I. Chistyakova, N. Bakalenko, A. Malashicheva, M. Atyukov, A. Petrov
{"title":"The role of Notch-dependent differentiation of resident fibroblasts in the development of pulmonary fibrosis","authors":"I. Chistyakova, N. Bakalenko, A. Malashicheva, M. Atyukov, A. Petrov","doi":"10.18705/2311-4495-2022-9-5-96-104","DOIUrl":"https://doi.org/10.18705/2311-4495-2022-9-5-96-104","url":null,"abstract":"Background. Molecular mechanisms of the development of pulmonary fibrosis are poorly understood. It is known that differentiation of resident lung cells into myofibroblasts plays a key role in this disease. The search for factors capable of regulating such differentiation is an urgent task. Objective. To evaluate the effect of Notch signaling pathway activation on resident lung fibroblasts by introducing the intracellular domains of each of the 4 Notch receptors (N1-4ICD). Design and methods. Primary cultures of pulmonary fibroblasts from donors (n = 4) were used. Notch-dependent activation of fibroblasts was carried out by introducing lentiviral vectors with/ without sequences of N1-4ICD domains. After 8 days, immunocytochemical staining was performed and the relative expression levels of the PDPN, HOPX, SLUG, SNAIL and ACTA2 genes were evaluated by qPCR. Results. Activation of the Notch signaling pathway by N1-4CD resulted in increased expression of SLUG, SNAIL and ACTA2. The most pronounced effect was observed with the introduction of Notch4-activating sequence. Induction of signaling by the introduction of N1-3ICD activating components contributed to an increase in PDPN expression, with the introduction of N4ICD, an increase in the level of HOPX expression was noted. Conclusion. Activation of each of the 4 intracellular Notch receptor domains is able to trigger the differentiation of resident alveolar fibroblasts into myofibroblasts, which are key players in the development of pulmonary fibrosis.","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49568248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Bergen, G. E. Trufanov, S. A. Alekхandrova, V. Sinitsyn, M. Shumilina, I. Rychina, A. Tarkova, V. Fokin, A. Skripnik, A. Dorofeev, M. Chernyavskiy, A. Chernyavskiy, E. Golukhova, E. Schlyakhto
{"title":"Expert consensus of national medical research centers in the field of cardiovascular surgery and the Russian society of radiologists: principles and technology for using radiology methods in pathology of brachiocephalic vessels","authors":"T. Bergen, G. E. Trufanov, S. A. Alekхandrova, V. Sinitsyn, M. Shumilina, I. Rychina, A. Tarkova, V. Fokin, A. Skripnik, A. Dorofeev, M. Chernyavskiy, A. Chernyavskiy, E. Golukhova, E. Schlyakhto","doi":"10.18705/10.18705/2311-4495-2022-9-5-5-19","DOIUrl":"https://doi.org/10.18705/10.18705/2311-4495-2022-9-5-5-19","url":null,"abstract":"","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42051315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Miroshnikov, K. T. Sultanova, M. Makarova, V. Makarov
{"title":"A comparative review of the activity of enzymes of the cytochrome P450 system in humans and laboratory animals. Prognostic value of preclinical models in vivo","authors":"M. Miroshnikov, K. T. Sultanova, M. Makarova, V. Makarov","doi":"10.18705/2311-4495-2022-9-5-44-77","DOIUrl":"https://doi.org/10.18705/2311-4495-2022-9-5-44-77","url":null,"abstract":"Cytochrome P450 enzymes play a key role in drug biotransformation. The expression and activity of each CYP450 is influenced by a unique combination of biochemical factors, species and genetic differences, age, sex, nutrition and etc.Cytochromes P450 are a family of heme-containing proteins involved in the metabolism of xenobiotics, drugs, and endogenous compounds. Drugs could act as inducers or inhibitors of cytochrome P450 enzymes. Understanding the mechanisms of inhibition or induction of enzymes is extremely important in preclinical studies and prescribing complex therapy. One of the main challenges in the development of therapeutic agents is to determine which animal species reflects the human ability to metabolize certain drugs. The study of CYPs and their interaction with drugs is an urgent problem in preclinical studies. Thus, an adequate and maximally similar experimental preclinical models are necessary to study the pharmacokinetic and pharmacodynamic properties of promising chemicals and their effect on certain cytochrome P450 enzymes.This review compares the main subfamilies