Biochemistry (Moscow)最新文献

{"title":"Quantitative Analysis of Phagocytosis in Whole Blood Using Double Staining and Visualization","authors":"Elena V. Lysakova,&nbsp;Alexander N. Shumeev,&nbsp;Sergei A. Chuvpilo,&nbsp;Viktor S. Laktyushkin,&nbsp;Natalia A. Arsentieva,&nbsp;Mikhail Yu. Bobrov,&nbsp;Stanislav A. Rybtsov","doi":"10.1134/S0006297924050122","DOIUrl":"10.1134/S0006297924050122","url":null,"abstract":"<p>Phagocytosis is an essential innate immunity function in humans and animals. A decrease in the ability to phagocytize is associated with many diseases and aging of the immune system. Assessment of phagocytosis dynamics requires quantification of bacteria inside and outside the phagocyte. Although flow cytometry is the most common method for assessing phagocytosis, it does not include visualization and direct quantification of location of bacteria. Here, we used double-labeled <i>Escherichia coli</i> cells to evaluate phagocytosis by flow cytometry (cell sorting) and confocal microscopy, as well as employed image cytometry to provide high-throughput quantitative and spatial recognition of the double-labeled <i>E. coli</i> associated with the phagocytes. Retention of pathogens on the surface of myeloid and lymphoid cells without their internalization was suggested to be an auxiliary function of innate immunity in the fight against infections. The developed method of bacterial labeling significantly increased the accuracy of spatial and quantitative measurement of phagocytosis in whole blood and can be recommended as a tool for phagocytosis assessment by image cytometry.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 5","pages":"923 - 932"},"PeriodicalIF":2.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191366","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}

{"title":"Lymphocyte Phosphatase-Associated Phosphoprotein (LPAP) as a CD45 Protein Stability Regulator","authors":"Natalia A. Kruglova,&nbsp;Dmitriy V. Mazurov,&nbsp;Alexander V. Filatov","doi":"10.1134/S0006297924050110","DOIUrl":"10.1134/S0006297924050110","url":null,"abstract":"<p>Lymphocyte phosphatase-associated phosphoprotein (LPAP) is a binding partner of the phosphatase CD45, but its function remains poorly understood. Its close interaction with CD45 suggests that LPAP may potentially regulate CD45, but direct biochemical evidence for this has not yet been obtained. We found that in the Jurkat lymphoid cells the levels of LPAP and CD45 proteins are interrelated and well correlated with each other. Knockout of LPAP leads to the decrease in the surface expression of CD45, while its overexpression, on the contrary, caused its increase. No such correlation was found in the non-lymphoid K562 cells. We hypothesize that LPAP regulates expression level of CD45 and thus can affect lymphocyte activation.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 5","pages":"912 - 922"},"PeriodicalIF":2.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191444","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}

{"title":"CAR Cells beyond Classical CAR T Cells: Functional Properties and Prospects of Application","authors":"Elizaveta P. Minina,&nbsp;Dmitry V. Dianov,&nbsp;Saveliy A. Sheetikov,&nbsp;Apollinariya V. Bogolyubova","doi":"10.1134/S0006297924050018","DOIUrl":"10.1134/S0006297924050018","url":null,"abstract":"<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":"89 5","pages":"765 - 783"},"PeriodicalIF":2.3,"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}

{"title":"Reverse Genetics Applied to Immunobiology of Tumor Necrosis Factor, a Multifunctional Cytokine","authors":"Sergey A. Nedospasov,&nbsp;Andrei A. Kruglov,&nbsp;Alexei V. Tumanov,&nbsp;Marina S. Drutskaya,&nbsp;Irina V. Astrakhantseva,&nbsp;Dmitry V. Kuprash","doi":"10.1134/S0006297924050067","DOIUrl":"10.1134/S0006297924050067","url":null,"abstract":"<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":"89 5","pages":"853 - 861"},"PeriodicalIF":2.3,"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}

{"title":"Humoral and Cellular Immune Response to SARS-CoV-2 S and N Proteins","authors":"Zulfiia E. Afridonova,&nbsp;Anna P. Toptygina,&nbsp;Ilya S. Mikhaylov","doi":"10.1134/S0006297924050080","DOIUrl":"10.1134/S0006297924050080","url":null,"abstract":"<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^high 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.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 5","pages":"872 - 882"},"PeriodicalIF":2.3,"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}

{"title":"Antigenic Cartography of SARS-CoV-2","authors":"Ekaterina A. Astakhova,&nbsp;Alexey A. Morozov,&nbsp;Julia D. Vavilova,&nbsp;Alexander V. Filatov","doi":"10.1134/S0006297924050079","DOIUrl":"10.1134/S0006297924050079","url":null,"abstract":"<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":"89 5","pages":"862 - 871"},"PeriodicalIF":2.3,"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}

{"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,&nbsp;Oksana S. Goryainova","doi":"10.1134/S0006297924050134","DOIUrl":"10.1134/S0006297924050134","url":null,"abstract":"<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":"89 5","pages":"933 - 941"},"PeriodicalIF":2.3,"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}

{"title":"Peptide-Based Inhibitors of the Induced Signaling Protein Interactions: Current State and Prospects","authors":"Vladimir Y. Toshchakov","doi":"10.1134/S000629792405002X","DOIUrl":"10.1134/S000629792405002X","url":null,"abstract":"<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":"89 5","pages":"784 - 798"},"PeriodicalIF":2.3,"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}

{"title":"Rational Design of Drugs Targeting G-Protein-Coupled Receptors: Ligand Search and Screening","authors":"Aleksandra P. Luginina,&nbsp;Andrey. N. Khnykin,&nbsp;Polina A. Khorn,&nbsp;Olga V. Moiseeva,&nbsp;Nadezhda A. Safronova,&nbsp;Vladimir A. Pospelov,&nbsp;Dmitrii E. Dashevskii,&nbsp;Anatolii S. Belousov,&nbsp;Valentin I. Borschevskiy,&nbsp;Alexey V. Mishin","doi":"10.1134/S0006297924050158","DOIUrl":"10.1134/S0006297924050158","url":null,"abstract":"<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":"89 5","pages":"958 - 972"},"PeriodicalIF":2.3,"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}

{"title":"Metabolic Adaptations and Functional Activity of Macrophages in Homeostasis and Inflammation","authors":"Taisiya R. Yurakova,&nbsp;Ekaterina A. Gorshkova,&nbsp;Maxim A. Nosenko,&nbsp;Marina S. Drutskaya","doi":"10.1134/S0006297924050043","DOIUrl":"10.1134/S0006297924050043","url":null,"abstract":"<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":"89 5","pages":"817 - 838"},"PeriodicalIF":2.3,"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}