Inhibition of HIF-prolyl 4-hydroxylases as a promising approach to the therapy of cardiometabolic diseases
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01.01.2018 |
Aitbaev K.
Murkamilov I.
Fomin V.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group. All rights reserved. Prolyl-4-hydroxylases of hypoxia-inducible factor (HIF-P4Hs) are enzymes that, under the conditions of normoxia, cause degradation of the HIF-transcriptional protein, which regulates a number of metabolic processes, including erythropoiesis, glucose level and lipid metabolism. In hypoxic conditions, on the contrary, their activity is suppressed and HIF stabilization takes place. This mechanism, i.e. stabilization of HIF by inhibition of HIF-P4Hs was the basis for the development of drugs designed for treatment of renal anemia, which are currently in stages 2 and 3 of clinical trials and are showing encouraging results. Recently, it has also been reported that inhibition of HIF-P4Hs can be effective in treatment of cardiometabolic diseases - coronary heart disease, hypertension, obesity, metabolic syndrome, diabetic cardiomyopathy and atherosclerosis. The review, based on the most recent data, discusses in detail molecular mechanisms of therapeutic effect of HIF-P4Hs inhibition in these pathological conditions and provides evidence that these mechanisms are associated with HIF stabilization and gene expression, improving perfusion and endothelial function, reprogramming metabolism from oxidative phosphorylation to anaerobic glycolysis, reducing inflammation and having beneficial effect on the innate immune system.
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LC-MS/MS identification and structural characterization of main biodegradation products of nitroproston-A novel prostaglandin-based pharmaceutical compound
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01.01.2018 |
Mesonzhnik N.
Moskaleva N.
Shestakova K.
Kurynina K.
Baranov P.
Gretskaya N.
Serkov I.
Lyubimov I.
Bezuglov V.
Appolonova S.
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Drug Metabolism Letters |
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1 |
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© 2018 Bentham Science Publishers. Background: Nitroproston is a novel prostaglandin-based compound modified by NO-donating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. Objective: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products. Methods: The principal biodegradation products of Nitroproston were identified in vitro using liquid chromatography/ion trap – time-of-flight mass-spectrometry. The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by liquid chromatography/triple –stage quadrupole mass spectrometry. Results: Nitroproston is rapidly hydrolyzed in rat plasma to generate glycerol-1,3-dinitrate and prostaglandin E2 . The latter can undergo conversion to cyclopentenone prostaglandins A2 and B2 . Thereby less than 5% of the parent compound was observed in rat plasma at the first moment of incubation. A similar pattern was observed for rabbit plasma where half-life (T1/2) of Nitroproston was about 2.0 minutes. Nitroproston biodegradation rate for human plasma was the slowest (T1/2 = 2.1 h) among tested species, occurred more rapidly in whole blood (T1/2 = 14.8 min). Conclusion: It was found that Nitroproston is rapidly hydrolyzed in rodent compared to human plasma incubations. Whereas Nitroproston is relatively stable in human plasma an enhanced hydrolytic activity was observed in whole human blood incubations. Extensive metabolism of Nitroproston in human whole blood was mainly associated with red blood cells. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies.
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Placental expression level of the PON1, PON2, and PON3 genes in pstients with uncomplicated pregnancy and preeclampsia
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01.01.2018 |
Antipova N.
Levakov S.
Sheshukova N.
Obukhova E.
Pavlyukov M.
Shakhparonov M.
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Akusherstvo i Ginekologiya (Russian Federation) |
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© Bionika Media Ltd. Objective. To determine the expression level of the genes encoding the paraoxonase family enzymes (PON1, PON2, and PON3) in the placentas of women with uncomplicated pregnancy and in the development of preeclampsia Materials and methods. The investigation enrolled 26 pregnant women aged 24 to 35 years, including 14 women with normal pregnancy and 12 with preeclampsia. The expression of the PON1, PON2, and PON3 genes was analyzed by real-time PCR using the primers specific to these genes. Results. Women whose pregnancy was complicated by preeclampsia showed a significant decrease in the placental expression of the PON2 gene. The lowest PON2 gene expression was found in the placentas of women with severe preeclampsia. There were no significant differences in the placental expression level of the PON1 and PON3 genes in women with preeclampsia compared to healthy women. Conclusion. In women with preeclampsia, the placental PON2 gene expression decreases; however, the expression level of the PON1 and PON3 genes does not differ from that of the PON1 and PON3 genes in the placentas of patients with physiological pregnancy. The placental expression of the PON2 gene depends on the severity of preeclampsia; is lower in severe preeclampsia than in moderate preeclampsia.
