N. A. Kolotyeva, F. N. Gilmiyarova, O. A. Gusyakova, E. A. Semashkova
{"title":"The role of PASS and STITCH in the verification of unknown properties of pyruvate and lactate. Literature review and fragments of authors’ own research","authors":"N. A. Kolotyeva, F. N. Gilmiyarova, O. A. Gusyakova, E. A. Semashkova","doi":"10.20538/1682-0363-2023-3-110-119","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-110-119","url":null,"abstract":"The aim of the study was to identify the predicted spectrum of biological activity of pyruvate and lactate using modern computer modeling methods and to determine potential protein partners in intermolecular interaction. Materials and methods. The biological activity spectrum of pyruvate and lactate by the structural formula was determined using the PASS (Prediction of Activity Spectra for Substances) software. Potential protein interaction partners for small molecules were predicted using the Search Tool for Interactions Chemicals (STITCH). Results. Analyzing the obtained results in silico reveals that pyruvate and lactate exhibit diverse biological activities, molecular mechanisms, and pharmacological effects. These include regulation of lipid, protein, and carbohydrate metabolism and effects on enzyme activity and gene expression. The data on the antihypoxic, antiischemic, antitoxic, immunomodulatory, antiinflammatory, antiviral, vasoprotective, and cytoprotective effects are presented. The neuroprotective and antineurotoxic effects of pyruvate and lactate are predicted. Conclusion. The spectrum of biological activities of lactate and pyruvate were revealed by computer modeling methods, and protein interaction partners were characterized. The small molecules we studied have a coordinating role in the functioning and modulation of mediator, hormonal, receptor, immune, inflammatory, antibacterial, and antiviral responses and gene expression. The use of natural intermediates as therapeutic agents for the treatment of ischemic stroke, acute neurological disorders, and neurodegeneration is discussed, which is underlain by the stimulating effect of metabolites on neuroplasticity. These properties may be manifested through conformational rearrangement of receptors, active binding centers, expression of multiple genes, and changes in the functional manifestations of catalytic and other proteins. The obtained data will obviously expand our understanding of the role of small molecules in intermolecular metabolite – protein interactions.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943485","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}
V. V. Kalyuzhin, A. T. Teplyakov, I. D. Bespalova, E. V. Kalyuzhina, G. E. Chernogoryuk, N. N. Terentyeva, E. V. Grakova, K. V. Kopeva, V. Yu. Usov, N. P. Garganeeva, I. K. Livshits, I. V. Petrova, T. V. Lasukova
{"title":"The role of endosarcomeric cytoskeleton proteins in the mechanisms of left ventricular diastolic dysfunction: focus on titin","authors":"V. V. Kalyuzhin, A. T. Teplyakov, I. D. Bespalova, E. V. Kalyuzhina, G. E. Chernogoryuk, N. N. Terentyeva, E. V. Grakova, K. V. Kopeva, V. Yu. Usov, N. P. Garganeeva, I. K. Livshits, I. V. Petrova, T. V. Lasukova","doi":"10.20538/1682-0363-2023-3-98-109","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-98-109","url":null,"abstract":"Recognizing the fact that isolated left ventricular (LV) diastolic dysfunction (DD) underlies approximately 50% of all heart failure cases requires a deep understanding of its principal mechanisms so that effective diagnostic and treatment strategies can be developed. Despite abundance of knowledge about the mechanisms underlying DD, many important questions regarding the pathophysiology of diastole remain unresolved. In particular, the role of endosarcomeric cytoskeleton pathology in the deterioration of the so-called active (relaxation of the LV myocardium and the atrioventricular pressure gradient at the beginning of diastole, closely related to it in a healthy heart) and passive (myocardial stiffness) characteristics of diastole needs to be clarified. The lecture briefly discusses the complex hierarchy of DD mechanisms (from the sarcomere to the whole heart) and covers the role of the giant protein titin in the latter, which is the main determinant of intracellular stiffness. Impairment of myocardial relaxation and deterioration of its wall compliance under a wide range of pathological conditions (pressure overload, ischemia, inflammation, cardiotoxic effects, oxidative stress, etc.) underlying DD can be explained by a shift in titin expression toward its more rigid N2B isoform, hypophosphorylation by protein kinases A and G or dephosphorylation by serine / threonine phosphatase 5 of its molecule in the extensible protein segment containing a unique N2B sequence, hyperphosphorylation of PEVK regions of titin by protein kinase C, as well as inhibition of the Ca 2 +-dependent titin – actin interaction. The results of deciphering these mechanisms can become a tool for developing new approaches to targeted therapy for diastolic heart failure that currently does not have effective treatment, on the one hand, and the key to understanding the therapeutic effects of drugs already used to treat chronic heart failure with preserved LV ejection fraction, on the other hand.