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The role of PASS and STITCH in the verification of unknown properties of pyruvate and lactate. Literature review and fragments of authors’ own research PASS和STITCH在丙酮酸和乳酸未知性质验证中的作用。文献综述和作者自己研究的片段
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-18 DOI: 10.20538/1682-0363-2023-3-110-119
N. A. Kolotyeva, F. N. Gilmiyarova, O. A. Gusyakova, E. A. Semashkova
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.
该研究的目的是利用现代计算机建模方法确定丙酮酸盐和乳酸盐的生物活性预测谱,并确定分子间相互作用中潜在的蛋白质伙伴。材料和方法。采用PASS (Prediction of activity Spectra for Substances)软件测定丙酮酸酯和乳酸酯的生物活性谱。使用相互作用化学搜索工具(Search Tool for Interactions Chemicals, STITCH)预测小分子潜在的蛋白质相互作用伙伴。结果。结果表明,丙酮酸酯和乳酸酯具有不同的生物活性、分子机制和药理作用。这些包括调节脂质、蛋白质和碳水化合物代谢以及对酶活性和基因表达的影响。介绍了其抗缺氧、抗缺血、抗毒性、免疫调节、抗炎、抗病毒、血管保护和细胞保护作用。预测了丙酮酸和乳酸的神经保护和抗神经毒性作用。结论。通过计算机模拟方法揭示了乳酸和丙酮酸的生物活性谱,并对蛋白质相互作用伙伴进行了表征。我们研究的小分子在介质、激素、受体、免疫、炎症、抗菌、抗病毒反应和基因表达的功能和调节中起协调作用。本文讨论了天然中间体作为治疗缺血性中风、急性神经系统疾病和神经退行性疾病的药物的使用,这是基于代谢物对神经可塑性的刺激作用。这些特性可能通过受体的构象重排、活性结合中心、多个基因的表达以及催化蛋白和其他蛋白功能表现的变化来表现。获得的数据将明显扩大我们对小分子在分子间代谢物-蛋白质相互作用中的作用的理解。
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引用次数: 0
The role of endosarcomeric cytoskeleton proteins in the mechanisms of left ventricular diastolic dysfunction: focus on titin 肌内细胞骨架蛋白在左心室舒张功能障碍机制中的作用:重点关注titin
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-18 DOI: 10.20538/1682-0363-2023-3-98-109
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
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.
认识到孤立性左室舒张功能障碍(DD)在所有心力衰竭病例中约占50%,需要深入了解其主要机制,以便制定有效的诊断和治疗策略。尽管对DD的机制有丰富的认识,但关于舒张的病理生理的许多重要问题仍未解决。特别是,肌内细胞骨架病理在所谓的主动(舒张开始时左室心肌松弛和房室压力梯度,与健康心脏密切相关)和被动(心肌僵硬)舒张特征恶化中的作用需要澄清。讲座简要讨论了DD机制的复杂层次(从肌节到整个心脏),并涵盖了巨蛋白titin在后者中的作用,后者是细胞内硬度的主要决定因素。在多种病理条件下(压力过载、缺血、炎症、心脏毒性作用、氧化应激等),DD的心肌舒张损伤和壁顺性恶化可以通过titin表达向更严格的N2B亚型转移、蛋白激酶a和G的低磷酸化或丝氨酸/苏氨酸磷酸酶5在包含独特N2B序列的可扩展蛋白片段中的分子去磷酸化来解释。蛋白激酶C对titin的PEVK区域的过度磷酸化,以及ca2 +依赖性的titin - actin相互作用的抑制。破译这些机制的结果一方面可以成为开发目前没有有效治疗方法的舒张性心力衰竭靶向治疗新方法的工具,另一方面也是了解已经用于治疗左室射血分数保留的慢性心力衰竭的药物治疗效果的关键。
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引用次数: 0
Application of multicolor flow cytometry in liquid biopsy of breast cancer 多色流式细胞术在乳腺癌液体活检中的应用
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-18 DOI: 10.20538/1682-0363-2023-3-165-170
E. V. Kaigorodova, M. Yu. Grishchenko
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.