and their enzymes of the cytochrome system of humans and laboratory animals involved in drug metabolism. The problems of choosing biological models in vivo in preclinical studies in the study of medicinal substances are considered. The predictive value of in vivo models of preclinical studies was analyzed from the point of view of the cytochrome P450 system in humans and laboratory animals.","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49046687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. G. Grischuk, E. Sviridov, S. Kuznetsov, D. V. Sorokin, V. A. Znamensky, L. U. Abdullina, M. R. Chubarova, A. D. Kiseleva, S. Minasyan, V. Postnov, N. V. Burkova
{"title":"Immobilized carbon nanotubes as activators of cellular elements of blood in contact interaction","authors":"I. G. Grischuk, E. Sviridov, S. Kuznetsov, D. V. Sorokin, V. A. Znamensky, L. U. Abdullina, M. R. Chubarova, A. D. Kiseleva, S. Minasyan, V. Postnov, N. V. Burkova","doi":"10.18705/2311-4495-2022-9-5-87-95","DOIUrl":"https://doi.org/10.18705/2311-4495-2022-9-5-87-95","url":null,"abstract":"Background. The use of nanotechnology achievements in medicine opens up prospects for the development and improvement of means and methods of prevention and treatment of diseases of various origins. Carbon nanotubes (CNTs) are a product of modern nanotechnologies, and in addition to their unique physical and chemical properties, they are promising for practical applications in medicine. CNTs are one of the most popular (comparable only with silver and titanium dioxide nanoparticles) objects of nanotoxicological research. Data on the effect of CNTs on blood cells are contradictory, so additional studies are necessary. Objective. To assess the activation capabilities of immobilized carbon nanotubes by the rate of adhesion of blood cell elements to their surface in vitro. Design and methods. Hemocontact interaction was carried out in bench conditions using donor blood in rotational mode. Blood samples were taken before the start of the experiment and after 5, 20, 40 and 60 min. Changes in the indicators of cell blood populations using the hematology analyzer SySmex XT 1800i (26 parameters). 50 experiments were conducted. To analyze the activation functions, a speed-time adhesive profile was used. Results. The highest rates of activation of cellular elements of the blood were recorded in contact with multi-walled carbon nanotubes SiloMUNT. Conclusion. The results of the study can be further implemented in the procedure of low-volume hemoperfusion in clinical practice.","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43393946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Galimova, D. Sadykova, T. Makarova, A. Kamalova, Y. Melnikova, E. Slastnikova, R. Rakhmaeva, M. A. Petrova, A. A. Mustafayeva, G. G. Semenova
{"title":"Assessment of global, segmental longitudinal deformation of the left ventricle and endothelial function in children with family hypercholesterolemia","authors":"L. Galimova, D. Sadykova, T. Makarova, A. Kamalova, Y. Melnikova, E. Slastnikova, R. Rakhmaeva, M. A. Petrova, A. A. Mustafayeva, G. G. Semenova","doi":"10.18705/2311-4495-2022-9-5-33-43","DOIUrl":"https://doi.org/10.18705/2311-4495-2022-9-5-33-43","url":null,"abstract":"","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48779472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Zolotova, O. Melnichnikova, M. Simakova, Y. Zhilenkova, O. Sirotkina, T. Vavilova
{"title":"Analysis of inter-individual variation and reference intervals of thrombin generation test indicators using different technologies","authors":"E. Zolotova, O. Melnichnikova, M. Simakova, Y. Zhilenkova, O. Sirotkina, T. Vavilova","doi":"10.18705/2311-4495-2022-9-5-78-86","DOIUrl":"https://doi.org/10.18705/2311-4495-2022-9-5-78-86","url":null,"abstract":"Background. The thrombin generation test (TGT) as an integral method for analyzing the activation cascade of natural pro- and anticoagulants is of practical importance in assessing the risk of thrombotic conditions and bleeding, however its application is limited by the lack of standardization. Objective. To define reference intervals within the laboratory and assess inter-individual variation in TGT values for different technologies. Design and methods. The study included 20 donors. TGT was performed using two technologies: a calibrated automated thrombogram on a semi-automatic fluorometer (Technology 1) and