Increase In Cholesterol Content Research Articles

Effects of Diet-Induced Weight Loss on Plasma Markers for Cholesterol Absorption and Synthesis: Secondary Analysis of a Randomized Trial in Abdominally Obese Men.

Cross-sectional studies have shown that obesity is associated with lower intestinal cholesterol absorption and higher endogenous cholesterol synthesis. These metabolic characteristics have also been observed in patients with type 2 diabetes, metabolic syndrome, steatosis or cholestasis. The number of intervention studies evaluating the effect of weight loss on these metabolic characteristics is, however, limited, while the role of the different fat compartments has not been studied into detail. In a randomized trial, abdominally obese men (N = 54) followed a 6-week very low caloric (VLCD) diet, followed by a 2 week weight-maintenance period. Non-cholesterol sterols were measured at baseline and after 8 weeks, and compared to levels in lean participants (N = 25). After weight loss, total cholesterol (TC)-standardized cholestanol levels increased by 0.18 µmol/mmol (p < 0.001), while those of campesterol and lathosterol decreased by 0.25 µmol/mmol (p < 0.05) and 0.39 µmol/mmol (p < 0.001), respectively. Moreover, after weight loss, TC-standardized lathosterol and cholestanol levels were comparable to those of lean men. Increases in TC-standardized cholestanol after weight loss were significantly associated with changes in waist circumference (p < 0.01), weight (p < 0.001), BMI (p < 0.001) and visceral fat (p < 0.01), but not with subcutaneous and intrahepatic lipids. In addition, cross-sectional analysis showed that visceral fat fully mediated the association between BMI and TC-standardized cholestanol levels. Intrahepatic lipid content was a partial mediator for the association between BMI and TC-standardized lathosterol levels. In conclusion, diet-induced weight loss decreased cholesterol synthesis and increased cholesterol absorption. The increase in TC-standardized cholestanol levels was not only related to weight loss, but also to a decrease in visceral fat volume. Whether these metabolic changes ameliorate other metabolic risk factors needs further study.

Study of cholesterol phase effect on the dynamics of DOPC and DPPC small vesicle membranes using single-molecule fluorescence correlation spectroscopy

The effect of gradual cholesterol increase on the dynamics of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes of small unilamellar vesicles (SUVs) sized below 50 nm was explored using single-molecule fluorescence correlation spectroscopy (SM-FCS). The dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine (DiD) was entrenched into the membrane as a fluorescent probe, and silica nanoparticles were used to obtain SUVs of similar size, termed Si-supported small unilamellar vesicles (Si-SUVs). Si-SUVs of three different compositions for each DOPC and DPPC with cholesterol were synthesized. Auto-correlation and cross-correlation methods were implemented to analyze the fluorescence trajectories of single DiD molecules to determine their diffusion frequencies and triplet state lifetimes. The rigidity of the DOPC membrane increased with increasing cholesterol concentration, which led to an increase of the triplet state lifetime and a decrease in the diffusion frequency of DiD molecules. Thus, pure DOPC Si-SUVs, homogeneous in nature, showed a single block in the 2D correlation plot between triplet state lifetime and diffusion frequency, whereas multiple blocks appeared in the case of cholesterol-added DOPC Si-SUVs due to the inhomogeneity of the rigid membrane. On the contrary, DPPC Si-SUVs showed a reverse effect, where the membrane rigidity decreased with increasing cholesterol concentration. Thus, three blocks in the 2D plot of pure DPPC Si-SUVs were merged into one block when the cholesterol concentration in the membrane reached 40% of the total molar concentration as the membrane became homogeneous.

Effects of cholesterol on the size distribution and bending modulus of lipid vesicles.

