The cumulative effect of the combined action of miR-101 and curcumin in a liposome on a model of Alzheimer's disease in mononuclear cells.

The leading pathological mechanisms of Alzheimer's disease (AD) are amyloidosis and chronic inflammation. The study of new therapeutic drugs of the corresponding action, in particular miRNAs and curcominoids, as well as methods for their packaging, is topical. The aim of the work was to study the effect of miR-101 + curcumin in a single liposome in a cellular AD model.

Effect of curcumin on accumulation in mononuclear cells and secretion in incubation medium of Аβ(40) and cytokines under local excess of Аβ(42)-homoaggregates.

The aim of the work was to investigate accumulation of endogenous Aβ40 and cytokines (IL-1β, TNFα, IL-6, IL-10) in mononuclear cells and their secretion into incubation medium under Aβ42-aggregates’ toxicity and anti-inflammatory effects of curcumin. Mononuclear cells were isolated in Ficoll-Urografin density gradient from venous blood of healthy donors, resuspended and used for testing of homoaggregates of Aβ42 (15 nM), curcumin (54 pM) and their combinations on various timescales (0, 1, 2, 3, 6 and 24 hours). Endogenous Aβ40 and cytokines were detected in mononuclear cells and (separately) in incubation medium by ELISA.

Effect of β-amyloid peptide 42 on the dynamics of expression and formation of Аβ40, IL -1β, TNF α, IL -6, IL -10 by peripheral blood mononuclear cells in vitro and its correction by curcumin.

The toxic effect of Аβ-oligomers accompanies chronic inflammation, with cytokines as main mediators. Therefore, the cytokine link of inflammation becomes a new target on the way to restrain amyloidosis. The aim of the study was the effect of aggregated Аβ42 on the dynamics of expression and formation of endogenous Аβ40 and cytokines (IL-1β, TNFα, IL-6, IL-10) by peripheral blood mononuclear cells in vitro and its correction by curcumin.

[Cytokines neuroinflammatory reaction to the action of homoaggregatic and liposomal forms of b-amyloid 1-40 in rats].

An injection model of preclinical stages of Alzheimer's disease has been reproduced in rats. It was accompanied by the decrease in the latent period of conditioned reflex avoidance, increasing levels of endogenous b-amyloid peptide 1-40 and activation of inflammatory cytokines (IL-1b, TNF-a, IL-6, IL-10) in the cerebral cortex, hippocampus and blood serum of experimental animals. We belive that changes identified at the biochemical level are prerequisite to modulate neuronal functions in rats induced by Ab40_Human administration.

[Effect of valproic acid on SMN protein level in peripheral blood mononuclear cells of patients with spinal muscular atrophy and different SMN2 copy numbers].

Objective: Spinal muscular atrophy (SMA) is currently untreatable hereditary disorder caused by few types of mutations in the SMN1 gene and respective lack of gene's product - survival motor neuron protein (SMN). Last decade studies have shown that phenotype of the disorder is substantially influenced by copy numbers of homologous SMN2 gene; also, an ability of valproic acid to increase the level of SMN in vitro and in vivo has been shown. We investigated an effect of valproic acid on SMN level in peripheral blood mononuclear cells derived from patients with SMA and their parents and sought for possible predictors for treatment efficacy.

[Intensive protein synthesis in neurons and phosphorylation of beta-amyloid precursor protein and tau-protein are triggering factors of neuronal amyloidosis and Alzheimer's disease].

Recently the studies of Alzheimer's disease have become particularly actual and have attracted scientists from all over the world to this problem as a result of dissemination of this dangerous disorder. The reason for such pathogenesis is not known, but the final image, for the first time obtained on microscopic brain sections from patients with this disease more than a hundred years ago, is well known to clinicists. This is the deposition of Abeta amyloid in the brain tissue of senile plaques and fibrils.

[A short-term effect of lovastatin on lipoprotein metabolism in patients with cerebrovascular lesions concomitant with diabetes mellitus II type].

Changes of lipoprotein (LP) metabolism after lovastatin therapy (20 mg/day for 2 months) have been studied in patients with cerebrovascular lesions (CBL) concomitant with diabetes mellitus type 2 (DM-2) and in CBL patients without DM-2. Initial effect of lovastatin appeared in decreasing chilomicrone content in both groups of patients. A distinct trend towards restoration of processes converting apoA-containing LP being accompanied by normalization of function of the peripheral lipoprotein lipase bound form was observed.

[Characteristics of lipid composition of blood serum lipoproteins in insulin resistance].