automatic measurement of GT on a coagulometer (Technology 2). Obtained results were normalized to pooled normal plasma. Results. Thrombogram parameters showed a high CVG (coefficient of interindividual variation): 14–32 % for Technology 1 and 7–36 % for Technology 2. CVG did not change significantly after normalization. Significant differences in ETP (endogenous thrombin potential) were noted. The reference intervals for Technology 1 were: ETR 1478.0–2595.0 nmol/ min and peak thrombin concentration (Peak thr.) 221.6–412.0 nmol. RI for Technology 2: ETP 2451.00–3161.00 nmol/min and Peak thr. 161.60–479.30 nmol. Conclusion. Comparison of the two laboratory TGT technologies revealed high inter-individual variation. Thus, the use of a study in dynamics for each specific individual is likely to be more informative than the use of RI obtained in the general population. Dynamic monitoring of the patient must be performed using one technology.","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47928410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Domnina, O. Krasnova, K. Kulakova, Yu. V. Sopova, V. Karelkin, O. Lesnyak, I. Neganova
{"title":"Role of G protein-associated membrane receptors in the pathogenesis of osteoporosis","authors":"A. Domnina, O. Krasnova, K. Kulakova, Yu. V. Sopova, V. Karelkin, O. Lesnyak, I. Neganova","doi":"10.18705/2311-4495-2022-9-4-41-61","DOIUrl":"https://doi.org/10.18705/2311-4495-2022-9-4-41-61","url":null,"abstract":"Osteoporosis is a chronic disease characterized by a pathological change in bone tissue, excessive fragility and a decrease in bone strength as a result of the predominance of bone resorption processes over the process of bone formation. This disease manifests in the form of low-traumatic fractures occurring in result of falling from a height of one’s height, or with little physical exertion. Osteoporosis could result in the fractures of the vertebral bodies and bones of the peripheral skeleton, causing a high level of disability. Of note, postmenopausal osteoporosis develops in women against the background of the cessation of the menstrual cycle. Here we overview the role of G-protein-associated membrane receptors (GPCR family) in the pathogenesis of this disease and the prospects for finding targets among these receptors for the diagnosis and treatment of osteoporosis. Malformations in the genes encoding GPCR lead to impaired bone tissue remodeling. Exploring the functions of GPCR family members is critical to the search for predisposition markers of bone tissue dysfunction and could improve the early diagnosis of osteoporosis. Studies on a model of osteoblasts differentiated from hIPSCs obtained from patients with osteoporosis associated with mutations in the genes of the GPCR family will allow a deeper understanding of the molecular nature of osteoporosis and the identification of new targets for osteoporosis treatment.","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47405659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Korostyshevskaya, A. Savelov, V. D. Abramova, M. Shtark
{"title":"Depression: magnetic resonance spectroscopy studies (review)","authors":"A. Korostyshevskaya, A. Savelov, V. D. Abramova, M. Shtark","doi":"10.18705/2311-4495-2022-9-4-20-32","DOIUrl":"https://doi.org/10.18705/2311-4495-2022-9-4-20-32","url":null,"abstract":"Magnetic resonance spectroscopy (MRS) is a non-invasive method for assessing the neurochemical state of the brain. In recent years, the growth in the number of high-field scanners has led to a rapid increase in such studies and improvement in the quality of MRS data, the development of mechanisms and technologies for obtaining and processing results.The review is devoted to the study of the possibilities of MRS in the study of brain neurochemistry in depression. The fundamentals of techniques and various approaches to MRS, technical requirements for the study material, advantages and disadvantages of the method, difficulties in interpreting the results, and prospects for combining MRS with fMRI and EEG are considered. Most spectroscopic studies performed in depression show an abnormal decrease in the concentrations of the amino acid neurotransmitters γ-aminobutyric acid and glutamate, which is consistent with the results of post-mortem histopathological studies. Multivariate studies are needed to determine the anatomical and clinical specificity of changes in Glx and GABA