Thromboxane a synthase: A new target for the treatment of cardiovascular diseases
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01.01.2018 |
Mesitskaya D.
Syrkin A.
Aksenova M.
Zhang Y.
Zamyatnin A.
Kopylov P.
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Cardiovascular and Hematological Agents in Medicinal Chemistry |
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1 |
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© 2018 Bentham Science Publishers. Atherothrombosis-related diseases are one of the world’s leading causes of mortality, and thus the search for new therapeutic approaches in this area remains a very urgent task. Modern pharmacogenomic technologies make it possible to obtain valuable data on disease pathogenesis and optimal therapeutic approaches. One promising research direction is the study of the thromboxane A2 - thromboxane A synthase - thromboxane A2 receptor axis. This review summarizes the recent evidence and suggests that systematic works in this area are creating new and promising opportunities in the treatment of patients with cardiovascular diseases.
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Influence of CYP3A activity on the efficacy and safety of fluvoxamine in patients depressive disorders and comorbid alcohol use disorder
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01.01.2018 |
Zastrozhin M.
Smirnov V.
Sorokin A.
Grishina E.
Ryzhikova K.
Bedina I.
Shipitsyn V.
Savchenko L.
Buzik O.
Koporov S.
Bryun E.
Sychev D.
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Vestnik Rossiiskoi Akademii Meditsinskikh Nauk |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. BACKGROUND: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder (DD), which worsens adversely affects the prognosis of the course of both diseases and their outcomes. For the treatment of DD, drugs from the group of selective serotonin reuptake inhibitors, whose representative is fluvoxamine, are used. Fluvoxamine therapy is often associated with a risk of development is shown to be ineffective, and a part of patients develop dose-dependent adverse drug reactions (ADR) and pharmacoresistance. OBJECTIVE: To study the effects of CYPD6 isoenzyme activity on the efficacy and safety of fluvoxamine therapy in patients with depressive disorders, comorbid with alcoholism. METHODS: The study was conducted on 117 Russian patients with DD, alcohol-dependent comorbid. For the purpose of correction of depressive disorders within the framework of cyclothymia, fluvoxamine (Fevarin) was administered to patients at a dosage of 50−150 mg/day. Genotyping was carried out by the method of polymerase chain reaction in Real-time mode with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of ADR. To evaluate the activity of CYP2D6, the method of high performance liquid chromatography with mass spectrometry was used to measure the urinary content of the endogenous substrate of this isoenzyme and its metabolite, the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline. RESULTS: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was statistically significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.0; 5.0] (p<0.001); safety indicator, estimated on a UKU scale: 3.0 [2.0; 4.0], (GA) 4.0 [4.0; 4.2] (p<0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.0] (p<0.001); safety indicator, estimated on a UKU scale: (GG) 9.0 [9.0; 10.0], (GA) 6.0 [6.0; 7.0] (p<0.001). The calculation of the correlation coefficients between the difference in the number of scores on psychometric scales and the metabolic ratio showed a statistically significant inverse correlation of the average power degree between the efficiency index estimated by the HAMD scale (r=-0.467, p<0.05). There was no connection with the difference on the UKU scale (r=0.173, p>0.05). CONCLUSION: In a study of a group of 117 patients with DD, comorbid with alcohol dependence, the effect of CYP2D6 activity, estimated by the ratio of the endogenous substrate concentrations of pinolin and its metabolite 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline, on the efficacy of fluvoxamine therapy. This effect was also shown using the results of genotyping. The results of genotyping also showed the existence of a difference in the safety index in patients with different genotypes from the polymorphic marker CYP2D6 1846G>A.
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Literature review and clinical observation of acquired idiopathic hemophilia with a new missense mutation in the factor VIII gene (His2026Arg)
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01.01.2018 |
Ershov V.
Gadaev I.
Budanova D.
Perina F.
Surin V.
Salomashkina V.
Pshenichnikova O.