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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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Prevalence, morbidity, phenotypes and other characteristics of severe bronchial asthma in Russian Federation
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01.01.2018 |
Avdeev S.
Nenasheva N.
Zhudenkov K.
Petrakovskaya V.
Izyumova G.
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Pulmonologiya |
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© 2018 Medical Education. All rights reserved. The article provides a review on prevalence, phenotypes, endotypes, and the control of severe bronchial asthma. Severe asthma is a widespread, heterogeneous disease that affects 5 - 20% of patients with bronchial asthma. Prevalence of severe asthma in Russia significantly exceeds the official statistics data, therefore it is necessary to maintain a national register of patients with severe asthma. The conventional therapy for severe asthma is not always effective due to the uncontrolled course of the disease and eosinophilic airway inflammation. The identification of asthma phenotype/endotype is reasonable to develop a personalized approach to treatment. This approach allows to achieve better control of the disease and to minimize the risk of asthma exacerbations, fixed airway obstruction and adverse effects of the pharmacological therapy. The main changes in the Global Strategy for Asthma Management and Prevention (GINA, 2018) concerning severe asthma therapy are highlighted in this article. It is also emphasized that the use of monoclonal IL-5 and IgE-antibodies could contribute to successful treatment of patients with uncontrolled severe asthma. Currently, two immunobiological drugs have been registered in Russia, omalizumab (anti-IgE antibody) and reslizumab (anti-IL-5 antibody).
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Rational supportive therapy for chemotherapy induced anemia: A pharmaco-economic analysis of erythropoietin therapy in cancer patients in Russian Federation
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01.01.2018 |
Larionova V.
Krysanov I.
Snegovoy A.
Zeinalova P.
Krysanova V.
Ermakova V.
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Oncogematologiya |
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© 2018 ABV-Press Publishing House. All rights reserved. Modern anticancer therapy due to its intensity and molecular biology orientation allows achieving higher efficiency and theoretically reducing the incidence of complications. However, the increase in efficacy in the modern oncology really exists, but reducing complication frequency, unfortunately, is far from being solved. In many respects the problems of diagnosis, treatment and complications monitoring are associated with the impact on the complex physiological processes occurring in oncological patient. Timely implementation of modern and adequate programs for the prevention and treatment of these complications defines the concept of "supportive therapy", which provides at least half the effectiveness of antitumor treatment. To date, according to most studies, the most frequent complications of antitumor therapy are hematologic, in particular - anemia. In clinical practice, blood transfusions, recombinant human erythropoietins, hemopoiesis stimulating cofactors are used to correct this type of complications. The need for anemia treatment is determined by its negative impact on quality of life, as well as a negative prognostic impact on the life expectancy of cancer patients, because hypoxia of tumor tissue can be associated with resistance to chemo- and radiation therapy, the stimulation of genetic mutations and neoangiogenesis, which make it difficult to control of tumor growth. In numerous studies using multivariate analysis confirmed the association of low hemoglobin levels and/or tumor tissue hypoxia with worsening prognosis and overall survival in many types of tumors. The modern anemia treatment should not be determined only by increased in hemoglobin level, but should be considered as an active prophylaxis for its reducing. Recombinant forms of human erythropoietin and intravenous forms of iron preparations should be the most popular correction methods in everyday practice. The high cost of complex anemia therapy and the social significance of oncological diseases necessitate a pharmaco-economic analysis of registered in Russia erythropoietin preparations and the optimization of existing anemia treatment regimens in cancer patients in order to reduce the expenditures of the health budget. At present, an active import substitution program is underway in the Russian Federation to support the development of the Russian pharmaceutical industry and provide the population with more affordable medicines while maintaining its quality and efficiency. The need to address these issues, and the effective use of the domestic biological analogue epoetin alfa, served as an excuse for performing a comparative clinical and economic analysis. They were selected drugs that differ in pharmacokinetic properties: Eralfon® - analogue of epoetin alfa and Aranesp® - darbepoetin alfa. The treatment model of adults oncological patients with anemia receiving chemotherapy was created, which takes into account various therapies using erythropoietin preparations. The total therapy cost for an oncological patient with anemia is less when using short-acting erythropoietin - epoetin alfa - 131 609 rubles in comparison with the long-acting erythropoietin - darbepoetin alfa - 245 159.2 rubles, the difference was 113 550.2 rubles (-46 %) in favor of the epoetin alfa. According to pharmaco-economic analysis, the treatment of anemia with a Russian-produced drug epoetin alfa (Eralfon®) is preferred in comparison to darbepoetin alfa (Aranesp) in adult cancer patients with nonmyeloid malignancies in the Russian Federation, as it allows increasing the number of treated patients at a cost reduction.