levels that are found in depressed patients.The presented material can be used and form the basis for further multimodal experiments using MRS, which may be relevant both for the informed development of more effective drugs, and last but not least, neurofeedback tools aimed at interactive interventions in the neural network organization in depressive disorders.","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46112443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Translational methods for the treatment of chronic back pain","authors":"A. Gorodnina, A. Ivanenko","doi":"10.18705/2311-4495-2022-9-4-5-12","DOIUrl":"https://doi.org/10.18705/2311-4495-2022-9-4-5-12","url":null,"abstract":"Background. Up to 83 % of the working population has a high level of social adaptation disorder due to the pain in the lumbosacral spine. The development of translational approaches in the treatment of degenerative diseases of the spine is becoming increasingly important. The key methods in the differentiated approach to the treatment are laser vaporization of the intervertebral disc and radiofrequency denervation of the facet joints in the case when the pain syndrome is facet-like.Objective. To evaluate the effectiveness of a differentiated approach in the use of minimally invasive surgical methods in patients with discogenic and vertebrogenic pain syndrome based on an analysis of the immediate results of treatment.Design and methods. A retrospective analysis of examination and treatment data of 101 patients with degenerative-dystrophic diseases of the lumbar spine, accompanied by pain, was carried out. In 29 (28.7 %) patients, laser vaporization of the intervertebral disc was performed; in 72 (71.3 %) cases, radiofrequency denervation of the facet joints of the lumbosacral spine was used.Results. Positive outcomes after laser vaporization were observed in 27 patients. A positive result was noted in 67 patients after radiofrequency destruction of the sinuvertebral nerve.Conclusions. Differentiated use of minimally invasive puncture methods for the treatment of osteochondrosis of the spine and adequate selection of patients for these procedures often lead to the positive result.","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42047173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Gorbatykh, O. E. Latkin, A. Prokhorikhin, D. D. Zubarev, M. A. Chernyavsky
{"title":"Modern view on the treatment of oncological diseases by endovascular methods","authors":"A. Gorbatykh, O. E. Latkin, A. Prokhorikhin, D. D. Zubarev, M. A. Chernyavsky","doi":"10.18705/2311-4495-2022-9-4-33-40","DOIUrl":"https://doi.org/10.18705/2311-4495-2022-9-4-33-40","url":null,"abstract":"In recent decades, the multidisciplinary development of medicine has led to an improved understanding of the molecular mechanisms of the development of oncological diseases. The idea of malignant neoplasms as heterogeneous objects containing cells with different genetic backgrounds made it possible to explain the selective effectiveness of one type of treatment for a certain part of the tumor cells in a patient. Numerous targeted therapies have formed the cornerstone in the treatment of various malignancies, alone or in combination with other treatments such as chemotherapy, radiation therapy, surgery and interventional radiology.Interventional oncology covers both diagnostics and treatment. Its methods are minimally invasive and highly specific to the patient. Currently, personalized procedures are actively develop and allow to detect cancer cells, selectively contact and treat them. Another important problems is to evaluate drug delivery and uptake in order to make adjustments to the treatment based on the received data from the procedures and, ultimately, to predict the response. Here we will consider such interventional oncological procedures and innovative methods that are under development as transarterial chemoembolization (TACE), oily transarterial chemoembolization (cTACE), catheter intra-arterial delivery of nanoparticles etc. Thus, interventional oncology has unique opportunities for selective impact on tumor lesions not only for diagnostic purposes, but also for a wide range of minimally invasive percutaneous treatments.","PeriodicalId":89863,"journal":{"name":"Translational medicine (Sunnyvale, Calif.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49051206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}