Zozulya N.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group. All rights reserved. The article provides review of possible mechanisms of inhibitor coagulopathies, in particular of acquired hemophilia A. This pathology is an extremely rare disease occurring in 1-2 cases in 1 million per year. In the present study we provide data for two clinical cases of hemophilia A in women. These cases had different development mechanisms, although both women have a newly discovered missense mutation His2026Arg in the VIII factor gene. The matter of main interest is the description of the disease development in the patient with an acquired idiopathic hemophilia A with a possible disease occurrence due to an asymmetric X-chromosome inactivation (lyonization). In this particular case lyonization led to the late manifestation of the hemophilia A carrier's state and development of severe form of the inhibitor-associated acquired hemophilia A. We also discuss therapeutic approaches to these forms of the disease, considering there are no concise protocols for case management due to an extreme rarity of the pathology. Acquainting the clinical personnel working it the different areas of medicine with suchlike inhibitor coagulopathies has a major practical importance.
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New local haemostatic technologies in surgical practice
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01.01.2018 |
Alekseyeva G.
Chilova R.
Kolobaev I.
Kukes V.
Vechorko V.
Tarasov I.
Proklova G.
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Voprosy Ginekologii, Akusherstva i Perinatologii |
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0 |
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© 2018 Dynasty Publishing House. All rights reserved. One of the most important tasks of clinical medicine is to stop bleeding as soon as possible. Despite the broad spectrum of modern haemostatic materials, the available local blood-stopping products are not without certain limitations and shortcomings when used in various clinical situations. The article discusses the potential of «Polygemostat», a Russian haemostatic for external and local use, which simultaneously has an antiseptic and wound-healing effect.
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Influence of interlejkines IL-1α, IL-1β and IL-1ra on development of male gamette in norm and hypospermatogenesis
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01.01.2018 |
Demyashkin G.
Kogan E.
Khodzhayan A.
Kulchenko N.
Demura T.
Gevandova M.
Shitov V.
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Medical News of North Caucasus |
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© 2018 Stavropol State Medical University. All rights reserved. Male fertility is based on complex intracellular signaling during spermatogenesis. Effect of Interleukin-1 (IL-1) and its homologues on spermatogenesis is actively studied. Nevertheless, its role in idiopathic infertility has not been sufficiently studied, especially in the phase of hypospermatogenesis. Aim: Evaluation of the expression of IL-1α, IL-1β and IL-1ra in human seminiferous tubules in idiopathic infertility. A retrospective study involved men (n=54) who complained of childlessness in a marriage for 2 years with the diagnosis of idiopathic infertility, established after a physical, medico-genetic, biochemical (hormone) and cytological (spermogram) analysis. The biopsy specimens obtained from the operation, as well as the autopsy material of men aged 22-35 years (n=10), were studied using the immunohistochemical method (antibodies: IL-1α, IL-1β and IL-1ra). At hypo-spermatogenesis, the maturation block, and Sertoli-cell syndrome, Leydig cells are marked to IL-1α, IL-1β labeling with a decrease in IL-1ra. Sertoli cells and germ cells show weak responses to IL-1α, IL-1β and their absence on IL-1ra. Thus, the different levels of expression of IL-1α, IL-1β and IL-1ra indicate that these cytokines control spermatogenesis and are one of the triggers in the formation of male infertility form-phases.
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Cognitive impairment in anxiety disorders
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01.01.2018 |
Volel B.
Petelin D.
Akhapkin R.
Malyutina A.
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Nevrologiya, Neiropsikhiatriya, Psikhosomatika |
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1 |
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© 2018 Ima-Press Publishing House. All rights reserved. Anxiety disorders are an important biomedical problem due to the high prevalence and significant negative impact on the quality of life and the course of concomitant somatic and neurological diseases. Cognitive impairment (CI) is one of the most intensively studied aspects of pathological anxiety. Impairments in attention, executive functions, memory, cognitive deficit, as well as abnormal cognitions and metacognitions are identified in anxiety disorders. Moreover, the treatment of the latter with the most frequently used drugs (antidepressants, atypical antipsychotics, anticonvulsants, tranquilizers) does not lead to a significant improvement in cognitive functions, and often contributes to their worsening. In this connection, in addition to psychotherapy, cognitive function-improving agents play a large role in treating anxiety diseases associated with cognitive dysfunction. Ginkgo Biloba extract (EGb 761, Tanakan®) that positively affects cognitive functions, especially in the domains of memory, concentration and attention deserves special attention.
