Pub Date : 2024-05-31DOI: 10.1134/s0006297924050079
Ekaterina A. Astakhova, Alexey A. Morozov, Julia D. Vavilova, Alexander V. Filatov
Abstract
Antigenic cartography is a tool for interpreting and visualizing antigenic differences between virus variants based on virus neutralization data. This approach has been successfully used in the selection of influenza vaccine seed strains. With the emergence of SARS-CoV-2 variants escaping vaccine-induced antibody response, adjusting COVID-19 vaccines has become essential. This review provides information on the antigenic differences between SARS-CoV-2 variants revealed by antigenic cartography and explores a potential of antigenic cartography-based methods (e.g., building antibody landscapes and neutralization breadth gain plots) for the quantitative assessment of the breadth of the antibody response. Understanding the antigenic differences of SARS-CoV-2 and the possibilities of the formed humoral immunity aids in the prompt modification of preventative vaccines against COVID-19.
{"title":"Antigenic Cartography of SARS-CoV-2","authors":"Ekaterina A. Astakhova, Alexey A. Morozov, Julia D. Vavilova, Alexander V. Filatov","doi":"10.1134/s0006297924050079","DOIUrl":"https://doi.org/10.1134/s0006297924050079","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Antigenic cartography is a tool for interpreting and visualizing antigenic differences between virus variants based on virus neutralization data. This approach has been successfully used in the selection of influenza vaccine seed strains. With the emergence of SARS-CoV-2 variants escaping vaccine-induced antibody response, adjusting COVID-19 vaccines has become essential. This review provides information on the antigenic differences between SARS-CoV-2 variants revealed by antigenic cartography and explores a potential of antigenic cartography-based methods (e.g., building antibody landscapes and neutralization breadth gain plots) for the quantitative assessment of the breadth of the antibody response. Understanding the antigenic differences of SARS-CoV-2 and the possibilities of the formed humoral immunity aids in the prompt modification of preventative vaccines against COVID-19.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1134/s0006297924050080
Zulfiia E. Afridonova, Anna P. Toptygina, Ilya S. Mikhaylov
Abstract
The pandemic of a new coronavirus infection that has lasted for more than 3 years, is still accompanied by frequent mutations in the S protein of SARS-CoV-2 and emergence of new virus variants causing new disease outbreak. Of all coronaviral proteins, the S and N proteins are the most immunogenic. The aim of this study was to compare the features of the humoral and T-cell immune responses to the SARS-CoV-2 S and N proteins in people with different histories of interaction with this virus. The study included 27 individuals who had COVID-19 once, 23 people who were vaccinated twice with the Sputnik V vaccine and did not have COVID-19, 22 people who had COVID-19 and were vaccinated twice with Sputnik V 6-12 months after the disease, and 25 people who had COVID-19 twice. The level of antibodies was determined by the enzyme immunoassay, and the cellular immunity was assessed by the expression of CD107a on CD8high lymphocytes after recognition of SARS-CoV-2 antigens. It was shown that the humoral immune response to the N protein was formed mainly by short-lived plasma cells synthesizing IgG antibodies of all four subclasses with a gradual switch from IgG3 to IgG1. The response to the S protein was formed by short-lived plasma cells at the beginning of the response (IgG1 and IgG3 subclasses) and then by long-lived plasma cells (IgG1 subclass). The dynamics of antibody level synthesized by the short-lived plasma cells was described by the Fisher equation, while changes in the level of antibodies synthesized by the long-lived plasma cells were described by the Erlang equation. The level of antibodies in the groups with the hybrid immunity exceeded that in the group with the post-vaccination immunity; the highest antibody content was observed in the group with the breakthrough immunity. The cellular immunity to the S and N proteins differed depending on the mode of immune response induction (vaccination or disease). Importantly, the response of heterologous CD8+ T cell to the N proteins of other coronaviruses may be involved in the immune defense against SARS-CoV-2.
