Bulletin of Siberian Medicine最新文献

{"title":"Functional analysis of a new splicing mutation in the MYBPC3 gene in hypertrophic cardiomyopathy","authors":"R. R. Salakhov, M. Golubenko, M. Skoblov, R. R. Savchenko, N. Valiakhmetov, E. N. Pavlyukova, M. S. Nazarenko","doi":"10.20538/1682-0363-2024-2-183-189","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-183-189","url":null,"abstract":"Aim. To study the pathogenic effect in the MYBPC3 splice-site variant in the patient with hypertrophic cardiomyopathy. Materials and methods. The study was conducted using a DNA sample obtained from a patient with hypertrophic cardiomyopathy, in whom a previously undescribed variant was identified in the splice donor site of intron 21. The methods used included constructing and cloning of minigenes (vector pSpl3-Flu2-TKdel) and transfection of a human cell culture (HEK293T), followed by isolation of mRNA, production of cDNA, PCR of the minigene region containing the analyzed fragment, agarose gel electrophoresis, and Sanger sequencing. Results. The chr11:47339649-A-C (hg38) variant, disrupting the splice donor site in intron 21 (NM_000256.3: c.2067+2T>G), was identified in the 23-year-old patient with obstructive hypertrophic cardiomyopathy. To directly analyze the effect of this variant on splicing, a vector containing exon 21, intron 21, exon 22, and partially introns 20 and 22 of the MYBPC3 gene was obtained. A comparison of mRNAs from the minigenes containing / not containing the variant showed that the chr11:47339649-A-C substitution led to exon 21 and exon 22 skipping during splicing. Conclusion. The study established the functional significance of the previously undescribed variant c.2067+2T>G in the MYBPC3 gene, resulting in disruption of the mRNA splicing mechanism in the patient with hypertrophic cardiomyopathy. This variant can be classified as pathogenic.","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"142 32","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141656144","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":"Precision medicine in oncology: role and prospects of mass spectrometry","authors":"E. S. Khmelevskaya, E. A. Perina, E. Buyko, A. A. Ufandeev, O. A. Kaidash, V. Ivanov, A. N. Baikov, E. Parochkina, E. V. Udut","doi":"10.20538/1682-0363-2024-2-162-182","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-162-182","url":null,"abstract":"The aim of this review was to analyze the accumulated data on the use of mass spectrometry in diagnosing, treating, and prognosing cancer from the perspective of precision medicine. Currently, universally accepted methods for early cancer diagnosis are not available, primarily due to low molecular specificity of pathological changes at early stages of cancer development. Additionally, the existing diagnostic modalities are notably limited in sensitivity. However, early detection is imperative for selection of the most suitable cancer treatment strategy and its successful implementation. In the realm of oncology, mass spectrometry approaches show great potential for advancement and utilization. Mass spectrometry is becoming an indispensable tool in basic and applied research due to its sensitivity, specificity, and accuracy. It allows for efficient analysis of complex biological compounds, even at low concentrations. Moreover, contemporary mass spectrometry technology is capable of automating the analysis, thereby facilitating its diverse clinical applications in diagnosis, drug therapy selection, and even potential assistance to surgical oncologists in the operating room. Considering all these characteristics and advantages, mass spectrometry methods for the analysis of biological samples can be defined as some of the most promising and dynamically developing tools in precision medicine, as they are capable of providing clinically valuable information based on omics technologies, taking into account personal characteristics of the patient. Over the next decade, introduction of mass spectrometry-based methods into clinical practice based on the principles of precision medicine is expected to optimize selection of personalized treatment strategies for cancer patients and provide significant economic benefits by reducing morbidity, disability, and mortality.This comprehensive review presents the analysis of 65 scientific publications, highlighting the results of clinical and experimental studies utilizing mass spectrometry methods for diagnosing cancer, investigating the underlying mechanisms of disease development, and evaluating the efficacy of therapeutic interventions. The review encompasses original articles published from January 1, 2018 to November 30, 2023. The majority of studies back the potential of mass spectrometry as a valuable tool for cancer diagnosis and treatment monitoring. Broadening application of mass