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Genotype-phenotype correlations of the course of cystic fibrosis in Russian children. the first description of eleven new mutations
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01.01.2018 |
Gorinova Y.
Savostyanov K.
Pushkov A.
Nikitin A.
Pen'Kov E.
Krasovskiy S.
Simonova O.
Namazova-Baranova L.
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Voprosy Sovremennoi Pediatrii - Current Pediatrics |
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© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. Cystic fibrosis is a hereditary disease that occurs as a result of mutations in the regulator gene of chloride ion transmembrane transport (CFTR). Finding mutations in the CFTR gene is necessary for identification of the clinical features of cystic fibrosis. Objective. Our aim was to identify genotype-phenotype correlations between mutations of the first class of pathogenicity and clinical manifestations of cystic fibrosis based on studying the prevalence and structure of CFTR gene mutations. Methods. The study included children under 18 years with cystic fibrosis admitted to hospital between 2013 and 2017. Biallelic mutations in the CFTR gene were the non-inclusion criterion. The CFTR gene variants were analyzed by next-generation sequencing method. Results. In 125 patients with cystic fibrosis, 59 different variants of the CFTR gene were detected, 11 of them not previously described. The most common was the deletion c.1521-1523del found in 98 (39.2%) of the 250 analyzed CFTR gene alleles and the deletion c.1545-1546del found in 22/250 (8.8%) alleles. It has been shown that the mutation c.1545-1546del, p.Y515∗ was more often found in children of the Chechen nation-odds ratio (OR) 139 (95% confidence interval 15-1,257). It has been established that meconium ileus, pancreatic deficiency and cirrhosis are more common in patients with mutations of the first category of pathogenicity: OR 3.9 (95% CI 1.0-15.0), 4.4 (95% CI 1.8-11.1), and 351 (95% CI 17.5-7,046), respectively. The association of CFTR gene mutations with the development of bronchiectases and polypous pancinusitis has not been found. Conclusion. Correlations between the genotype and clinical manifestations of cystic fibrosis in Russian children with CFTR gene mutations of the first class of pathogenicity have been established.
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Influence of ABCB1 and CYP3A5 gene polymorphisms on pharmacokinetics of apixaban in patients with atrial fibrillation and acute stroke
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01.01.2018 |
Kryukov A.
Sychev D.
Andreev D.
Ryzhikova K.
Grishina E.
Ryabova A.
Loskutnikov M.
Smirnov V.
Konova O.
Matsneva I.
Bochkov P.
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Pharmacogenomics and Personalized Medicine |
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10 |
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© 2018 Kryukov et al. Introduction: Difficulties in non-vitamin K anticoagulant (NOAC) administration in acute stroke can be associated with changes in pharmacokinetic parameters of NOAC such as biotransformation, distribution, and excretion. Therefore, obtaining data on pharmacokinetics of NOAC and factors that affect it may help develop algorithms for personalized use of this drug class in patients with acute cardioembolic stroke. Patients and methods: Pharmacokinetics of apixaban in patients with acute stroke was studied earlier by Kryukov et al. The present study enrolled 17 patients with cardioembolic stroke, who received 5 mg of apixaban. In order to evaluate the pharmacokinetic parameters of apixaban, venous blood samples were collected before taking 5 mg of apixaban (point 0) and 1, 2, 3, 4, 10, and 12 hours after drug intake. Blood samples were centrifuged at 3000 rpm for 15 minutes. Separate plasma was aliquoted in Eppendorf tubes and frozen at —70°C until analysis. High-performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Genotyping was performed by real-time polymerase chain reaction. CYP3A isoenzyme group activity was evaluated by determining urinary concentration of endogenous substrate of the enzyme and its metabolite (6-β-hydroxycortisol to cortisol ratio). Statistical analysis was performed using SPSS Statistics version 20.0. The protocol of this study was reviewed and approved by the ethics committee; patients or their representatives signed an informed consent. Results: ABCB1 (rs1045642 and rs4148738) gene polymorphisms do not affect the pharmacokinetics of apixaban as well as CYP3A5 (rs776746) gene polymorphisms. Apixaban pharmacokinetics in groups with different genotypes did not differ statistically significantly. Correlation analysis showed no statistically significant relationship between pharmacokinetic parameters of apixaban and the metabolic activity of CYP3A. Conclusion: Questions such as depending on genotyping results for apixaban dosing and implementation of express genotyping in clinical practice remain open for NOACs. Large population studies are required to clarify the clinical significance of genotyping for this drug class.
