Clinical, Anamnestic, and Demographic Characteristics of Patients with Myocardial Infarction in Russian Federation According to the Russian Registry of Acute Myocardial Infarction - REGION-IM.

AIM: Based on data from the Russian REGION-MI registry, to characterize patients with myocardial infarction (MI) hospitalized in Russian hospitals, describe their historical, demographic, and clinical characteristics, and compare the results with the data of previous Russian and international registries of acute coronary syndrome. MATERIAL AND METHODS: REGION-MI is a multicenter prospective observational study. The follow-up period was divided into three stages: during the hospital stay, at 6 and 12 months after the inclusion in the registry. Demographic and historic data and information about the present case of MI were entered into the patient's individual record card. RESULTS: The median age of all patients was 63 years; 68% of patients were men. The mean age of women was older than that of men. Among all MI cases, 70% were ST-segment elevation myocardial infarction (STEMI). Patients with non-ST-segment elevation myocardial infarction (NSTEMI) were older and had more comorbidities than patients with STEMI. The median time from the first symptoms to ECG recording was two hours, and from the first symptoms to CAG 7 hours. CAG was performed in 91% of patients with STEMI and 84% of patients with NSTEMI. Stenting was performed in 69% of patients. Although many patients had a complicated cardiovascular history, at the time of admission only 31.5% of patients were taking at least one drug from the groups of antiplatelets, oral anticoagulants, statins, and beta-blockers. CONCLUSION: Patients with MI in the Russian Federation are younger than patients with MI in European countries. Among the clinical and historical characteristics, conspicuous is the presence of modifiable risk factors in many patients, as well as the presence of a previous diagnosis of ischemic heart disease. Furthermore, a small proportion of patients took statins, antiplatelet agents or anticoagulants at the outpatient stage, which indicates a great reserve of both primary and secondary prevention of cardiovascular diseases in the Russian Federation. The delayed seeking medical help is also noticeable, which indicates the need for increasing the public awareness of the symptoms of MI and the importance of timely hospitalization.

Effect of Activated Immunocompetent Cells on the Content of Multipotent Stromal Cells in Splenic Transplants of CBA and CBA/N Mice Administered with Polyvinylpyrrolidone.

One day after intraperitoneal injection of polyvinylpyrrolidone (PVP) to recipient CBA and CBA/N mice, the count of multipotent stromal cells (MSC) in the 4-month-old splenic transplants was minimum in CBA/N→CBA/N group in comparison with the transplants of intact recipients (0.6 from the control level), but increased by 2.3, 3.2, and 3.7 times in CBA/N→CBA, CBA→CBA, and CBA→CBA/N groups, respectively. In the blood serum of recipient CBA/N mice with 4-month splenic transplants of CBA donors, the levels of some cytokines (IL-5, TNFα, and IL-2) was significantly increased 1 and 24 h after PVP injection in contrast to mice with bone marrow transplants, which attests to activation of the innate immunity mechanisms in this (splenic) transplantation variant. Probably, this phenomenon can be explained by the fact that the splenic transplants contain a sufficient number of CD+B-1a lymphocytes that can restore the response of recipient CBA/N mice to PVP. Thus, similar to bone marrow transplants [5], MSC count in splenic transplants increased only in groups, where the recipients were capable of responding to PVP. In other words, after injection of PVP to recipient mice, MSC counts in the spleen and bone marrow at this moment are determined by availability of activated immunocompetent cells. Overall, the novel data attest to close relationships between the stromal tissue of hematopoietic and lymphoid organs, on the one hand, and immune system, on the other.

Phenotypic traits differentiating the genetic resources of pea (Pisum sativum L.) by the type of use.

