Search

Calpainopathy is the most common form of limb-girdle muscular dystrophy, prevalence in the population is approximately 1 in 15,00042,700 individuals. In the Russian Federation, there is an insufficient number of studies, which researched prevalence of calpainopathy among patients with limb-girdle muscular dystrophy, but according to available data, approximately in 43% of cases the disease is associated with mutations of the CAPN3 gene. Molecular genetic analysis is the main method for diagnosing these patients. Studies indicate many pathogenic mutations that cause calpainopathy with corresponding phenotypes, however, it is quite difficult to establish clear correlations between genotype and phenotype due to the high variability of symptoms and severity, even among patients with the same CAPN3 gene mutations. Currently, there is no effective etiotropic treatment for limb-girdle muscular dystrophy, but new technologies are developing to improve patients condition and quality of life. This research collects data from various studies on the prevalence of calpainopathy in different countries and the main molecular genetic features of the CAPN3 gene and calpain-3 protein, which will further allow the development of possible treatment options for patients with limbgirdle muscular dystrophy.

The relationship between the liver and the peritoneum is an important element in a body homeostasis maintaining. Morphofunctional changes occurring in the liver in response to fecal peritonitis allow a better understanding of this relationship. Despite the existing researches, some aspects of the pathological changes occurring in the liver in fecal peritonitis require a special study. Purpose: to describe the composition and dynamics of the lymphocytic-leukocytic infiltrate in the liver in conditions of experimental fecal peritonitis. The study was conducted on Balb/c (n=5) mice with artificially induced fecal peritonitis. One animal was euthanized on 1, 3, 5, 7 and 14 day of the experiment. Immunophenotyping of inflammatory infiltrate cells was performed on liver tissue samples using antibodies to CD3, CD45, CD163. Morphometric analysis was carried out with the calculation of the number of cells per unit area. It was shown that the highest intensity of infiltration by CD45+-cells is observed on the 3rd day of the experiment with a subsequent decrease; infiltration by CD3+-cells increases by the 5th day of the experiment without further dynamics; infiltration of CD163+-cells by day 7 without further changes. Conclusions: the severity of the liver parenchyma infiltration by immune cells in dynamics reflects the organ reaction to experimental fecal peritonitis.

A relatively recently described population of cells, apparently belonging to the tissue system of the internal environment, are the telocytes. Their peculiarities are not only the co-expression of CD117- and CD34-molecules, but also thin, indistinguishable processes at the light-optical level, whose length can be many times greater than the diameter of the cell body. In this regard, transmission electron microscopy remains the method of choice for their detection in tissues. Telocytes were found in the myocardium, connective tissue of the gallbladder, in gastrointestinal tract, in the stroma of the exocrine glands, the placenta, some vessels. However, data on the detection of telocytes in striated skeletal muscle tissue are either absent or still rare. This brief report demonstrates cells that, by their ultrastructural characteristics, can be identified as telocytes in the endomysium of gastrocnemius muscle in Bla/J mice (mutation in the dysferlin gene, DYSF).

The article presents data on the regeneration of the auricle tissues of Acomys cahirinus mice (n=12) and Balb/c mice (n=12). Two experimental models were used: a full-thickness perforated defect with a diameter of 3 mm and subtotal removal of the auricle. Macrophotography and histological examination using general histological stains and detection of elastic fibers were performed after 2, 5, 15, 21, 30, 60, 90, and 120 days. It was found that regeneration in Acomys is more pronounced, which manifested itself in the complete elimination of the defect by 30-60 days in contrast to the control (Balb/c). A feature of this was less pronounced post-traumatic inflammation in Acomys mice. It was established the growth of a full-fledged auricle in case of its surgical removal. An important feature of regeneration in this case is the development of new cartilage tissue both from the edges of the original cartilage and developed in the form of separate islands of cartilage tissue. The newly formed cartilage was characterized by high cel-lularity, a smaller volume of the matrix, in the structure of which elastic fibers were formed. However, it should be noted that within 30-60 days. the recovery process, apparently, is not completed, the formed tissue regenerate enters the remodeling phase.