The purpose of this investigation was to study lipid composition of apoB- and apoA-containing lipoproteines in conditions of insulin resistance pathology. It was shown that hypertriglycerolemia and hypercholesterolemia were determined by triglycerole and cholesterol surplus in the composition of both apoB- and apoA-containing lipoproteins. Phospholipid deficiency in the composition of all lipoproteins fractions were established.

[The lipoprotein metabolism in arterial hypertension, type II diabetes mellitus, and metabolic syndrome].

The apoA- and apoB-containing lipoprotein (LP) fractions, activity of free and linked forms of lipoprotein lipases (LPL) of liver and extrahepatic tissues, and also activity of lecithin:cholesterol acyltransferase (LCAT) were examined in the blood serum of patients with arterial hypertension, type II diabetes mellitus (DM-II), and metabolic syndrome (MS). Patients with DM-II had the most pronounced changes of all investigated LP fractions compared with healthy persons and patients of other groups examined. Decrease of LCAT activity corresponded to declining level of apoA-containing LP in DM-II and MS.

[Lipoprotein metabolism in patients with diabetes of type II].

Changes in contents of blood serum lipoproteins (LP) and activity of enzymes of their transformation were investigated in patients with diabetes mellitus of type II. It was found out that mechanisms of increasing of apoB-containing LP in these patients were on the one hand in enhancing of the processes of their new-formation in the liver. On the other hand, retardation of their arrival to peripheral tissues might be observed, that as a whole resulted in continuous LPLD circulation in blood.

[Changes in the lipoprotein metabolism in alcoholism do not recover during of prolonged remission].

Contents of lipoproteins (LP), activity of lipoprotein lipase (LP-lipase) and cholesterol esterification activity of blood serum were examined in patients with alcoholism at the periods of intoxication, alcohol abstinence and under conditions of prolonged remission. During remission a general pattern of apoB-containing LP was similar to the period of intoxication. Processes of transformation of this class LP significantly delayed in isolated blood serum in vitro.

[Depression of serum esterase and lipoprotein lipase activities in acute and longitudinal actions of ethanol].

Esterase (LCAT) and lipoprotein lipase (LPL) activities of blood serum, and a range of blood serum lipoproteins (LP) in acute and chronic ethanol intoxication were examined in healthy persons and patients with alcohol abuse. Ethanol inhibited LCAT and LPL activities, and increased apoA-containing LP in blood serum. These changes are considered as a basis for depression of a direct and reverse transportation of cholesterol in blood circulation under the action of ethanol.

[Role of heparin in the formation of food lipemia].

Influence of endogenic and exogenic heparin in vivo on the basic forms of serum lipids content: cholesterol ethers, triacylglycerols, free fatty acids; as well as that glycosaminoglycan effect in vivo and in vitro on total lipoproteine lipase (LPL) activity and lecithin-cholesterol acyltransferase (LCAT) activity of human blood serum were investigated on food lipidemia model. The decrease of intercell reserve heparin content and increase of the background and post-heparin levels of blood serum LPL activity were indicated after two hours food load. The role of two factors, endogenic heparin being one of them, in the increase of postprandial LPL activity of blood serum were discussed.

[Lipid-mobilizing effect of reduced glutathione and its intensifying action on lecithin-cholesterol acyltransferase activity in blood serum of rats].

Effect of reduced glutathione (50 mg/100 g) on lipid distribution between organs (liver and kidney) and lecithin-cholesterol acyltransferase (LCAT) activity in blood serum of rats was investigated. The accumulation of common lipids as a result of speeding up the absorbtion of blood serum unsaturated fatty acids and relative decrease of lipids unsaturation in the liver and lipid content dynamics in kidneys owing to the intensification of two processes in this organ: the transport of polyene fatty acids in composition of blood serum lipoprotein lipids to kidney cells and peroxidation of membrane phospholipids were found out. The activating effect of GSH (in vivo and in vitro) on LCAT activity of rat blood serum was shown.

[Investigation of lipoprotein metabolism in persons with abstinence].

Lipoprotein (LP) metabolism was investigated in the blood serum of persons with abstinence after ethanol intake in a single dose of (0.7-1.0) g/kg.

[Content and composition of lipoproteins of rat blood and liver and various parameters of oxidative stress during administration of cobalt chloride].

Cobalt chloride effect on rat liver and serum blood lipoproteins content and composition and on some characteristics of lipid peroxidation and oxidative stress was investigated. The activation of free-radical oxidation and oxidative stress development were judged from the dynamics of lipid peroxidation products accumulation, from cathepsin D unsedimental activity and from the alteration of microsomal cytochrome P-450 content and from activity of a number antioxidative enzymes. In order to evaluate the state of glutathione-defence system the activities of glutathione peroxidase, glutathione S-transferase, glutathione reductase and some NADPH-generating enzymes and reduced glutathione level alteration were studied in liver.