The paper presents an analysis of the data obtained for pea accessions from the VIR collection studied at the Adler Experiment Station in the setting of the Krasnodar Territory in 2017-2019. It was for the f irst time that these accessions were studied for a set of phenotypic traits. The object of the study was a sample of 494 pea accessions originated from 43 countries and 18 regions and territories of the Russian Federation. The work was carried out in compliance with the methodological guidelines developed at VIR. Statistica 13.3 software was employed for statistical data processing. An assessment of four qualitative, 10 quantitative and four phenological traits in the accessions made it possible to differentiate them by the type of use, that is, as dry, forage and garden peas. The varieties differing in the type of use signif icantly differed by the values of such traits as stem length, number of pods per plant, number of nodes to the f irst f lower, number of f lowers in the inf lorescence, the maximum number of seeds per pod, pod length, and a narrower pod of forage pea compared to that of dry and garden peas. The average values of these traits were recorded for the peas with different types of use. The maximum difference was noted between garden and forage pea varieties. Dry pea varieties occupied an intermediate position. The complex of phenotypic traits identif ied determines the differences between three types of pea use, which is important when selecting the initial material for breeding appropriate varieties.

Simultaneous Administration of NOD-2 (MDP) and TLP-4 (LPS) Ligands to Bone Marrow Donors 24 h before Transplantation Increases the Content of Multipotent Stromal Cells (MSCs) in Bone Marrow Grafts in CBA Mice Compared to the Total Result of Their Isolated Administration.

In 3-month bone marrow transplants of CBA mice from bone marrow donors receiving single injections of TLR-4 ligand (LPS) or NOD-2 ligand (muramyl dipeptide, MDP) 24 h before transplantation, an increase in the total number of MSCs (by 2.6 and 1.9 times, respectively), as well as a slight increase in the number of nuclear cells and the mass of bone capsules (by 1.3 and 1.2 times) were observed. After combined administration of MDР and LPS to donors, the total content of MSCs in the grafts was higher by 1.6 times in comparison with the total result of their isolated administration (and by 7.2 times in comparison with the control). At the same time, the concentration of osteogenic MSCs in the grafts of all groups was almost the same and corresponded to the control level. The number of nuclear cells and the mass of bone capsules of the grafts after combined administration of LPS and MDP were close (~80%) to the sum of the results of their isolated administration. These findings suggest that activation of the stromal tissue and the success of bone marrow transplantation depend on the intensity of innate immune responses. These data can be useful for the development of optimal methods of tissue transplantation.

[Herd immunity to SARS-CoV-2 in the Novosibirsk Region population amid the COVID-19 pandemic].

AIM: To determine the level of SARS-CoV-2 seroprevalence among the Novosibirsk Region population against the background of the COVID-19 pandemic. MATERIAL AND METHODS: The work was carried out in 2 phases: 1) a cross-sectional cohort study performed 28.06- 15.07.2020; 2) longitudinal cohort 3-stage seromonitoring: 1st stage 28.06-15.07.2020; 2nd 14.09-04.10.2020; 3rd 10-30.12.2020 The work was carried out according to a unified methodology developed by Rospotrebnadzor with the participation of St-Petersburg Pasteur Institute, taking into account the recommendations of the WHO. IgG antibodies to the SARS-CoV-2 nucleocapsid protein were detected by ELISA using a kit of reagents produced by the SRCMSB (Obolensk) according to the manufacturer's instructions. Statistical analysis was performed using Microsoft Excel 2010 and other programs. RESULTS: The seroprevalence in the region's population was 9.1% (95% CI 8.0-10.2): maximum in children 14-17 years old (17.6%, 95% CI 12.3-23.9) and persons over 75 years (14.8%, 95% CI 11.4-18.8), minimum among persons 30-39 years old (4.9%, 95% CI 3.0-8.0). Increased rate was noted among the unemployed (15.4%, 95% CI 9.9-17.1) and other individuals (13.0%, 95% CI 8.6-18.5). Seroprevalence was 33.3% (95% CI 16.3-59.0) in COVID-19 convalescents and 19.0% (95% CI 13.9-25.0) in contact persons. More than 94.7% (95% CI 91.2-97.2) of seropositive individuals were asymptomatic. During the serological monitoring, seroprevalence increased from 7.4% (95% CI 6.2-8.9) at 1st stage 1 to 12.4% (95% CI 10.6-14.3) at 2nd , and 31% (95% CI 28.8-33.3) at 3rd stage. CONCLUSION: SARS-CoV-2 herd immunity has not reached the threshold level, this does not exclude exacerbation of the epidemic process.

[Diet therapy for irritable bowel syndrome].

