that is comparable to that induced on PC:SM membranes.

Effect of Tannins on Cholesterol Content and Its Oxidation in Egg Pasta as Related to Different Pasta Shapes

Egg pasta contains high amount of cholesterol, that upon oxidation, generates oxysterols (COPs), which play a key role in the onset of several human diseases. In this study, the effect of two tannins (esters of ellagic acid, A; esters of gallic acid, B) at three different concentrations (0.25%, 0.50%, 1.00%) was tested in egg pasta considering two different pasta shapes (squared, S; rectangular, F). When tannin B was added, the total phenolic content (TPC) in fresh pasta increased (p < 0.01) and after cooking its content was greater than those obtained with tannin A. The pasta shape affected the presence of cholesterol; its amount in uncooked F shape samples (27.67 ± 0.28 mg/g pasta) was higher than that found in S shape (21.18 ± 0.49 mg/g pasta). In addition, tannin B significantly (p < 0.01) increased the presence of cholesterol in the cooking water (up to 1.04 ± 0.05 μg/mL), in particular in S pasta shape. Tannin B was also greater than tannin A to reduce the content of COPs in fresh egg pasta, while the cooking process did not impact (p > 0.05) the oxidation of cholesterol. The results suggest that tannin B could be applied in the formulation of egg pasta as a strategy for reducing the content of cholesterol and its oxidation products.

Effect of Ratio Span 60 - Cholesterol on the Characteristic of Niosomes Vitamin D3

Vitamin D3 (Cholecalciferol) is a fat-soluble vitamin that is claimed to be an ingredient added to food and beverage products such as cheese and milk. However, due to its unstable nature, it causes vitamin D3 to be degraded in the product. Niosomes are a vesicle drug delivery system formed by nonionic surfactants and cholesterol that can protect both hydrophilic and lipophilic compounds by entrapping them in their vesicle system. Span 60 is the surfactant most often used to form niosomes and cholesterol because it is known to have a higher entrapment ability than other nonionic surfactants. Using Design-Expert version 10 with the Simplex Lattice Design (SLD) model, eight formulas with varying concentrations of Span 60 cholesterol were obtained. SLD analysis results showed a negative interaction (interaction coefficient -301.35) between Span 60 cholesterol on particle size so that the Span 60 Cholesterol mixture reduced the size of niosome particles. However, cholesterol has a more significant positive effect (coefficient value + 279.45) on niosome particle size than Span 60 (coefficient value + 243.20), which means a formula with a higher amount of cholesterol causes a larger particle size. Contrary to zeta potential, Span 60 shows a more significant negative effect (coefficient value -47.54) than cholesterol (coefficient value-29.25), which means, Formula with a higher number of Span 60 causes the zeta potential to be more negative.

Enterotoxic potential of dietary cholesterol autoxidation products

Background In both Western and Westernized diets, together with a relatively high amount of cholesterol, variable amountsof its oxidized metabolites, oxysterols, are consistently consumed. These oxysterols, mostly of non-enzymatic origin, are produced during sterol autoxidation in foodstuff manufacturing and storage. Objective This study aimed to analyze the potential enterotoxic effects of all main oxysterols of non-enzymatic origin so far identified in a variety of foods. Experimental plan Differentiated human intestinal cell monolayers (CaCo-2) were incubated up to 48 h in the presence or absence of 0.5, 1 or 5 µM with one out of seven non-enzymatic oxysterols, prior to the verification of minimal irreversible cell damage within the chosen concentration range. Results All tested oxysterols were proven to exert damaging effects on cell monolayers in vitro. The inflammatory interleukin-8 and monocyte chemotactic protein-1 were mostly upregulated by 7-ketocholesterol and 7β-hydroxycholesterol, respectively, then to a lower extent by 5α,6α-epoxycholesterol, 7α-hydroxycholesterol and 5β,6β-epoxycholesterol. 7-Ketocholesterol and 7β-hydroxycholesterol also appeared to be most effective in impairing claudin-1, occludin and E-cadherin proteins, followed by 25-hydroxycholesterol and triol. Conclusions The oxysterols consistently derived by food autoxidation were tested; they potentially impaired the integrity of the intestinal epithelial barrier and triggered an inflammatory response within 0.5–5 µM concentrations, easily reachable in a single Western meal. Significance Statement This comprehensive analysis focused on the potential impairment of the intestinal barrier by the main dietary non-enzymatic oxysterols, should guide further nutrition research aiming at defining a threshold amount of these cholesterol derivatives in order not to derange the physiological gut–brain axis.

