Renalase – a new instrument in multicomponent heart failure assessment

Heart failure (HF) remains a serious problem in Russian and world health care due to the growing morbidity and mortality from complications of heart failure, despite the development and implementation of programs for the early detection and treatment of heart failure in asymptomatic patients. Currently, a large number of new biological markers have been studied that could serve as a laboratory tool for diagnosing and predicting the course of heart failure, but only brain natriuretic peptides have found application in real clinical practice. Renalase is a recently discovered cytokine that is synthesized by the kidneys and released into the blood. To date, seven subtypes of renalase have been found, each of which plays a different physiological role in the human body. Renalase is usually positioned as a signaling molecule that activates cytoprotective intracellular signals, leading to a decrease in blood pressure and protection of the heart muscle. The concentration of renalase freely circulating in the bloodstream of an adult is approximately 3–5 ng / ml. Currently, the level of renalase is determined by the enzyme immunoassay with a detection range of 3.12 to 200 ng / ml, while the minimum detectable concentration of the marker is less than 1.38 ng / ml. The presence of missense polymorphism of renalase is associated with myocardial dysfunction. Data from animal and human studies have shown that renalase plays a key role in the metabolism of catecholamines and in cardioprotective processes. Studies have shown the contribution of renalase to the occurrence of cardiovascular diseases: ischemic heart disease, arterial hypertension, diabetes mellitus, and aortic stenosis. Moreover, detailed protocols of multicenter prospective studies have demonstrated that functional polymorphism of the renalase gene was associated with myocardial hypertrophy in patients with aortic stenosis, hypertension, metabolic syndrome, unstable angina pectoris and stable forms of coronary artery disease, as well as in patients receiving renal replacement therapy. Based on these data and further studies, renalase has been proposed as a predictive biomarker of ischemia in patients with coronary microvascular dysfunction, as well as a predictor of clinically significant progression of chronic kidney disease in patients with cardiovascular diseases.Our review presents data on the role of renalase in heart failure. Further study of the structure and function of renalase, as well as future clinical studies, will allow determining the diagnostic, prognostic and, possibly, therapeutic significance of this biological marker in HF and other cardiovascular diseases

Междисциплинарный интегративный подход к ведению беременности при доброкачественных и пограничных опухолях яичника: клинический случай и обзор литературы

The management and treatment of patients with various malignancies during pregnancy appears to be a pressing issue to date. Ovarian tumors take the 4th place among all neoplasms diagnosed during pregnancy. The study aimed to investigate an interdisciplinary integrative approach to pregnancy management in case of benign and borderline ovarian tumors.The article presents the analysis of the pregnancy course in women with borderline and malignant ovarian tumors. When detecting a tumor during pregnancy, obstetric and surgical tactics is determined in a multidisciplinary team together with an oncologist.It is possible not only to prolong pregnancy without additional chemotherapy but also to preserve fertility in the future in patients with borderline tumors and stage I malignant tumors.Ведение и лечение пациенток с онкологическими заболеваниями на фоне беременности сегодня представляется очень актуальной проблемой. Среди всех онкологических заболеваний, выявляемых при беременности, опухоли яичников занимают 4 место. Цель исследования — изучить междисциплинарный интегративный подход к ведению беременности при доброкачественных и пограничных опухолях яичника.В статье представлены данные по анализу течения беременности у женщин с пограничными и злокачественными опухолями яичников.При обнаружении опухолей во время беременности акушерская и хирургическая тактика определяются индивидуально совместно с онкологом.При пограничных опухолях, а также злокачественных опухолях Iа стадии возможно не только пролонгирование данной беременности без дополнительного химиотерапевтического лечения, но и сохранение фертильности в дальнейшем

Web Based Postgraduate Thesis/Dessertation System - A Prototype

With the advancement of information communication technology in Malaysia, education field should take advantage to upgrade their learning and management techniques. Students should be allowed to learn anytime, anywhere and at their own place. However administration and lecture should be able to manage their work more effective and flexible. The web-based system is effective way to learning and managing education works. This report outlines the development of a web-based postgraduate thesis/dissertation management system (WPTS), which aimed to assist thesis/dissertation administration, supervisor and students in the better integration during students doing the thesis/dissertation works. This prototype system base on case study with a group of MSC(IT), administration, lecturer and students who participate in thesis/dissertation management activities. This report also presenting the tests conducted with users, it also contributed some perspective regarding benefits that gain by administration, supervisor and students, and recommends future application of the approach