The review provides present information on the pathogenesis of irritable bowel syndrome (IBS), the relationship of endogenous and exogenous factors with the development of IBS-symptoms, questions of diet therapy are discussed, diets traditionally prescribed in IBS treatment and diets, such as FODMAP and gluten-free diet, which are the most promising and have a positive effect on the symptoms of IBS.

DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity.

Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.

Colloid-SEM method for the investigation of magnetic domain structures.

The paper presents scanning electron microscopy (SEM) studies on the magnetic domain structure (DS) using magnetic colloid. The possibility of colloid-SEM method for observing the DS of mono- and polycrystalline samples in the secondary (SEI) and backscattered electrons modes (BEC) is demonstrated. Owing to the large focal depth of SEM, it is possible to observe the overall DS and fine features, even in unpollished samples.

Involvement of Bone Marrow Multipotent Stromal Cells in the Processes Presumably Provoking Vascular Calcification.

During serial transplantation of bone marrow derived from young and aged donor CBA mice to 5-month-old recipients, the counts of multipotent stromal cells (MSC) in transplants from young donors assessed at each passage surpassed those of aged donors by 3.2, 7.8, 3.0, and 2.2 times attesting to the age-related decrease of active pool of bone marrow MSC. The medullary curettage in mouse femur increased the total number of MSC and the number of osteogenic MSC both in the contralateral femur and in the bone marrow transplants attesting to spread of the effects of osteogenic factors after bone injury onto the bone tissue of the body even if this tissue if not topographically related to the skeleton. Combined and simultaneous administration of antigenic complex of S. typhimurium (or LPS) with BMP-2 markedly increased the count of osteogenic medullary MSC by 3.6 or 4.6 times in comparison with intact control or by 2.1 and 2.7 times in comparison with administration of BMP-2 alone, which probably resulted from enlargement of the pool of osteogenesis-inducible MSC due to inflammation. Addition of BMP-2 to the culture of splenic stromal cells where osteogenesis does not occur under normal conditions provoked appearance of MSC colonies with alkaline phosphatase activity attesting to involvement of inducible osteogenic MSC in vascular calcification. It can be hypothesized that the reaction to the age-related changes in the bone tissue and osteoporosis is similar to the reaction to bone marrow injury and includes initiation of systemic inflammation and elevation of blood BMP-2, both of which are prerequisite for vascular calcification.

Effect of Activated Immunocompetent Cells on the Number of Multipotent Stromal Cells in Bone Marrow Transplants of CBA and CBA/N Mice in a Short Time after Polyvinylpyrrolidone Administration to Animals.

One hour after polyvinylpyrrolidone administration, the content of multipotent stromal cells in the spleen of CBA and CBA/N mice increased almost equally (by 2.5 and 2.9 times, respectively), but in 24 h, the effectiveness of multipotent stromal cell cloning in the spleen of CBA/N mice decreased almost to the control level, whereas in CBA mice, the number of multipotent stromal cells continued to increase. Serum concentration of IL-5, TNFα, and IL-2 in both lines was elevated in 1 h after polyvinylpyrrolidone administration, which is likely to reflect activation of the innate immunity. One day after polyvinylpyrrolidone administration, the number of multipotent stromal cells in bone marrow transplants in the CBA/N→CBA/N and CBA→CBA/N groups remained practically unchanged, while in groups CBA→CBA and CBA/N→CBA it was equally increased (by 3.6 and 3.4 times, respectively). Thus, the number of multipotent stromal cells in bone marrow transplants after 1 day was increased only in groups where recipients (CBA mice) were capable of responding to polyvinylpyrrolidone administration, i.e. the number of stromal cells by this term, was apparently determined by the presence of activated immunocompetent cells. These findings also indicate that activation of the stromal tissue dur ing immune response can have a two-phasic pattern: the first phase (1 h after antigen adminis tration) can be determined by activation of innate immunity receptors (in multipotent stromal cells or other cells) observed in CBA and CBA/N mice, and the second phase occurs during further development of the immune response (that was observed in CBA mice, but not in CBA/N mice due to absence of CD+B-1a lymphocytes). The findings attest to close interactions between the stromal tissue and the immune system.

[Modified method for determining the normal values of the aortic root diameter in the focus of aortic pathology in individuals with congenital connective tissue disorders].