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943487","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":"Application of multicolor flow cytometry in liquid biopsy of breast cancer","authors":"E. V. Kaigorodova, M. Yu. Grishchenko","doi":"10.20538/1682-0363-2023-3-165-170","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-165-170","url":null,"abstract":"As a result of the clinical study NCT04817501 “Phenotypic characterization of circulating tumor cells (CTCs) in tumors of the female reproductive system”, we developed a method for preoperative prediction of a recurrence risk in patients with stage T1 endometrial cancer (Patent No. 2762493 of 21.12.2021). The article presents a clinical case of the use of multicolor flow cytometry in liquid biopsy of breast cancer (BC). CTCs were detected in the blood of a patient with T2N0M0 BC, stage IIA before the initiation of treatment. Using multicolor flow cytometry, various CTC phenotypes were studied and the Her2/neu and ki-67 markers were determined. These markers were also studied in the biopsy and surgical material of the BC tissue using immunohistochemistry. As a result of the study, it was shown that the molecular profile of CTCs in the blood taken before fine needle aspiration biopsy coincided with that of cancer cells in the BC tissue. In addition, the calculated risk of tumor progression before biopsy predicted recurrence of cancer in this patient 20 months before its occurrence. The obtained results show the practical utility of multicolor flow cytometry in liquid biopsy of cancers. The ability to evaluate CTCs by various molecular parameters can be useful for diagnosing, predicting, monitoring, and determining treatment strategies for cancer patients.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"145 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943484","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}
P. V. Kosareva, R. A. Konev, A. P. Godovalov, L. V. Sivakova, E. I. Samodelkin
{"title":"Possible role of features of the intestinal microbiome in patients with colorectal cancer as a cause of anastomotic leak","authors":"P. V. Kosareva, R. A. Konev, A. P. Godovalov, L. V. Sivakova, E. I. Samodelkin","doi":"10.20538/1682-0363-2023-3-120-131","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-120-131","url":null,"abstract":"Aim. Following the analysis of literature data, to determine significant factors of intestinal obstruction in patients with colorectal cancer. Materials and methods. We analyzed 84 literature sources from the Scopus, Web of Science, Google Scholar, and PubMed databases, as well as open access articles on Google. Results. The predominant causes of anastomotic leaks after operations for colorectal cancer are discussed, the role of the microbiome in the development of postoperative complications is analyzed. The intestinal microbiome of patients with colorectal cancer contains bacteria that are not normally found under physiological conditions. These bacteria contribute to the development of disease, suture failure after surgery for intestinal obstruction, and progression of carcinogenesis. This effect is due to the production of bacterial metabolites, the effect on the human immunity, and competition with obligate intestinal microflora. On the other hand, the use of drug therapy, including antibiotics, leads to mass death of obligate bacteria. Therefore, it is important to search for drugs and treatment methods that, if possible, do not have a significant negative impact on the microbiome, but are capable of destroying pathogenic microorganisms. The concept of Russian authors was proposed, which consists in the intraluminal use of rifaximin-α for the prevention of purulent and septic complications and anastomotic leaks during reconstructive surgeries on the distal colon.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"243 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943486","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. S. Repina, Y. V. Kosteley, A. Sh. Bureev, S. Yu. Yuriev, I. A. Petrov, O. A. Tikhonovskaya, G. A. Mikheenko