Gastric Microbiota in Patients with Dyspepsia: Metatranscriptomic Analysis

Aim: to assess the composition of the microbiota of the mucous membrane of the body and the antrum of the stomach.Materials and methods. Sixty patients with dyspeptic symptoms were included into the study. Two biopsy samples of the gastric mucosa (from the body of the stomach and the antrum) were obtained from each patient. The presence of H. pylori infection was confirmed by PCR; RNA was isolated and then libraries were prepared for metatranscriptomic analysis of the 16S rRNA gene. Sequencing was performed on MiSeq (Illumina, USA) using MiSeq Reagent Kit v3 (600-cycle) (Illumina, USA).Results. The bacterial diversity decreases with the predominance of Helicobacter pylori species in H. pylori-positive patients. These results were confirmed by the Shannon index, the average value of which was 3.6 in the H. pylori-positive group and 5.4 in the H. pylori-negative group. In H. pylori-negative patients an increase in the representation of Streptococcus, Prevotella and Alloprevotella genera was observed. The level of H. pylori contamination of the gastric mucosa varies in the antrum and body of the stomach, in some cases reaching a 3.5-fold difference. Representation of other bacteria in the body and antrum of the stomach does not differ significantly.Conclusion. The bacterial composition of the stomach is dependent on the presence of H. pylori. H. pylori leads to the decrease of the bacterial diversity with the predominance of H. pylori in gastric microbiome

Gamma-glutamyl transpeptidase is a promising biological marker of heart failure

Introduction. Currently, the search and study of new biological markers that can help early diagnosis of heart failure, serve as a laboratory tool for assessing the effectiveness of therapy, be a predictive marker of possible adverse clinical outcomes and a significant criterion for risk stratification is very relevant. While cardiospecific markers, including natriuretic peptides, their precursors, and highly sensitive troponins, are widely used in clinical practice, the need to use other markers does not have sufficient evidence. aspect of a biological marker of heart failure.Gamma-glutamyl transpeptidase is an enzyme localized on the outer side of cell membranes and involved in the metabolism of glutathione and cysteine. This enzyme is a dimeric glycoprotein (68 kDa), consisting of 2 subunits – a large and a small (46 and 22 kDa). Gamma-glutamyl transpeptidase is encoded by a multigene family consisting of at least 7 different genes located on chromosome 22; however, only 1 of these genes is involved in the formation of a functional enzyme. Gamma-glutamyl transpeptidase was found in all cells except erythrocytes. There is a significant variability in enzyme activity, which is especially high in tissues with a secretory and absorptive function, such as the kidneys, biliary tract, intestines, and epididymis.Purpose of the review is to present an overview of current publications devoted to the study of γ-glutamyl transpeptidase in the aspect of a biological marker of heart failure.Materials and methods. The analysis of literature sources (foreign and domestic articles) was carried out in the databases: PubMed, RSCI, MedLine, Google Scholar, Science Direct. The search was performed according to the following keywords: biological markers, heart failure, γ-glutamyl transpeptidase, biological markers, heart failure, γ-glutamyl transpeptidase.Results. In addition to its clinical use as a test for liver disease, biliary tract disease, and alcohol abuse, γ-glutamyl transpeptidase is of great interest because of its association with cardiovascular disease, diabetes, metabolic syndrome, and cancer. In the literature available to us, we found a small number of works devoted to the study of γ-glutamyl transpeptidase in patients with heart failure. In the review, we have presented data from experimental and clinical studies indicating a clear link between γ-glutamyl transpeptidase and heart failure. The pathogenetic mechanism of the possible relationship between γ-glutamyl transpeptidase and heart failure is not completely clear. The localization of this enzyme in tissues with a transport function has led to the assumption that it is involved in the transport of amino acids through the γ-glutamyl cycle.Conclusion. Further deeper understanding of the structure and function of the enzyme is needed, as well as future clinical studies to determine the diagnostic, prognostic and possibly therapeutic significance of this biological marker

