Role of macrophages in pathomorphogenesis of alcoholic liver disease

Alcoholic liver disease combines various structural and functional impairments of liver caused by excessive alcohol consumption. Alcohol, as a direct hepatotoxic agent, is metabolized in the liver and affects both resident cells and their microenvironment. These changes are reflected in the resulting imbalance of pro- and anti-inflammatory mediators synthesized by the liver macrophages. To date, it is known about the polarization and phenotypic diversity of this cell population, and about macrophages and monocytes involvement in the development of alcoholic hepatitis. These facts allow us to consider macrophages as potential therapeutic targets. However, the available data do not fully disclose the mechanisms of inter- and intradifferon interactions in the human body. The review discusses the results of current studies on the involvement of liver macrophages in the pathomorphogenesis of alcoholic liver disease and the potential for their use in the treatment of this disease

Caroli syndrome: a clinical case with detailed histopathological analysis

© 2018, Japanese Society of Gastroenterology. Herein we present a clinical case of the Caroli syndrome caused by the compound heterozygous mutation in the PKHD1 gene. Histopathological assessment of liver detected biliary cirrhosis, numerous dilated bile ducts of various sizes, hyperplastic cholangiocytes containing a large amount of acid mucopolysaccharides, decreased ß-tubulin expression and increased proliferation of cholangiocytes. A significant proportion of hepatic tissue was composed of giant cysts lined with a single layer of cholangiocytes, containing pus and bile in its lumen and surrounded by granulation tissue. An accumulation of neutrophils in the lumen of the bile ducts was observed, as well as an infiltration of the ducts and cysts surrounding connective tissue by CD4+ and to a lesser extent CD8+ lymphocytes. This may be caused by the expression of HLA-DR by cholangiocytes. Atrophy and desquamation of the epithelium of collecting tubules with the formation of microcysts were detected in the kidneys without a clinically significant loss of renal function. Morphopathogenetic mechanisms of the Caroli syndrome can be targets for a potential pathogenetic therapy and prevention of its manifestations and complications

Ordinary and Activated Bone Grafts: Applied Classification and the Main Features

© 2015 R. V. Deev et al. Bone grafts are medical devices that are in high demand in clinical practice for substitution of bone defects and recovery of atrophic bone regions. Based on the analysis of the modern groups of bone grafts, the particularities of their composition, the mechanisms of their biological effects, and their therapeutic indications, applicable classification was proposed that separates the bone substitutes into "ordinary" and "activated." The main differential criterion is the presence of biologically active components in the material that are standardized by qualitative and quantitative parameters: growth factors, cells, or gene constructions encoding growth factors. The pronounced osteoinductive and (or) osteogenic properties of activated osteoplastic materials allow drawing upon their efficacy in the substitution of large bone defects

Can co-management improve governance of a common-pool resource? : lessons from a framed field experiment in a marine protected area in the Colombian Caribbean

Complexities associated with the management of common pool resources (CPR) threaten governance at some marine protected areas (MPA). In this paper, using economic experimental games (EEG), we investigate the effects of both external regulation and the complementarities between internal regulation and non-coercive authority intervention—what we call comanagement— on fishermen’s extraction decisions. We perform EEG with fishermen inhabiting the influence zone of an MPA in the Colombian Caribbean. The results show that comanagement exhibits the best results, both in terms of resource sustainability and reduction in extraction, highlighting the importance of strategies that recognize communities as key actors in the decision-making process for the sustainable use and conservation of CPR in protected areas

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

Gene- and cell-based therapy of muscle system hereditary disorders: State-of-art

Genetic disorders primarily affecting skeletal muscles can be caused by dysfunction of more than 30 genes. To date there is no effective etiotropic and pathogenetic treatment of such disorders. Investigators focus on search for new therapeutic agents based on gene and cell technologies, small molecules as well. There are numerous preclinical and several dozens of clinical studies in the world. Unfortunately tested technologies did not lead to significant advance in treatment of patients with such disorders. At the same time resulting data allow to determine the most feasible directions of future development combining of genome correction methods with cell delivery of corrected genome to skeletal muscles. This review is intended to give general information about etiology of skeletal muscles genetic disorders, the main directions of biotechnological development and results of the clinical studies

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

Combined use of plasmid drug pCMV-VEGFA and autodermoplasty for stimulation of skin defects healing in the experiment

© 2018 Human Stem Cell Institute. All rights reserved. To find effective ways to stimulate chronic skin wounds healing (including deep burns, diabetic and trophic ulcers) is an actual multidisciplinary task. The aim of our study was to assess the potential of using autodermoplasty in combination with plasmid drug pCMV-VEGFA to optimize skin defects repair in the experiment. Autodermoplasty was performed on Wistar rats. The size of the skin flap was 22 cm. Immediately after surgery the animals of the test group (n=8) underwent intradermal injection in the periphery of autotransplant with 1 ml solution containing 0.3 mg of supercoiled plasmid DNA pCMV-VEGFA, rats of the control group (n=8) received 1 ml of 0.9 % NaCl. The results were analyzed in 3, 6, 9 12, 18 days using macroscopic evaluation, laser Doppler flowmetry, histological methods. Macroscopically in the test group necrosis of the transplanted skin flap was found at later periods of observation, in one case complete survival of autotransplant was observed. The results of laser Doppler flowmetry in the group with plasmid DNA did not have statistically significant differences with control. The wound defect diameter in the test group at 12 days was 5,52± 4.80 mm, in the control 12,45±0,82 mm (p=0,03); 2,53±of 2,94 mm and 4,23±3,5 mm (p=0,067) at 18 days, respectively. At 18 days, the average number of vessels under the flap in the central zone were: of 26±2,9 in the test group and 20±8 in control; it the peripheral zone 27±3,4 and of 12,1±3,9 (p=0,035), respectively; in the skin muscle 21,2±of 3,9 and 12,4±3,6 (p=0,04), respectively. Thus, the use of plasmid drug pCMV-VEGFA improved the skin healing after autodermoplasty

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