摘要 新型冠状病毒感染大流行已持续 3 年多，SARS-CoV-2 的 S 蛋白仍频繁发生变异，并出现新的病毒变种，导致新的疾病爆发。在所有冠状病毒蛋白中，S 蛋白和 N 蛋白的免疫原性最强。本研究的目的是比较与 SARS-CoV-2 S 和 N 蛋白有不同相互作用史的人对该病毒的体液免疫和 T 细胞免疫反应的特点。研究对象包括：27 名接种过一次 COVID-19 的人，23 名接种过两次 Sputnik V 疫苗但未接种过 COVID-19 的人，22 名接种过 COVID-19 并在病后 6-12 个月接种过两次 Sputnik V 疫苗的人，以及 25 名接种过两次 COVID-19 的人。抗体水平通过酶免疫测定法测定，细胞免疫则通过识别 SARS-CoV-2 抗原后 CD8high 淋巴细胞上 CD107a 的表达进行评估。结果表明，对 N 蛋白的体液免疫反应主要是由短效浆细胞合成所有四个亚类的 IgG 抗体形成的，并逐渐从 IgG3 转向 IgG1。对 S 蛋白的反应在开始时由短寿命浆细胞形成（IgG1 和 IgG3 亚类），然后由长寿命浆细胞形成（IgG1 亚类）。短寿命浆细胞合成的抗体水平的动态变化用费雪方程来描述，而长寿命浆细胞合成的抗体水平的变化用厄朗方程来描述。混合免疫组的抗体水平超过了接种后免疫组；突破免疫组的抗体含量最高。对 S 蛋白和 N 蛋白的细胞免疫因免疫应答诱导方式（疫苗接种或疾病）的不同而不同。重要的是，异源 CD8+ T 细胞对其他冠状病毒 N 蛋白的反应可能参与了对 SARS-CoV-2 的免疫防御。
{"title":"Humoral and Cellular Immune Response to SARS-CoV-2 S and N Proteins","authors":"Zulfiia E. Afridonova, Anna P. Toptygina, Ilya S. Mikhaylov","doi":"10.1134/s0006297924050080","DOIUrl":"https://doi.org/10.1134/s0006297924050080","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The pandemic of a new coronavirus infection that has lasted for more than 3 years, is still accompanied by frequent mutations in the S protein of SARS-CoV-2 and emergence of new virus variants causing new disease outbreak. Of all coronaviral proteins, the S and N proteins are the most immunogenic. The aim of this study was to compare the features of the humoral and T-cell immune responses to the SARS-CoV-2 S and N proteins in people with different histories of interaction with this virus. The study included 27 individuals who had COVID-19 once, 23 people who were vaccinated twice with the Sputnik V vaccine and did not have COVID-19, 22 people who had COVID-19 and were vaccinated twice with Sputnik V 6-12 months after the disease, and 25 people who had COVID-19 twice. The level of antibodies was determined by the enzyme immunoassay, and the cellular immunity was assessed by the expression of CD107a on CD8<sup>high</sup> lymphocytes after recognition of SARS-CoV-2 antigens. It was shown that the humoral immune response to the N protein was formed mainly by short-lived plasma cells synthesizing IgG antibodies of all four subclasses with a gradual switch from IgG3 to IgG1. The response to the S protein was formed by short-lived plasma cells at the beginning of the response (IgG1 and IgG3 subclasses) and then by long-lived plasma cells (IgG1 subclass). The dynamics of antibody level synthesized by the short-lived plasma cells was described by the Fisher equation, while changes in the level of antibodies synthesized by the long-lived plasma cells were described by the Erlang equation. The level of antibodies in the groups with the hybrid immunity exceeded that in the group with the post-vaccination immunity; the highest antibody content was observed in the group with the breakthrough immunity. The cellular immunity to the S and N proteins differed depending on the mode of immune response induction (vaccination or disease). Importantly, the response of heterologous CD8<sup>+</sup> T cell to the N proteins of other coronaviruses may be involved in the immune defense against SARS-CoV-2.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1134/s0006297924050067
Sergey A. Nedospasov, Andrei A. Kruglov, Alexei V. Tumanov, Marina S. Drutskaya, Irina V. Astrakhantseva, Dmitry V. Kuprash
Abstract
Tumor necrosis factor (TNF) is one of many cytokines – protein molecules responsible for communication between the cells of immune system. TNF was discovered and given its grand name because of its striking antitumor effects in experimental systems, but its main physiological functions in the context of whole organism turned out to be completely unrelated to protection against tumors. This short review discusses “man-made” mouse models generated by early genome-editing technologies, which enabled us to establish true functions of TNF in health and certain diseases as well as to unravel potential strategies for improving therapy of TNF-dependent diseases.
