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HUMAN GENOME EDITING
стр.4-14
The rapidly evolving genome editing techniques are steadily moving from research laboratories to clinical practice. Fundamentally new methods of editing the genome of human embryos in the early stages of development have been developed. Tools for correction of genetic disorders in people of any age have also been created. In fact, the doctor is becoming a corrector of genetic instructions on construction and functioning of the human body. This review generalizes the data on the current state of genome editing techniques and existing approaches to applying them in clinical practice.
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MODIFICATION OF THE METHOD FOR ANALYSIS OF GENOME EDITING RESULTS USING CRISPR/CAS9 SYSTEM ON PREIMPLANTATION MOUSE EMBRYOS
стр.15-20
Dimitrieva T.V., Reshetov D.A., Zhernovkov V.E., Vlodavets D.V., Zotova E.D., Ermolkevich T.G., Deykin A.V.
Genetically modified animals are an important tool for biomedical research. The CRISPR/Cas9 editing genome system is increasingly being used for production of such animals. Through microinjection, complex with guide RNA and Cas9 protein is delivered in fertilized eggs from which the animal subsequently develops with a modification in the genome. Generally, analysis of the specificity and efficiency of the system in each case is carried out after obtaining a progeny with the likely mutation. However, analysis at the preimplantation stage would allow reducing the time of the experiment, as well as understanding the reason for the birth of a small number of transgenic animals, or even lack of them in the offsprings. The paper proposes a modification of the method of preparation of total DNA from mouse blastocysts. The modification allows to easier and faster detect the results of microinjection of the CRISPR/Cas9 complex in the zygote. Having applied the method described in this paper, we successfully identified short deletions in intron 34 of dystrophin gene (DMD) in 12 out of 13 treated embryos and insertion in the break site in intron 8 of the DMD gene in 11 out of 21 samples analyzed. Using for analysis the total DNA prepared by the method proposed, you can analyze up to 20 different sites in the mouse embryo genome at the blastocyst stage without the need for full genomic amplification.
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ANALYSIS OF PHENOTYPE EXPRESSIONS OF DELETIONS IN THE DYSTROPHIN GENE IN TERMS OF EFFICIENCY OF EXON SKIPPING AS A METHOD FOR TREATMENT OF HEREDITARY DYSTROPHINOPATHIES
стр.21-26
Zotova E.D., Reshetov D.A., Zhernovkov V.E., Vlodavets D.V., Dimitrieva T.V., Deykin A.V.
Duchenne muscular dystrophy (DMD) is a common genetic disease caused by a mutation of the dystrophin gene. It leads to death in childhood. At the time of writing this paper, patients had access to supportive therapy only. However, DMD treatment methods are actively being developed. Exon skipping is a promising method. Exon skipping involves restoration of the reading frame within a gene by inducing alternative splicing. This leads to synthesis of truncated but still functional dystrophin. The paper assesses the functionality of the truncated forms of dystrophin resulting from correction of nonsense mutations and internal exon indels by exon-skipping technique. The assessment was made based on data on the phenotype of carriers of mutations in the dystrophin gene taken from the Leiden Open Variation Database (LOVD). It was revealed that the same mutation could manifest itself as a variety of phenotypes. This, perhaps, is as a result of the patients having different genetic background. For example, deletion of exon 48, for which there is 97 records in LOVD, resulted in asymptomatic diseases in 2 % of cases, Duchenne muscular dystrophy in 60 %, Becker muscular dystrophy (characterized by milder symptoms than DMD) in 12 % and intermediate phenotype in 26 % of cases. High phenotypic variability of mutations of the dystrophin gene raises the issue of limits of applying exon skipping for treatment of inherited myopathies.
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GADOLINIUM-AND CURCUMIN-LOADED MICELLES BASED ON α-FETOPROTEIN FUNCTIONALIZED AMPHIPHILIC BLOCK COPOLYMERS
стр.27-33
Pozdniakova N.V., Grigorieva E.Yu., Shevelev A.B.