spectrometry techniques in the field of oncology holds significant promise and represents a relevant area for future research.","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"56 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141658152","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":"Urinary tract microbiota in patients with multiple sclerosis and neurogenic pelvic dysfunction","authors":"E. I. Luzanova, M. I. Karpova, O. Abramovskikh, E. Chetvernina, S. V. Kupriyanov","doi":"10.20538/1682-0363-2024-2-133-141","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-133-141","url":null,"abstract":"Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system common among young people. Neurogenic bladder often is a common symptom of the disease. Young people with MS often have to make treatment and family planning decisions at the same time. The possibility of realizing reproductive plans is closely related to urological complications of the disease, high risk of urinary tract infections, and sexual dysfunction. In addition, disease modifying therapies for MS play a significant role in increasing the likelihood of infectious complications. Therefore, the issue of infection prevention in MS is critical. Effective personalized prevention of urogenital infections is possible with a clear understanding of the microbiota composition. DNA sequencing methods have changed the conventional idea that normal urine is sterile and gave rise to the concepts of asymptomatic bacteriuria in healthy people. Moreover, data on the genitourobiome of patients with neurological diseases have recently emerged. Extended knowledge about the microbiology in the genitourinary system of neurological patients is necessary to unleash the capacity of health-preserving technologies. The aim of the review was to integrate currently available data concerning the microbiocenosis of the lower urinary tract and vagina with underlying neurogenic pelvic dysfunction, including MS, as well as to present data on the association between closely located biotopes and the effect of MS therapy on the risks of developing genitourinary infections. ","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"75 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141655335","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":"Pyroptosis and its therapeutic potential","authors":"I. A. Odintsova, V. Chirsky, D. R. Slutskaya, E. A. Andreeva, T. I. Berezovskaya","doi":"10.20538/1682-0363-2024-2-142-150","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-142-150","url":null,"abstract":"The review examines present data on pyroptosis – a type of programmed cell death associated with infection with various pathogens. During pyroptosis. specific molecular complexes, inflammasomes, are formed, caspases are activated, and proinflammatory cytokines are produced. We consider the mechanisms of pyroptosis activation, including canonical and non-canonical pathways, as well as methods for its detection in cells. The review substantiates the relevance of studying the role of pyroptosis in pathological processes in different tissues. We focus on the therapeutic potential of pyroptosis, including its role in the treatment of sepsis. Pyroptosis is involved in sepsis-induced tissue damage in various organs, so regulation of this type of cell death can serve as the basis for the development of innovative treatment methods. ","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"81 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141657818","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":"Features of cystic fibrosis development in a patient with coinfection by Mycobacterium abscessus and Mycobacterium tuberculosis (clinical case report)","authors":"O. Filinyuk, E. A. Kruk, A. V. Teteneva, Yu. A. Loginova, E. P. Kostoyakova, I. D. Bespalova, K. Tetenev, A. I. Karzilov, E. Mishustina","doi":"10.20538/1682-0363-2024-2-190-198","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-190-198","url":null,"abstract":"The article presents a clinical case describing a favorable clinical outcome of mycobacterial infection and pulmonary tuberculosis caused by coinfection of M. abscessus and M. tuberculosis in a patient with pulmonary manifestations of cystic fibrosis one year after delivery. This outcome was achieved due to timely diagnosis and treatment of pulmonary tuberculosis and non-tuberculous mycobacterial infection in the patient with cystic fibrosis. Due to the development of molecular identification of mycobacteria species in the Tomsk region, mycobacterial lung disease was verified, which was challenging in the recent past. Previously, all cases with microscopic examination results positive for mycobacteria were classified as tuberculosis. ","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"46 