{"title":"Monitoring of the intrauterine state of the fetus. Question history. New possibilities of phonocardiography","authors":"E. S. Repina, Y. V. Kosteley, A. Sh. Bureev, S. Yu. Yuriev, I. A. Petrov, O. A. Tikhonovskaya, G. A. Mikheenko","doi":"10.20538/1682-0363-2023-3-141-149","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-141-149","url":null,"abstract":"The problem of decreasing perinatal mortality is one of the pressing problems in modern obstetrics. Unfortunately, current methods of monitoring the intrauterine state of the fetus that are at the disposal of an obstetrician – gynecologist (сardiotocography, Doppler velocimetry) do not guarantee fetal wellbeing in the near-term outlook, and the number of tests is limited due to safety concerns. Consequently, there is ongoing search for alternative methods of obtaining information about the intrauterine state of the fetus (phonocardiography, electrocardiography). Using IT and mathematical data analysis has considerably enlarged the phonocardiography potential, including implementation of remote monitoring of the fetal health state. A Tomsk-based company Diagnostika + LCC developed software and hardware appliance FetalCare aimed at 24-hour monitoring of the intrauterine state of the fetus based on audio data on the fetal cardiovascular system. Cardiointervalograms (CIG) obtained by phonocardiography allow to estimate the state of the fetus based on standard assessment criteria: basal heart rate, heart rate variability, presence of accelerations and decelerations, short-term variation (STV), and long-term variation (LTV). The developed appliance is non-invasive, relatively cheap, portable, and safe both for the mother and the fetus.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943489","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":"Diabetic ketoacidosis and cognitive impairment in children and adolescents","authors":"K. Sh. Magomedova, Yu. V. Bykov, V. A. Baturin","doi":"10.20538/1682-0363-2023-3-132-140","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-132-140","url":null,"abstract":"The aim of the literature review was to highlight modern scientific sources on the formation and clinical manifestations of cognitive impairment in children and adolescents with type 1 diabetes mellitus (DM) after diabetic ketoacidosis (DKA). Type 1 DM is one of the most prevalent endocrine disorders in childhood and adolescence. DKA is the most common acute complication of type 1 DM that may cause cognitive impairment. Cerebral edema is the main cause of cerebral vascular insufficiency in patients with DKA. However, the mechanisms underlying the development of cognitive dysfunction in DKA have not been fully elucidated. The leading hypotheses include development of neuroinflammation, oxidative stress, disruption of neurogenesis, and neurodegeneration. Hypoxic – ischemic injury and changes in the brain neuroanatomy may also cause cognitive dysfunction. Disruption of some brain structures has been reported after DKA episodes, primarily affecting the white matter. Clinical studies in the pediatric population support the presence of a correlation between the severity and frequency of DKA and the severity of cognitive impairment. Cognitive dysfunction in children and adolescents after a DKA episode can manifest through decreased attention, impaired memory and executive function, and reduced IQ. The earliest possible diagnosis of cognitive impairment in pediatric patients with symptoms of DKA in the context of type 1 DM can improve the treatment prognosis for this endocrinopathy.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943341","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. S. Sokolova, V. N. Malchuk, A. D. Zaytseva, O. S. Fedorova, M. R. Karpova
{"title":"Metabolic potential of gut microbiota in helminth infections as a way to achieve bronchial asthma control","authors":"T. S. Sokolova, V. N. Malchuk, A. D. Zaytseva, O. S. Fedorova, M. R. Karpova","doi":"10.20538/1682-0363-2023-3-150-158","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-150-158","url":null,"abstract":"The aim of the review was to analyze modern experimental studies and clinical trials aimed at assessing metabolic activity of gut microbiota in bronchial asthma (BA) and helminth infections. Being one of the most common chronic heterogeneous respiratory diseases, bronchial asthma secures its place among global health problems of great socioeconomic importance. In recent years, a lot of data has been accumulated indicating that the state of gut microbiota is an important factor determining the state of human health and affecting immune mechanisms underlying the development of allergic diseases in childhood. Dysbiosis of gut microbiota is due not only to changes in its composition, but also to disturbances in its metabolism. In accordance with the “gut – lung axis” concept, maintaining healthy gut microbiota and correcting its disorders, including strategies aimed at activating synthesis of short-chain fatty acids in the intestine, may become a new way to prevent and treat chronic respiratory diseases in childhood. In turn, experimental and epidemiological studies have shown the immunomodulatory activity of helminths. It is assumed that their impact on the composition and function of gut microbiota is one of the mechanisms by which helminths influence the immune response of the host and the course of BA.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"80 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135942725","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. A. Zakharyan, D. V. Shatov, P. E. Grigoriev, M. S. Radkovskaya