This article describes a method of obtaining curcumin- and gadolinium-loaded micelles based on triblock amphiphilic polyethylene glycol and polypropylene glycol copolymers Pluronic F-127 and Pluronic P-123 (Sigma-Aldrich, USA) superficially functionalized with recombinant human α-fetoprotein. The size of nanoparticles was measured using dynamic light scattering and amounted to an average of 50 to 100 nm. The micelles were stable: stored at +4 °C for 10 days, they exhibited no changes in their properties that would not fall within the standard error of measurement for the methods used for the analysis. Preliminary experiments conducted on mice showed no conspicuous toxicity of micelles with the maximum possible concentration of gadolinium, which enables their use in tumor tissue imaging .
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IMMUNOMODULATORIMUNOFAN AFFECTS CELL PROFILE OF MORPHOFUNCTIONALZONES OF RATTHYMUS AND DELAYS ITS AGE-RELATED INVOLUTION
стр.34-38
The immunomodulatory agent Imunofan (Bionox, Russia) is widely used in clinical practice. It affects the immune and endocrine systems and enhances cell-mediated and humoral immunity. The aim of this study was to investigate the cell profile (lymphoblasts, small, medium and large lymphocytes, macrophages, mitotic cells and damaged cells) in the subcapsular and inner zones of the thymic cortex and thymic medulla of random-bred male albino rats with conspicuous age-related changes after stimulating their immune system with Imunofan. The animals in the experimental group (n = 30) were administered to intramuscular injections of the drug (0.7 mg/kg) on the 1 st, 3rd, 5th, 7th and 9th days of the experiment; the controls (n = 30) were administered to the equivalent amount of normal saline on the same days. Rats were decapitated on the 1st, 7th, 15th, 30th and 60th days after the final injection. Thymic sections were studied using Olympus CX-41 microscope, Olympus SP 500UZ camera (Olympus, Japan) and Morpholog software (Ukraine). Thymic morphology was similar in the experimental and control groups; however, cell profiles were different. On the 7th, 15th and 30th days, lymphoid cells and macrophages prevailed over damaged cells, the number of which decreased (p
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ANALYSIS OF TLRS GENES EXPRESSION AND POLYMORPHISMS ASSOCIATION IN CHILDREN WITH BRONCHIAL ASTHMA
стр.39-43
Zаitsеvа М.A., Bragvadze B.G., Svitich O.A., Namazova-Baranova L.S., Gankovskaya L.V.
Bronchial asthma (BA) is one of the most common respiratory system diseases. The role of innate immunity components in the pathogenesis of bronchial asthma is studied widely, with particular focus on the antimicrobial peptides. Those include beta defensins that prevent pathogen intrusion into the respiratory tract mucosa, the most active of such pathogens being β-defensin-1 (human betadefensin-1, HBD-1) encoded by the gene. We studied the association of three single nucleotide polymorphisms in the 5'-untranslated region of the gene, namely, , and , with bronchial asthma in children. We also evaluated gene expression of toll-like receptors , and . The experimental group included 48 patients of 3 to 7 years of age with BA and 70 healthy children. The AA genotype of the polymorphism and the CC genotype of the polymorphism were reliably associated with the disease, while the GG genotype of the polymorphism and the AA genotype of the polymorphism were found protective. Also, the AA genotype of the polymorphism was associated with the reduced expression of , the human beta defensin-1 encoding gene, while the AG genotype was associated with its increased expression. In children with BA, expression increased 19.5 times in comparison with the controls; expression increased 9.5 times, while expression increased 8.3 times.
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DIAGNOSTIC ERRORS AND MANAGEMENT OF FOOT FRACTURES IN PATIENTS WITH MULTIPLE OR CONCOMITANT INJURIES
стр.44-50
Korolev M.A., Yarmak D.O., Miroschnikova C.A., Moldakulov J.M., Skoroglyadov A.V., Korobushkin G.V.
