The rationality of using DNA diagnostics in sports cardiology

NGS is becoming an integral part of medical practice, including in cardiology. The role of genes in the formation of diseases of the cardiovascular system has been actively studied for the last 20 years. Currently, heart diseases with a hereditary component are usually divided into two large groups: monogenic syndromes that lead to an unfavorable outcome, including sudden cardiac death at a young age, and polygenic conditions that manifest after 35 years and are accompanied by deterioration in the quality of life. In professional sports, changes in the myocardium are almost inevitable, however, the first phenotypic signs of hereditary myocardial disease may be hidden behind adaptive changes, which are commonly called “athlete’s heart”. The carriage of causative genes radically changes the approach to the management of an athlete: his admission to training and competitive activities is reviewed, the volume of permissible load and the frequency of visits to a cardiologist are discussed. In this paper, we tried to identify clinical markers — «red flags» that would indicate the need for genetic testing on the example of athletes who underwent an in-depth medical examination in 2021–2022

Pre- and posttranscriptional genetic information modification in muscular dystrophy treatment

Nowadays, a whole range of genetherapeutic methods is being used to restore a lost protein function due to mutation, a big number of preclinical and clinical studies of potential drugs that may allow to implement an etiotropic approach is being performed. One of the most prevalent and socially significant groups of genetic pathologies is musculardystrophy, including such diseases as Duchenne muscular dystrophy and dysfelinopathy. Despite a large number ofstudies in this field, there is no effective method of gene therapy for these diseases yet. This work is intended to review main genetherapeutic methods in myodystrophy treatment, especially pre- and posttranscriptional genetic (biosynthetic) information modification, and analyze most optimal of them

Approaches to the classification of sports disciplines, taking into account their influence on the biochemical profile of an athlete

There are many classifications of sports disciplines, which base on various approaches, which separately take into account the patterns of training activity, physiology, the risk of collision and injury, etc. In our opinion, it most fully reflects the specifics of sports changes that occur in the body of athletes under the influence of intense physical activity, at the level of biochemical processes. The classification of sports disciplines proposed by us takes into account the influence of the nature of the training process, the specifics of sports loads, the leading type of energy supply of sports work on the biochemical profile of an athlete, which makes it possible to identify the key features that occur in the body of an athlete under the influence of a specific load

Formation of the recombinant adenovirus encoding codon-optimized dysferlin gene and analysis of the recombinant protein expression in cell culture in vitro

Dysferlinopathies belong to neuromuscular diseases associated with aberrant expression and/or function of dysferlin protein in skeletal muscle, which is caused by mutations in the dysf (dystrophy-associated fer-1-like, DYSF) gene. Because of the large size of the codon-optimized dysf coding region (6243 bp), adenoviral vectors are suitable for the creation of genetic constructs, which are capable of delivering a large amount of recombinant genetic information into both dividing and non-dividing cells, as well as provide a high level of transgene expression. We generated a recombinant adenovirus serotype 5 encoding a codon-optimized gene for human dysferlin (Ad5-Dysf) and analysed recombinant protein expression in vitro in HEK-293T cell line

Modern (rational) methods for detecting genetic features of athletes

Molecular genetic methods are an integral part of recent medicine. Polymerase chain reaction, Sanger sequencing, next-generation sequencing are widely used in many areas: diagnostics of infectious, inherited, oncological diseases, prenatal screening, study of polymorphisms that increase the risk of developing multifactorial diseases or promoting development physical qualities necessary to achieve success in sports and competitive activity. The growing demand for genotyping raises a number of ethical and social issues affecting the degree of usefulness of genotyping a healthy person and the scientific reliability of the data obtained using direct-to-consumer genetic testing.The review presents and systematizes the laboratory diagnostic methods used today to study nucleic acids that carry important information about human health and physical qualities

Modeling and gene therapy of dysferlinopathy

Dysferlinopathies is a group of autosomal-recessive inherited neuromuscular diseases, which are characterized by defect in mRNA expression or in functionioning of dysferlin protein, appearing in about 1/200 000 births. Dysferlin is encoded by DYSF gene (Dystrophy-associated fer-1- like). It's disruption can cause various types of primary dysferlinopathies, which include Miyoshi myopathy (MM), Limb-girdle Muscular Dystrophy type 2B (LGMD2B) and distal myopathy with anterior tibial onset. Also, dysferlin deficiency can be associated with other diseases, such as caveolin- And calpainopathies. Here we discuss dysferlin protein structure and function, it's clinical phenotypes, known animal models and developing treatment strategies for dysferlinopathies. © Human stem cells institute, 2013