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.

"Metaplasia” is a concept of differentiated cells and tissues transformation that has been discussed since the second half of the19th century. The issues of the research were the essence, mechanisms and role in histogenetic and pathological process. The aim of this review is an attempt to trace and analyse the evolution of ideas about cells and tissues transformation possibilities beginning from the R. Virchow observations (1958). Also there is a need to correlate them with the modern understanding of the issues of the of opportunities in cell differentiation and the underlying pathological processes.

The bone plates that forming the turtle shell differ in histogenesis. Thus, the costal and neural plates of the carapace (dorsal shield) have mesenchymal origin and develop by indirect perichondral osteogenesis from vertebrae and ribs. The bone plates of the plastron - abdominal shield, are known to be formed from neuroectodermal cells of the neural crest and develop by intramembrane osteogenesis in the dermis of the skin. The aim of the study was to compare the reparative regeneration of histogenetically different bone tissue of the carapace and plastron of freshwater red-eared turtles Trachemys scripta. The experiment was performed on freshwater red-eared turtles Trachemys scripta aged 3 months. 2 defects of carapace and plastron bone plates with a diameter of 5 mm and a depth of up to "soft tissues” were formed with further histological examination. It was found that the regeneration of the bone plates of the plastron is characterized by the formation of bone tissue in a larger volume and at an earlier date. After 30 days a layer of continuous newly formed bone tissue is formed. By 90 days the proportion of bone tissue in the carapace regenerate was 40,5% of the defect area, while in the plastron the regenerate occupied 47,4%. Thus, intramembranous formed bone tissue of neuroectodermal histogenesis has a more pronounced regenerative potential compared to perichondral formed bone of mesenchymal origin.

"Flexibility” is a physical quality of a person, which is characterized by the ability to perform movements with a large amplitude. Flexibility is important for success in such activities as sports (artistic and rhythmic gymnastics, figure skating, etc.), as well in classical choreography, for example, ballet. Extracellular matrix producing cells and structural proteins of connective tissues take an active part in the formation of mobility of the elements of the musculoskeletal system. Connective tissues are a complex structural and functional system, the components of which are encoded by many genes. Mutations in them lead to various hereditary diseases that increase or decrease "flexibility”. The role of genes in the formation of conditions encoded in the ICD-11 LD28.Z remains unclear - "Syndromes involving connective tissue as the main feature, unspecified”, and their prognostic significance for people experiencing intense physical exertion. The purpose of this review is to generalize modern ideas about the role of genes, extracellular matrix and cells producing it in the formation of such a physical quality as flexibility.

Introduction. The identification of early edematous changes using MRI and the assessment of the nature of their distribution among the muscles is important for the diagnosis of dysferlinopathy and the differentiation of hereditary muscular dystrophies from inflammatory myopathies. Purpose of the study: to assess the capabilities of STIR and T2 MSME methods in the diagnosis of early edematous changes in the muscles of patients with LGMDR2. Materials and methods: We examined 20 patients with clinical manifestations of dysferlinopathy, with an average age of 35 (24; 44) years. Magnetic resonance imaging of the muscles of the pelvic girdle and lower extremities was performed by 20 patients and a control group equivalent in sex and age.Results. The T2 MSME (ms) method based on the calculation of relaxation time has the highest diagnostic accuracy in detecting early edematous changes in muscles. The sensitivity of the STIR method was 56%, and the specificity was 100%. Conclusion. Dysferlinopathy is characterized by diffuse edema of the least affected muscles. STIR is optimal for differential diagnosis of myopathies characterized by edematous changes. Whereas, for the assessment of minimal edematous changes, T2 MSME is the most acceptable.