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Association of polymorphisms of HLA-DRB1 and TNF-308 G/A with radiographic joint damage in patients with early rheumatoid arthritis with high inflammatory activity, treated according to the principle of "Treat to target" (REMARKA study)
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01.01.2018 |
Guseva I.
Smirnov A.
Demidova N.
Krylov M.
Avdeeva A.
Samarkina E.
Luchikhina E.
Karateev D.
Abramov D.
Nasonov E.
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Terapevticheskii Arkhiv |
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© 2018 Media Sphera Publishing Group. All rights reserved. Objective. To clarify the association between HLA-DRB1 and TNFα (-308G>A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (<6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to "Treat to target" strategy. Materials and Methods. The study included 85 patients with early RA and duration of symptoms <6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G>A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of ∗04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1∗01, ∗04:01, ∗04:04, ∗04:05, ∗04:08, ∗10 alleles were categorized as SE+ (Shared Epitope) alleles. Results. As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (ρ<0,005, and ρ<0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (Δ) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1∗(SE) genotypes: The carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (ρ<0,028, ρ<0,019, ρ<0,035 respectively). Conclusion. Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G>A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to "Treat to target" stratagy.
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Novel combination of the angiotensin converting enzyme inhibitor perindopril and highly selective β-adrenoblocker bisoprolol: Prime among the equal
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01.01.2018 |
Ostroumova O.
Kochetkov I.
Starodubova V.
Guseva F.
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Cardiovascular Therapy and Prevention (Russian Federation) |
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© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. The article is focused on a broad evidence of antihypertension efficacy of perindopril and bisoprolol. The issues considered, of the drugs usage in patients with arterial hypertension, ischemic heart disease and chronic heart failure according to the international and local clinical guidelines. Special attention is paid for the influence of perindopril and bisoprolol on prognosis - the risk of cardiovascular complications from the evidence based medicine perspective. The data provided on a novel unique combination of these medications, and the benefits are accounted, as the mechanism of complimentary interaction; the results of randomized trials, clinical trials provided, that point on the high potential of this sort of combinational treatment.
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Myocarditis with outcome in dilated cardiomyopathy complicated by refractory heart failure and requiring heart transplantation
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01.01.2018 |
Balykova L.
Leontyeva I.
Urzyaeva N.
Schekina N.
Petrushkina Y.
Ivyanskaya N.
Soloviev V.
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Rossiyskiy Vestnik Perinatologii i Pediatrii |
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© Team of authors, 2018. The article describes the clinical case of subacute myocarditis in a child with an outcome in dilated cardiomyopathy, complicated with congestive heart failure. Difficulties in diagnosing the disease that manifested with cardiac arrhythmia are discussed. The main signs suggesting postmiocardic cardiomyopathy included a reduced deflection voltage and frequent ventricular extrasystoles with episodes of the ventricular tachycardia in the onset of the disease, left ventricular dilatation, a significant decrease in ejection fraction, increased activity of natriuretic peptide, findings of perfusion scintigraphy and magnetic resonance imaging. Medical therapy and implantation of a cardioverter defibrillator were ineffective. The child repeatedly suffered from syncopal conditions with circulatory arrest, which required resuscitation. Due to the ineffectiveness of drug therapy conducted in the leading federal centres, considering cardiac transplantation abroad was recommended.
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Special aspects of implantation of a heart pump support system avk-n as a bridge to heart transplantation
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01.01.2018 |
Khalilulin T.
Zacharevich V.
Poptsov V.
Itkin G.
Shevchenko
Saitgareev R.
Goltz A.
Zakiryanov A.
Koloskova N.
Abramova N.
Zacharevich N.
Nikitina E.
Danilina M.
Gautier S.