{"title":"A clinical case of myocardial infarction after coronary artery bypass grafting using the internal mammary artery","authors":"E. A. Zakharyan, D. V. Shatov, P. E. Grigoriev, M. S. Radkovskaya","doi":"10.20538/1682-0363-2023-3-159-164","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-159-164","url":null,"abstract":"Coronary artery bypass grafting (CABG) is the most preferred method of myocardial revascularization in multivessel coronary artery disease and severe progressive forms of the disease. The material of choice for CABG of the left anterior descending artery (LADA) is the internal mammary artery (IMA). However, even when using IMA as a conduit for CABG, one should be aware of a possibility of graft failure, which indicates a need for constant vigilance in this category of patients. Endovascular interventions on coronary arteries make it possible to efficiently and safely revascularize an occluded bypass graft, minimizing existing risks and improving both the quality of life of patients and their subsequent survival. The article considers a clinical case of the development of recurrent anterior myocardial infarction in the patient due to occlusion of the mammary graft to the LADA.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"261-262 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943488","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}
V. I. Konenkov, A. V. Shevchenko, V. F. Prokofiev, A. N. Trunov, V. V. Chernykh
{"title":"Constitutional risk factors for the development of glaucoma and cataracts in the Europioid population of Russia","authors":"V. I. Konenkov, A. V. Shevchenko, V. F. Prokofiev, A. N. Trunov, V. V. Chernykh","doi":"10.20538/1682-0363-2023-3-43-53","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-43-53","url":null,"abstract":"Aim. To identify endogenous risk factors for the development of glaucoma and cataracts based on the results of a comparative analysis of the nature of complex genetic trait distribution, including variants of genes for a number of cytokines and receptors for them, metalloproteinases, and their tissue inhibitors included in the genome of patients. Materials and methods. The study included 501 people of the Caucasian race born and living in the Siberian region of Russia. They were divided into three groups of patients – patients with primary open-angle glaucoma (POAG) (n = 99), patients with senile cataract (n = 100), and the control group (n = 302) without ophthalmic pathology. Genotyping of the analyzed polymorphic loci was carried out by real-time PCR using the SYBRGreen I dye and TaqMan probes and by restriction fragment length polymorphism (RFLP) for different polymorphisms. Results. The results of the study on the frequency of the analyzed genetic traits among patients with POAG compared to the control group showed the presence of combined genetic traits. The frequency of their detection in POAG was high and characterized by the two-digit value of the odds ratio, high values of specificity (99–100%), and high diagnostic coefficient. A direct comparison of the distribution of two ensembles of genes which protein products are involved in the extracellular matrix remodeling revealed a significant number of genetic traits characteristic of both diseases. This indicates significant differences in the implementation of the genetic predisposition to their development. Conclusion. The data obtained indicate the possibility of developing reliable laboratory criteria (riskometers) for predicting predisposition to the development of POAG and early diagnosis at the stage of preclinical manifestations.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136038637","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. D. Bespalova, D. S. Romanov, O. A. Denisova, E. Yu. Bragina, Yu. I. Koshchavtseva, U. M. Mitrichenko, A. V. Teteneva, E. V. Kalyuzhina, Ya. V. Porovskiy, E. B. Bukreeva
{"title":"Sarcoidosis as a disease associated with metabolic syndrome","authors":"I. D. Bespalova, D. S. Romanov, O. A. Denisova, E. Yu. Bragina, Yu. I. Koshchavtseva, U. M. Mitrichenko, A. V. Teteneva, E. V. Kalyuzhina, Ya. V. Porovskiy, E. B. Bukreeva","doi":"10.20538/1682-0363-2023-3-80-87","DOIUrl":"https://doi.org/10.20538/1682-0363-2023-3-80-87","url":null,"abstract":"The review summarizes and analyzes the results of domestic and major foreign studies of recent years concerning the prevalence of metabolic syndrome components and the explanation of their role in the mechanisms of sarcoidosis development. A deep understanding of the pathogenesis of metabolic syndrome (MS) in terms of the role in it of risk factors for a severe course and complications of most socially sensitive noncommunicable diseases clustered within MS can underly the development of effective pathogen-specific approaches to MS treatment.","PeriodicalId":43691,"journal":{"name":"Byulleten Sibirskoy Meditsiny","volume":"84 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136038636","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}