There is a strong unmet need for bone grafts and substitutes combining osteoinductive capacities and biophysical properties for using them in minimally invasive surgical interventions. We have developed three variants of injectable gene-activated bone substitutes containing three components: octacalcium phosphate microgranules (OCP), plasmid DNA delivering the gene of vascular endothelial growth factor, and one of the hydrogels based on sodium alginate, type I collagen, and hyaluronic acid. The molecules of the gene constructs were contained both in the hydrogel and on the surface of the OCP microgranules. In the model of a critical-sized bone defect in rabbit parietal bone, we found that all the gene-activated hydrogels contributed to bone tissue regeneration, however, the largest amount of newly formed bone, including those in the central part of the defect, was detected in the groups with gene-activated materials based on hyaluronic acid and collagen. Thus, the developed materials can be considered as candidates for medical devices, but additional studies are required to assess the dose-depended effect and optimize the materials composition.

Two variants of gene-activated hydrogels based on sodium alginate containing plasmid DNA with the gene of vascular endothelial growth factor (VEGF-A) are developed. The former represented alginate hydrogel without additional components; the latter contained up to 25 wt % of octacalcium phosphate (OCP) micrograins. Alginate-based hydrogels without OCP are characterized by a honeycomb structure with the pore size of 50–200 μm and mechanical compression strength of 0.2 MPa. Addition of OCP micrograins results in filling of the polymer framework by them and an increase in the compression strength to 0.57 MPa at 16.7 wt % of OCP with a decrease to 0.49 MPa with an increase in the OCP content to 20 wt %. Both variants of gene-activated hydrogels induce reparative myogenesis in the central zone of muscle defect; a larger number of MyoG+ cells and newly formed MyH7B+ muscle fibers are identified as compared to analogous hydrogels without plasmid DNA after two weeks after surgery (p < 0.05).

Development of effective methods for cartilage tissue repair is highly relevant for surgical practice. One of the promising approaches in this area is the use of gene-activated materials that capable to change the production of certain factors involved in reparative chondrogenesis regulation in the damaged area within a certain time. In this study, we developed two gene-activated hydrogels based on hyaluronic acid delivering plasmid DNA encoding vascular endothelial growth factor (VEGF-A) gene. One of the hydrogels also contained octacalcium phosphate microgranules. The materials were implanted into the defects of cranial bones, articular and auricle cartilages in rabbits. Control groups consisted of the same materials without plasmid DNA. We found that gene-activated materials formed a larger volume of cartilaginous tissue with complete restoration of the auricle by 90 days. Healing of the articular cartilage and subchondral bone was also more efficient at the 30 and 60 days follow-up, but by 90 days, remodeling of the newly formed cartilage into fibroelastic and fibrous connective tissues was observed in all groups. Cranial bone defects were filled with newly formed bone tissue in the test group by day 90, while in the control a residual defect filled by fibrous connective tissue was retained. Thus, developed variants of the gene-activated hydrogels are promising candidates to be medical devices for treatment of patients with bone and cartilage pathology.

The presented controversial hypothesis is an attempt to reflect on the role of the adaptive immune response in carcinogenesis. It is a well-known fact that the most of the signaling pathways which are participating in embryogenesis and regeneration are also active in tumor growth. Considering their presence in different evolutionary groups, there's such a contradiction that with same mechanisms of proliferation, animals with high regenerative potential are less predisposed to malignancy than mammals. Comparing these two groups, it's being discovered that despite the importance of immune control as a factor impeding carcinogenesis, the animals' immune system with high regenerative potential is less developed. The above is a reading of the complete or partial absence of the adaptive link of immunity. These described distinctions have formed the basis of the hypothesis of the procarcino-genic role of the adaptive immune response.

The study assessed reactivity of stromal-vascular skeletal muscle differons to acute chemical injury. Dysferlin-deficient Bla/J mice and the wild-type С57BL/6 mice were intramuscularly injected with 100 μl of 0.5% procaine solution. The middle segment of gastrocnemius muscle was taken on postsurgery days 2, 4, 10, and 14 for routine histological examination. To evaluate proliferation and vascularization, the paraffin sections were stained immunohistochemically with antibodies to α-smooth muscle actin and Ki-67. The connective tissue was stained according to Mallory. The study revealed diminished proliferative activity of stromal-vascular differons and decreased vascular density in muscles of Bla/J mice. Thus, mutations in the DYSF gene coding dysferlin down-regulate the reparation processes in all differons of skeletal muscle.