{"title":"Reverse Genetics Applied to Immunobiology of Tumor Necrosis Factor, a Multifunctional Cytokine","authors":"Sergey A. Nedospasov, Andrei A. Kruglov, Alexei V. Tumanov, Marina S. Drutskaya, Irina V. Astrakhantseva, Dmitry V. Kuprash","doi":"10.1134/s0006297924050067","DOIUrl":"https://doi.org/10.1134/s0006297924050067","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Tumor necrosis factor (TNF) is one of many cytokines – protein molecules responsible for communication between the cells of immune system. TNF was discovered and given its grand name because of its striking antitumor effects in experimental systems, but its main physiological functions in the context of whole organism turned out to be completely unrelated to protection against tumors. This short review discusses “man-made” mouse models generated by early genome-editing technologies, which enabled us to establish true functions of TNF in health and certain diseases as well as to unravel potential strategies for improving therapy of TNF-dependent diseases.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1134/s0006297924050018
Elizaveta P. Minina, Dmitry V. Dianov, Saveliy A. Sheetikov, Apollinariya V. Bogolyubova
Abstract
Chimeric antigen receptors (CARs) are genetically engineered receptors that recognize antigens and activate signaling cascades in a cell. Signal recognition and transmission are mediated by the CAR domains derived from different proteins. T cells carrying CARs against tumor-associated antigens have been used in the development of the CAR T cell therapy, a new approach to fighting malignant neoplasms. Despite its high efficacy in the treatment of oncohematological diseases, CAR T cell therapy has a number of disadvantages that could be avoided by using other types of leukocytes as effector cells. CARs can be expressed in a wide range of cells of adaptive and innate immunity with the emergence or improvement of cytotoxic properties. This review discusses the features of CAR function in different types of immune cells, with a particular focus on the results of preclinical and clinical efficacy studies and the safety of potential CAR cell products.
摘要 嵌合抗原受体（CAR）是经基因工程改造的受体，可识别抗原并激活细胞内的信号级联。信号识别和传输由来自不同蛋白质的 CAR 结构域介导。携带针对肿瘤相关抗原的 CAR 的 T 细胞已被用于开发 CAR T 细胞疗法，这是一种对抗恶性肿瘤的新方法。尽管 CAR T 细胞疗法在治疗肿瘤疾病方面具有很高的疗效，但它也存在一些缺点，而使用其他类型的白细胞作为效应细胞则可以避免这些缺点。CAR 可在多种适应性免疫和先天性免疫细胞中表达，并具有或改善细胞毒性特性。本综述将讨论 CAR 在不同类型免疫细胞中的功能特点，尤其关注临床前和临床疗效研究的结果以及潜在 CAR 细胞产品的安全性。
{"title":"CAR Cells beyond Classical CAR T Cells: Functional Properties and Prospects of Application","authors":"Elizaveta P. Minina, Dmitry V. Dianov, Saveliy A. Sheetikov, Apollinariya V. Bogolyubova","doi":"10.1134/s0006297924050018","DOIUrl":"https://doi.org/10.1134/s0006297924050018","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Chimeric antigen receptors (CARs) are genetically engineered receptors that recognize antigens and activate signaling cascades in a cell. Signal recognition and transmission are mediated by the CAR domains derived from different proteins. T cells carrying CARs against tumor-associated antigens have been used in the development of the CAR T cell therapy, a new approach to fighting malignant neoplasms. Despite its high efficacy in the treatment of oncohematological diseases, CAR T cell therapy has a number of disadvantages that could be avoided by using other types of leukocytes as effector cells. CARs can be expressed in a wide range of cells of adaptive and innate immunity with the emergence or improvement of cytotoxic properties. This review discusses the features of CAR function in different types of immune cells, with a particular focus on the results of preclinical and clinical efficacy studies and the safety of potential CAR cell products.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1134/s0006297924050134
Sergei V. Tillib, Oksana S. Goryainova
Abstract
