[The sirtuin family of proteins: the role in the aging processes and regulation of cell metabolism.].

In recent years, the key role of sirtuins in the regulation of the most important cellular processes has been established. Sirtuins are involved in histone deacetylation, regulation of fat and glucose metabolism. Violations of their synthesis and secretion can induce carcinogenesis, aging and cell death.

Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery.

Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity.

Anti-angiogenic treatment of endometriosis via anti-VEGFA siRNA delivery by means of peptide-based carrier in a rat subcutaneous model.

Development of gene therapy for endometriosis requires inhibition of vascularization in endometrial lesions. We have previously developed CXCR4 receptor-targeted siRNA carrier L1 and observed efficient RNAi-mediated down-regulation of VEGFA gene expression in endothelial cells followed by decrease in VEGFA protein production and inhibition of cell migration. In this study we evaluated L1 carrier as non-viral vector for anti-VEGFA siRNA delivery into endometrial implants in rat subcutaneous endometriosis model created by subcutaneous auto-transplantation of uterus horn's fragments.

DYNC1H1 gene methylation correlates with severity of spinal muscular atrophy.

Methylation profiles of CpG islands within the SLC23A2, CDK2AP1, and DYNC1H1 genes and their association with spinal muscular atrophy (SMA) severity were studied. High clinical heterogeneity of SMA suggests the existence of different factors modifying SMA phenotype with gene methylation as a plausible one. The genes picked up in our earlier genome-wide methylation studies of SMA patients demonstrated obvious differences in their methylation patterns, thus suggesting the likely involvement of their protein products in SMA development.

Interactions of NK Cells and Trophoblast Cells. Methodological Aspects.

NK cells present in different organs differ by their functional characteristics, in particular, proliferative activity. For studying tissue-resident NK cells, tissue-specific microenvironment should be reproduced. In case of decidual NK cells, this microenvironment is created by trophoblast cells.

Mass-Spectrometric Analysis of Proteome of Microvesicles Produced by NK-92 Natural Killer Cells.

Membrane extracellular microvesicles serve as carriers of a wide range of molecules, the most important among these are proteins, lipids, and nucleic acids. Cytotoxic proteins of natural killer cells play a key role in the realization of their cytolytic functions. An important stage in understanding of the distant communication of cells and mechanisms of its regulation is analysis of the proteome composition of microvesicles.

Molecular Factors Involved in Spinal Muscular Atrophy Pathways as Possible Disease-modifying Candidates.

Spinal Muscular Atrophy (SMA) is a neuromuscular disorder caused by mutations in the SMN1 gene. Being a monogenic disease, it is characterized by high clinical heterogeneity. Variations in penetrance and severity of symptoms, as well as clinical discrepancies between affected family members can result from modifier genes influence on disease manifestation.

Matrix Metalloproteinases MMP-1 and MMP-9 and Their Inhibitor TIMP-1 as Markers of Dilated Cardiomyopathy in Patients of Different Age.

We studied the expression of MMP-2, MMP-9, and inhibitor TIMP-1 in myocardial autopsy samples from subjects of different age and in cardiomyocyte cultures in the norm and in dilated cardiomyopathy. In autopsy samples of normal myocardium and in cardiomyocyte cultures, expression of molecules involved in extracellular matrix remodeling did not change during aging. In dilation cardiomyopathy, expression of MMP-2, MMP-9, and TIMP-1 and their ratios in autopsy material and in cultures was elevated by 1.

Dienogest treatment after ovarian endometrioma removal in infertile women prior to IVF.

Background: Severe forms of genital endometriosis are known to be associated with infertility and its subsequent treatment failure. Both gonadotropin-releasing hormone analogs (a-GnRH) and dienogest have been suggested as additional hormone therapy for patients with endometriomas. However, the result of hormonal suppression before an in vitro fertilization (IVF) cycle remains undetermined.

Role of LIF Cytokine and CD34 Angiogenesis Marker in Non-Developing Pregnancy.

The expression of cytokine LIF (leukemia inhibiting factor) in the endometrium of women of young reproductive age with non-developing pregnancy of unknown genesis is higher than in older women and women with infection-related miscarriages by 1.26 and 1.43 times, respectively.

Arginine-rich cross-linking peptides with different SV40 nuclear localization signal content as vectors for intranuclear DNA delivery.

The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensation, endosomal escape promotion and interpeptide cross-linking, respectively.

Differential DNA Hydroxymethylation in Human Uterine Leiomyoma Cells Depending on the Phase of Menstrual Cycle and Presence of MED12 Gene Mutations.

