Biomeditsinskaya khimiya最新文献_第4页

In silico and in cellulo approaches for functional annotation of human protein splice variants. 人类蛋白质剪接变体功能注释的硅学和细胞学方法。

Biomeditsinskaya khimiya Pub Date : 2024-09-01 DOI: 10.18097/PBMC20247005315

O I Kiseleva, V A Arzumanian, I Yu Kurbatov, E V Poverennaya

{"title":"In silico and in cellulo approaches for functional annotation of human protein splice variants.","authors":"O I Kiseleva, V A Arzumanian, I Yu Kurbatov, E V Poverennaya","doi":"10.18097/PBMC20247005315","DOIUrl":"https://doi.org/10.18097/PBMC20247005315","url":null,"abstract":"The elegance of pre-mRNA splicing mechanisms continues to interest scientists even after over a half century, since the discovery of the fact that coding regions in genes are interrupted by non-coding sequences. The vast majority of human genes have several mRNA variants, coding structurally and functionally different protein isoforms in a tissue-specific manner and with a linkage to specific developmental stages of the organism. Alteration of splicing patterns shifts the balance of functionally distinct proteins in living systems, distorts normal molecular pathways, and may trigger the onset and progression of various pathologies. Over the past two decades, numerous studies have been conducted in various life sciences disciplines to deepen our understanding of splicing mechanisms and the extent of their impact on the functioning of living systems. This review aims to summarize experimental and computational approaches used to elucidate the functions of splice variants of a single gene based on our experience accumulated in the laboratory of interactomics of proteoforms at the Institute of Biomedical Chemistry (IBMC) and best global practices.","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 5","pages":"315-328"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340536","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

Biosensing platforms for DNA diagnostics based on CRISPR/Cas nucleases: towards the detection of nucleic acids at the level of single molecules in non-laboratory settings. 基于 CRISPR/Cas 核酸酶的 DNA 诊断生物传感平台：在非实验室环境中实现单分子水平的核酸检测。

Biomeditsinskaya khimiya Pub Date : 2024-09-01 DOI: 10.18097/PBMC20247005287

S A Khmeleva, K G Ptitsyn, L K Kurbatov, O S Timoshenko, E V Suprun, S P Radko, A V Lisitsa

{"title":"Biosensing platforms for DNA diagnostics based on CRISPR/Cas nucleases: towards the detection of nucleic acids at the level of single molecules in non-laboratory settings.","authors":"S A Khmeleva, K G Ptitsyn, L K Kurbatov, O S Timoshenko, E V Suprun, S P Radko, A V Lisitsa","doi":"10.18097/PBMC20247005287","DOIUrl":"https://doi.org/10.18097/PBMC20247005287","url":null,"abstract":"The use of CRISPR/Cas nucleases for the development of DNA diagnostic systems in out-of-laboratory conditions (point-of-need testing, PONT) has demonstrated rapid growth in the last few years, starting with the appearance in 2017-2018 of the first diagnostic platforms known as DETECTR and SHERLOCK. The platforms are based on a combination of methods of nucleic acid isothermal amplification with selective CRISPR/Cas detection of target amplicons. This significantly improves the sensitivity and specificity of PONT, making them comparable with or even superior to the sensitivity and specificity of polymerase chain reaction, considered as the \"gold standard\" of DNA diagnostics. The review considers modern approaches to the coupling of CRISPR/Cas detection using Cas9, Cas12a, Cas12b, Cas13a, Cas14, and Cas3 nucleases to various methods of nucleic acid isothermal amplification, with an emphasis on works in which sensitivity at the level of single molecules (attomolar and subattomolar concentrations of the target) is achieved. The properties of CRISPR/Cas nucleases used for targeted DNA diagnostics and the features of methods of nucleic acid isothermal amplification are briefly considered in the context of the development of diagnostic biosensing platforms. Special attention is paid to the most promising directions for the development of DNA diagnostics using CRISPR/Cas nuclease.","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 5","pages":"287-303"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340556","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