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Association between polymorphic markers in candidate genes and the risk of manifestation of endocrine ophthalmopathy in patients with Graves' disease
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01.01.2018 |
Petunina N.
Martirosian N.
Trukhina L.
Saakyan S.
Panteleeva O.
Burdennyy A.
Nosikov V.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group.All Rights Reserved. Aim. To analyze the association between the polymorphic markers in CTLA4, TNF, IL10 and IL16 genes and the risk of manifestation of endocrine ophthalmopathy (EO) in patients with Graves' disease (GD). Materials and methods. Case-control study included 248 patients with GD. Using polymerase chain reaction we studied the distribution of alleles and genotypes of polymorphic markers such as A60G (rs3087243) in CTLA4 gene, G(-308)A (rs1800629) in TNF gene, G(-1082)A (rs1800896) in IL10 gene, T3249C (rs4778641) in IL16 gene among 141 patients with Graves' disease and EO and 107 patients with GD without EO. Results and discussion. The frequencies of A alleles and the AA genotypes were significantly increased and the frequencies of G alleles and the GG genotype polymorphic markers rs3087243 of CTLA4 gene and rs1800896 of IL10 gene, as well as the GG genotype polymorphic marker rs1800629 of TNF gene were reduced in patients with GD and EO. The polymorphism in CTLA4 gene was also associated with the activity and the severity of EO. The comparative analysis of the allele and genotype frequency distribution of polymorphic markers of IL16 gene did not show the significant difference. Conclusion. The risk of manifestation and the development of EO in patients with Graves' disease can be caused by not only environmental, but also genetic risk factors.
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Mesenchymal stem cell therapy for ischemic heart disease: Advances and challenges
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01.01.2018 |
Konoplyannikov M.
Kotova S.
Baklaushev V.
Konoplyannikov A.
Kalsin V.
Timashev P.
Troitskiy A.
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Current Pharmaceutical Design |
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3 |
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© 2018 Bentham Science Publishers. Ischemic Heart Disease (IHD) has been recognized as the main cause of mortality in the modern world. Application of cell therapy technologies for the IHD treatment has been actively studied from the beginning of 2000s. The review is dedicated to the use of mesenchymal stem cells (MSC) in the therapy of IHD. The strategies of the MSC modification in vitro for improvement of their regenerative potential are extensively discussed, including preconditioning to enhance the cell survival, boosting their paracrine effect and manipulating their car-diomyogenic differentiation. The optimization of the MSC delivery and opportunities related to the use of biomaterials as cell carriers are also discussed. The results of the most important clinical studies on the MSC-based IHD therapy are presented, including those completed and published in the literature and the ongoing clinical trials registered at clinicaltrials.gov by June 2018.
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The technology of laser fabrication of cell 3D scaffolds based on proteins and carbon nanoparticles
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01.01.2018 |
Gerasimenko A.
Zhurbina N.
Kurilova U.
Polokhin A.
Ryabkin D.
Savelyev M.
Suetina I.
Mezentseva M.
Ichkitidze L.
Ignatov D.
Garcia-Ramirez M.
Guzman Gonzalez J.
Podgaetsky V.
