Multicomponent Lipid Nanoparticles for RNA Transfection.

Despite the wide variety of available cationic lipid platforms for the delivery of nucleic acids into cells, the optimization of their composition has not lost its relevance. The purpose of this work was to develop multi-component cationic lipid nanoparticles (LNPs) with or without a hydrophobic core from natural lipids in order to evaluate the efficiency of LNPs with the widely used cationic lipoid DOTAP (1,2-dioleoyloxy-3-[trimethylammonium]-propane) and the previously unstudied oleoylcholine (Ol-Ch), as well as the ability of LNPs containing GM3 gangliosides to transfect cells with mRNA and siRNA. LNPs containing cationic lipids, phospholipids and cholesterol, and surfactants were prepared according to a three-stage procedure.

The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells.

GPR55 is a non-canonical cannabinoid receptor, important for cancer proliferation. Depending on the ligand, it induces either cell proliferation or death. The objective of the study was to establish the mechanisms of this multidirectional signaling.

GPR55 Receptor Activation by the -Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation.

GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation.

The Influence of the Cholesterol Level in Cells on Endovanilloid Cytotoxicity.

The influence of the cellular cholesterol content on the cytotoxicity of endovanilloids acyldopamines was studied in MDA-MB-231 and MCF 10A cells. The activity of acyldopamines depends on the cellular cholesterol content, and a decrease in cholesterol content increases the cytotoxicity of acyldopamines.

Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System.

Cholines acylated with unsaturated fatty acids are a recently discovered family of endogenous lipids. However, the data on the biological activity of acylcholines remain very limited. We hypothesized that acylcholines containing residues of arachidonic (AA-CHOL), oleic (Ol-CHOL), linoleic (Ln-CHOL), and docosahexaenoic (DHA-CHOL) acids act as modulators of the acetylcholine signaling system.

[Molar-incisor hypomineralization among 12-years old children in Arkhangelsk region].

Aim: To estimate the prevalence of molar incisor hypomineralisation (MIH) across genders and place of residence as well as its association with dental caries among 12-years-old children in Northwest Russia.

Method: A cross-sectional study included 1233 (653 girls) randomly selected 12-years-old children from 7 urban and 5 rural areas of Arkhangelsk region. MIH and its severity were diagnosed using Weerheijm et al (2003) and Mathu-Muju & Wright (2006) criteria.

Cytotoxicity of Endogenous Lipids N-acyl Dopamines and their Possible Metabolic Derivatives for Human Cancer Cell Lines of Different Histological Origin.

Background/aim: Dopamine amides of long chain fatty acids are a family of endogenous mammalian lipids with an unknown function; they are anti-proliferative for the C6 glioblastoma cell line. To assess their possible anti-cancer activity we evaluated their cytotoxicity for a set of cancer cell lines.

Materials And Methods: Anti-proliferative and cytotoxic actions of these substances were evaluated in HOS, IMR-32, MCF-7, Namalwa, K-562 and HEK 293 cell lines (18 h incubation time) using MTT and lactate dehydrogenase (LDH) tests, accordingly.

Sulfation of N-acyl dopamines in rat tissues.

Sulfation of N-acyl dopamines has been shown for the first time in cytosolic fractions of rat liver and nervous system. Sulfation of dopamine amides of docosahexaenoic and oleic acids occurred in all tissues studied, N-arachidonoyl dopamine was sulfated in the liver and spinal cord, and N-stearoyl dopamine was sulfated only in the liver. Depending on the substrate and tissue, the sulfation activity varied from 0.

[Nanocomplexes of recombinant proteins and polysialic acid: preparation, characteristics, and biological activity].

A preparation of nanocomplexes containing recombinant proteins (interferons alpha2b and beta1b, insulin, and human granulocyte colony stimulating factor) and natural polysialic acid (PSA) has been described. The incorporation of protein into the complex changes its electrophoretic mobility. Atomic force microscopy reveals the average size of 23-kD insulin complexes with PSA of 10-20 nm and demonstrates that more than 60% of glycopolymer molecules carry a single protein molecule.

[Modification of recombinant proteins by covalent polysialation illustrated with the example of human insulin].

Methods of selective and nonselective covalent immobilization of genetically engineered proteins on molecules of natural polysialic acid are described by the example of human insulin. Such modification increases insulin lifetime in vivo.

[Cerebrovascular and antiaggregative effects of GABA-docosahexaenoyldopamine conjugate].

The effects of GABA - docosahexaenoyldopamine (DHED) conjugate on the cerebral haemodynamics and thrombocyte aggregation were evaluated and compared to these of docosahexaenoyldopamine alone. The GABA - DHED conjugate was shown to significantly enhance the cerebral circulation in rats with a model of global transient cerebral ischemia, as compared to the intact animals. Administered alone, DHED increased the blood supply of both intact and ischemic brains to an equal extent.

Antioxidant and neuroprotective properties of N-docosahexaenoyl dopamine.

N-Docosahexaenoyl dopamine exhibited antioxidant activity in the test with a stable oxygen radical galvinoxyl. This compound produced a dose-dependent protective effect on cultured granular cells from rat cerebellum under conditions of oxidative stress. N-Docosahexaenoyl dopamine decelerated the development of symptoms of Parkinson's disease in mice receiving neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

[Hygienic assessment of the hazard of ambient air carcinogenic factors].

The paper shows an extremely greater danger of aerogenic doses of carcinogenic substances entering with smoking products than that of an aerogenic load in the industrial centers. The individual and population risks of cancer due to smoking of the Ukraine's common cigarettes and the economic damage caused by the treatment of this number of patients to the country have been calculated. For a full assessment of the carcinogenic risk of tobacco smoke, it is necessary to determine all its carcinogenic constituents, their precursors, and possible transformation groups at high temperatures.

[Comparative assessment of the cancer risk of the products of smoking and ambient air pollution].

Danger from aerogenic dose carcinogens entering the body with smoking products is shown to be essentially greater than that from aerogenic loading in industrial centers. The individual and population risks for smoking-induced cancer and the economic damage to the country, associated with the treatment of a large number of patients are given. To make a complete assessment of the carcinogenic risk of tobacco smoking, it is necessary to estimate all its carcinogenic constituents, their precursors, and possible transformation products at elevated temperatures.

[Arachidonoylcholine and N,N-dimethylaminoethyl arachidonate are new cholinergic compounds].

Choline and N,N-dimethylaminoethyl esters of arachidonic and some other fatty acids were synthesized. Experiments on the embryos and larvae of sea urchins, sensitive to cholinergic compounds, showed that arachidonoylcholine exhibited cholinomimetic activity similar to that of nicotine whereas N,N-dimethylaminoethyl arachidonate acted as an acetylcholine antagonist. The corresponding esters of docosahexaenoic acid displayed similar biological properties.

Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine.

New amides of different fatty acids from the C18, C20, and C22 series with dopamine were synthesized. Pharmacological characterization in binding assays with rat brain membrane preparations and in the 'tetrad' of cannabinoid behavioral tests showed that, for these compounds, cannabinoid-like activity was dependent on the fatty acid moiety. Our data demonstrate that polyenoic fatty acid amides with dopamine comprise a new family of synthetic cannabimimetics.

[Isolation of yeast nuclei and characteristics of their lipid composition].

Intact nuclei of a high purity degree were isolated from Candida utilis protoplasts, and their lipid content and composition were determined.