Tenascin-C as a cardiovascular marker

Novel biological markers, such as fibrosis marker galectin-3, peptide hormone adrenomedullin, soluble ST2, chemokine CX3CL1, surrogate marker of vasopressin, and others, are every year one step closer to being introduced into health practice. Over the past decades, significant progress has been made in the study of cardiovascular biomarkers. A key moment was the introduction of deter mining the concentration of natriuretic peptides used as markers for the diagnostic and prognostic evaluation of patients with heart failure. Currently, in order to search for novel markers for early diagnosis and risk stratification, studies have been conducted on the analysis of promising inflammatory marker tenascin-C (TNC) in cardiovascular patients. Data have been obtained that allow us to consider TNC as a tool for risk stratification and assessment of cardiovascular disease prognosis. The combination of TNC with other biological markers, in particular brain natriuretic peptide, may improve prognostic power. Nevertheless, serial testing to assess the prognosis and effectiveness of ongoing treatment, including in the conditions of a multimarker model, requires further research

Efficiency of Organelle Capture by Microtubules as a Function of Centrosome Nucleation Capacity: General Theory and the Special Case of Polyspermia

Transport of organelles along microtubules is essential for the cell metabolism and morphogenesis. The presented analysis derives the probability that an organelle of a given size comes in contact with the microtubule aster. The question is asked how this measure of functionality of the microtubule aster is controlled by the centrosome. A quantitative model is developed to address this question. It is shown that for the given set of cellular parameters, such as size and total tubulin content, a centrosome nucleation capacity exists that maximizes the probability of the organelle capture. The developed general model is then applied to the capture of the female pronucleus by microtubules assembled on the sperm centrosome, following physiologically polyspermic fertilization. This application highlights an unintuitive reflection of nonlinearity of the nucleated polymerization of the cellular pool of tubulin. The prediction that the sperm centrosome should lower its nucleation capacity in the face of the competition from the other sperm is a stark illustration of the new optimality principle. Overall, the model calls attention to the capabilities of the centrosomal pathway of regulation of the transport-related functionality of the microtubule cytoskeleton. It establishes a quantitative and conceptual framework that can guide experiment design and interpretation

Monitoring of Gene Expression in Bacteria during Infections Using an Adaptable Set of Bioluminescent, Fluorescent and Colorigenic Fusion Vectors

A family of versatile promoter-probe plasmids for gene expression analysis was developed based on a modular expression plasmid system (pZ). The vectors contain different replicons with exchangeable antibiotic cassettes to allow compatibility and expression analysis on a low-, midi- and high-copy number basis. Suicide vector variants also permit chromosomal integration of the reporter fusion and stable vector derivatives can be used for in vivo or in situ expression studies under non-selective conditions. Transcriptional and translational fusions to the reporter genes gfpmut3.1, amCyan, dsRed2, luxCDABE, phoA or lacZ can be constructed, and presence of identical multiple cloning sites in the vector system facilitates the interchange of promoters or reporter genes between the plasmids of the series. The promoter of the constitutively expressed gapA gene of Escherichia coli was included to obtain fluorescent and bioluminescent expression constructs. A combination of the plasmids allows simultaneous detection and gene expression analysis in individual bacteria, e.g. in bacterial communities or during mouse infections. To test our vector system, we analyzed and quantified expression of Yersinia pseudotuberculosis virulence genes under laboratory conditions, in association with cells and during the infection process

Glioblastoma Therapy with Cytotoxic Mesenchymal Stromal Cells Optimized by Bioluminescence Imaging of Tumor and Therapeutic Cell Response

Genetically modified adipose tissue derived mesenchymal stromal cells (hAMSCs) with tumor homing capacity have been proposed for localized therapy of chemo- and radiotherapy resistant glioblastomas. We demonstrate an effective procedure to optimize glioblastoma therapy based on the use of genetically modified hAMSCs and in vivo non invasive monitoring of tumor and therapeutic cells. Glioblastoma U87 cells expressing Photinus pyralis luciferase (Pluc) were implanted in combination with hAMSCs expressing a trifunctional Renilla reniformis luciferase-red fluorescent protein-thymidine kinase reporter in the brains of SCID mice that were subsequently treated with ganciclovir (GCV). The resulting optimized therapy was effective and monitoring of tumor cells by bioluminescence imaging (BLI) showed that after 49 days GCV treatment reduced significantly the hAMSC treated tumors; by a factor of 104 relative to controls. Using a Pluc reporter regulated by an endothelial specific promoter and in vivo BLI to image hAMSC differentiation we gained insight on the therapeutic mechanism. Implanted hAMSCs homed to tumor vessels, where they differentiated to endothelial cells. We propose that the tumor killing efficiency of genetically modified hAMSCs results from their association with the tumor vascular system and should be useful vehicles to deliver localized therapy to glioblastoma surgical borders following tumor resection