Introduction. Research on skin radiation injury remains topical due to the development of X-ray diagnosis and therapy in medical practice. Materials and methods. We studied structural and ultrastructural features of high-dose ionizing radiation exposure to the skin (110 Gy, X-ray) at early stages of damage (days 3, 8, and 14). The study was conducted on Wistar rats (N=39) that were exposed to a single irradiation on the interscapular skin region with an LNK–268 (RAP 100–10) X-ray machine (Russia). To analyze the morphologic changes, light (hematoxylin and eosin stain and toluidine blue stain) and transmission electron microscopy were used. Results. Regardless of clinical manifestations on day 3, subepidermal edema, intercellular edema and epithe-lial layer contact disruption, mitochondria damage to the keratinocytes, and dermal histiocytes developed in the area of radiation exposure. These signs intensified by days 8 and 14, leading to tissue death both at the central and peripheral parts of irradiation. On days 8–14, damage to the vascular endothelial cells became noticeable, the mitochondrial death being the major one. Morphometric data indicate an increase both in the epidermis edema up to its desquamation by day 14 and in total cellularity due to various forms of leukocytes in the papillary and reticular dermis. Conclusion. Local 110-Gy irradiation leads to irreversible changes in the cells and their necrosis within two weeks that may result in ulcer formation later in life. Keywords: radiation ulcer, damage, skin, cell death, ultrastructure

The turtles skeleton plan is an evolutionary developmental novelty in connection with the formation of a tortoise-specific carapacial ridge, which induces the growth of ribs in the dorsal direction and the subsequent formation of several carapace plates. The bone plates of these reptiles have different histogenesis: the neural and costal plates develop according to the mechanism of indirect osteogenesis by perichondral ossification of the axial skeleton elements (vertebrae and ribs), the peripheral and plastron bones develop according to the mechanism of direct osteogenesis in the dermis of the skin - these are the so-called «skin bones», which are derived from individual osteogenic cells outside the axial skeleton and develop by intramembranous osteogenesis. An experiment was carried out to study the post-traumatic osteogenesis of the carapace bone plates on a freshwater turtles Trachemys scripta at the age of 3 months. Two defects of carapace costal plates with a diameter of 4 mm and a depth to the fascia were performed with further routine histological examination. It was found that already on the 90th day the turtles carapace bones were restored with the formation of a full-fledged bone regenerate by the mechanism of indirect osteogenesis.

The new coronavirus infection is a highly contagious infection caused by the SARS-CoV-2 virus that has become a global public health problem. The pathogenesis of this virus has not yet been clearly understood, the principles of hyperinflammatory immune response in critically ill patients, which leads to acute respiratory distress syndrome and multiple organ failure, innate and adaptive immune responses in the process of structuring the data under study. The interaction of the virus and a macroorganism includes 4 stages: infection, dissemination, cytokine storm, pulmonary fibrosis. This review analyzes the predictors of infection, its possible pathogenesis, the immune response of the macroorganism, as well as the histological characteristics of damage to immune organs; shows receptors for SARS-CoV-2 (ACE2, TMPRSS2) in some organs.

The material contains a conversation between doctors-developers, administrators and clinicians on the introduction of banking of umbilical cord blood and umbilical cord cells into healthcare practice. The data on clinical studies conducted in the world to assess the safety and effectiveness of the use of umbilical cord blood cells are presented.