The influence of cholesterol fraction in the membranes of giant unilamellar vesicles (GUVs) on their size distributions and bending moduli has been investigated. The membranes of GUVs were synthesized by a mixture of two elements: electrically neutral lipid 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and cholesterol and also a mixture of three elements: electrically charged lipid 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG), DOPC and cholesterol. The size distributions of GUVs have been presented by a set of histograms. The classical lognormal distribution is well fitted to the histograms, from where the average size of vesicle is obtained. The increase of cholesterol content in the membranes of GUVs increases the average size of vesicles in the population. Using the framework of Helmholtz free energy of the system, the theory developed by us is extended to explain the experimental results. The theory determines the influence of cholesterol on the bending modulus of membranes from the fitting of the proper histograms. The increase of cholesterol in GUVs increases both the average size of vesicles in population and the bending modulus of membranes.

Effect of immunocastration using Improvac on the regulation of adiponectin and leptin in the testes of Landrace boars

Immunological castration of male pigs is an attractive alternative to surgical castration used in many countries to reduce the production of the main androgen, androstenone, and skatole, responsible for meat taint. To understand the effect of gonadoliberin (GnRH) vaccination with Improvac on the functional status of Landrace pig testes at the molecular level the role of adipokines was studied. Using western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay, we explored adipokine and leptin signaling and evaluated cholesterol concentrations. In control testis, adiponectin and its receptors were localized to interstitial Leydig cells and spermatogenic cells (especially adiponectin and its receptor 2) while in immunocastrates spermatogenic cells were negative. In control, leptin was exhibited by spermatids and Leydig cells while its receptor only by the later cells. In immunocastrates, leptin immunosignal was not found in spermatogenic cells. In addition, for all studied proteins, the immunosignal was of moderate or weak intensity when compared to the control. Concomitantly, decreased expression of all proteins (p&lt;0.5) was detected. Similarly, in immunocastrates, cholesterol concentrations were increased (p&lt;0.01). In summary, we showed for the first time the coincidence of disturbed adiponectin signaling and leptin signaling together with increased cholesterol concentration and attenuated spermatogenesis as a result of halted androstenone production. Altered GnRH signaling affects the adipokine system in testes of Landrace castrates which may impact further functional changes leading to complete spermatogenesis alteration, as well as lipid homeostasis and fattening perturbances

Analysis of the effects of caffeine and dioxidine on biochemical indicators of blood in mouse

Relevance . In connection with the widespread use of caffeine, an important issue is the study of its interaction with substances that can exhibit toxic effects. Objective. The aim of the study is to assess the degree of influence of caffeine and dioxidine on the biochemical parameters of blood in mice in the forced swimming test. Materials and methods. The studies were carried out on 6 groups of male mice: control and five experimental. During 15 days of the experiment, the animals of the control group were injected with physiological saline, and the experimental animals were injected with caffeine at a dose of 40 mg/kg or 100 mg/kg (1 and 2), dioxidine in an amount of 200 mg/kg (3), and caffeine was combined and dioxidine (4 and 5). Biochemical parameters were used to determine the content of glucose, cholesterol, urea, creatinine, the activity of aspartic and alanine aminotransferases. Results . The introduction of caffeine at a dose of 40 mg/kg led to a decrease in glucose levels below normal and an increase in cholesterol and urea concentrations. The use of caffeine at a dose of 100 mg/ kg caused a decrease in glucose levels below normal and an increase in urea concentration. With the introduction of dioxidine at a dose of 200 mg/kg, an increase in the level of glucose, cholesterol, urea, as well as the activity of AST and ALT was taken. The combined use of caffeine and dioxidine by the 15th day led to 100 % mortality in experimental animals. Conclusions . The results of the experiment indicate that the introduction of caffeine at a dose of 40 mg/kg and 100 mg/kg leads to an increase in most of the measured parameters relative to the control values, but they do not go beyond normal values, however, a decrease in glucose levels is noted. These changes in indicators are due to the predominance of catabolic processes over anabolic ones. In animals treated with dioxidine, a significant increase in the concentration of metabolites and the activity of blood enzymes was found, especially an increase in AST and ALT was noted, which indicates a predominant lesion of cardiomyocytes. The mortality rate of the experimental groups receiving caffeine and dioxidine together by the last day of the experiment is due to the action of an excessive stress factor leading to the depletion of the adaptive capabilities of the organism and the death of experimental animals.