INTRODUCTION: Enlargement of the aortic root of occurs in many cases with cardiovascular disease, including congenital connective tissue disorders (CCTD), especially its differentiated and undifferentiated forms (UCCTD). A common deficiency of the generally accepted methods for diagnosing an aortic root dilation may be that persons with CCTD and cardiovascular diseases of potentially having a broader aortic root diameter could be included in the reference groups. The purpose of our study was to develop a modified method for determining the normal aortic root diameter in group of individuals without CCTD and cardiovascular diseases. MATERIALS AND METHODS: The study included 464 apparently healthy people, men and women aged 15 to 65 years. All patients underwent general clinical examination, echocardiography. On the basis of external and internal signs of CCTD, patients with UCCTD were identified - the UCCTD group (n = 208) and without this pathology - the main group (n = 256). The calculation of the normal aortic root diameter (NARD) was made in accordance with the methods of Roman M. J. et al. (1989) and Devereux R. B. et al. (2012). The upper limit values of NARD (UL NARD) were calculated according to the algorithms of Roman M. J. et al. (1989), Devereux R. B. et al. (2012), Campens L. et al. (2014). RESULTS: The data obtained in the main group was used to develop a modified method for the determination of NARD. The mean values by echocardiography and calculated values of the aortic root by modified method of this study were practically the same in the main group, whereas the mean value of NARD calculated by the methods of Roman M. J. et al. and Devereux R. B. et al. in this sample were significantly higher in relation to the listed values. As the NARD values, the UL NARD were significantly higher for all evaluated algorithms in comparison with the modified method. In the group of patients with UCCTD, 13 cases of aortic root dilation were found according to the method of Roman M. J., compared to 19 cases by the modified method. At the same time, 3 patients with aortic root enlargement by the mew method had 7 points of systemic involvement, thus corresponding to the Ghent criteria of Marfan syndrome. The methods of Campens L. and Devereux R. B. were less sensitive, revealing only 5 and 1 patients with aortic root dilatation, respectively. CONCLUSIONS: The results of the study demonstrate that, in order to obtain more reliable information on the condition of the root of the aorta and its proper values, the modified method obtained in the course of the study can be used. This method is more sensitive in detecting the enlargement of the aortic root in CCTD and in diagnosing syndromic CCTD.

Alanine Scanning Mutagenesis of the MEDI4893 (Suvratoxumab) Epitope Reduces Alpha Toxin Lytic Activity In Vitro and Staphylococcus aureus Fitness in Infection Models.

Alpha toxin (AT) is a cytolytic pore-forming toxin that plays a key role in Staphylococcus aureus pathogenesis; consequently, extensive research was undertaken to understand the AT mechanism of action and its utility as a target for novel prophylaxis and treatment strategies against S. aureus infections. MEDI4893 (suvratoxumab) is a human anti-AT IgG1 monoclonal antibody (MAb) that targets AT and is currently in phase 2 clinical development. As shown previously, the MEDI4893-binding epitope on AT is comprised of the highly conserved amino acid regions 177 to 200 and 261 to 271, suggesting these amino acids are important for AT function. To test this hypothesis and gain insight into the effect of mutations in the epitope on AT neutralization by MEDI4893, nine MEDI4893 contact residues in AT were individually mutated to alanine. Consistent with our hypothesis, 8 out of 9 mutants exhibited >2-fold loss in lytic activity resulting from a defect in cell binding and pore formation. MEDI4893 binding affinity was reduced >2-fold (2- to 27-fold) for 7 out of 9 mutants, and no binding was detected for the W187A mutant. MEDI4893 effectively neutralized all of the lytic mutants in vitro and in vivo When the defective mutants were introduced into an S. aureus clinical isolate, the mutant-expressing strains exhibited less severe disease in mouse models and were effectively neutralized by MEDI4893. These results indicate the MEDI4893 epitope is highly conserved due in part to its role in AT pore formation and bacterial fitness, thereby decreasing the likelihood for the emergence of MAb-resistant variants.