ОБМЕННЫЕ ПРОЦЕССЫ У ЧИСТОПОРОДНЫХ И ПОМЕСНЫХ СВИНЕЙ В РАЗНЫЕ ВОЗРАСТНЫЕ ПЕРИОДЫ

The article presents data concerning changes in the content of total lipids and cholesterol in hybrid gilts in comparison with purebred gilts at different ages. When examining total lipids and cholesterol, it was found that hybrid gilts contained higher amounts of cholesterol and total lipids in the blood serum. Thus, an increase in serum cholesterol in the experimental gilts was observed from two to eight months of age; the increase in total lipids continued until four months of age, from four to six months of age their presence decreased, and from six to eight months of age in all the groups studied it also slightly decreased. In the purebred groups, the lipid content decreased by 4.0% at six months of age. The results showed that the increase in cholesterol and total lipids throughout the study period was greater in hybrid gilts.

EPA and DHA differentially modulate membrane elasticity in the presence of cholesterol

Polyunsaturated fatty acids (PUFAs) modify the activity of a wide range of membrane proteins and are increasingly hypothesized to modulate protein activity by indirectly altering membrane physical properties. Among the various physical properties affected by PUFAs, the membrane area expansion modulus (Ka), which measures membrane strain in response to applied force, is expected to be a significant controller of channel activity. Yet, the impact of PUFAs on membrane Ka has not been measured previously. Through a series of micropipette aspiration studies, we measured the apparent Ka (Kapp) of phospholipid model membranes containing nonesterified fatty acids. First, we measured membrane Kapp as a function of the location of the unsaturated bonds and degree of unsaturation in the incorporated fatty acids and found that Kapp generally decreases in the presence of fatty acids with three or more unsaturated bonds. Next, we assessed how select ω-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), affect the Kapp of membranes containing cholesterol. In vesicles prepared with high amounts of cholesterol, which should increase the propensity of the membrane to phase segregate, we found that inclusion of DHA decreases the Kapp in comparison to EPA. We also measured how these ω-3 PUFAs affect membrane fluidity and bending rigidity to determine how membrane Kapp changes in relation to these other physical properties. Our study shows that PUFAs generally decrease the Kapp of membranes and that EPA and DHA have differential effects on Kapp when membranes contain higher levels of cholesterol. Our results suggest membrane phase behavior and the distribution of membrane-elasticizing amphiphiles impact the ability of a membrane to stretch.

Tailored liposomal nanotraps for the treatment of Streptococcal infections

BackgroundStreptococcal infections are associated with life-threatening pneumonia and sepsis. The rise in antibiotic resistance calls for novel approaches to treat bacterial diseases. Anti-virulence strategies promote a natural way of pathogen clearance by eliminating the advantage provided to bacteria by their virulence factors. In contrast to antibiotics, anti-virulence agents are less likely to exert selective evolutionary pressure, which is a prerequisite for the development of drug resistance. As part of their virulence mechanism, many bacterial pathogens secrete cytolytic exotoxins (hemolysins) that destroy the host cell by destabilizing their plasma membrane. Liposomal nanotraps, mimicking plasmalemmal structures of host cells that are specifically targeted by bacterial toxins are being developed in order to neutralize-by competitive sequestration-numerous exotoxins.ResultsIn this study, the liposomal nanotrap technology is further developed to simultaneously neutralize the whole palette of cytolysins produced by Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis-pathogens that can cause life-threatening streptococcal toxic shock syndrome. We show that the mixture of liposomes containing high amounts of cholesterol and liposomes composed exclusively of choline-containing phospholipids is fully protective against the combined action of exotoxins secreted by these pathogens.ConclusionsUnravelling the universal mechanisms that define targeting of host cells by streptococcal cytolysins paves the way for a broad-spectrum anti-toxin therapy that can be applied without a diagnostic delay for the treatment of bacterial infections including those caused by antibiotic-resistant pathogens.