Particition of Sodium-potassium Adenosine Triphosphatases in Homeostasis Regulation

A literature review presented an analysis of data regarding the mechanisms of the Na pump in nephron and hormonal regulators of enzyme activity, including enzymatic catalysts. Investigating the regulatory mechanisms of metabolic processes can facilitate the development of new strategies to repair various pathological conditions. Among these functional proteins, Na+/K+ATPase is responsible for the regulation of hydroionic homeostasis and signaling. Ion transport in different parts of the nephron is mediated via sodium transporters, which are characterized by a clear topographical expression. In the oligomeric Na+/K+ATPase molecule, the α-subunit comprises 10 transmembrane domains and performs a catalytic function. The signal function of Na+/K+ATPase and its interaction with the molecular environment in lipid microdomains involve rafts and caveolae. Analysis of the literature data demonstrated an important function of Na+/K+ATPase, along with its interaction with caveolin-1, in the regulation of intracellular cholesterol traffic. Moreover, reciprocal interactions of enzymes and cholesterol have been indicated. The status of Na+/K+ATPase activity is affected by hypoxia, reactive oxygen species, lipid peroxidation (LPO), increased cholesterol concentrations, and the viscosity of the cytoplasmic membrane. Ecological pollutants, including heavy metals, have significant effects on enzyme activity in nephron, hepatocytes and cardiomyocytes. Thus, available literature data indicate an important role of Na+/K+ATPase in the regulation of metabolic processes.

Axonal plasma membrane-mediated toxicity of cholesterol in Alzheimer's disease: A microsecond molecular dynamics study

Alzheimer's disease is increasingly being recognized as an immune-mediated disease of brain. Since physiological brain health and brain immune function is dependent upon homeostatic neuronal membrane structure and function, alterations in membrane lipid biochemistry may predispose to disease. Brain is rich in cholesterol, and cholesterol metabolism dysfunction is a known risk factor for AD. Employing extensive microsecond all-atom molecular dynamics simulations, we investigated the properties of model neuronal membranes as a function of cholesterol concentration; phospholipid and phospholipid/cholesterol bilayers were also simulated to compare against available experimental data. Increased cholesterol concentrations compact and stiffen the lipid membrane, reducing permeability while modulating local water densities in the peri-membranous environment. Conversely, lower cholesterol mole fraction yields membranes with increased molecular disorder, enhanced fluidity, higher molecular tilting, and augmented interdigitation between bilayer leaflet lipids. Our findings provide a molecular insight on effect of cholesterol composition on various biochemical processes occurring at neuronal axon plasma membrane. These calculations also endeavor to establish a membrane-based link between cholesterol as an AD risk factor and possible AD pathology.

Hypercholesterolemia in children and adolescents: focus on the familial variant

Familial hypercholesterolemia is characterized by a significant increase in serum low-density lipoprotein cholesterol concentration, which even in the absence of other risk factors leads to the development of atherosclerotic vascular lesions beginning in childhood. With significant prevalence in the population, familial hypercholesterolemia is rarely diagnosed in time due to the Long absence of clinical manifestations. Today the urgent task is to develop and implement programs of primary detection of familial hypercholesterolemia in children and adolescents. Early detection of patients with familial hypercholesterolemia and timely initiation of adequate lipid-lowering therapy will curb the rate of atherosclerosis progression, which will significantly reduce disability and mortality from cardiovascular diseases in older age groups. There are four types of screening: cascade, targeted, opportunistic and universal. Cascade screening is currently considered the most effective and cost-effective way to identify new patients with familial hypercholesterolemia among relatives of an index patient, the patient with the established diagnosis. Targeted screening is based on searching for individuals with familial hypercholesterolemia among groups of patients with the early development of atherosclerotic vascular lesions, for example, in cardiology or neurology hospitals. Opportunistic screening is a non-systematic, sporadic determination of cholesterol levels in patients seeking medical care for any reason. It is most applicable in primary care health care settings. Universal screening is a mass screening of certain age groups and is a highly effective way of early diagnosis, especially in combination with reverse cascade screening of parents, siblings, and other relatives of the index patient. Implementation of programs of early childhood detection of familial hypercholesterolemia, setting up systems of adequate routing of patients, timely prescription of effective lipid-lowering therapy will contribute to health preservation and prolongation of working age, development, and preservation of labor potential of the country.