Technology of production of single-domain antibodies (NANOBODY® molecules, also referred to as nanoantibodies, nAb, or molecules based on other stable protein structures) and their derivatives to solve current problems in biomedicine is becoming increasingly popular. Indeed, the format of one small, highly soluble protein with a stable structure, fully functional in terms of specific recognition, is very convenient as a module for creating multivalent, bi-/oligo-specific genetically engineered targeting molecules and structures. Production of nAb in periplasm of E. coli bacterium is a very convenient and fairly universal way to obtain analytical quantities of nAb for the initial study of the properties of these molecules and selection of the most promising nAb variants. The situation is more complicated with production of bi- and multivalent derivatives of the initially selected nAbs under the same conditions. In this work, extended linker sequences (52 and 86 aa) between the antigen-recognition modules in the cloned expression constructs were developed and applied in order to increase efficiency of production of bispecific nanoantibodies (bsNB) in the periplasm of E. coli bacteria. Three variants of model bsNBs described in this study were produced in the periplasm of bacteria and isolated in soluble form with preservation of functionality of all the protein domains. If earlier our attempts to produce bsNB in the periplasm with traditional linkers no longer than 30 aa were unsuccessful, the extended linkers used here provided a significantly more efficient production of bsNB, comparable in efficiency to the traditional production of original monomeric nAbs. The use of sufficiently long linkers could presumably be useful for increasing efficiency of production of other bsNBs and similar molecules in the periplasm of E. coli bacteria.
{"title":"Extending Linker Sequences between Antigen-Recognition Modules Provides More Effective Production of Bispecific Nanoantibodies in the Periplasma of E. coli","authors":"Sergei V. Tillib, Oksana S. Goryainova","doi":"10.1134/s0006297924050134","DOIUrl":"https://doi.org/10.1134/s0006297924050134","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Technology of production of single-domain antibodies (NANOBODY® molecules, also referred to as nanoantibodies, nAb, or molecules based on other stable protein structures) and their derivatives to solve current problems in biomedicine is becoming increasingly popular. Indeed, the format of one small, highly soluble protein with a stable structure, fully functional in terms of specific recognition, is very convenient as a module for creating multivalent, bi-/oligo-specific genetically engineered targeting molecules and structures. Production of nAb in periplasm of <i>E. coli</i> bacterium is a very convenient and fairly universal way to obtain analytical quantities of nAb for the initial study of the properties of these molecules and selection of the most promising nAb variants. The situation is more complicated with production of bi- and multivalent derivatives of the initially selected nAbs under the same conditions. In this work, extended linker sequences (52 and 86 aa) between the antigen-recognition modules in the cloned expression constructs were developed and applied in order to increase efficiency of production of bispecific nanoantibodies (bsNB) in the periplasm of <i>E. coli</i> bacteria. Three variants of model bsNBs described in this study were produced in the periplasm of bacteria and isolated in soluble form with preservation of functionality of all the protein domains. If earlier our attempts to produce bsNB in the periplasm with traditional linkers no longer than 30 aa were unsuccessful, the extended linkers used here provided a significantly more efficient production of bsNB, comparable in efficiency to the traditional production of original monomeric nAbs. The use of sufficiently long linkers could presumably be useful for increasing efficiency of production of other bsNBs and similar molecules in the periplasm of <i>E. coli</i> bacteria.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1134/s0006297924050158
Aleksandra P. Luginina, Andrey. N. Khnykin, Polina A. Khorn, Olga V. Moiseeva, Nadezhda A. Safronova, Vladimir A. Pospelov, Dmitrii E. Dashevskii, Anatolii S. Belousov, Valentin I. Borschevskiy, Alexey V. Mishin
Abstract
G protein-coupled receptors (GPCRs) are transmembrane proteins that participate in many physiological processes and represent major pharmacological targets. Recent advances in structural biology of GPCRs have enabled the development of drugs based on the receptor structure (structure-based drug design, SBDD). SBDD utilizes information about the receptor–ligand complex to search for suitable compounds, thus expanding the chemical space of possible receptor ligands without the need for experimental screening. The review describes the use of structure-based virtual screening (SBVS) for GPCR ligands and approaches for the functional testing of potential drug compounds, as well as discusses recent advances and successful examples in the application of SBDD for the identification of GPCR ligands.