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Vestnik Transplantologii i Iskusstvennykh Organov |
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© 2018 Russian Transplant Society. All rights reserved. Aim: To develop an optimal surgical tactic for implantation of "AVK-N" system as a "bridge" to heart transplantation. Materials and methods. 17 patients were included. They were operated in the period from 2012 to October 2017 in Federal State Budgetary Institution V.I. Shumakov National Medical Research Center of Transplantology and Artifi cial Organs. A tiny implantable system Portable device for assisting cardiac circulation (AVK-N; Russia) was used for replacing the pumping function of the left ventricle. All patients were examined according to the program of potential recipients for heart transplantation, before the applying of prolonged mechanical circulatory support. Among the operated patients there were 16 (94.1%) men and 1 (5.9%) woman, the average age was 52.64 ± 10.56 (from 33 to 67 years). All patients had congestive heart failure III-IV functional class according to NYHA, refractory to optimal drug therapy. Heart failure was triggered by dilated cardiomyopathy in 12 (70,58%) cases, and by postinfarction systolic dysfunction of the left ventricle in 5 (29,42%). Implantation of AVK-N system was performed to potential recipients of the donor heart with terminal stage of CHF with a decrease in LV ejection fraction up to 10%. Results. As a result of this study there were developed several technological aspects facilitating the subsequent heart transplantation. Conclusion. Our experience in optimizing the surgical tactics of the "AVK-N" system implantation as a bridge to heart transplantation, demonstrated the possibility and safety of its active use in both patients with terminal heart failure on the waiting list of heart transplantation and patients having temporary contraindications to HTX.
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Forensic medical criteria for the evaluation of the unfavourable outcomes of the roentgeno-endovascular operations on the arteries of the lower extremities
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01.01.2018 |
Goloshchapov-Aksenov R.
Pigolkin Y.
Kicha D.
Morozov K.
Lakunin K.
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Sudebno-Meditsinskaya Ekspertiza |
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0 |
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© 2018 Lippincott Williams and Wilkins. All rights reserved. The objective - of the present work was to develop the forensic medical criteria for the evaluation of the unfavourable outcomes of the roentgeno-endovascular operations (REVO) on the arteries of the lower extremities. The study included the analysis of the conclusions based on the results of the commission forensic medical examinations, attorney inquiry reports, query response, medical histories of the hospitalized patients who had undergone the roentgeno-endovascular operations on the arteries of the lower extremities. The criteria for the forensic medical evaluation of the unfavourable outcomes of the roentgeno-vascular operations on the arteries of the lower extremities have been proposed together with the indications for REVO, methods and tools for the performance of these surgical procedures. Particular attention was given to the identification of the signs and prognostics of the unfavourable outcomes of the roentgeno-endovascular operations (both intraoperatively and during the early postoperative period and the subsequent stay in the hospital) and to the risks of the development of the unfavourable outcomes of the surgical interventions following the technically adequate REVO. Special emphasis is placed on the cause-and-effect relationship between the actions or a failure to act on the part of an emergency physician and/or an attending surgeon/cardiovascular surgeon and the possibility of the unfavourable outcomes of the roentgeno-endovascular operations.
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Systemic lupus erythematosus: Clinical recommendations. Part 2
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01.01.2018 |
Alexeeva E.
Dvoryakovskaya T.
Nikishina I.
Denisova R.
Podchernyaeva N.
Sukhorukikh O.
Shubina L.
Chasnyk V.
Kostik M.
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Voprosy Sovremennoi Pediatrii - Current Pediatrics |
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© 2018 Publishing House of the Union of Pediatricians. All rights reserved. The article presents modern ideas about the treatment of systemic lupus erythematosus (SLE). The details of the management of patients with SLE during immunosuppressive and genetically engineered therapy is given. The article also reflects the aspects of rehabilitation, prevention of exacerbations, and follow-up care of children with SLE. The criteria for assessing the quality of medical care for children with SLE are presented. The detailed information on systemic lupus erythematosus for patients with SLE and their parents is outlined specifically.
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Sapphire capillary interstitial irradiators for laser medicine
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01.01.2018 |
Shikunova I.
Dolganova I.
Dubyanskaya E.
Mukhina E.
Zaytsev K.
Kurlov V.
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Progress in Biomedical Optics and Imaging - Proceedings of SPIE |
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2 |
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© COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only. In this paper, we demonstrate instruments for laser radiation delivery based on sapphire capillary needles. Such sapphire irradiators (introducers) can be used for various medical applications, such as photodynamic therapy, laser hyperthermia, laser interstitial thermal therapy, and ablation of tumors of various organs. Unique properties of sapphire allow for effective redistribution of the heat, generated in biological tissues during their exposure to laser radiation. This leads to homogeneous distribution of the laser irradiation around the needle, and lower possibility of formation of the overheating focuses, as well as the following non-transparent thrombi.