Effects of an 8-week aerobic exercise program on plasma markers for cholesterol absorption and synthesis in older overweight and obese men

BackgroundIncreased physical activity is inversely related to the risk to develop cardiovascular disease (CVD). In a recent systematic review, it was reported that CVD patients had an increased cholesterol absorption and a decreased synthesis as compared with control participants. As increased physical activity levels reduce CVD risk, we hypothesized that exercise training will reduce cholesterol absorption and increase endogenous cholesterol synthesis in older overweight and obese men.MethodsA randomized, controlled, crossover trial was performed. Seventeen apparently healthy older overweight and obese men were randomized to start with an aerobic exercise or no-exercise control period for 8 weeks, separated by 12 weeks washout. Fasting serum total cholesterol (TC) and non-cholesterol sterol concentrations were measured at baseline, and after 4 and 8 weeks.ResultsThe aerobic exercise program did not affect serum TC concentrations. In addition, exercise did not affect TC-standardized serum concentrations of sitosterol and cholestanol that are markers for cholesterol absorption. However, a trend for reduced TC-standardized campesterol concentrations, which is another validated marker for cholesterol absorption, was observed as compared with control. Lathosterol concentrations, reflecting cholesterol synthesis, did not differ between both periods.ConclusionsAerobic exercise training for 8 weeks did not lower serum TC concentrations in older overweight and obese men, but a trend towards a decrease in the cholesterol absorption marker campesterol was found. The cholesterol synthesis marker lathosterol did not change.Trial registrationposted on www.clinicaltrials.gov as NCT03272061 on 7 September 2017.

BIOCHEMICAL EFFECT OF THYROID HORMONES ON HEART FAILURE

Thyroid hormones and heart-failure disease (HF) are inextricably linked, as the fact has been established the thyroid causes heart muscle weakness. The goal of the study estimates the link of thyroid hormones and the risk of heart failure disease by measuring T4, T3, fT4, fT3, cholesterol, TG, HDL, LDL, VLDL and BMI in serum of 65 patients of heart failure disease and 40 control group. The results showed a decrease significantly in the concentration of T4, T3, fT4, fT3 and HDL compared to the healthy group at P≤0.001 (53.88±29.5 nmol/ml), P=0.02 (1.77±0.8 nmol/ml), P≤0.001 (8.94±4.1 pmol/ml), P≤0.001(2.85±1.5 pmol/ml) and P≤0.001(31.13±8.2 mg/dL), respectively. Further, there was a significant increase in total cholesterol concentration, TG, LDL, VLDL and BMI compared to the healthy group at P≤0.001 (348.16±87.6 mg/dL), P≤0.001 (172.41±52.9 mg/dL) P≤0.001 (303.22±117.3 mg/dL), P≤0.001 (34.48±10.6 mg/dL) and P≤0.001 (28.68±4.5 Kg/m2), respectively. The study showed that there is a strong correlation between thyroid hormones and total cholesterol, LDL with high BMI. Therefore, we conclude that thyroid hormones spatially fT3 is a new indicates the increase of heart failure disease.

Cholesterol Hinders the Passive Uptake of Amphiphilic Nanoparticles into Fluid Lipid Membranes.

Plasma membranes represent pharmacokinetic barriers for the passive transport of site-specific drugs within cells. When engineered nanoparticles (NPs) are considered as transmembrane drug carriers, the plasma membrane composition can affect passive NP internalization in many ways. Among these, cholesterol-regulated membrane fluidity is probably one of the most biologically relevant. Herein, we consider small (2–5 nm in core diameter) amphiphilic gold NPs capable of spontaneously and nondisruptively entering the lipid bilayer of plasma membranes. We study their incorporation into model 1,2-dioleoyl-sn-glycero-3-phosphocholine membranes with increasing cholesterol content. We combine dissipative quartz crystal microbalance experiments, atomic force microscopy, and molecular dynamics simulations to show that membrane cholesterol, at biologically relevant concentrations, hinders the molecular mechanism for passive NP penetration within fluid bilayers, resulting in a dramatic reduction in the amount of NP incorporated.