Proteome of plasma extracellular vesicles as a source of colorectal cancer biomarkers. 作为结直肠癌生物标志物来源的血浆细胞外囊泡蛋白质组。

Biomeditsinskaya khimiya Pub Date : 2024-09-01 DOI: 10.18097/PBMC20247005356

N A Soloveva, S E Novikova, T E Farafonova, O V Tikhonova, V G Zgoda, A I Archakov

{"title":"Proteome of plasma extracellular vesicles as a source of colorectal cancer biomarkers.","authors":"N A Soloveva, S E Novikova, T E Farafonova, O V Tikhonova, V G Zgoda, A I Archakov","doi":"10.18097/PBMC20247005356","DOIUrl":"https://doi.org/10.18097/PBMC20247005356","url":null,"abstract":"The search for minimally invasive methods for diagnostics of colorectal cancer (CRC) is the most important task for early diagnostics of the disease and subsequent successful treatment. Human plasma represents the main type of biological material used in the clinical practice; however, the complex dynamic range of substances circulating in it complicates determination of CRC protein markers by the mass spectrometric (MS) method. Studying the proteome of extracellular vesicles (EVs) isolated from human plasma represents an attractive approach for the discovery of tissue-secreted CRC markers. We performed shotgun mass spectrometry analysis of EV samples obtained from plasma of CRC patients and healthy volunteers. This MS analysis resulted in identification of 370 proteins (which were registered by at least two peptides). Stable isotope-free relative quantitation identified 55 proteins with altered abundance in EV samples obtained from plasma samples of CRC patients as compared to healthy controls. Among the EV proteins isolated from blood plasma we found components involved in cell adhesion and the VEGFA-VEGFR2 signaling pathway (TLN1, HSPA8, VCL, MYH9, and others), as well as proteins expressed predominantly by gastrointestinal tissues (polymeric immunoglobulin receptor, PIGR). The data obtained using the shotgun proteomic profiling may be added to the panel for targeted MS analysis of EV-associated protein markers, previously developed using CRC cell models.","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 5","pages":"356-363"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340538","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

Clinical metabolomics: current state and prospects in Russia. 临床代谢组学：俄罗斯的现状与前景。

Biomeditsinskaya khimiya Pub Date : 2024-09-01 DOI: 10.18097/PBMC20247005329

P G Lokhov, E E Balashova, O P Trifonova, D L Maslov, A P Lokhov, E A Ponomarenko, A V Lisitsa, M V Ugrumov, I S Stilidi, N E Kushlinskii, D B Nikityuk, V A Tutelyan, M V Shestakova, I I Dedov, A I Archakov

{"title":"Clinical metabolomics: current state and prospects in Russia.","authors":"P G Lokhov, E E Balashova, O P Trifonova, D L Maslov, A P Lokhov, E A Ponomarenko, A V Lisitsa, M V Ugrumov, I S Stilidi, N E Kushlinskii, D B Nikityuk, V A Tutelyan, M V Shestakova, I I Dedov, A I Archakov","doi":"10.18097/PBMC20247005329","DOIUrl":"https://doi.org/10.18097/PBMC20247005329","url":null,"abstract":"Using analytical technologies it is possible now to measure the entire diversity of molecules even in a small amount of biological samples. Metabolomic technologies simultaneously analyze thousands of low-molecular substances in a single drop of blood. Such analytical performance opens new possibilities for clinical laboratory diagnostics, still relying on the measurement of only a limited number of clinically significant substances. However, there are objective difficulties hampering introduction of metabolomics into clinical practice. The Institute of Biomedical Chemistry (IBMC), consolidating the efforts of leading scientific and medical organizations, has achieved success in this area by developing a clinical blood metabogram (CBM). CBM opens opportunities to obtain overview on the state of the body with the detailed individual metabolic characteristics of the patient. A number of scientific studies have shown that the CBM is an effective tool for monitoring the state of the body, and based on the CBM patterns (signatures), it is possible to diagnose and monitor the treatment of many diseases. Today, the CBM creation determines the current state and prospects of clinical metabolomics in Russia. This article, dedicated to the 80th anniversary of IBMC, is a review of these achievements focused on a discussion of their implementation in clinical practice.","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 5","pages":"329-341"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340557","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