COMPARATIVE ANALYSIS OF MARKERS EFFICIENCY OF VISCERAL OBESITY DETECTION IN MEN WITH METABOLIC SYNDROME

The purpose of the study was to carry out comparative and quantitative assessment of surrogate markers of visceral obesity and their connection with the severity of clinical, biochemical and hormonal disorders in men with the metabolic syndrome and obesity. Material and methods. 136 men, aged from 23 to 68 years, who were patients of therapeutic clinic were observed. Clinical, anthropometric, biochemical and hormonal screening was taken. Transthoracic echocardiography was performed in all patients. Criteria of international experts’ consensus in the fields of cardiology and endocrinology (2009) were used to identify metabolic syndrome. Results and discussion. It was shown that among the all surrogate markers of visceral obesity (waist circumference; waist circumference measured in the lying position; waist circumference measured without the thickness of the subcutaneous tissue; the ratio of waist circumference to the circumference of the hips; sagittal abdominal diameter; thickness of epicardial adipose tissue) the largest number of statistically significant correlations with the clinical-biochemical, hormonal and adipokine characteristics of men was found for the waist circumference, measured in the lying position, and the waist circumference, measured without the thickness of the subcutaneous tissue. Intermediate position among the estimated markers was taken by a waist circumference measured in a standing position. Fewer number of correlation connections were revealed for thickness of the epicardial fat, sagittal abdominal diameter and the ratio of waist circumference to the circumference of the hips. Conclusion. The received results demonstrate objectivity of the selection of the surrogate markers of the severity of visceral obesity reviewed in the study, among which the waist circumference measured in the lying position had the greatest efficiency

TWO-PHASE DYNAMICS OF BONE MARROW MULTIPOTENT MESENCHYMAL STROMAL CELLS (MMSC) ACTION ON LIVER AT MODELING OF FIBROTIC HEPATITIS

Under the modeling of chronic fibrousing hepatitis in rats (n = 75) the dynamics of fibrolytic effect of bone mar- row MMSC was examined after one or two-time infusion of these cells at the early stage of liver fibrosis. By dynamic measuring of liver fibrotic area and the expression of activated stellate cell markers (desmin, α-SMA) and markers of cell apoptosis (caspase-3 and caspase-9) within 90 days two phases of the development of bone marrow MMSC fibrolytic effect were found. It is shown that the development of fibrolytic effect includes the primary phase of intensification of fibrosis, which is followed by the phase of enhanced fibrolytic process in the liver. It was determined that the two-phase dynamics of liver regeneration was more intensive after two-time infusion of bone marrow MMSC

Phenotypic heterogeneity and diagnostic features of transthyretin amyloidosis with polyneuropathy

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic progressive fatal disease, for which a modifying therapy has recently been proposed that delays the progression of the disease and improves the patient’s quality of life. The delay in the diagnosis of ATTR-amyloidosis is associated with the heterogeneity of the manifestations of the disease, as well as insufficient awareness of doctors of different specialties about the disease. A review of recent studies on the symptomatology, diagnosis, molecular genetic characteristics of ATTR-amyloidosis and the most common forms of the disease with the predominant involvement of peripheral nerves and the heart, as well as the kidneys, gastrointestinal tract, and eyes is presented. The international consensus recommendations for the diagnosis of suspected ATTR-amyloidosis using modern methods that facilitate early and accurate diagnosis are discussed. The reasons and the most frequent misdiagnoses of ATTR-amyloidosis, which also lead to a delay in the timely appointment of therapy, are considered. Molecular genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy and cardiomyopathy. A diagnostic algorithm based on the initial symptoms and manifestations of the cardiovascular and nervous systems facilitates the identification of a patient with clinical suspicion of ATTR-amyloidosis by the general practitioner. Early diagnosis is critically important for patients with ATTR polyneuropathy, since the early prescription of Vyndaqel (tafamidis), registered in the Russian Federation in 2017, allows a significant clinical effect to be obtained. Timely administration of Vyndaqel significantly slows down the progression of the disease, improves the prognosis and quality of life in patients with ATTR polyneuropathy

Corrigendum: Twenty-year clinical progression of dysferlinopathy in patients from Dagestan [Front Neurol, 8, (2017) (77)] doi: 10.3389/fneur.2017.00077

The "Funding" section should be: This work was funded by Human Stem Cells Institute PJSC and Roman V. Deev. Theoretical part of this work was supported by Russian Scientific Foundation grant (14-15-00916). Ivan A. Yakovlev and Mikhail O. Mavlikeev were supported by the Russian Government Program of Competitive Growth of Kazan Federal University. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way