Role of cholesterol flip-flop in oxidized lipid bilayers

We performed a series of molecular dynamics simulations of cholesterol (Chol) in nonoxidized 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine (PLPC) bilayer and in binary mixtures of PLPC-oxidized-lipid-bilayers with 0–50% Chol concentration and oxidized lipids with hydroperoxide and aldehyde oxidized functional groups. From the 60 unbiased molecular dynamics simulations (total of 161 μs), we found that Chol inhibited pore formation in the aldehyde-containing oxidized lipid bilayers at concentrations greater than 11%. For both pure PLPC bilayer and bilayers with hydroperoxide lipids, no pores were observed at any Chol concentration. Furthermore, increasing cholesterol concentration led to a change of phase state from the liquid-disordered to the liquid-ordered phase. This condensing effect of Chol was observed in all systems. Data analysis shows that the addition of Chol results in an increase in bilayer thickness. Interestingly, we observed Chol flip-flop only in the aldehyde-containing lipid bilayer but neither in the PLPC nor the hydroperoxide bilayers. Umbrella-sampling simulations were performed to calculate the translocation free energies and the Chol flip-flop rates. The results show that Chol’s flip-flop rate depends on the lipid bilayer type, and the highest rate are found in aldehyde bilayers. As the main finding, we shown that Chol stabilizes the oxidized lipid bilayer by confining the distribution of the oxidized functional groups.

Intensity of CD36 expression by monocyte subpopulations and blood lipid spectrum parameters in patients without established atherosclerotic cardiovascular disease

Introduction. At the current stage of the study of atherosclerosis, it has been established that chronic activation of innate immunity, causing persistent low-intensity sterile inflammation, plays a crucial role at all stages of atherogenesis. Laboratory evaluation of signaling pathways associated with molecular patterns (DAMPs) in atherosclerosis and related to cardiovascular diseases (CVD) may contribute to the discovery of new diagnostic and prognostic markers. Objective: to study the relationship between lipid metabolism parameters and CD36 exposure to circulating monocytes in patientwithout established CVD. Material and methods . The study included 42 patients aged 40–64 years without established atherosclerotic CVD, 19 (45.2 %) men and 23 (54.7 %) women. Dyslipidemia was detected in 95.2 % of patients. The blood serum concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, glucose, glycated hemoglobin, high-sensitivity C-reactive protein (hs-CRP), creatinine were determined with subsequent calculation of glomerular filtration rate. Phenotyping of circulating monocyte subpopulations was performed by flow cytometry on a Navios 6/2 device (Beckman Coulter, USA). Results and discussion . According to the results of correlation analysis, non-HDL cholesterol levels were inversely correlated with absolute ( r = –0.394; p = 0.013) and relative ( r = –0.432; p = 0.006) content of CD14 + CD16 ++ CD36 + TLR2 + monocytes. LDL cholesterol levels were also inversely correlated with the relative content of CD14 + CD16 + CD36 + TLR2 + monocytes ( r = –0.417; p = 0.018). According to correlation analysis, the level of non-HDL cholesterol inversely correlated with the intensity of CD36 expression on classical ( r = –0.650; p &lt; 0.0001), intermediate ( r = –0.323; p = 0.045) and non classical ( r = –0.480; p = 0.002) monocytes. Also, CD36 expression intensity on classical ( r = –0.449; p = 0.004) and non-classical ( r = –0.382; p = 0.016) monocytes was inversely correlated with remnant cholesterol levels. In addition, increased non-HLA cholesterol levels were associated with decreased TLR2 expression on CD14 + CD16 ++ monocytes ( r = –0.381; p = 0.018). It should be noted that a decrease in CD36 expression on intermediate monocytes was also associated with an increase in hs-CRP ( r = –0.657; p = 0.003). Conclusion . In patients without established atherosclerotic CVD, an increase in cholesterol content of atherogenic lipoprotein fractions was associated with a decrease in the number of CD14 + CD16 ++ and CD14 + CD16 + monocytes co-expressing CD36 and TLR2 as well as with a decrease in CD36 expression on classical, intermediate and non-classical monocytes.