Fundamentals of protein chemistry at the Institute of Biomedical Chemistry. 生物医学化学研究所的蛋白质化学基础。

Biomeditsinskaya khimiya Pub Date : 2024-09-01 DOI: 10.18097/PBMC20247005263

A V Kolesnichenko, T O Pleshakova

引用次数: 0

AFM-fishing technology for protein detection in solutions. 用于检测溶液中蛋白质的原子力显微镜捕鱼技术。

Biomeditsinskaya khimiya Pub Date : 2024-09-01 DOI: 10.18097/PBMC20247005273

T O Pleshakova, M O Ershova, A A Valueva, I A Ivanova, Yu D Ivanov, A I Archakov

引用次数: 0

Bioinformatic identification of proteins with altered PTM levels in a mouse line established to study the mechanisms of the development of fibromuscular dysplasia. 用生物信息学方法鉴定为研究纤维肌发育不良发病机制而建立的小鼠品系中PTM水平发生变化的蛋白质。

Biomeditsinskaya khimiya Pub Date : 2024-08-01 DOI: 10.18097/PBMC20247004248

A I Voronina, Yu V Miroshnichenko, V S Skvortsov

{"title":"Bioinformatic identification of proteins with altered PTM levels in a mouse line established to study the mechanisms of the development of fibromuscular dysplasia.","authors":"A I Voronina, Yu V Miroshnichenko, V S Skvortsov","doi":"10.18097/PBMC20247004248","DOIUrl":"https://doi.org/10.18097/PBMC20247004248","url":null,"abstract":"Data from a mass spectrometry experiment of a mouse line developed to study the mechanisms of fibromuscular dysplasia and deposited by d'Escamard et al. in ProteomeXchange (PXD051750) have been analyzed. Identification of peptides with post-translational modifications (PTMs) was repeated using more stringent conditions than in the original work. The following modifications were considered during analysis of changes in the PTM levels in experimental and control groups of mice: acetylation of lysine residue and N-terminal protein peptide, ubiquitination of lysine residue, phosphorylation of serine, threonine and tyrosine residues, and deamination of asparagine and glutamine residues. The multistage analysis resulted in selection of 23 proteins with PTMs for which different levels of modification between experimental and control groups could be assumed. These included six proteins with N-terminal protein acetylation, which were particularly interesting: P80318 (T-complex protein 1 subunit gamma), P43274 (Histone H1.4), P97823 (Acyl-protein thioesterase 1), P63242 (Eukaryotic translation initiation factor 5A-1), Q3UMT1 (Protein phosphatase 1 regulatory subunit 12C), Q9D8Y0 (EF-hand domain-containing protein D2). Thus, repeated bioinformatic analysis of the data deposited in the specialized databases resulted in detection of changes in the level of N-terminal acetylation of proteins that might be functionally significant in the mechanisms underlying the development of fibromuscular dysplasia.","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 4","pages":"248-255"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139208","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

MicroRNAs as promising diagnostic and prognostic markers for the human genitourinary cancer. 作为人类泌尿生殖系统癌症诊断和预后标志物的微小核糖核酸。