Using immunofluorescence with specific antibodies, we analyzed DNA hydroxymethylation in uncultured cells from 25 human uterine leiomyomas considering the menstrual cycle phase during surgery and the presence of MED12 gene mutations. It was found that each tumor node had specific DNA hydroxymethylation level that did not depend on the presence of mutations in MED12 gene, but depended on the phase of menstrual cycle. The degree of DNA hydroxymethylation was significantly lower in cells of leiomyomas excised during the luteal phase compared to the follicular phase (p=0.

Expression of Signal Molecules in Culture of Human Endothelial Cells in Atherosclerosis and Restenosis.

We compared the expression of signal molecules in the culture of human endothelial cells under normal conditions and in atherosclerosis and restenosis. Expression of connexin-37 and sirtuin-1 in atherosclerosis and restenosis surpassed the normal by 2 and 5 times, respectively, and expression of endothelin-1 3-fold surpassed the normal. In restenosis, changes in the expression connexin-37 and endothelin-1 became more pronounced in comparison with atherosclerosis.

Combined value of placental alpha microglobulin-1 detection and cervical length via transvaginal ultrasound in the diagnosis of preterm labor in symptomatic patients.

Aim: We aimed to evaluate the combined value of placental alpha microglobulin-1 (PAMG-1) and cervical length (CL) via transvaginal ultrasound for assessing risk of imminent spontaneous preterm delivery in patients presenting with threatened preterm labor (PTL).

Methods: Clinical exam, PAMG-1 test, cardiotocography, and CL measurement via transvaginal ultrasound were performed on all patients meeting inclusion criteria. Ninety-nine patients at 22 -36 gestational weeks with the symptoms of PTL were included.

Comprehensive global genome dynamics of show ancient diversification followed by contemporary mixing and recent lineage expansion.

is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes.

Effect of Cytokines on the Formation Tube-Like Structures by Endothelial Cells in the Presence of Trophoblast Cells.

Despite ample data on cytokine secretion in the uteroplacental interface, the influence of microenvironment cells, in particular, trophoblast cells on angiogenesis and the role of cytokines in this process remain poorly studied. We studied the influence of cytokines on the formation of tube-like structures by endothelial cells in the presence of trophoblast cells and showed that trophoblast cells suppressed the angiogenic potential of endothelial cells. Antiangiogenic cytokines IFN-γ, IL-10, TNF-α, and TGFβ via modulation of trophoblast cells stimulated the formation of tube-like structures by endothelial cells.

Prenatal Hyperhomocysteinemia Impairs Hypothalamic Regulation of Reproductive Cycles in Rat Progeny.

Effects of prenatal hyperhomocysteinemia on hypothalamic regulation of estrous cycles were studied in female rats. In mature rats exposed to prenatal hyperhomocysteinemia, changes in the catecholamine content in hypothalamic areas responsible for the formation of the preovulatory surge of gonadotropin-releasing hormone were revealed: the level of norepinephrine in the medial preoptic area decreased and concentration of dopamine in the median eminence with arcuate nuclei increased. Administration of melatonin attenuated the observed changes, which can be related to neuroprotective effects of this hormone determined by its antioxidant properties.

Prevalence of macrolide and fluoroquinolone resistance-mediating mutations in Mycoplasma genitalium in five cities in Russia and Estonia.

Background And Objective: Resistance in the sexually transmitted bacterium Mycoplasma genitalium to all recommended therapeutic antimicrobials have rapidly emerged. However, to date, internationally reported resistance surveillance data for M. genitalium strains circulating in Eastern Europe are entirely lacking.

Clinical strains of Streptococcus agalactiae carry two different variants of pathogenicity island XII.

Streptococcus agalactiae or Group B streptococci (GBS) are a common cause of serious diseases of newborns and adults. GBS pathogenicity largely depends on genes located on the accessory genome including several pathogenicity islands (PAI). The present paper is focused on the structure and molecular epidemiological analysis of one of the GBS pathogenicity islands-the pathogenicity island PAI XII (Glaser et al.

[Effects of urokinase plasminogen activator on cultured human retinal epithelial cells].

Aim: to study the effects of urokinase plasminogen activator (UPA) on the human retinal pigment epithelium (hRPE) cell culture.

Material And Methods: The toxicity of 50 U/ml UPA was studied with the trypan blue exclusion test. Cell migration was assessed by the wound healing and modified Boyden chamber assays.

Effect of THP-1 Cells on the Formation of Vascular Tubes by Endothelial EA.hy926 Cells in the Presence of Placenta Secretory Products.

We studied the effect of THP-1 cells on the formation of vessel-like structures by endothelial cells in the presence of placenta-conditioned media. Addition of THP-1 cells to endothelial cells cultured in the presence of media conditioned by first-trimester placentas led to an increase in the length of cell tubes and reduced their number in comparison with endothelial cell monoculture. In the presence of media conditioned by third-trimester placentas, THP-1 cells did not affect the length and number of cell tubes formed by endothelial cells.