Analysis of functional components and radical scavenging activity of 21 algae species collected from the Japanese coast

The functional chemical substances and the antioxidant activity of lipids in 21 marine algae along the Japanese coast were investigated. Principal component analysis was performed to detect any correlation between the chemical substances and algae phylum. Chlorophyta contained a high level of β-carotene. Rhodophyta contained high amounts of cholesterol, β-sitosterol, and saturated fatty acids. Phaeophyta were rich in fucosterol, α-tocopherol, fucoxanthin, and polyphenol. Phaeophyta algae also showed the highest antioxidant activity compared with other phylum. This suggests that Phaeophyta has the greatest potential to be used as a functional food. Consumption of the beneficial Phaeophyta species, such as Eisenia arborea Areschoug and Ecklonia cava Kjellman should be encouraged as not only as food products but also as nutraceuticals and dietary supplements. These beneficial ingredients should be encouraged to be studied in depth with the possibility to develop specific formulated products target to special consumer’s population with added nutritional value.

Efek Ekstrak Biji Alpukat (Persea americana Mill) sebagai Antihiperkolesterol Darah Mencit (Mus musculus)

Cholesterol is an important element in the body needed to regulate chemical processes in the body, but high amounts of cholesterol can lead to atherosclerosis which ultimately will have an impact on coronary heart disease. This study aims to know phytochemicals contained in an avocado (persea americana mill) seeds’ extract and determines the concentration of the avocado (persea americana mill) seeds’ extract can lower mice’s blood (mus musculus) hyper cholesterol levels in optimum. The animals tested were male mice which totaled 15 mice induced by propylthiouracil and high-fat feed. The mice were divided into 5 groups with different treatment. The treatment I, II, and III were given avocado seeds’ extract with a concentration of 10%, 20% and 40% respectively, treatment IV was given simvastatin as a positive control (+), and treatment V was given standard food and aquades as negative control (-). The data gained was analyzed through analysis of variance (ANOVA) statistical test which was followed by Duncan’ stest. The research findings show that avocado seeds’ extract is considered as positive to contain flavonoids, saponins, and tannins. The concentration of the avocado seeds’ extract which lowers blood hypercholesterol levels in an optimum way is 10% (b/v).

Expression of caveolin-1 in the interfollicular but not the follicle-associated epithelial cells in the bursa of fabricius of chickens.

The surface epithelium of the bursa of Fabricius consists of interfollicular (IFE) and follicle-associated epithelium (FAE). The IFE comprises (i) cylindrical-shaped secretory cells (SC) and (ii) cuboidal basal cells (BCs). The FAE provides histological and two-way functional connections between the bursal lumen and medulla of the follicle. We used a carbon solution and anti-caveolin-1 (Cav-1) to study the endocytic activity of FAE. Carbon particles entered the intercellular space of FAE, but the carbon particles were not internalized by the FAE cells. Cav-1 was not detectable in the FAE cells or the medulla of the bursal follicle. The absence of Cav-1 indicates that no caveolin-mediated endocytosis occurs in the FAE cells, B cells, bursal secretory dendritic cells (BSDC), or reticular epithelial cells. Surprisingly, a significant number of Cav-1 positive cells can be found among the SC, which are designated SC II. Cav-1 negative cell are called SC I, and they produce mucin for lubricating the bursal lumen and duct. Occasionally, BCs also express Cav-1, which suggests that BC is a precursor of a SC. Transmission electron microscopy confirmed the existence of type I and II SC. The SC II are highly polarized and have an extensive trans-Golgi network that is rich in different granules and vesicles. Western blot analysis of bursa lysates revealed a 21-23 kDa compound (caveolin) and Filipin fluorescence histochemistry provided evidence for intracellular cholesterol. High amount of cholesterol in the feces shows the cholesterol efflux from SC II. The presence of Cav-1 and cholesterol in SC II indicates, that the bursa is a complex organ in addition to possessing immunological function contributes to the cholesterol homeostasis in the chickens.

Abstract 601: Global and Liver Specific Bmal1 Deficient Mice Regulate Intestinal Lipid Absorption