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Proceedings of SPIE - The International Society for Optical Engineering |
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© 2018 SPIE. The technology of cell 3D scaffolds laser fabrication is developed. 3D scaffolds are designed to repair osteochondral defects, which are poorly restored during the organism's life. The technology involves the use of an installation, the laser beam of which moves along a liquid nanomaterial and evaporates it layer by layer. Liquid nanomaterial consists of the water-protein (collagen, albumin) suspension with carbon nanoparticles (single-walled carbon nanotubes). During laser irradiation, the temperature in the region of nanotubes defects increases and nanotubes are combined into the scaffold. The main component of installation is a continuous laser operating at wavelengh of 810 nm. The laser beam moves along 3 coordinates, which makes it possible to obtain samples of the required geometric shape. The internal and surface structure of the samples at the micro- A nd nanoscale levels were studied using the X-ray microtomography and scanning electron microscopy. In vitro studies of cell growth during 48 and 72 hours demonstrated the ability of cell 3D scaffolds to support the proliferation of osteoblasts and chondroblasts. Using fluorescence and atomic force microscopy, it was found that the growth and development of cells on a sample with a larger concentration of nanotubes occurred faster compared to samples with a smaller concentration of nanotubes.
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TAS3 miR390-dependent loci in non-vascular land plants: Towards a comprehensive reconstruction of the gene evolutionary history
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01.01.2018 |
Morozov S.
Milyutina I.
Erokhina T.
Ozerova L.
Troitsky A.
Solovyev A.
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PeerJ |
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© 2018 Morozov et al. Trans-acting small interfering RNAs (ta-siRNAs) are transcribed from protein noncoding genomic TAS loci and belong to a plant-specific class of endogenous small RNAs. These siRNAs have been found to regulate gene expression in most taxa including seed plants, gymnosperms, ferns and mosses. In this study, bioinformatic and experimental PCR-based approaches were used as tools to analyze TAS3 and TAS6 loci in transcriptomes and genomic DNAs from representatives of evolutionary distant non-vascular plant taxa such as Bryophyta, Marchantiophyta and Anthocerotophyta. We revealed previously undiscovered TAS3 loci in plant classes Sphagnopsida and Anthocerotopsida, as well as TAS6 loci in Bryophyta classes Tetraphidiopsida, Polytrichopsida, Andreaeopsida and Takakiopsida. These data further unveil the evolutionary pathway of the miR390-dependent TAS3 loci in land plants. We also identified charophyte alga sequences coding for SUPPRESSOR OF GENE SILENCING 3 (SGS3), which is required for generation of ta-siRNAs in plants, and hypothesized that the appearance of TAS3-related sequences could take place at a very early step in evolutionary transition from charophyte algae to an earliest common ancestor of land plants.
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Molecular genetic testing of accp-positive patients with rheumatoid arthritis and high inflammatory disease activity (A remarca study)
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01.01.2018 |
Guseva I.
Luchikhina E.
Demidova N.
Avdeeva A.
Soroka N.
Abramov D.
Cherkasova M.
Samarkina E.
Karateev D.
Nasonov E.