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141658343","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":"Monkeys excluding apes as a model for studies on metabolic syndrome","authors":"S. Orlov, Y. Uspensky, Yu. A. Fominykh, Yu. A. Kolesnik, A. V. Panchenko","doi":"10.20538/1682-0363-2024-2-151-161","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-151-161","url":null,"abstract":"Aim. To summarize the results of research on metabolic syndrome in monkeys excluding apes and to conduct a comparison with humans.A search for full-text publications in PubMed and Scopus databases was carried out using the following keywords: nonhuman primate, monkey, obesity, diabetes mellitus, metabolic syndrome, insulin, atherosclerosis, hypertension. Articles were selected that describe studies involving the following monkey species: cynomolgus monkeys (Macaca fascicularis), rhesus macaques (Macaca mulatta), baboons (Papio sp.), grivets (Cercopithecus aethiops), and common marmosets (Callithrix jacchus). The development of various metabolic syndrome criteria was demonstrated in all monkey species reviewed. Many similarities with humans were revealed: macaques with obesity, insulin resistance, and type 2 diabetes mellitus demonstrated an increase in total cholesterol, triglycerides, and free fatty acids and a decrease in the concentration of high-density lipoprotein cholesterol. Obesity and insulin resistance were precursors to impaired carbohydrate metabolism. Blood pressure increased along with the progression of insulin resistance. The similarity of genetic and environmental risk factors between humans and monkeys is important in the development of metabolic syndrome. The reviewed data suggest that the use of monkeys in biomedical research remains an indispensable resource for the study of pathogenesis and assessment of the efficacy and safety of new therapeutic strategies targeting clinically important metabolic diseases, including obesity, dyslipidemia, atherosclerosis, type 2 diabetes mellitus, and, possibly, other conditions associated with metabolic syndrome.","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"134 48","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141656397","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":"The role of estrogens in mitochondrial metabolism","authors":"O. I. Kit, E. Frantsiyants, A. Shikhlyarova, I. V. Neskubina, S. A. Ilchenko","doi":"10.20538/1682-0363-2024-2-123-132","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-123-132","url":null,"abstract":" Central organelles in cells are mitochondria, which are essential for many fundamental biological processes. In the course of evolution, mitochondria have been transformed into signaling centers in biological systems that can cause changes in the cell via secreted factors and affect physiology of humans and animals. Along with performing many key functions for the cell, mitochondria have also evolved into active hubs that can both control cellular programs through interaction with other compartments, such as the endoplasmic reticulum, and affect tissues, determining the health of the body via mechanisms that we are only beginning to understand.","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"8 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141662569","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":"Syndrome frailty and his features in Parkinson’s disease","authors":"O. V. Guseva","doi":"10.20538/1682-0363-2024-2-114-122","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-114-122","url":null,"abstract":"Syndrome frailty is widespread all over the world and its appearance is associated with an increase in life expectancy. The lecture shows the multifactorial nature of the syndrome: changes in physical health, social and psychological factors, gender characteristics and age. The classic diagnosis of the syndrome consists in assessing physical weakness according to the Fried phenotype. The modern view of the problem complements the diagnosis with indices of weakness to characterize the multifactorial development and the use of digital wearable technologies for long-term monitoring of the patient’s functional parameters.The lecture provides a detailed justification of the effect of comorbidity on the development of syndrome frailty. The syndrome frailty is difficult diagnosed in Parkinson’s disease, because it has high prevalence in these. Studies of syndrome frailty in Parkinson’s disease are few, probably due to the similarity of the symptoms of the disease and the syndrome. The lecture identifies the possible risks of syndrome frailty in Parkinson’s disease: the influence of various forms of Parkinson’s disease, gender, cognitive and functional disorders, polypharmacy, levodopa doses. The role of multidisciplinary rehabilitation’s team and independent physical activity in the