Circadian rhythms controlled by clock genes affect plasma lipids, known risk factors for atherosclerosis. Clock and Bmal1 are critical clock genes that positively regulate circadian rhythms. We have shown that Clock plays an important role in lipid absorption. Additionally, we showed that global ablation of Bmal1 in Apoe –/– and Ldlr –/– mice, and liver-specific ablation of Bmal1 in Apoe –/– (L -Bmal1 –/– Apoe –/– ) mice increases atherosclerosis. However, it is unknown whether Bmal1 regulates intestinal lipid absorption. We studied cholesterol and triglyceride absorption in normal and lipase-inhibited Bmal1 –/– and Bmal1 –/– Apoe –/– mice with global Bmal1 deficiency and compared it with Bmal1 +/+ and Bmal1 +/+ Apoe –/– , respectively. To study the effect of liver-specific Bmal1 deficiency, studies were performed in L- Bmal1 –/– and L- Bmal1 –/– Apoe –/– mice and data were compared with Bmal1 fl/fl and Bmal1 fl/fl Apoe –/– mice. In addition, enterocytes isolated from these mice were used to study uptake and secretion of cholesterol and oleic acid. Further, protein and mRNA levels of candidate genes involved in lipid uptake, lipoprotein assembly and secretion were quantified. Both normal and lipase-inhibited Bmal1 –/– mice absorbed significantly higher amounts of cholesterol and triglyceride. Further, uptake and secretion of cholesterol and fatty acids by enterocytes was increased in Bmal1 –/– mice. As reported previously, liver-specific Bmal1 ablation increased VLDL production. Surprisingly, postprandial plasma lipids were also significantly increased in L- Bmal1 –/– mice than in control Bmal1 fl/fl mice. Further, enterocytes isolated from L- Bmal1 –/– took up more lipids and secreted more lipoproteins. Moreover, in vivo lipid absorption in L- Bmal1 –/– was increased. Gene expression quantifications revealed that intestinal MTP, DGAT1, CD36 and NPC1L1 mRNA levels were increased in global and hepatic Bmal1 deficient animals. Global and liver-specific ablation of Bmal1 increases intestinal lipoprotein production by increasing the expression of genes involved in lipid uptake and lipoprotein assembly. These data for the first time suggest that intestinal lipoprotein assembly is regulated by hepatic Bmal1.

Some Qualitative and Rheological Properties of Virgin Olive Oil- Apple Vinegar Salad Dressing Stabilized With Xanthan Gum.

Purpose: Lipid oxidation and rheological properties are the main qualitative parameters determined in food emulsions. Salad dressings are food emulsions important in our daily diet, but conventional salad dressings have high amounts of cholesterol and saturated fatty acids because of egg yolk in their formulations. There are many studies on the modification of salad dressing formulations to replace egg yolk and saturated fats. The present study describes new formulation of salad dressing with olive oil and apple vinegar to produce a functional food product. Methods: This study investigated the qualitative properties, oxidative stability, rheological behavior and microstructure of the salad dressing without egg yolk. Oil-in-water emulsions were prepared with virgin olive oil and apple vinegar stabilized with various percentages of xanthan (T1: 0.25%, T2: 0.5%. T3: 0.75%). Samples were stored at refrigerator for 90 days and experiments were performed at production day and during storage. Results: The obtained results showed that peroxide value was increased for all samples during storage, but it was at an acceptable level. Fatty acid changes were not significant during storage. Droplet size was reduced by increasing xanthan gum. T2 had the best rheological properties during storage. Generally, T2 and T3 had higher scores and were more acceptable in organoleptic assay. Conclusion: Obtained results showed that T2 had suitable qualitative and rheological properties and can be a proper egg yolk free salad dressing to introduce to the market.

Omega-3 Fatty Acids and Cholesterol Have a Main Role in Antidepression Diet of Iranian Traditional Medicine.

Depression is one of the major health problems of our world. Recent studies have revealed the relationship between diet and depression. In Iranian traditional medicine, there is a therapeutic diet that is recommended in melancholic diseases like depression. One of the main components of this diet is meat. Meats are divided into 2 groups: recommended and abstinent. The aim of this study was to clarify the logic of this diet through comparing nutritional elements of the 2 groups with each other. For this purpose, prominent books on Iranian traditional medicine were searched for abstinent and recommended meats traditionally prescribed for depressed patients. The results of each group were compared with the other by using Mann-Whitney Test (SPSS version 16). The results showed that recommended meats contain higher amounts of polyunsaturated fatty acids ( P = .01) especially omega-3 ( P = .03). Both groups contain high amounts of cholesterol. Iranian traditional medicine recommends consumption of meats that contains cholesterol with omega-3 fatty acids in depression.