Pretreatment with Antiviral Preparation Kagocel Normalizes the Content of Bone Marrow Multipotent Stromal Cells and TNFα in Blood Serum of CBA Mice Disturbed by Administration of S. typhimurium Antigen Complex In Vivo and Maintains High Concentration of IL-10 and Th1 Cytokines.

Pretreatment with the active substance of antiviral preparation Kagocel, inductor of type I endogenous IFN, in a daily therapeutic dose (30 µg/mouse) 3 h prior to administration of S. typhimurium antigens to CBA mice reduced the number of bone marrow multipotent stromal cell (significantly increased by 3.2 times on the next day after antigen injection) to the initial level. Thus, activation of the stromal tissue induced by administration of the bacterial antigen was blocked. In addition, preliminary administration of Kagocel modulated the cytokine profile of the blood serum affected by S. typhimurium antigens: reduced 1.6-fold elevated concentration a proinflammatory cytokine TNFα to the control level (in 4 h after antigen injection) and maintained this level in 20 h after antigen administration. Kagocel also maintained the concentration of anti-inflammatory cytokine IL-10 at the level surpassing the normal by 1.6 times and high concentrations of Th1 cytokines (IL-2, IFNγ, and IL-12). These results suggest that Kagocel can reduce the immune response to bacterial antigens (similar to type I IFN [7]), which can contribute to its therapeutic and preventive effects in addition to its well documented antiviral activity and then this preparation can be used for the therapy of diseases accompanied by excessive or chronic inflammation.

Multimechanistic Monoclonal Antibodies (MAbs) Targeting Staphylococcus aureus Alpha-Toxin and Clumping Factor A: Activity and Efficacy Comparisons of a MAb Combination and an Engineered Bispecific Antibody Approach.

Secreted alpha-toxin and surface-localized clumping factor A (ClfA) are key virulence determinants in Staphylococcus aureus bloodstream infections. We previously demonstrated that prophylaxis with a multimechanistic monoclonal antibody (MAb) combination against alpha-toxin (MEDI4893*) and ClfA (11H10) provided greater strain coverage and improved efficacy in an S. aureus lethal bacteremia model. Subsequently, 11H10 was found to exhibit reduced affinity and impaired inhibition of fibrinogen binding to ClfA002 expressed by members of a predominant hospital-associated methicillin-resistant S. aureus (MRSA) clone, ST5. Consequently, we identified another anti-ClfA MAb (SAR114) from human tonsillar B cells with >100-fold increased affinity for three prominent ClfA variants, including ClfA002, and potent inhibition of bacterial agglutination by 112 diverse clinical isolates. We next constructed bispecific Abs (BiSAbs) comprised of 11H10 or SAR114 as IgG scaffolds and grafted anti-alpha-toxin (MEDI4893*) single-chain variable fragment to the amino or carboxy terminus of the anti-ClfA heavy chains. Although the BiSAbs exhibited in vitro potencies similar to those of the parental MAbs, only 11H10-BiSAb, but not SAR114-BiSAb, showed protective activity in murine infection models comparable to the respective MAb combination. In vivo activity with SAR114-BiSAb was observed in infection models with S. aureus lacking ClfA. Our data suggest that high-affinity binding to ClfA sequesters the SAR114-BiSAb to the bacterial surface, thereby reducing both alpha-toxin neutralization and protection in vivo These results indicate that a MAb combination targeting ClfA and alpha-toxin is more promising for future development than the corresponding BiSAb.

Highly doped InP as a low loss plasmonic material for mid-IR region.

We study plasmonic properties of highly doped InP in the mid-infrared (IR) range. InP was grown by metal-organic vapor phase epitaxy (MOVPE) with the growth conditions optimized to achieve high free electron concentrations by doping with silicon. The permittivity of the grown material was found by fitting the calculated infrared reflectance spectra to the measured ones. The retrieved permittivity was then used to simulate surface plasmon polaritons (SPPs) propagation on flat and structured surfaces, and the simulation results were verified in direct experiments. SPPs at the top and bottom interfaces of the grown epilayer were excited by the prism coupling. A high-index Ge hemispherical prism provides efficient coupling conditions of SPPs on flat surfaces and facilitates acquiring their dispersion diagrams. We observed diffraction into symmetry-prohibited diffraction orders stimulated by the excitation of surface plasmon-polaritons in a periodically structured epilayer. Characterization shows good agreement between the theory and experimental results and confirms that highly doped InP is an effective plasmonic material aiming it for applications in the mid-IR wavelength range.