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Prediction of activity and severity of endocrine ophthalmopathy by multidimensional linear regression modeling
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01.01.2018 |
Lihvantseva V.
Afanasev M.
Rudenko E.
Karaulov A.
Afanasev S.
Korosteleva E.
Vygodin V.
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Vestnik Oftalmologii |
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© 2018 Media Sfera. All rights reserved. Endocrine ophthalmopathy (EOP) is a severe chronic autoimmune disease associated with autoimmune thyroid pathology that leads to loss of sight, cosmetic defects and quality of life decrease. EOP is difficult to give prognosis for due to various factors affecting its course and outcome. Purpose - to develop a reliable and precise prognosis method for EOP activity and severity based on personalized combination of risk factors in specific patients by multidimensional linear regression modeling. Material and methods. A group of 139 patients (278 orbits) with newly diagnosed EOP associated with toxic diffuse goiter was observed during 1 year by an ophthalmologist and an endocrinologist; patient examination interval was 6 months. More than 250 indices were dynamically analyzed in the course of the study. Linear regression analysis was chosen as the research method; it allowed detection of linear dependencies between dependent and explanatory variables. Results. More than 600 various linear regression equations were derived that enabled prediction of EOP onset risk and development timeline, estimation of activity and/or severity of the disease, duration of active period in specific patients for the immediate and long-term outcome. From the derived models, the most reliable and safest for practical application were picked out. The present study introduces nine optimized models that can be used for patient follow-up since day one. Conclusion. The onset risk, progression and outcome of the disease can be determined by a combination of factors revealed in the study.
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Approach for identifying of treatment option for pediatric patients in Guillain—Barre syndrome considering results of pharmacoeconomic analysis
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01.01.2018 |
Shakaryan A.
Rakhteenko A.
Yagudina R.
Kulikov A.
Serpik V.
Mitrofanova I.
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Zhurnal Nevrologii i Psihiatrii imeni S.S. Korsakova |
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© 2018, Media Sphera Publishing Group. All rights reserved. Objective. A pharmacoeconomic analysis of direct costs on treatment with high dose intravenous immunoglobulins (IVIG) and plasmapheresis (PP) in children. Material and methods. Literature data on the pathogenesis of Guillain—Barre syndrome (GBS) were analyzed. The results of pharmacoeconomic analysis of direct costs on treatment of GBS using IVIG and PP are presented. Risks for complications during treatment with IVIG and PP are calculated. Results and conclusion. The pharmacoeconomic analysis demonstrates comparable costs of treatment with IVIG or PP in the Russian Federation. Nevertheless, a less number of complications, convenience in use and the good safety and tolerability profile make it more preferable to this group of patients. In a clinical case of a 7-year child described in the article, treatment with 10% IVIG — privigen in dose 2 g/kg during 5 days started in the 3rd week of disease showed a marked positive effect.
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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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0 |
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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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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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Computer-assisted cystoscopy diagnosis of bladder cancer
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01.01.2018 |
Gosnell M.
Polikarpov D.
Goldys E.
Zvyagin A.
Gillatt D.
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Urologic Oncology: Seminars and Original Investigations |
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© 2018 Elsevier Inc. Objectives One of the most reliable methods for diagnosing bladder cancer is cystoscopy. Depending on the findings, this may be followed by a referral to a more experienced urologist or a biopsy and histological analysis of suspicious lesion. In this work, we explore whether computer-assisted triage of cystoscopy findings can identify low-risk lesions and reduce the number of referrals or biopsies, associated complications, and costs, although reducing subjectivity of the procedure and indicating when the risk of a lesion being malignant is minimal. Materials and methods Cystoscopy images taken during routine clinical patient evaluation and supported by biopsy were interpreted by an expert clinician. They were further subjected to an automated image analysis developed to best capture cancer characteristics. The images were transformed and divided into segments, using a specialised color segmentation system. After the selection of a set of highly informative features, the segments were separated into 4 classes: healthy, veins, inflammation, and cancerous. The images were then classified as healthy and diseased, using a linear discriminant, the naïve Bayes, and the quadratic linear classifiers. Performance of the classifiers was measured by using receiver operation characteristic curves. Results The classification system developed here, with the quadratic classifier, yielded 50% false-positive rate and zero false-negative rate, which means, that no malignant lesions would be missed by this classifier. Conclusions Based on criteria used for assessment of cystoscopy images by medical specialists and features that human visual system is less sensitive to, we developed a computer program that carries out automated analysis of cystoscopy images. Our program could be used as a triage to identify patients who do not require referral or further testing.