根据临床研究NCT04817501“女性生殖系统肿瘤中循环肿瘤细胞(CTCs)的表型特征”,我们开发了一种T1期子宫内膜癌患者复发风险的术前预测方法(专利号:2762493,2021年12月21日)。本文报道一例应用多色流式细胞术进行乳腺癌液体活检的临床病例。在开始治疗前,在T2N0M0期BC患者的血液中检测到ctc。采用多色流式细胞术研究了CTC的各种表型,并测定了Her2/neu和ki-67标记物。这些标记物也在BC组织的活检和手术材料中使用免疫组织化学进行了研究。研究结果表明,细针穿刺活检前血液中ctc的分子谱与BC组织中癌细胞的分子谱一致。此外,活检前计算的肿瘤进展风险预测了该患者癌症发生前20个月的复发。结果显示了多色流式细胞术在肿瘤液体活检中的实际应用。通过各种分子参数评估ctc的能力可用于癌症患者的诊断、预测、监测和确定治疗策略。
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引用次数: 0
Possible role of features of the intestinal microbiome in patients with colorectal cancer as a cause of anastomotic leak 结肠直肠癌患者肠道微生物群特征作为吻合口瘘原因的可能作用
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-18 DOI: 10.20538/1682-0363-2023-3-120-131
P. V. Kosareva, R. A. Konev, A. P. Godovalov, L. V. Sivakova, E. I. Samodelkin
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.
的目标。通过对文献资料的分析,确定结直肠癌患者肠梗阻的显著因素。材料和方法。我们分析了来自Scopus、Web of Science、Google Scholar和PubMed数据库的84篇文献来源,以及Google上的开放获取文章。结果。探讨结直肠癌术后吻合口瘘的主要原因,分析微生物群在术后并发症发生中的作用。结直肠癌患者的肠道微生物群中含有生理条件下通常不存在的细菌。这些细菌有助于疾病的发展,肠梗阻手术后缝合失败和癌变的进展。这种影响是由于细菌代谢产物的产生,对人体免疫的影响,以及与专性肠道微生物群的竞争。另一方面,使用药物治疗,包括抗生素,导致专性细菌的大量死亡。因此,重要的是寻找药物和治疗方法,如果可能的话,不会对微生物群产生显著的负面影响,但能够破坏致病微生物。俄罗斯作者提出的概念是,在远端结肠重建手术中,在腔内使用利福昔明-α来预防化脓性和脓毒性并发症和吻合口泄漏。
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引用次数: 0
Monitoring of the intrauterine state of the fetus. Question history. New possibilities of phonocardiography 宫内胎儿状态的监测问题的历史。心音图的新可能性
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-18 DOI: 10.20538/1682-0363-2023-3-141-149
E. S. Repina, Y. V. Kosteley, A. Sh. Bureev, S. Yu. Yuriev, I. A. Petrov, O. A. Tikhonovskaya, G. A. Mikheenko
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.
降低围产期死亡率是现代产科亟待解决的问题之一。不幸的是,目前由妇产科医生使用的监测胎儿宫内状态的方法(心脏造影、多普勒测速仪)并不能保证胎儿近期的健康,而且出于安全考虑,检测的数量有限。因此,人们一直在寻找获取胎儿宫内状态信息的替代方法(心音图、心电图)。利用信息技术和数学数据分析大大扩大了心音图的潜力,包括实施胎儿健康状态的远程监测。托木斯克公司diagnostics + LCC开发了软件和硬件设备FetalCare,旨在基于胎儿心血管系统的音频数据对胎儿的宫内状态进行24小时监测。心音图获得的心间期图(CIG)可以根据标准的评估标准来估计胎儿的状态:基础心率、心率变异性、加速和减速、短期变化(STV)和长期变化(LTV)。该装置是非侵入性的,相对便宜,便携,对母亲和胎儿都是安全的。
{"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":null,"pages":null},"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}
引用次数: 0
Diabetic ketoacidosis and cognitive impairment in children and adolescents 儿童和青少年糖尿病酮症酸中毒与认知障碍
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-18 DOI: 10.20538/1682-0363-2023-3-132-140
K. Sh. Magomedova, Yu. V. Bykov, V. A. Baturin
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.
本文综述了儿童和青少年1型糖尿病(DM)酮症酸中毒(DKA)后认知功能障碍的形成和临床表现的现代科学资料。1型糖尿病是儿童和青少年最常见的内分泌疾病之一。DKA是1型糖尿病最常见的急性并发症,可引起认知障碍。脑水肿是DKA患者脑血管功能不全的主要原因。然而,DKA中认知功能障碍发展的机制尚未完全阐明。主要的假设包括神经炎症、氧化应激、神经发生破坏和神经变性的发展。缺氧缺血性损伤和脑神经解剖结构的改变也可引起认知功能障碍。据报道,DKA发作后一些脑结构破坏,主要影响白质。儿科人群的临床研究支持DKA的严重程度和频率与认知障碍的严重程度之间存在相关性。儿童和青少年DKA发作后的认知功能障碍可表现为注意力下降、记忆和执行功能受损以及智商下降。在1型糖尿病合并DKA症状的儿童患者中,尽早诊断出认知功能障碍可以改善这种内分泌病的治疗预后。
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引用次数: 0
Metabolic potential of gut microbiota in helminth infections as a way to achieve bronchial asthma control 肠道微生物群在寄生虫感染中的代谢潜力作为实现支气管哮喘控制的一种方式
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-18 DOI: 10.20538/1682-0363-2023-3-150-158
T. S. Sokolova, V. N. Malchuk, A. D. Zaytseva, O. S. Fedorova, M. R. Karpova
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.
