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Belogurov Jr. A.A.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry | Stepanov A.V.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry | Smirnov I.V.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry | Melamed D.,Assaf Harofeh Medical Center | And 11 more authors.
FASEB Journal | Year: 2013

Multiple sclerosis (MS) is a severe inflammatory and neurodegenerative disease with an autoimmune background. Despite the variety of therapeutics available against MS, the development of novel approaches to its treatment is of high importance in modern pharmaceutics. In this study, experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats has been treated with immunodominant peptides of the myelin basic protein (MBP) encapsulated in mannosylated small unilamellar vesicles. The results show that liposome-encapsulated MBP46-62 is the most effective in reducing maximal disease score during the first attack, while MBP124-139 and MBP147-170 can completely prevent the development of the exacerbation stage. Both mannosylation of liposomes and encapsulation of peptides are critical for the therapeutic effect, since neither naked peptides nor nonmannosylated liposomes, loaded or empty, have proved effective. The liposome-mediated synergistic effect of the mixture of 3 MBP peptides significantly suppresses the progression of protracted EAE, with the median cumulative disease score being reduced from 22 to 14 points, compared to the placebo group; prevents the production of circulating autoantibodies; down-regulates the synthesis of Th1 cytokines; and induces the production of brain-derived neurotrophic factor in the central nervous system. Thus, the proposed formulation ameliorates EAE, providing for a less severe first attack and rapid recovery from exacerbation, and offers a promising therapeutic modality in MS treatment. © The Author(s).


Gabashvili A.N.,rogov National Research Medical University | Baklaushev V.P.,Russian National Research Medical University | Mel'nikov P.A.,rogov National Research Medical University | Cherepanov S.A.,rogov National Research Medical University | And 2 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2016

The tumor-suppressive effect of rat mesenchymal stem cells against low-differentiated rat C6 glioma cells during their direct and indirect co-culturing and during culturing of C6 glioma cells in the medium conditioned by mesenchymal stem cells was studied in an in vitro experiment. The most pronounced antitumor activity of mesenchymal stem cells was observed during direct co-culturing with C6 glioma cells. The number of live C6 glioma cells during indirect co-culturing and during culturing in conditioned medium was slightly higher than during direct co-culturing, but significantly differed from the control (C6 glioma cells cultured in medium conditioned by C6 glioma cells). The cytotoxic effect of medium conditioned by mesenchymal stem cells was not related to medium depletion by glioma cells during their growth. The medium conditioned by other “non-stem” cells (rat astrocytes and fibroblasts) produced no tumor-suppressive effect. Rat mesenchymal stem cells, similar to rat C6 glioma cells express connexin 43, the main astroglial gap junction protein. During co-culturing, mesenchymal stem cells and glioma C6 cells formed functionally active gap junctions. Gap junction blockade with connexon inhibitor carbenoxolone attenuated the antitumor effect observed during direct co-culturing of C6 glioma cells and mesenchymal stem cells to the level produced by conditioned medium. Cell–cell signaling mediated by gap junctions can be a mechanism of the tumor-suppressive effect of mesenchymal stem cells against C6 glioma cells. This phenomenon can be used for the development of new methods of cell therapy for high-grade malignant gliomas. © 2016 Springer Science+Business Media New York


Tverskaya M.S.,rogov National Research Medical University | Sukhoparova V.V.,rogov National Research Medical University | Klyuchikov V.Y.,rogov National Research Medical University | Alipov N.N.,rogov National Research Medical University | And 2 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2016

Histoenzymological methods were used to study metabolism of smooth muscle cells of intramural myocardial arteries during experimental aortic or pulmonary artery stenosis. Aortic stenosis was accompanied by changes in smooth muscles of the left ventricle manifested by deceleration of tricarboxylic acid cycle, inhibition of oxidation of free fatty acids and their metabolites, flux redistribution in the glycolytic cascade, and inhibition of shuttle systems and biosynthetic processes. Similar metabolic alterations were observed in vessels of the ventricular septum, but they were not revealed in vessels of the right ventricle (except glycolysis stimulation). Under conditions of pulmonary artery stenosis, histoenzymological alterations in vascular smooth muscle of both ventricles and ventricular septum were similar, which attested to acceleration of tricarboxylic acid cycle, stimulation of oxidation of the free fatty acids with their metabolites, acceleration of glycolysis, and activation of the shuttle systems and biosynthetic processes. Comparative analysis of histoenzymological alterations revealed substantial differences in the character of metabolic changes under conditions of increased left and right ventricular afterload, which can be caused by peculiarities in myocardial blood flow, severity of circulatory disorders, severity of hypoxia, and intensity of processes maintaining ionic homeostasis in vascular smooth muscles and transport across the histohematic barriers. The data attest to important metabolic role of glycolysis in vascular smooth muscles of the myocardium, especially under conditions of enhanced afterload of the right ventricle. © 2016, Springer Science+Business Media New York.


Stenina M.A.,rogov National Research Medical University | Krivov L.I.,rogov National Research Medical University | Voevodin D.A.,rogov National Research Medical University | Savchuk V.I.,rogov National Research Medical University | And 2 more authors.
Bulletin of Experimental Biology and Medicine | Year: 2012

Differences in the pools of 10 cytokine were found in blood samples from the caudal vein of mice with normal and abnormal heart rhythm. Both groups were albino mice bred by us and differing from mdx albino mice by the absence of mutation in muscular dystrophin gene. Mice with normal heart rhythm had low IL-17 content and elevated concentrations of proinflammatory cytokines IL-6 and IL-1α in comparison with the normal (according to published data). In mice with bradyarrhythmias, increased blood levels of IL-10, IL-6, IL-5, IL-2, IL-1α, IL-17, IL-4, TNF-α, and granulocyte-macrophage colony-stimulating factor were detected. The relative content of IL-4 and IL-17 in the total cytokine pool increased. The lifespan of mice with bradyarrhythmias and cytokine hyperexpression was shorter by 2-3 months in comparison with mice without heart rhythm disturbances and moderate changes in the cytokine pool. © 2012 Springer Science+Business Media, Inc.

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