Characterization of the milk lipid fraction in non-dairy sheep breeds

Abstract. Studies regarding the composition of milk fat are mostly conducted on dairy breeds. The aim of our studies was to evaluate the fatty acid, cholesterol and phospholipid amount in the milk of two non-dairy sheep breeds. The study was conducted on 60 ewes (Żelaźnieńska strain of Polish Lowland sheep – 30 ewes; Wrzosówka breed – 30 ewes) from one flock which were kept under the same conditions and maintenance. There were no differences in the amount of the basic components of milk in these two breeds. In the lipid fraction of Wrzosówka sheep (a more primitive breed), higher amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (P ≤ 0.05), a higher amount of polyunsaturated fatty acids (PUFAs) n-3 (P ≤ 0.01) and a lower ratio of n-6 / n-3 (P ≤ 0.01) were recorded compared to Żelaźnieńska sheep. The milk of Żelaźnieńska sheep had a higher amount of cholesterol (P ≤ 0.05). There were no differences in concentrations of phospholipids. With regard to the two non-dairy sheep breeds, a higher amount of PUFAs n-3 and a more favorable ratio of n-6 / n-3 was observed in the milk of the more primitive breed (i.e., Wrzosówka sheep).

Effect of U18666a on Beta-Glucosidase, Sphingomyelinase, and Beta-Galactosidase Activities in Astrocytes of Young Rats

Niemann-Pick type C disease (NPC) is a neurodegenerative genetic disorder caused by accumulation of lipids, especially cholesterol, in the perinuclear space. U18666A is a cholesterol transport-inhibiting agent, being used to mimic NPC, mainly in fibroblasts. The objective of this study was to observe the effect of the drug U18666A, which causes the accumulation of cholesterol in the cytoplasm of astrocytes from newborn rats, on some lysosomal hydrolase activities. Filipin staining and fluorescence microscopy, through CellM software, were used for visualization and quantification of cholesterol. The dose of U18666A that provided the greatest accumulation of cholesterol was that of 0.25 µg/mL in incubation for 48 h. Primary rat astrocytes incubated with the drug (NPC) showed a significantly higher amount of cholesterol than those without U18666A (controls). The measurement of activity of enzymes sphingomyelinase and beta-glucosidase in astrocytes of rats with NPC was significantly lower than that of control astrocytes, which is consistent with the disease in humans. The activity of the enzyme beta-galactosidase showed no significant difference between both groups. We concluded that U18666A appears to be an excellent intracellular cholesterol transport-inhibiting agent affecting some metabolic pathways in astrocytes of young rats, which mimics NPC in these animals. Just like the change in the activity of lysosomal enzymes has been demonstrated, other biochemical parameters of the cell can be tested with this animal model, thus contributing to a better understanding of the disease.

Hypolipidemic potential of squid homogenate irrespective of a relatively high content of cholesterol.

BackgroundOur previous study has shown that regardless of a relatively high amount of cholesterol, squid homogenate lowers serum and hepatic cholesterol in animals. Since this work, we have developed a new method to inhibit autolysis of squid proteins with sodium citrate. This study aims to investigate how squid homogenate prepared with sodium citrate affects lipid metabolism in Sprague–Dawley rats at the molecular level.MethodsWe prepared squid homogenate with sodium citrate to inhibit autolysis of squid protein. In Experiment 1 (Exp. 1), rats were given a cholesterol-free control diet or a squid diet, with squid homogenate added at the level of 5% as dietary protein for 4 weeks. Blood, the liver and adipose tissue were taken after 6 hours fasting. Serum and hepatic lipids and activities of enzymes related to lipid metabolism were measured. In Experiment 2 (Exp. 2), the above-mentioned diets had cholesterol added at the level of 0.1% and given to rats. Lipid parameters, enzyme activities, and gene expression of proteins involved in lipid metabolism in the liver and the small intestine were determined. In addition, feces were collected for two days at the end of Exp. 2 to measure fecal excretion of steroids.ResultsIn Exp.1, serum triglyceride and cholesterol were ~50% and ~20% lower, respectively, in the squid diet-fed rats than in the control diet-fed animals while hepatic cholesterol was ~290% higher in the squid diet-fed rats. When cholesterol was included into the diets (Exp. 2), serum lipids were significantly lower in the squid group while no difference of hepatic lipid was seen between two groups. Activities of hepatic lipogenic enzymes were significantly lower in rats on the squid diet while the enzyme responsible for fatty acid oxidation was not modified (Expt. 1 and 2). Hepatic level of mRNA of microsomal triglyceride transfer protein was significantly lower in the squid group. In the small intestine, the squid diet exhibited significantly lower gene expression of proteins involved in fatty acid transport and cholesterol absorption. Fecal secretion of acidic steroids, but not neutral steroids, was higher in rats fed the squid diet than in those fed the control diet.ConclusionThese results imply that newly-developed squid homogenate has hypolipidemic potential primarily through decreased absorption of bile acids in the small intestine and suppressed lipogenesis in the liver.