This work summarizes data obtained in experiments in which we studied the effectiveness of syngeneic multipotent mesenchymal stem cells (MMSC) of adipose tissue in treating severe radiation skin lesions. Experiments were performed on rats of the Wistar–Kyoto inbred line, which were subjected to local X-ray irradiation in the back area in a dose of 110 Gy (30 kV tube voltage, amperage 6.1 mA, filter 0.1 mm Al) at a dose rate of 17.3–20.0 Gy/min. Local exposure led to the development of severe nonhealing (for up to 3.5 months) radiation skin ulcers. MMSCs were injected subcutaneously around the injured zone at various time intervals after exposure: in the early period prior to ulcer formation, in the period of the formed ulcer, and the period of active regeneration of injured tissue. Both single and double cell transplantations were performed. It is shown that only the double injection of MMSCs (with an interval of one week between injections) stimulates the regenerative processes and accelerates healing of the radiation ulcer. The therapeutic effect is more pronounced under conditions of double MMSC injection in the period when the radiation ulcer is already formed and regenerative processes in the affected skin are activated.

Dental implantation in the area of previously lost teeth is a modern way to rehabilitate edentulous patients. The search for osteoplastic materials and methods of preimplantation osteoplasty remains topical. One of these materials is an autogenous dentin matrix (ADM), which is based on a crushed extracted tooth. ADM production and application technologies are different and insufficiently tested. Nevertheless, the application of this technique may open up new clinical possibilities. The study on the use of ADM involved 20 patients from 18 to 65 years old. The patients underwent complex surgical and orthopedic treatment to restore chewing function. At the first stage, the extraction of teeth was performed with the simultaneous preservation of the socket of the extracted tooth ADM. The second stage was carried out 3-4 months later, which included the collection of bone biopsy specimen and subsequent dental implantation in the area of the previously extracted tooth. 42 specimens obtained 12-17 weeks after removal were subjected to histological examination. According to its structure, the bone tissue formed in the hole is reticulofibrous bone. Which allows us to conclude that by the time of 15-17 weeks, the processes of active reparative bone formation in the hole are completed, and the necessary local conditions for dental implantation have been created.

The number of studies related with gene-activated matrices is increasing annually; the first-in-class product has been already implemented into clinical practice for bone grafting indications. Considering specificity of the gene-activated matrices mechanism of action determined by gene constructs, there is a demand to standardize the methods allowing to characterize all the stages of biological action in vivo. Here, using on the example of a gene-activated hydrogel consisting of type I collagen and plasmid DNA with the vascular endothelial growth factor gene (VEGF165), the main steps of the plasmid DNA mechanism of action were confirmed by various methods. For this, a fluorescent Cy3, reporter plasmid DNA with the firefly luciferase gene (Luc), RT-PCR and ELISA, immunohistochemical study with antibodies to CD31 were used. The results were compared with the other scientific papers, some recommendations were formulated to determine a minimally required list of studies for the development of gene-activated materials.

Cilia (cilia) are organelles that are characteristic exclusively for eukaryotes and are found in protozoa, on somatic and germ cells of multicellular, as well as gametes of many plants. In humans, two main types of cilia are distinguished: motile and sensory; also in embryogenesis, it is customary to isolate special nodular cilia necessary for the normal course of gastrulation and possibly subsequent histo- and organogenesis. Motile cilia provide the movement of the liquid medium relative to the cell in the respiratory tract, the ventricular system of the brain and the fallopian tubes, or the movement of the cell itself in the case of sperm. The main function of sensory cilia is the perception of changes in the external environment and the signal molecules inside it and their conversion into intracellular signals that regulate proliferation, differentiation, and programmed cell death. Ciliopathies, a group of pathological conditions associated with impaired development, structure, and functioning of cilia, are of clinical interest. The most studied ciliopathies include polycystic kidney disease, nephronophysis, Barde-Beadle, Joubert, Mekel, Kartagener, Karoli etc. Clinical nephronophthisis and morphological analysis of the case of Caroli, syndrome is given.

The environment for the development of products containing live cells as an active substance is being set up in Russia for several years. However, the acceptable regulatory framework, which would have allowed to develop and place cell therapy products on the market, complying with international requirements for safety, efficacy, and quality, has not been yet established. Moreover, in addition to the national legal framework, the Eurasian Economic Union regulatory model has emerged that introduces in parallel a more straightforward pathway for the development and clinical use of this important medical product category. In this paper we address the domestic and Eurasian regulatory systems for products containing live cells as an active ingredient and suggest certain possible approaches to support this area of biotechnology.