Delayed or missed diagnosis of foot fractures in patients with multiple or concomitant injuries often leads to the inadequate choice of treatment and causes serious long-term effects. This article reports the most common mistakes accompanying diagnostic procedures and therapy of this injury type. The study conducted in 2007-2015 enrolled 67 patients. Patients were divided into two groups: a prospective experimental group (n = 31) and a retrospective control group (n = 36). For both groups, diagnostic procedures and the range of therapeutic interventions applied were the same, but with the experimental group we used a stepped care approach, followed a specific sequence of activities and adjusted therapy considering the limb condition and the patient’s overall state. In total, we identified 40 and 69 foot fractures in the prospective and retrospective groups, respectively. In the prospective group there were 5 delayed and 3 missed fracture diagnoses; in the second group those numbers were 7 and 9, respectively. The most common factors contributing to diagnostic errors were: excluding radiographic evaluation, severity of patient’s overall condition, poor medical history. Missed fractures were often due to a combination of various factors. A one-step approach was prevalent in the controls (41 fractures); the experimental group underwent a multistep treatment (30 fractures). Therapy outcomes were assessed by Visual Analogue Scale. The results were statistically higher in the prospective group (Mann-Whitney U was 347), which indicates a better treatment applied in this group. The study also showed that using minimally invasive fixation for foot fractures improves treatment outcome.
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EVALUATION OF MICROCIRCULATION IN CHILDREN OF 8 AND 10 YEARS OF AGE USING INSPIRATORY BREATH HOLD
стр.51-56
Gas diffusion and transcapillary exchange take place in the microvasculature. Therefore, the evaluation of skin blood flow regulation and functional capacities of the microcirculatory system at various ontogenesis stages is of great importance. Using laser Doppler flowmetry in the group of boys (n = 15) and girls (n = 13) of 8 and 10 years of age, skin microcirculation and its regulatory mechanisms were evaluated. The study found an increase in the perfusion index in children between the age of 8 and 10 induced by the shifting roles of mechanisms of the microcirculatory regulation. The comparison of basal microcirculatory parameters did not display statistically significant differences related to sex in 8- and 10-year old participants. However, almost equal perfusion in boys and girls was maintained by different contributions of regulatory mechanisms. The breath holding test showed an increase in the initial microcirculation index and capillary blood flow reserve in the group of 10-year-old boys and girls. Our study revealed differences in various microcirculation parameters, in the intensity of active and passive rhythms of blood flow oscillations and response to inspiratory breath hold, which indicates age-related transformations of microcirculation system.
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IMPACT OF LEARNING ENVIRONMENTS ON THE PHYSICAL DEVELOPMENT OF MOSCOW SCHOOLCHILDREN: HYGIENE ASPECTS
стр.57-62
Bokareva N.A., Milushkina O.Yu., Ovchinnikova Z.A., Pivovarov Yu.P., Sheina N.I.
Physical development and health of today’s schoolchildren are influenced by various factors, including the way the learning process is organized. This article presents data on some aspects of physical development of 1585 teenagers (15 to 17 years old) from 35 Moscow schools, including general education schools, specialized schools, schools with optional advanced courses in biomedical sciences, and health promoting schools. We studied basic anthropometric characteristics of the participants (body height and weight), assessed their psychoemotional status using the Children’s Form of Manifest Anxiety Scale and their lifestyle using questionnaire surveys. The control group included teenagers from general education schools. The study showed that the number of teenagers with no abnormalities in their physical development was significantly higher in health promoting school while the number of overweight students there was significantly lower, compared to the controls (p
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HOW AWARE ARE MEMBERS OF THE MEDICAL UNIVERSITY COMMUNITY OFTHE RISKS AND CONSEQUENCES OF SKIN TATTOOING? RESULTS OF THE ONLINE SURVEY
стр.63-68
Trushina E.V., Minkina O.V., Dvornikov A.S., Skripkina P.A., fon Zimfer E.I., Konyshev Ya.I.
This article presents the results of an anonymous online survey on skin tattooing conducted in the community of medical students and professors. The article covers issues of tattoing from medical and sociocultural perspectives. The survey was carried out in Pirogov Russian National Research University and included 210 participants of different ages. The results demonstrate the insufficient knowledge of medical indications, contraindications and potential complications associated with tattooing. The obtained data can be a good starting point for developing programs aimed at raising awareness among young people, especially in higher medical institutions. The opinion expressed in this article is not necessarily shared by students and professors from other institutions for higher medical education and does not necessarily reflect the level of expertise in other medical communities. This work is an example of how socially oriented practical training can be organized for the 3rd- and 4th-year students of the Faculty of General Medicine at Pirogov Russian National Research Medical University.
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