Plant Ingredient diet supplemented with lecithin as fish meal and fish oil alternative affects growth performance, serum biochemical, lipid metabolism and growth‐related gene expression in Nile tilapia

The current study evaluated the effects of replacing fish meal (FM) and fish oil (FO) with plant ingredients without or with lecithin supplementation on Nile tilapia growth, blood biochemistry, intestinal morphology, growth- and lipid-metabolism-related gene expression. Fingerlings were assigned to six dietary groups: FM and FO (G1), FM and plant oil (G2), plant protein and plant oil (G3), and the same three treatments but with lecithin supplementation (G4–G6) respectively. Fingerlings in G1 and G2 showed higher body weight than fish in G3 (p > 0.05). Lecithin supplementation improved (p < 0.05) growth, particularly in fish fed plant ingredients (G6). Fish fed different diets showed a significant increase (p < 0.05) in serum total cholesterol and low-density lipoprotein concentrations compared with G1. Albumin concentration was significantly reduced in G3 and G6. Partial or complete replacement of FO and FM with plant ingredients, with or without lecithin, significantly modulated (p < 0.05) expression levels of some regulatory genes related to growth and lipid metabolism, with the highest expression in lecithin-supplemented fish. It could be concluded that the complete replacement of FM and FO with plant ingredients (plant protein and oil) non-significantly reduced fish performance. Nevertheless, with lecithin supplementation, Nile tilapia can effectively utilize this plant-based diet as reflected with enhanced growth.

Lipid Nanoparticle Spherical Nucleic Acids for Intracellular DNA and RNA Delivery.

Lipid nanoparticle SNAs (LNP-SNAs) have been synthesized for the delivery of DNA and RNA to targets in the cytoplasm of cells. Both the composition of the LNP core and surface-presented DNA sequences contribute to LNP-SNA activity. G-rich sequences enhance the activity of LNP-SNAs compared to T-rich sequences. In the LNP core, increased cholesterol content leads to greater activity. Optimized LNP-SNA candidates reduce the siRNA concentration required to silence mRNA by 2 orders of magnitude compared to liposome-based SNAs. In addition, the LNP-SNA architectures alter biodistribution and efficacy profiles in mice. For example, mRNA within LNP-SNAs injected intravenously is primarily expressed in the spleen, while mRNA encapsulated by LNPs (no DNA on the surface) was expressed primarily in the liver with a relatively small amount in the spleen. These data show that the activity and biodistribution of LNP-SNA architectures are different from those of conventional liposomal SNAs and therefore potentially can be used to target tissues.

The protective effects of Spirulina against Nonalcoholic fatty liver disease induced by high fat diet in rats

The ultimate goal of this study is to investigate the bimolecular changes in a rat model of high fat diet induced Nonalcoholic fatty liver disease (NAFLD). Also, the lipotropic, antioxidant and anti-inflammatory effects of spirulina platensis treatment were clarify through evaluation of certain biochemical and molecular parameters in the blood and liver tissue of rats. Twenty one adult white albino rats were separated into three groups. Group I (Normal control): received no drugs and balanced diet, Group II (NAFLD- induced group): rats fed high fat diet for 8 weeks followed by normal basal ration feeding for another 8 weeks. Group III (NAFLD + spirulina): rats treated with spirulina orally at a dose of (150 mg/kg b.wt/day) for 8 weeks after induction of NAFLD. The obtained results showed a significant increase in serum total cholesterol (TC) and triacylglycerols (TAG) concentrations with significant up-regulation of liver gene expression TNF-α, IL-1β, NF-kβ, PPAR-α, ACC, FAS and SREBT-1in NAFLD- induced rats. Also, various histopathological alterations were detected in liver tissue of induced NAFLD rats. Treatment with spirulina in NAFLD-induced rats parameters measured near the normal level of rats group (G1). Also, spirulina potentially improved molecular hepatic function alterations related to NAFLD. Interestingly, histopathological findings supported that spirulina markedly attenuates harmful effects of NAFLD and protects liver tissue. We conclude that, spirulina has a great role as antioxidant, anti-obesity and anti-inflammatory via inhibition of liver lipid metabolic disturbance, steatosis and oxidative stress singling.