Effect of serum, cholesterol and low density lipoprotein on the functionality and structure of lung surfactant films.

Lung surfactant is a complex mixture of lipid and protein, responsible for alveolar stability, becomes dysfunctional due to alteration of its structure and function by leaked serum materials in disease. Serum proteins, cholesterol and low density lipoprotein (LDL) were studied with bovine lipid extract surfactant (BLES) using Langmuir films, and bilayer dispersions using Raman spectroscopy. While small amount of cholesterol (10 wt%) and LDL did not significantly affect the adsorption and surface tension lowering properties of BLES. However serum lipids, whole serum as well as higher amounts of cholesterol, and LDL dramatically altered the surface properties of BLES films, as well as gel-fluid structures formed in such films observed using atomic force microscopy (AFM). Raman-spectroscopic studies revealed that serum proteins, LDL and excess cholesterol had fluidizing effects on BLES bilayers dispersion, monitored from the changes in hydrocarbon vibrational modes during gel-fluid thermal phase transitions. This study clearly suggests that patho-physiological amounts of serum lipids (and not proteins) significantly alter the molecular arrangement of surfactant in films and bilayers, and can be used to model lung disease.

Resurrection plants of the genus Ramonda: prospective survival strategies – unlock further capacity of adaptation, or embark on the path of evolution?

Paleoendemic species of the monophyletic genus Ramonda (R. myconi, R. serbica and R.~nathaliae) are the remnants of the Tertiary tropical and subtropical flora in Europe. They are the rare resurrection plants of Northern Hemisphere temperate zone. Ramonda serbica and R. nathaliae are chorologically differentiated in the Balkan Peninsula and occupy similar habitats in calcareous, northward slopes in canyons and mountainsides. They remain well-hydrated during spring, late autumn and even in winter. In summer and early autumn when plants are subjected to drought and thermal stress, their desiccation tolerance comes into operation and they fall into anabiosis. Investigations revealed the permanent presence of ubiquitine and its conjugates, high amounts of oxalic acid and proline. Both species are homoiochlorophyllous. It enables them to rapidly resume photosynthesis upon rehydration, but also makes them susceptible to reactive oxygen species formation. Dehydration induces activation of antioxidative enzymes (ascorbate peroxidase, glutathione reductase, polyphenol oxidase), increase in amounts of AsA and GSH, phenolic acids, dehydrins, sucrose, and inorganic ions. Plasma membranes, characterized by high amount of cholesterol, are subjected to decrease in membrane fluidity mostly on account of increased level of lipid saturation. Cytogenetic analysis revealed that R. nathaliae is a diploid (2n = 48) and probably evolutionary older species, while R. serbica is a hexaploid (2n = 144). Two species live together in only two localities forming hybrid individuals (2n = 96). Polyploidization is the major evolutionary mechanism in the genus Ramonda that together with hybridization ability indicates that these relict species which have preserved an ancient survival strategy are not the evolutionary “dead end.”The species of the genus Ramonda are promising sources of data important for understanding the complex strategy of resurrection plants’ survival, appraised through a prism of their evolutionary and adaptive potential for multiple environmental stresses.

Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition

BackgroundThe activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the response to chemotherapy in multidrug resistant (MDR) tumors.MethodsWe studied the effect of omega 3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in human chemosensitive colon cancer HT29 cells and in their MDR counterpart, HT29-dx cells.ResultsMDR cells, which overexpressed Pgp and MRP1, had a dysregulated cholesterol metabolism, due to the lower expression of ubiquitin E3 ligase Trc8: this produced lower ubiquitination rate of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCoAR), higher cholesterol synthesis, higher cholesterol content in MDR cells. We found that DHA and EPA re-activated Trc8 E3 ligase in MDR cells, restored the ubiquitination rate of HMGCoAR to levels comparable with chemosensitive cells, reduced the cholesterol synthesis and incorporation in DRMs. Omega 3 PUFAs were incorporated in whole lipids as well as in DRMs of MDR cells, and altered the lipid composition of these compartments. They reduced the amount of Pgp and MRP1 contained in DRMs, decreased the transporters activity, restored the antitumor effects of different chemotherapeutic drugs, restored a proper tumor-immune system recognition in response to chemotherapy in MDR cells.ConclusionsOur work describes a new biochemical effect of omega 3 PUFAs, which can be useful to overcome chemoresistance in MDR colon cancer cells.