combination of Parkinson’s disease and syndrome frailty is shown.","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"44 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141660125","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 Charlson Comorbidity Index to assess prognosis of 18-month mortality in patients with acute myocardial infarction","authors":"T. H. Hoang, V. Maiskov, I. Merai, Z. Kobalava","doi":"10.20538/1682-0363-2024-2-91-100","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-91-100","url":null,"abstract":"Aim. To evaluate the prognostic value of the Charlson Comorbidity Index (CCI) for predicting 18-month all-cause mortality and develop a nomogram for predicting 18-month mortality in acute myocardial infarction (MI) patients. Materials and methods. The prospective, single-center, observational study included 712 consecutive patients with acute MI undergoing coronary angiography within 24 hours after hospitalization. The primary endpoint was 18-month all-cause mortality. The logistic regression analysis was adopted to identify independent prognostic factors. A nomogram for predicting the endpoint was developed using the multivariate analysis. The discriminative ability of the CCI and a nomogram were evaluated using the receiver-operating characteristic (ROC) curve analysis. Results. Of the patients, 61% were male, median age was 65 years (interquartile range (IQR) was 56–74 years). Median CCI was 4 (IQR: 3–6) points. The mortality rate was 12.1% at 18 months with the area under the curve (AUC) of 0.797 for CCI (95% confidence interval (CI) 0.746–0.849; p < 0.001). The multivariate analysis revealed that CCI (odds ratio (OR) 1.28; 95% CI 1.08–1.52; p = 0.004), age (OR 1.06; 95% CI 1.02–1.09; p = 0.002), and three-vessel coronary artery disease (OR 2.60; 95% CI 1.36–4.98; p = 0.004), incorporated into the nomogram, were independent predictive factors of an adverse outcome. The nomogram showed good discrimination in predicting 18-month mortality in patients with acute MI (AUC = 0.819; 95% CI 0.767–0.870; p < 0.001; sensitivity 65.1%; specificity 88.2%). Conclusion. CCI was independently associated with and moderately predicted 18-month mortality in patients with acute MI. The proposed nomogram facilitated early identification of high-risk patients, allowing for the implementation of more effective treatment strategies and reducing acute MI mortality","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"9 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141660325","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":"Results of UGT1A1 gene sequencing in individuals with the Gilbert syndrome phenotype","authors":"A. A. Ivanova, N. E. Apartseva, A. P. Kashirina, E. G. Nemcova, Ju. V. Ivanova, M. Kruchinina, S. A. Kurilovich, V. N. Maksimov","doi":"10.20538/1682-0363-2024-2-65-73","DOIUrl":"https://doi.org/10.20538/1682-0363-2024-2-65-73","url":null,"abstract":"Aim. To evaluate the effectiveness of automated Sanger sequencing of the UGT1A1 gene to search for pathogenic mutations in individuals with the Gilbert syndrome phenotype. Materials and methods. Automated Sanger sequencing of exons and part of the promoter in the UGT1A1 gene was carried out for 24 people with unconjugated hyperbilirubinemia, in whom all other causes except for genetic ones were excluded and DNA analysis was performed to determine the number of TA repeats in the promoter of the UGT1A1 gene (rs3064744). Distribution of rs3064744 genotypes in the group was the following: 5 people – 7TA/7TA genotype, 5 people – 6TA/6TA genotype, 12 people – 6TA/7TA genotype, 1 person – 5TA/7TA genotype, 1 person – 6TA/8TA genotype. DNA was isolated using phenol – chloroform extraction or express methods. The sequencing was performed by capillary electrophoresis on the Hitachi 3500 Genetic Analyzer (Applied Biosystems, USA). Results. Single nucleotide variants of uncertain significance were identified: rs3755319 (in 21 people) and rs28899472 (in three people with the 7TA/7TA genotype of rs3064744) in the promoter of the UGT1A1 gene, rs2125984650 in the first exon of the UGT1A1 gene (in one person with the 5TA/7TA genotype of rs3064744). In two individuals with the 6TA/7TA genotype of rs3064744, gene variants were identified that were pathogenic or likely pathogenic for the Gilbert syndrome according to some sources (rs4148323, rs1273237448). Conclusion. According to the results of the study, automated Sanger sequencing of the UGT1A1 gene may be the next stage of DNA analysis after determining the rs3064744 genotype for individuals with 6TA/6TA, 6TA/7TA rs3064744 genotypes and suspected Gilbert syndrome.","PeriodicalId":256912,"journal":{"name":"Bulletin of Siberian Medicine","volume":"25 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141660706","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}