Optimization of the reparative regeneration of striated skeletal muscle tissue is actual for clinical practice. Volumetric muscle loss usually heals through the fibrous scar formation. Herein, there are numerous of methods under developed focused on reparative myogenesis induction. One of the promising approaches in this area is formed by gene-activated materials, particularly, in the hydrogel form. We developed a gene-activated hydrogel based on hyaluronic acid and plasmid DNA with the gene of vascular endothelial growth factor A (VEGF-A). Firstly, we showed a biocompatibility of the product in the subcutaneous test in mice. Using marker plasmid DNA carrying the luciferase gene, prolonged delivery of gene constructs to cells in vivo with a peak in transgene expression at day 7 was confirmed, while the same plasmid DNA in an aqueous solution provided a maximum level of delivery at day 1. Being implanted into a volumetric defect of the anterior tibial muscle in rats the gene-activated hydrogel activated angiogenesis in 2 weeks after surgery and induced MYH7B+-muscle fibers formation in the central zone of the defect at average number 50,0±16,1 and 21,8±10,5 in 2 and 4 weeks, respectively, whereas a hydrogel without plasmid DNA did not have any myogenic effects. Thus, plasmid DNA with VEGFA in the sodium alginate-based hydrogel induced angiogenesis in the volumetric muscle loss model and stimulated reparative myogenesis that could be used for further development of products effective for treatment of patients with muscle pathology.

The review presents the modern concept of the pathogenesis of diffuse alveolar damage, including acute respiratory distress sYndrome in coronavirus infection. It has been established that the so-called "cytokine storm”, which consists in the increased release of substances that are biologically active against the vascular wall and effector cells, leading to the progressive damage to endotheliocytes and alveolocytes, the development of alveolar and interstitial pulmonary edema with fatal respiratory failure and coagulopathy. An important factor in interstitial aggression is the appearance of autoreactive clones of plasma cells, dissemination of virusinfected leucocytes throughout the body with the involvement of various organs and systems, which exacerbates multiple organ failure. A poor prognosis for patients, the likelihood of developing pulmonary fibrosis after infection, according to several researchers, can be corrected by cell therapy. Allogeneic multipotent mesenchymal stromal cells (mesenchymal stem cells) are considered as first-line therapeutic cells. The accumulated experience of preclinical experiments made it possible to urgently proceed to conduct clinical trials of the safety of their use in patients with ARDS and to search for optimal indications to obtain maximum benefits for patients after transplantation. The combined efforts of many research groups can lead to reliable information on the cell therapy benefit and the need to include it in the standards of treatment of patients with this extremely severe pathology.

Introduction. Rhabdomyolysis is destruction syndrome of striated skeletal muscle characterized by myalgia, an increase of creatine phosphokinase level (CPK), serum myoglobin and myoglobulinuria. This review presents the analysis of five cases of acute postexercise rhabdomyolysis happened to militaries, complicated by pigmentary nephropathy with the description of clinical and laboratory studies, magnetic resonance imaging (MRI), electroneuromyographic and morphological features. The purpose of the study is the clinical assessment of MRI for the diagnosis of postexercise rhabdomyolysis.Results. A comparative assessment demonstrated that in the presented clinical cases in the muscle groups with minimal edematous changes, an increase in the MR signal was observed at T2-WISPAIR, as well as in diffusion-weighted images (factor b — 0, 500, 1000), at the same time on all other pulse sequences (including STIR) changes in signal intensity were not detected. Conclusion. There was shown that in mild cases of rhabdomyolysis, the regression of MR manifestations corresponds to a decrease in laboratory parameters of CPK and myoglobin, whereas in severe forms of rhabdomyolysis, the regression of MR manifestations is significantly slowed down relative to laboratory indicators, and in the place of necrosis areas, the foci of degeneration form (hyperintensive on T1 and T2-WI, hypo-intensive on T1-WI-SPIR and T2-WI-SPAIR). Morphologically confirmed the fact of pronounced hemorrhage in the compartment syndrome due to postload rhabdomyolysis (hyperintensive sites on T1-WI and T1-WI-SPIR, iso-, hypointensive on T2-WI, T2-WI-SPAIR).