{"title":"Rational Design of Drugs Targeting G-Protein-Coupled Receptors: Ligand Search and Screening","authors":"Aleksandra P. Luginina, Andrey. N. Khnykin, Polina A. Khorn, Olga V. Moiseeva, Nadezhda A. Safronova, Vladimir A. Pospelov, Dmitrii E. Dashevskii, Anatolii S. Belousov, Valentin I. Borschevskiy, Alexey V. Mishin","doi":"10.1134/s0006297924050158","DOIUrl":"https://doi.org/10.1134/s0006297924050158","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>G protein-coupled receptors (GPCRs) are transmembrane proteins that participate in many physiological processes and represent major pharmacological targets. Recent advances in structural biology of GPCRs have enabled the development of drugs based on the receptor structure (structure-based drug design, SBDD). SBDD utilizes information about the receptor–ligand complex to search for suitable compounds, thus expanding the chemical space of possible receptor ligands without the need for experimental screening. The review describes the use of structure-based virtual screening (SBVS) for GPCR ligands and approaches for the functional testing of potential drug compounds, as well as discusses recent advances and successful examples in the application of SBDD for the identification of GPCR ligands.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1134/s000629792405002x
Vladimir Y. Toshchakov
Abstract
Formation of the transient protein complexes in response to activation of cellular receptors is a common mechanism by which cells respond to external stimuli. This article presents the concept of blocking interactions of signaling proteins by the peptide inhibitors, and describes the progress achieved to date in the development of signaling inhibitors that act by blocking the signal-dependent protein interactions.
{"title":"Peptide-Based Inhibitors of the Induced Signaling Protein Interactions: Current State and Prospects","authors":"Vladimir Y. Toshchakov","doi":"10.1134/s000629792405002x","DOIUrl":"https://doi.org/10.1134/s000629792405002x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Formation of the transient protein complexes in response to activation of cellular receptors is a common mechanism by which cells respond to external stimuli. This article presents the concept of blocking interactions of signaling proteins by the peptide inhibitors, and describes the progress achieved to date in the development of signaling inhibitors that act by blocking the signal-dependent protein interactions.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1134/s0006297924050043
Taisiya R. Yurakova, Ekaterina A. Gorshkova, Maxim A. Nosenko, Marina S. Drutskaya
Abstract
In recent years, the role of cellular metabolism in immunity has come into the focus of many studies. These processes form a basis for the maintenance of tissue integrity and homeostasis, as well as represent an integral part of the immune response, in particular, inflammation. Metabolic adaptations not only ensure energy supply for immune response, but also affect the functions of immune cells by controlling transcriptional and post-transcriptional programs. Studying the immune cell metabolism facilitates the search for new treatment approaches, especially for metabolic disorders. Macrophages, innate immune cells, are characterized by a high functional plasticity and play a key role in homeostasis and inflammation. Depending on the phenotype and origin, they can either perform various regulatory functions or promote inflammation state, thus exacerbating the pathological condition. Furthermore, their adaptations to the tissue-specific microenvironment influence the intensity and type of immune response. The review examines the effect of metabolic reprogramming in macrophages on the functional activity of these cells and their polarization. The role of immunometabolic adaptations of myeloid cells in tissue homeostasis and in various pathological processes in the context of inflammatory and metabolic diseases is specifically discussed. Finally, modulation of the macrophage metabolism-related mechanisms reviewed as a potential therapeutic approach.