Biomeditsinskaya khimiya Pub Date : 2024-08-01 DOI: 10.18097/PBMC20247004191

E V Kugaevskaya, O S Timoshenko, T A Gureeva, S P Radko, A V Lisitsa

{"title":"MicroRNAs as promising diagnostic and prognostic markers for the human genitourinary cancer.","authors":"E V Kugaevskaya, O S Timoshenko, T A Gureeva, S P Radko, A V Lisitsa","doi":"10.18097/PBMC20247004191","DOIUrl":"https://doi.org/10.18097/PBMC20247004191","url":null,"abstract":"Genitourinary cancer (GUC) represents more than one fifth of all human cancers. This makes the development of approaches to its early diagnosis an important task of modern biomedicine. Circulating microRNAs, short (17-25 nucleotides) non-coding RNA molecules found in human biological fluids and performing a regulatory role in the cell, are considered as promising diagnostic and prognostic biomarkers of cancers, including GUC. In this review we have considered the current state of research aimed at assessing microRNAs as biomarkers of such human GUC types as malignant tumors of the bladder, kidney, prostate, testicles, ovaries, and cervix. A special attention has been paid to studies devoted to the identification of microRNAs in urine as a surrogate \"liquid biopsy\" that may provide the simplest and cheapest approach to mass non-invasive screening of human GUC. The use of microRNA panels instead of single types of microRNA generally leads to higher sensitivity and specificity of the developed diagnostic tests. However, to date, work on the microRNAs assessment as biomarkers of human GUC is still of a research nature, and the further introduction of diagnostic tests based on microRNAs into practice requires successful clinical trials.","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 4","pages":"191-205"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139210","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

Molecular mechanisms of the regulatory action of high-density lipoproteins on the endothelial function. 高密度脂蛋白对内皮功能调节作用的分子机制。

Biomeditsinskaya khimiya Pub Date : 2024-08-01 DOI: 10.18097/PBMC20247004206

O N Poteryaeva, I F Usynin

引用次数: 0

Internalization of extracellular vesicles of cancer patients by peripheral blood mononuclear cells during polychemotherapy: connection with neurotoxicity. 多化疗过程中外周血单核细胞对癌症患者细胞外囊泡的内化：与神经毒性的关系。

Biomeditsinskaya khimiya Pub Date : 2024-08-01 DOI: 10.18097/PBMC20247004240

N V Yunusova, E V Kaigorodova, P A Panfilova, N O Popova, I N Udintseva, I V Kondakova, D A Svarovsky, V E Goldberg

{"title":"Internalization of extracellular vesicles of cancer patients by peripheral blood mononuclear cells during polychemotherapy: connection with neurotoxicity.","authors":"N V Yunusova, E V Kaigorodova, P A Panfilova, N O Popova, I N Udintseva, I V Kondakova, D A Svarovsky, V E Goldberg","doi":"10.18097/PBMC20247004240","DOIUrl":"https://doi.org/10.18097/PBMC20247004240","url":null,"abstract":"Extracellular vesicles (EVs), exhibiting their functional activity after internalization by recipient cells, are involved in the pathogenesis of drug-induced polyneuropathy (DIPN), a common complication of antitumor therapy. In this work, the internalization of EVs obtained from colorectal cancer patients undergoing polychemotherapy and its relationship with neurotoxicity were assessed using a model system of mononuclear leukocytes. Circulating EVs were isolated from 8 colorectal cancer patients who received antitumor therapy according to the FOLFOX or XELOX regimens before the start of chemotherapy (point 1) and after 3-4 courses (point 2). Mononuclear leukocytes of a healthy donor served as a cellular model system for EV internalization in vitro. EV internalization was assessed using fluorescence microscopy. It was shown that internalization of EVs obtained from colorectal cancer patients with high neurotoxicity was higher than in the group with low neurotoxicity. The ability of CD11b-positive (CD11b⁺) and CD11b-negative (CD11b⁻) mononuclear leukocytes of a healthy donor to internalize EVs obtained from patients before and after chemotherapy did not reveal significant differences. A direct relationship was found between the relative number of CD11b⁻ cells with internalized EVs and the integral index of neurotoxicity according to the NRS scale at the peak of its manifestation (point 2) (r=0.675, p.","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":"70 4","pages":"240-247"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139209","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