Post-traumatic stress disorder (PTSD) develops as a delayed consequence of psychological trauma and is accompanied by characteristic changes in the levels of biogenic amines. The aim of the present work was to carry out a complex study of the dynamics of changes in measures of behavioral activity and noradrenaline and dopamine contents taking cognizance of the activity of the enzyme metabolizing them, i.e., monoamine oxidase A (MAO-A), and the level of the inhibitory transmitter GABA in PTSD. PTSD was modeled in Wistar rats using cat odor. Behavioral changes were studied in the elevated plus maze test. Contents of GABA and catecholamines were determined, along with MAO-A activity levels. The development of poststress anxiety was found to be linked with changes in neurotransmitter levels in the brain. The onset of anxiogenic disorders was preceded by an anxiolytic phase, associated on day 3 with an increase in the GABA level and on day 7 with a decrease in the noradrenaline level in the brain. Only on day 10 was an increase in the noradrenaline content seen, this being synchronized with increases in anxiety. Thus, a significant relationship between the development of behavioral signs of PTSD and an increase in noradrenaline content in the brain was identified.

November 4, 2020 marked the 100th anniversary of the birth of one of the leading pathologists of Russia, Honored Scientist of Russia, Corresponding Member of the Russian Academy of Medical Sciences, President of the Russian Association of Pathologists, Honorary Doctor of St. Petersburg Academy of Postgraduate Education Oleg Khmelnitsky - a man of bright, multifaceted, effective in his work, who had numerous pupils and followers.4 ноября 2020 г. исполнилось 100 лет со дня рождения одного из ведущих патологов России, заслуженного деятеля науки России, члена-корреспондента РАМН, президента Российской ассоциации патологов, почетного доктора Санкт-Петербургской академии последипломного образования Олега Константиновича Хмельницкого — человека яркого, многогранного, результативного в своей работе, имевшего многочисленных учеников и последователей.

The study assessed reactivity of stromal-vascular skeletal muscle differons to acute chemical injury. Dysferlin-deficient Bla/J mice and the wild-type С57BL/6 mice were intramuscularly injected with 100 μl of 0.5% procaine solution. The middle segment of gastrocnemius muscle was taken on postsurgery days 2, 4, 10, and 14 for routine histological examination. To evaluate proliferation and vascularization, the paraffin sections were stained immunohistochemically with antibodies to α-smooth muscle actin and Ki-67. The connective tissue was stained according to Mallory. The study revealed diminished proliferative activity of stromal-vascular differons and decreased vascular density in muscles of Bla/J mice. Thus, mutations in the DYSF gene coding dysferlin down-regulate the reparation processes in all differons of skeletal muscle.

The aim of the study was the development of three-dimensional (3D) printed gene-activated implants based on octacalcium phosphate (OCP) and plasmid DNA encoding VEGFA. The first objective of the present work involved design and fabrication of gene-activated bone substitutes based on the OCP and plasmid DNA with VEGFА gene using 3D printing approach of ceramic constructs, providing the control of its architectonics compliance to the initial digital models. X-ray diffraction, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and compressive strength analyses were applied to investigate the chemical composition, microstructure, and mechanical properties of the experimental samples. The biodegradation rate and the efficacy of plasmid DNA delivery in vivo were assessed during standard tests with subcutaneous implantation to rodents in the next stage. The final part of the study involved substitution of segmental tibia and mandibular defects in adult pigs with 3D printed gene-activated implants. Biodegradation, osteointegration, and effectiveness of a reparative osteogenesis were evaluated with computerized tomography, SEM, and a histological examination. The combination of gene therapy and 3D printed implants manifested the significant clinical potential for effective bone regeneration in large/critical size defect cases.