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MicroRNA in ischemic stroke
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01.01.2018 |
Aitbaev K.
Murkamilov I.
Fomin V.
Murkamilova J.
Yusupov F.
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Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova |
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Today, stroke is the third most common pathology after cardiovascular disease and cancer, as well as the leading cause of disability in the world. Although some progress has been made in the field of primary and secondary stroke prevention over the past few decades, a deeper knowledge of the pathophysiology of the disease is needed to significantly improve diagnosis and therapy. MicroRNA (miRNA) is an important, recently identified class of posttranscriptional regulators of gene expression. MiRNA can be used as a tool for therapeutic interventions. This review considers a role of miRNAs in the regulation of experimental stroke and in the development of carotid artery stroke. A potential role of miRNAs as promising biomarkers of stroke is discussed.
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An attributive component of the condition of people with the diagnosis of “ischemic heart disease. Effort angina”
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01.01.2018 |
Kasimovskaya N.
Fattakhutdinova E.
Khuziakhmetov A.
Kutlin N.
Kostina Y.
Kochetkov I.
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Electronic Journal of General Medicine |
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5 |
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© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The article is devoted to the study of attributive components of people diagnosed with Ischemic heart disease. Effort angina. The results of empirical studies of the attributive process are discussed in the article. Now more and more researchers, both domestic and foreign, are beginning to consider attribution as one of the principles of human existence. Attributive processes initially began to be developed in line with the cognitive orientation of social psychology. Currently, they are actively considered in the framework of the psychology of social cognition. Method: We conducted a study on 24 subjects with an average cholesterol level of 7.426 mmol / l (concomitant diseases-hypertension, diabetes, obesity, metabolic syndrome), who underwent treatment in the Central City Clinical Hospital in the rehabilitation department with the diagnosis of Ischemic Heart Disease. Effort Angina. Initially, we conducted the survey of subjects in order to identify their subjective judgment about the cause of the disease. They were asked a question: “In your opinion, what is the cause of your heart disease?” Results: The results of the survey conducted testify that only a small percentage of the subjects believe that they could exert any influence on their health and, for example, to reduce environmental or biological factors. One would assume that such results may be a specific demonstration of the fact that an individual gains experience that it is precisely human health that is difficult to correct and change and simply does not solve it due to the complexity of the problem. However, data obtained in the course of other experiments and studies [19] show that a person is inclined to explain what is happening by circumstances or situational causes, rather than personal ones. The results obtained with the help of T. Dembo’s cognitive self-assessment technique indicate that women believe that they actually have much less physical exertion and their daily routine is more correct than people who are close to them, in their opinion, think about it. We can assume that introjects are more often peculiar to women than men that are related to housekeeping, which sometimes requires considerable physical activity and time. When a woman has to, at the insistence of a doctor, reduce her physical activity and somehow comply with the daily regimen, she feels discomfort because of which she believes that she “does nothing at all”, although her relatives continue to persuade her to have a rest. Here it is appropriate, in our opinion, to raise the problem of accepting oneself and, as a sequence, to take adequate care of oneself. Significant differences in the self-attributive and reflexive components were also discovered in the emotional sphere of the female subjects. In their opinion, they experience low intensity of negative emotions, such as fear and anger, but at the same time they believe that their close relatives radically disagree. This situation can be explained either by the fact that they assume that they have negative emotions more strongly than they would like (and what they admit to this in the study), or they are judged by the words of relatives who can also make their judgments by interpreting the facts with varying degrees of adequacy. Conclusion: In conclusion, it should be noted that during the analysis we encountered at least two facts that require further empirical research. Firstly, we identified three types of explanations (attributions) in the subjects’ answers: adverbial, subjective and personal, and the latter type of causal attribution is not expressed clearly in the subjects of the study. This poses new questions: does a particular type of situation contribute to this perception, or are there any other factors (including personal ones) playing the role here. Secondly, the following questions arise: how exactly does a subject choose only one alternative from a variety of explanatory reasons. All these questions will be understood as a part of our further research.
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