Beneficial effects of Omega-3 polyunsaturated fatty acids in treatment of non-alcoholic fatty liver disease in rats.

Nonalcoholic fatty liver disease (NAFLD) is sickness with different causes and it is the most hepatic illness. The objective of this work is to investigate the bimolecular changes in a model of high fat diet induced- NAFLD in rats. Also, the hypolipidemic, antioxidant and anti-inflammatory effects of omega-3 were clarify via evaluation of some biochemical and molecular parameters in the liver tissue of rats.Twenty one adult white albino rats were divided into three groups. Group I (Normal control): received no drugs and fed balanced diet, Group II (NAFLD- induced group): rats fed high fat diet for 8 weeks followed by normal basal ration for additional 8 weeks. Group III (NAFLD + omega-3): rats administrated omega-3 (300 mg/kg b.wt/day), orally for 8 weeks post-induction of NAFLD. The obtained results showed a significant increase in serum Total cholesterol and Triacylglycerols (TAG) concentrations, L-MDA and TAC in liver tissuewith significant up-regulation in CPT-1α, FAS, SREBP-1c, PPAR-α, Nrf2 and TAK1gene expression in NAFLD-induced rats. Treatment with Omega-3 to NAFLD induced rats potentially improved molecular hepatic cell function and oxidative alterations related to NAFLD near its normal ranges. Meanwhile, histo-pathological findings supported that Omeg-3 markedly attenuates harmful effects of NAFLD and protected liver cell. On conclusion, Omega-3 plays an important role as potent anti-oxidant, anti-obesity, anti-inflammatory via inhibition of hepatic steatosis and oxidative stress singling.

Characterization and in-vivo toxicological evaluation of imidacloprid nanoemulsion in rats

Acute pesticide poisoning is an important public health problem worldwide and accounts for a significant number of deaths occurring each year. The present article aimed to investigate toxic effects of imidacloprid (IMD) nanoemulsion formulated using ultrasound dispersion technique, and characterized using FTIR, TEM anddynamic light scattering in adult rats. The synthesized Nano-emulsion droplets are mainly spherical in shape and their sizes ranged between (19nm –128 nm) with zeta potential of −38.8± 0.mV. Also, The median lethal dose (LD50) of nano imidacloprid in rats was 39 mg/kg body weight. Administration of different doses of 3, 1.4 and 0.8 mg.kg mg/kg b.wt. of IMD Nano emulsion to rats for 21 days, adversely affects the body weight and weight gain, and resulted in a significant increase in serum serum ALT, AST activities , glucose, Creatinine, urea and cholesterol concentrations, as well as reduced serum total proteins, Albumin and globulin as compared to control rats. The results clearly suggest that treatment with IMD nanoemulsion adversely affects the liver &amp; kidney functions which confirmed by the histopathological findings. Nanoemulsion form and also increases the DNA damage as confirmed by the comet test