{"title":"Metabolic Adaptations and Functional Activity of Macrophages in Homeostasis and Inflammation","authors":"Taisiya R. Yurakova, Ekaterina A. Gorshkova, Maxim A. Nosenko, Marina S. Drutskaya","doi":"10.1134/s0006297924050043","DOIUrl":"https://doi.org/10.1134/s0006297924050043","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>In recent years, the role of cellular metabolism in immunity has come into the focus of many studies. These processes form a basis for the maintenance of tissue integrity and homeostasis, as well as represent an integral part of the immune response, in particular, inflammation. Metabolic adaptations not only ensure energy supply for immune response, but also affect the functions of immune cells by controlling transcriptional and post-transcriptional programs. Studying the immune cell metabolism facilitates the search for new treatment approaches, especially for metabolic disorders. Macrophages, innate immune cells, are characterized by a high functional plasticity and play a key role in homeostasis and inflammation. Depending on the phenotype and origin, they can either perform various regulatory functions or promote inflammation state, thus exacerbating the pathological condition. Furthermore, their adaptations to the tissue-specific microenvironment influence the intensity and type of immune response. The review examines the effect of metabolic reprogramming in macrophages on the functional activity of these cells and their polarization. The role of immunometabolic adaptations of myeloid cells in tissue homeostasis and in various pathological processes in the context of inflammatory and metabolic diseases is specifically discussed. Finally, modulation of the macrophage metabolism-related mechanisms reviewed as a potential therapeutic approach.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.1134/s0006297924040059
Alexandra P. Yan, Paul A. Salnikov, Maria M. Gridina, Polina S. Belokopytova, Veniamin S. Fishman
Abstract
Chromosome conformation capture techniques have revolutionized our understanding of chromatin architecture and dynamics at the genome-wide scale. In recent years, these methods have been applied to a diverse array of species, revealing fundamental principles of chromosomal organization. However, structural organization of the extrachromosomal entities, like viral genomes or plasmids, and their interactions with the host genome, remain relatively underexplored. In this work, we introduce an enhanced 4C-protocol tailored for probing plasmid DNA interactions. We design specific plasmid vector and optimize protocol to allow high detection rate of contacts between the plasmid and host DNA.
摘要 染色体构象捕获技术彻底改变了我们对全基因组范围染色质结构和动态的理解。近年来，这些方法已被应用于多种物种，揭示了染色体组织的基本原理。然而，染色体外实体（如病毒基因组或质粒）的结构组织及其与宿主基因组的相互作用仍相对缺乏探索。在这项工作中，我们引入了一种专门用于探测质粒 DNA 相互作用的增强型 4C 方案。我们设计了特定的质粒载体，并优化了方案，以实现质粒与宿主 DNA 之间接触的高检测率。
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Pub Date : 2024-05-06DOI: 10.1134/s0006297924040072
Alexander A. Ukraintsev, Mikhail M. Kutuzov, Olga I. Lavrik
Abstract
Chromatin is an epigenetic platform for implementation of DNA-dependent processes. Nucleosome, as a basic level of chromatin compaction, largely determines its properties and structure. In the study of nucleosomes structure and functions physicochemical tools are actively used, such as magnetic and optical “tweezers”, “DNA curtains”, nuclear magnetic resonance, X-ray crystallography, and cryogenic electron microscopy, as well as optical methods based on Förster resonance energy transfer. Despite the fact that these approaches make it possible to determine a wide range of structural and functional characteristics of chromatin and nucleosomes with high spatial and time resolution, atomic force microscopy (AFM) complements the capabilities of these methods. The results of structural studies of nucleosome focusing on the AFM method development are presented in this review. The possibilities of AFM are considered in the context of application of other physicochemical approaches.
摘要 染色质是实现 DNA 依赖过程的表观遗传平台。核小体作为染色质的基本组成层次，在很大程度上决定了染色质的性质和结构。在核小体结构和功能的研究中，物理化学工具得到了积极的应用，如磁性和光学 "镊子"、"DNA帘子"、核磁共振、X射线晶体学和低温电子显微镜，以及基于佛斯特共振能量转移的光学方法。尽管这些方法能够以较高的空间和时间分辨率确定染色质和核小体的各种结构和功能特征，但原子力显微镜（AFM）是对这些方法能力的补充。本综述介绍了以原子力显微镜方法开发为重点的核小体结构研究结果。本文还结合其他物理化学方法的应用，探讨了原子力显微镜的可能性。
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