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Nauchno-Prakticheskaya Revmatologiya |
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0 |
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Rheumatoid arthritis (RA) is a multifactorial disease, in which the interaction of the genetic component and environmental factors, determines not only the development of the disease, but also its pronounced clinical polymorphism. We assume that the high inflammatory activity of RA may be determined by the genes, the products of which trigger inflammatory processes. Objective: to investigate allele and genotype distribution of gene polymorphic variants in active anti-cyclic citrullinated peptide (aCCP)-positive patients with RA from the REMARCA program versus a control group of healthy blood donors. Subjects and methods. A molecular genetic study enrolled 146 aCCP-positive patients from the REMARCA program and a control group of 314 healthy blood donors without autoimmune diseases and their presence in the history, who were matched with the study group for gender and sex. The polymorphic variants of the genes PTPN22 (+1858C>T, rs2476601), TNFAIP3 (rs6920220, rs10499194), CTLA4 (+49A>G, rs231775), TNF? (-308A>G, rs1800629), IL6 (-174G>C, rs1800795), IL6R (+358A>C, rs8192284), IL10 (-592A>C, rs1800872, -892 C>T, rs1800871, -1082 A>G, rs1800896), and MCP1/CCL2 (+2518A>G, rs1024611) were genotyped by a real-time polymerase chain reaction assay. Results and discussion. The genotype and allele frequencies of polymorphic variants of the genes CTLA4 (+49A>G), IL-6R (+358A>C), and IL10 (- 592A>C) in the RA group significantly differed from those in the control group. When comparing with the control group, the minor alleles of the CTLA4 and IL10 genes were markers for the risk of aCCP-positive RA with a high inflammatory activity (OR=1.4 [1.1; 1.9], p=0.02 and OR=1.9 [1.4; 2.5]; p=0.0001, respectively). At the same time, the minor C allele of the IL6R gene served as a marker of protection (OR=0.7 [0.5; 0.9]; p=0.03). Logistic regression analysis revealed that there was a statistically significant correlation of the high inflammatory activity indices SDAI, CDAI, and DAS28 with the minor homozygous GG genotype of the CTLA4 gene (OR=2.5 [1.1; 6.0]; p=0.03, OR=2.6 [1.1–6.4], p=0.03 and OR=3.4 [1.3–8.8]; p=0.01, respectively). In addition, the inflammatory activity indices SDAI and CDAI rather than DAS28-ESR were associated with at least one minor A allele (the AA/AC genotypes) of the IL10 gene (OR=2.4 [1.2; 5.1], p=0.02 and OR=2.2 [1.1; 4.7]; p=0.03, respectively). The levels of ESR and CRP were not associated with the examined polymorphisms. Conclusion. The findings may suggest that there is a relationship of the polymorphisms of the genes CTLA4 (+49A>G, rs231775), IL6R (+358A>C, rs8192284), and IL10 (-592A>C, rs1800872) to high inflammatory activity in the group of aCCP-positive patients from the REMARCA study.
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Current possibilities and potential development of molecular enterovirus surveillance. Experience of Russian Federation
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01.01.2018 |
Lukashev A.
Golitsina L.
Vakulenko Y.
Akhmadishina L.
Romanenkova N.
Sapega E.
Morozova N.
Novikova N.
Trotsenko O.
Ivanova O.
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Russian Journal of Infection and Immunity |
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© 2018 Saint Petersburg Pasteur Institute.All Rights Reserved. Enteroviruses are small RNA viruses, which are ubiquitous and commonly cause outbreaks with various clinical manifestations. In 2006, the Program on enterovirus surveillance was approved in the Russian Federation. Over the last years, molecular-biological and bioinformatics methods for enterovirus epidemiology studies have been developed both in Russia and worldwide. Currently, identification of enteroviruses is carried out by analyzing nucleotide sequence of the full-length VP1 genome region (ca. 900 nt). Routinely, it is sufficient to obtain a partial VP1 genome region sequence (ca. 300 bp) for enteroviruse verification in most cases; however, a more stringent type criterion of 80% sequence identity should be used compared to the 75% sequence identity cut-off for the complete VP1 genome region. Further sequence analysis may be performed by using Bayesian phylogenetic methods, which allow using molecular clock to trace outbreak emergence. Enteroviruses accumulate about 0.5–1% nucleotide substitutions per year. Therefore, a short genome fragment may be used to analyze virus phylodynamics at the level of international transfers and circulating virus variants. On a shorter timescale, a full-length VP1 genome region or a complete genome sequence are preferred for investigating molecular epidemiology, because a short sequence allows to reliably distinguish not more than 1–2 transmission events per year. Thus, determining enterovirus sequences for full-length VP1 genome region or full-genome sequence is preferred for examining viral outbreaks. It is increasingly apparent that analyzing available enterovirus nucleotide sequences reveals limitations related to uneven surveillance efficacy in various countries and short length of genome fragment measured in routine control. As a result, a proper global-scale analysis of enterovirus molecular epidemiology remains problematic. Over the last 20 years, the number of available enterovirus nucleotide sequences increased by hundred times, but understanding emergence of enterovirus infection outbreaks remains limited. Further development of enterovirus surveillance would require new methods for sewage monitoring, affordable high-throughput sequencing and harmonization of global surveillance systems.