STUDY OF SEMEN CHARACTERISTICS AT SEXUAL MATURITY IN AWASSI LAMBS FED ON LOW DEGRADABLE SUNFLOWER MEAL AND SEEDS

This study was conducted using 18 Awassi male lambs with an average initial weight 33.57 ± 0.69 kg for the period from 9-12 months of age. Lambs were distributed randomly into three treatments each, included 6 lambs. Lambs in the first treatment (T1) were fed a diet that includes 11% of sunflower meal, the second treatment (T2) fed diet includes 11% of low degradable sunflower meal, and the third treatment (T3) were fed on a diet containing 11% low degradable sunflower seed. The results were indicated a significant increase (P≤ 0.05) in semen volume in (T2) 2.77 ml compared with the (T1) 1.98 ml and (T2)1.69 ml. Significant improve (p≤ 0.05) was noted in T2 and T3 in individual motility 87.33 and 87.70% and sperm concentration 2.45 and 2.62 × 109 / ml compared to the T1 the individual motility was 84.95% and sperm concentration 2.10 × 109 / ml, respectively. Seminal plasma concentration of total protein, globulin, and urea were higher (P≤ 0.05) in T2 as compared other treatments. Whereas, feeding low degradable sunflower seed (T3) resulted in a significant increase (P≤ 0.01) of cholesterol concentration 140.05 mg/dl in seminal plasma compared with the T1 122.78 mg/dl and T2 125.81 mg/dl, while triglycerides was decreased (P≤ 0.05) in T1 37.49 mg/dl than T2 and T3 52.72 and 58.92 mg/dl respectivly. This study was conducted using 18 Awassi male lambs with an average initial weight 33.57 ± 0.69 kg for the period from 9-12 months of age. Lambs were distributed randomly into three treatments each, included 6 lambs. Lambs in the first treatment (T1) were fed a diet that includes 11% of sunflower meal, the second treatment (T2) fed diet includes 11% of low degradable sunflower meal, and the third treatment (T3) were fed on a diet containing 11% low degradable sunflower seed. The results were indicated a significant increase (P≤ 0.05) in semen volume in (T2) 2.77 ml compared with the (T1) 1.98 ml and (T2)1.69 ml. Significant improve (p≤ 0.05) was noted in T2 and T3 in individual motility 87.33 and 87.70% and sperm concentration 2.45 and 2.62 × 109 / ml compared to the T1 the individual motility was 84.95% and sperm concentration 2.10 × 109 / ml, respectively. Seminal plasma concentration of total protein, globulin, and urea were higher (P≤ 0.05) in T2 as compared other treatments. Whereas, feeding low degradable sunflower seed (T3) resulted in a significant increase (P≤ 0.01) of cholesterol concentration 140.05 mg/dl in seminal plasma compared with the T1 122.78 mg/dl and T2 125.81 mg/dl, while triglycerides was decreased (P≤ 0.05) in T1 37.49 mg/dl than T2 and T3 52.72 and 58.92 mg/dl respectivly.

Investigation of water-insoluble hydrophobic polyethylenimines as RNAi vehicles in chronic myeloid leukemia therapy.

The discovery of RNA interference (RNAi) more than two decades ago opened avenues for avant-garde cancer treatments that possess the ability to evade issues hampering current chemotherapeutic strategies, owing to its specific gene sequence-driven mechanism of action. A potent short interfering RNA (siRNA) delivery vehicle designed to overcome physiological barriers is imperative for successful RNAi therapy. For this purpose, this study explored the characteristics and therapeutic efficacy of low-molecular weight (MW) polyethylenimine (PEI) with high cholesterol substitution, yielding water-insoluble polymers, in chronic myeloid leukemia (CML) K562 cells. A strong impact of cholesterol grafting on the physicochemical attributes of the resultant polymers and their corresponding complexes with siRNA was observed, with the siRNA binding capacity of polymers increasing and complex dissociation sensitivity decreasing with increase in cholesterol content of the polymers. The modified polymer complexes were significantly smaller in size and possessed higher cationic charge compared to the parent polymer. The interaction with anionic heparan sulfate preoteoglycans present on the cell surface was significant in cellular uptake of the complexes. The therapeutic efficacy of siRNA/polymer complexes was reflected in their ability to effectively silence the reporter green fluorescent protein gene and endogenous CML oncogene BCR-ABL as well as significantly inhibit colony formation by K562 cells post BCR-ABL silencing. The results of this study demonstrated beneficial effects of high levels of hydrophobic substitution on low MW PEI on their functional performance bestowing them the potential to be potent RNAi agents for CML therapy.