[Aortic valve replacement with stentless bioprosthesis].

AIM: To evaluate prospectively the hemodynamic performance of «BioLAB Mono¼ stentless bioprosthesis implanted into aortic position. MATERIAL AND METHODS: Twenty seven patients (mean age 71 (67; 73); 17 women) with severe aortic stenosis underwent aortic valve replacement with «BioLAB Mono¼ stentless bioprosthesis from 2012 to 2014. The valves were implanted into supra-annular position using continuous polypropylene suture. RESULTS: In the early postoperative period 1 patient (3.7%) died for acute heart failure. The mean aortic cross-clamping time was 81 (75; 90) min. Echocardiographic peak pressure gradient were 18 (16; 23) mmHg (postoperative). There were no cases of valve dysfunction in early postoperative period. Level of thrombocytes recovered after 10 days postoperatively. CONCLUSION: «BioLAB Mono¼ aortic bioprosthesis implantation is easy and reproducible. The valve has excellent hemodynamic performance in early postoperative period.

Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model.

Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups.

THE ANALYSIS OF LGI1 GENE EPIGENETIC ALTERATIONS BY MEANS OF POSTTRANSLATIONAL H3 HISTONE MODIFICATIONS IN MALIGNANT GLIOMAS.

Although there is a progress in understanding the causes and consequences of genetic and epigenetic changes in glioma malignant transformation, many details remain obscure and need further investigation. It is known that process of malignant transformation of gliomas is accompanied by gradual loss of LGI1 gene expression. However, genetic defects causing LGI1 inactivation have not been revealed. In this paper, we have analyzed the LGI1 gene expression in primary cultures of malignant gliomas, and compared these data with epigenetic indicators of transcriptional activity ­ posttranslational H3 histone modifications. We have show the presence of an epigenetic marker of gene repression H3K9me3 near the site of LGI1 transcription initiation in most (5 from 6) studied gliomas. There was not LGI1 expression in these gliomas. Only one glioma showed LGI1 expression, and in this glioma there was no association of LGI1gene with H3K9me3 modification. Thus, we are the first to show a correlation between LGI1 gene expression and the epigenetic indicator H3K9met3 in malignant gliomas. Marker of actively transcribed chromatin Í3K4àñ have not been found in this area of the genome. The data obtained strongly suggest the possibility of gene LGL1 inactivation by epigenetic mechanism: modified «histone code¼.

EVALUATION OF VASCULOGENIC POTENTIAL OF MODIFIED FIBRIN HYDROGEL.

In recent years, engineering of blood vessels, which can provide the effective transport of nutrients and various metabolites, is one of the major challenges in tissue reconstruction. Many researches are carried out to develop cell-seeded bioconstructs based on natural polymers, particularly on PEGylated fibrin. Therefore, the aim of this study was to reveal the optimal component ratio for modified fibrin hydrogels in order to provide favorable conditions for vascular development of endothelial and mesenchymal stem cell co-culture. It has been found out that the PEGylated fibrin hydrogels can support 3D cell growth in HUVECs and hASCs co-culture. The microporous filamentous hydrogel prepared from PEGylated 5 : 1 fibrinogen and using the 1 : 0.2 protein to thrombin ratio had the most favorable microenvironment for cell distribution, growth and development in the studied co-culture that resulted in high levels of expression of proteins required for angiogenesis.

Evaluation of risk factors in atherosclerosis in workers with chronic fluorine intoxication.

Complex medical examination covered 87 metallurgists of aluminium production with chronic fluorine intoxication and 43 metallurgists witout occupational diseases, aged 40 to 60, to evaluate factors associated with multi-focal atherosclerosis risk in aluminium production workers with chronic fluorine intoxication. Findings are increased incidence of ischemic heart disease and combined atherosclerosis of extracranial and peripheral arteries in workers with long exposure to fluorine compounds. Metallurgists with chronic fluorine intoxication appeared to have more frequent hyperfibrinogenemia and coronary personality type A, if compared to those without occupational diseases.