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Braga E.A.,Russian Academy of Medical Sciences | Khodyrev D.S.,Federal Medical and Biological Agency of Russia | Loginov V.I.,Russian Academy of Medical Sciences | Pronina I.V.,Russian Academy of Medical Sciences | And 4 more authors.
Russian Journal of Genetics | Year: 2015

The methylation of CpG islands in promoter regions, together with the interaction of miRNAs with the mRNAs of their target genes on the posttranscriptional level, are complex epigenetic mechanisms that perform the delicate and dynamic regulation of genes and signal transduction pathways in the cell. This review summarizes the results obtained by the authors, as well as the literature data, on the roles of methyla- tion in regulating the protein-coding genes of chromosome 3 and a number of miRNA genes in clear-cell renal cell carcinomas. The results are based on the use of genomic NotI-microarrays (which allow the iden- tification of both methylation and deletions in genes containing CpG islands) and on some other approaches. The application of NotI-microarray technology to the analysis of the chromosome-3 short arm, a region of frequent deletions in tumors, gave us the opportunity to identify many novel genes associated with kidney cancer pathogenesis. The relationship between alterations in the expression levels and methylation of chro- mosome 3 genes, kidney cancer progression, and metastasis was shown. New microRNAs involved in kidney cancer pathogenesis were identified as well. The functions of microRNA genes methylated in kidney cancer © Pleiades Publishing, Inc., 2015. Source


Burgova E.N.,RAS Semenov Institute of Chemical Physics | Tkachev N.A.,RAS Semenov Institute of Chemical Physics | Adamyan L.V.,Moscow University of Medicine and Dentistry | Mikoyan V.D.,RAS Semenov Institute of Chemical Physics | And 3 more authors.
European Journal of Pharmacology | Year: 2014

Dinitrosyl iron complexes (DNIC) with glutathione exert a cytotoxic effect on endometrioid tumours in rats with surgically induced experimental endometriosis. Intraperitoneal treatment of rats (Group 1) with DNIC (12.5 μmoles/kg, daily, for 12 days), beginning with day 4 after the surgical operation (implantation of two 2 mm-thick uterine fragments onto the abdominal wall) followed by 14-day keeping of animals on a standard feeding schedule (without medication) resulted in complete inhibition of the growth of endometrioid implants (EMI) in the majority of experimental animals. The ratio of mean EMI volumes in control and experimental rats of Group 1 was 14:1. In Group 2 rats, the use of a similar treatment protocol 4 weeks after surgery changed this ratio to 1.4:1. Noteworthy, the decrease of this ratio was irrelevant to deceleration of EMI growth at later periods after surgery. The histopathological analysis of EMI samples from experimental rats of Group 2 demonstrated complete disappearance of endometrial cysts suggesting a cytotoxic effect of DNIC on the tumours. The data obtained demonstrate that DNIC with glutathione and, probably, with other thiol-containing ligands hold considerable promise in the design of drugs for treating endometriosis in female patients. © 2014 Elsevier B.V. Source


Burgova E.N.,RAS Semenov Institute of Chemical Physics | Tkachev N.A.,RAS Semenov Institute of Chemical Physics | Paklina O.V.,RAS Semenov Institute of Chemical Physics | Mikoyan V.D.,Federal Medical and Biological Agency of Russia | And 2 more authors.
European Journal of Pharmacology | Year: 2014

It has been established that intraperitoneal bolus administration of S-nitrosoglutathione (GS-NO) (12.5 μmoles/kg; 10 injections in 10 days), beginning with day 4 after transplantation of two 2-mm autologous fragments of endometrial tissue onto the inner surface of the abdominal wall of rats with surgically induced (experimenta) endometriosis failed to prevent further growth of endometrioid (EMT) and additive tumors, while treatment of animals with dinitrosyl iron complexes (DNIC) with glutathione (12.5 μmoles/kg, 10 injections in 10 days) suppressed tumor growth virtually completely. The histological analysis of EMT samples of GS-NO-treated rats revealed pathological changes characteristic of control (non-treated with GS-NO or DNIC) rats with experimental endometriosis. EPR studies established the presence of the active form of ribonucleotide reductase, a specific marker for rapidly proliferating tumors, in EMT samples of both control and GS-NO-treated animals. Noteworthy, in small-size EMT and adjacent tissues of DNIC-treated rats the active form of ribonucleotide reductase and pathological changes were not found. © 2014 Elsevier B.V. Source


Braga E.A.,Russian Academy of Medical Sciences | Loginov V.I.,Russian Academy of Medical Sciences | Pronina I.V.,Russian Academy of Medical Sciences | Khodyrev D.S.,Federal Medical and Biological Agency of Russia | And 6 more authors.
Biochemistry (Moscow) | Year: 2015

Methylation of CpG-islands in promoter regions as well as interaction of miRNAs with messenger RNAs of target genes are related to multilayer mechanisms regulating gene expression. The goal of this study was to assess a possibility for miRNA gene methylation to influence indirectly activation of their target genes in lung tumors. By using a unified collection of samples of non-small cell lung cancer, it was demonstrated that elevated levels of mRNA for RHOA and NKIRAS1 genes were significantly (Spearman rank correlation, P < 10-11) associated both with loss of methylation in their CpG-islands and methylation in a number of miRNA genes, which, according to the miRWalk database, were predicted to possess regulatory functions. Novel potential regulatory miRNAs for RHOA (miR-9-1/-3, -34b/c, -129-2, -125b-1, -375, -1258) and NKIRAS1 (miR-34b/c, -129-2, -125b-1, -193a, -124a-1/-2/-3, -212, -132) genes in lung cancer were identified. © 2015 Pleiades Publishing, Ltd. Source


Galochkina T.,Federal Medical and Biological Agency of Russia | Zlenko D.,Moscow State University | Kovalenko I.,Federal Medical and Biological Agency of Russia | Nesterenko A.,Moscow State University
2015 IEEE 15th International Conference on Bioinformatics and Bioengineering, BIBE 2015 | Year: 2015

The cell wall of Gram-negative bacteria plays a crucial role in the bacteria resistance to certain antimicrobials and its adaptation to the host environment. The first line of cell defense is its outer membrane composed of glycerophos-pholipids in the inner monolayer, lipopolysaccharides (LPS) in the outer monolayer and integral proteins. To understand the details of the outer membrane structure we build a molecular model of the Ra-LPS/LPS bilayer containing 8 β-barrels of the OmpA protein. We pay particular attention to the structural evolution of the outermost part of the LPS molecules (O-antigen) and analyze its conformational behavior using different computational criteria. © 2015 IEEE. Source

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