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Association of obesity in shift workers with the minor allele of a single-nucleotide polymorphism (rs4851377) in the largest circadian clock gene (NPAS2)
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01.01.2018 |
Dorokhov V.
Puchkova A.
Arsen’ev G.
Slominsky P.
Dementienko V.
Sveshnikov D.
Putilov A.
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Biological Rhythm Research |
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© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. A growing body of evidence has hinted at the involvement of the largest gene of the circadian clock family, NPAS2, in the regulatory mechanisms underlying the link between metabolic diseases and circadian rhythm disruption. We tested whether one of single-nucleotide polymorphisms in NPAS2 (rs4851377) is associated with obesity and alternations of sleep times in 126 male rotational shift workers (bus drivers). We confirmed positive association of Body Mass Index (BMI) with the difference between free and working days in sleep times, but this difference was smaller in the homozygotes for the minor allele. Moreover, BMI above 30 (obesity) was revealed in the majority of these homozygotes and in the minority of homozygotes for the major allele (11 of 21 or 52.4% and 3 of 40 or 7.5%, respectively). Further studies are required to replicate these results and to elucidate the mechanisms linking NPAS2ʹpolymorphism in with obesity in shift workers.
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Assessing genetic and morphological variation in populations of Eastern European Lucilia sericata (Diptera: Calliphoridae)
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01.01.2018 |
Diakova A.
Schepetov D.
Oyun N.
Shatalkin A.
Galinskaya T.
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European Journal of Entomology |
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2 |
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© 2018 Czech Academy of Sciences. The population structures of different species of Calliphoridae flies are highly diverse at different locations. We investigated populations of the Eastern European L. sericata using chaetotaxy and eight microsatellite loci. Our results strongly indicate that a panmictic population of L. sericata exists in the area studied, possibly with a high rate of intra-population gene flow. Analysis of chaetotaxy also supports the panmictic population hypothesis.
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Low-invasive reconstruction of spine discs under thermo-mechanical effect of fiber laser
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01.01.2018 |
Sobol E.
Baskov A.
Borshchenko I.
Shekhter A.
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Progress in Biomedical Optics and Imaging - Proceedings of SPIE |
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0 |
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© COPYRIGHT SPIE. The paper considers physical processes and mechanisms of laser reparation of spine cartilage, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reconstruction of spine discs. Possible mechanisms of laser-induced regeneration include: (1) Space and temporary modulated laser beam induces non-homogeneous and pulse repetitive thermal expansion and stress in the irradiated zone of cartilage. Mechanical effect due to controllable thermal expansion of the tissue and micro and nano gas bubbles formation in the course of the moderate (up to 50 °C) heating of the NP activate biological cells (chondrocytes) and promote cartilage regeneration. (2) Non-destructive laser radiation leads to the formation of nano and micro-pores in cartilage matrix in the in the immediate vicinity of chondrocytes. That promotes water permeability and increases the feeding of biological cells. Results provide the scientific and engineering basis for the novel low-invasive laser procedures to be used in neurosurgery and orthopedics for the treatment cartilages of spine. The technology and equipment for laser reconstruction of spine discs have been tested first on animals, and then in a clinical trial. Since 2001 the laser reconstruction of intervertebral discs have been performed (i) for more than 3,200 patients with chronic symptoms of low back or neck pain who failed to improve with non-operative care; and (ii) for 1100 patients underwent hernia removal surgery. Substantial relief of back pain was obtained in 92.5% of patients treated who returned to their daily activities. LRD allowed also to decrease secondary surgeries more than three times. Optical fiber technique based on light scattering measurements have been used to promote safety and efficacy of the laser procedures.
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Risk of stroke after exacerbation of ischemic heart disease: Data of 3-years follow-up
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01.01.2018 |
Brazhnik V.
Minushkina L.
Evdokimova M.
Galyavich A.
Tereshchenko S.
Koziolova N.