本综述的目的是分析旨在评估支气管哮喘(BA)和寄生虫感染中肠道微生物群代谢活性的现代实验研究和临床试验。作为最常见的慢性异质性呼吸系统疾病之一,支气管哮喘在具有重大社会经济意义的全球健康问题中占有重要地位。近年来,大量的数据积累表明肠道微生物群的状态决定的状态是一个重要的因素影响人类健康和免疫机制在儿童过敏性疾病的发展。肠道菌群的失调不仅是由于其组成的变化,而且是由于其代谢的紊乱。根据“肠-肺轴”的概念,维持健康的肠道菌群并纠正其紊乱,包括旨在激活肠道短链脂肪酸合成的策略,可能成为预防和治疗儿童慢性呼吸系统疾病的新途径。反过来,实验和流行病学研究表明了蠕虫的免疫调节活性。据推测,它们对肠道菌群组成和功能的影响是蠕虫影响宿主免疫反应和BA病程的机制之一。
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引用次数: 0
A clinical case of myocardial infarction after coronary artery bypass grafting using the internal mammary artery 乳内动脉冠状动脉旁路移植术后心肌梗死1例
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-18 DOI: 10.20538/1682-0363-2023-3-159-164
E. A. Zakharyan, D. V. Shatov, P. E. Grigoriev, M. S. Radkovskaya
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.
冠状动脉旁路移植术(CABG)是多支冠状动脉疾病和严重进展型冠状动脉疾病的首选心肌血运重建方法。左前降支(LADA) CABG的材料选择是乳腺内动脉(IMA)。然而,即使使用IMA作为冠脉搭桥导管,也应注意移植物衰竭的可能性,这表明需要对这类患者保持警惕。冠状动脉血管内介入治疗可以有效、安全地对闭塞的旁路移植术进行血运重建,最大限度地降低现有风险,提高患者的生活质量和生存率。本文报道一例因乳腺移植物阻塞LADA而发生复发性前路心肌梗死的临床病例。
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引用次数: 0
Constitutional risk factors for the development of glaucoma and cataracts in the Europioid population of Russia 俄罗斯类欧洲人群青光眼和白内障发生的体质危险因素
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-17 DOI: 10.20538/1682-0363-2023-3-43-53
V. I. Konenkov, A. V. Shevchenko, V. F. Prokofiev, A. N. Trunov, V. V. Chernykh
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.
的目标。通过对患者基因组中多种细胞因子及其受体、金属蛋白酶及其组织抑制剂的基因变异等复杂遗传性状分布的比较分析,确定青光眼和白内障发生的内源性危险因素。材料和方法。这项研究包括了501名出生并生活在俄罗斯西伯利亚地区的高加索人。将患者分为原发性开角型青光眼(POAG)患者(99例)、老年性白内障患者(100例)和无眼部病理的对照组(302例)。采用SYBRGreen I染料和TaqMan探针对分析的多态性位点进行实时PCR分型,并对不同多态性进行限制性片段长度多态性(RFLP)分析。结果。研究结果显示,与对照组相比,POAG患者中所分析遗传性状的频率显示存在组合遗传性状。它们在POAG中的检出率高,其特点是优势比值为两位数,特异性值高(99-100%),诊断系数高。对参与细胞外基质重塑的蛋白产物的两个基因群分布的直接比较揭示了这两种疾病的显著遗传特征。这表明在遗传易感性对其发展的实施方面存在显著差异。结论。获得的数据表明,有可能制定可靠的实验室标准(风险计)来预测POAG发展的易感性,并在临床前表现阶段进行早期诊断。
{"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":null,"pages":null},"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}
引用次数: 0
Sarcoidosis as a disease associated with metabolic syndrome 结节病与代谢综合征相关
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-17 DOI: 10.20538/1682-0363-2023-3-80-87
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
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.
本文综述并分析了近年来国内外主要关于代谢综合征成分的流行情况及其在结节病发生机制中的作用的研究结果。深入了解代谢综合征(MS)的发病机制,以及在MS中聚集的大多数社会敏感非传染性疾病的严重病程和并发症的危险因素在其中的作用,可以为开发有效的病原体特异性治疗方法提供基础。
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引用次数: 0
期刊
Byulleten Sibirskoy Meditsiny
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