Glezer M.
Yagoda A.
Khorolets E.
Dankovtseva E.
Boeva O.
Konstantinov V.
Zateishchikov D.
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Kardiologiya |
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© 2018 Media Sphera Publishing Group. All rights reserved. Purpose: to analyze possible associations of clinical and genetic factors with development of ischemic stroke after exacerbation of ischemic heart disease (IHD). Materials and methods: The Russian multicenter study aimed at assessment of risk of unfavorable outcomes after exacerbation of IHD "Exacerbation of IHD: logical probabilistic ways to course prognostication for optimization of treatment" (meaning of Cyrillic acronym-oracle) was conducted in 16 centers of 7 cities in Russia. We included into the study 1 208 patients with unstable angina and ST-elevation or non-ST-elevation myocardial infarction (MI). Data on outcomes were known for 1 193 patients, 15 patients were lost for follow-up. Results. Mean duration of follow-up was 64414.45 (4-1 995) days. Shortest, longest, and mean time before development of stroke was 22, 1433 and 38956.6 days after inclusion. Patients with strokes were older, more often had history of IHD prior to index hospitalization, arterial blood pressure level compatible with stage 3 arterial hypertension, less often were smokers, and more often had MI recurrences or repetitive episodes of severe ischemia during the index hospitalization. Patients also more often had documented atrial fibrillation during hospitalization, and lower level of glomerular filtration rate. Of studied genetic markers carriage of A allele of polymorphic marker G (-1082) A of interleukin-10 gene was significantly associated with risk of stroke development. Using linear regression analysis, we constructed a model of estimation of the stroke development risk. Comparison of diagnostic value of different scales for stroke risk assessment showed that area under the curve was 0.656, 0.686, and 0.756 for the GRACE, CHA2DS2-VASc, and ORACLE scores, respectively.
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Type 3 Diabetes Mellitus: A Novel Implication of Alzheimers Disease
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Тарасов В. В.
Баранова А.М.
Несвижский Юрий Владимирович
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CURRENT TOPICS IN MEDICINAL CHEMISTRY |
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Background: The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine that promotes neurogenesis and angiogenesis in the brain. In animal models, it has been shown that environmental enrichment and exercise, two non-pharmacological interventions that are beneficial decreasing the progression of Alzheimer disease (AD) and depressive-like behavior, enhance hippocampal VEGF expression and neurogenesis. Furthermore, the stimulation of VEGF expression promotes neurotransmission and synaptic plasticity processes such as neurogenesis. It is thought that these VEGF actions in the brain, may underly its beneficial therapeutic effects against psychiatric and other neurological conditions.
Conclusion: In this review, evidence linking VEGF deficit with the development of AD as well as the potential role of VEGF signaling as a therapeutic target for cotinine and other interventions in neurodegenerative conditions are discussed.
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Native and Activated Hepatic Stellate Cells Stimulate Liver Regeneration in Rats After Partial Hepatectomy and 2-Acetylaminofluorene Injection
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Шахмарданова С.А.
Замятнин А. А.
Несвижский Юрий Владимирович
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BioNanoScience |
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One the current challenges of modern hepatology is to find new approaches to stimulate liver regeneration and to find new methods for liver disease treatment. Cell therapies, which are based on using regional stem cells for disease treatment, are under active development. However, studies, devoted to their transplantation, are currently scarce. In recent years, hepatic stellate cells are considered to be hepatic stem cells. It is known that activated hepatic stellate cells can transdifferentiate into myofibroblasts and lead to liver fibrosis. The aim of our work was to study the influence of native and activated hepatic stellate cells in vivo by lead nitrate injection after transplantation into partial hepatectomized rats, which is considered to be a classical model to study liver regeneration. Injection of 2-acetylaminofluorene (AAF), which selectively eliminates hepatocyte proliferation, was used to understand the hepatic stellate cells role in liver regeneration process better. Our results suggest that transplanted native and activated hepatic stellate cells can differentiate into hepatocyte-like cells and positively influence liver regeneration without inducing liver fibrosis.
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