Biochemistry (Moscow)最新文献

{"title":"Methods for Functional Characterization of Genetic Polymorphisms of Non-Coding Regulatory Regions of the Human Genome","authors":"Aksinya N. Uvarova,&nbsp;Elena A. Tkachenko,&nbsp;Ekaterina M. Stasevich,&nbsp;Elina A. Zheremyan,&nbsp;Kirill V. Korneev,&nbsp;Dmitry V. Kuprash","doi":"10.1134/S0006297924060026","DOIUrl":"10.1134/S0006297924060026","url":null,"abstract":"<p>Currently, numerous associations between genetic polymorphisms and various diseases have been characterized through the Genome-Wide Association Studies. Majority of the clinically significant polymorphisms are localized in non-coding regions of the genome. While modern bioinformatic resources make it possible to predict molecular mechanisms that explain influence of the non-coding polymorphisms on gene expression, such hypotheses require experimental verification. This review discusses the methods for elucidating molecular mechanisms underlying dependence of the disease pathogenesis on specific genetic variants within the non-coding sequences. A particular focus is on the methods for identification of transcription factors with binding efficiency dependent on polymorphic variations. Despite remarkable progress in bioinformatic resources enabling prediction of the impact of polymorphisms on the disease pathogenesis, there is still the need for experimental approaches to investigate this issue.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 6","pages":"1002 - 1013"},"PeriodicalIF":2.3,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297924060026.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141550531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pore-Forming VDAC Proteins of the Outer Mitochondrial Membrane: Regulation and Pathophysiological Role","authors":"Natalia V. Belosludtseva,&nbsp;Mikhail V. Dubinin,&nbsp;Konstantin N. Belosludtsev","doi":"10.1134/S0006297924060075","DOIUrl":"10.1134/S0006297924060075","url":null,"abstract":"<p>Voltage-dependent anion channels (VDAC1-3) of the outer mitochondrial membrane are a family of pore-forming β-barrel proteins that carry out controlled “filtration” of small molecules and ions between the cytoplasm and mitochondria. Due to the conformational transitions between the closed and open states and interaction with cytoplasmic and mitochondrial proteins, VDACs not only regulate the mitochondrial membrane permeability for major metabolites and ions, but also participate in the control of essential intracellular processes and pathological conditions. This review discusses novel data on the molecular structure, regulatory mechanisms, and pathophysiological role of VDAC proteins, as well as future directions in this area of research.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 6","pages":"1061 - 1078"},"PeriodicalIF":2.3,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141550535","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":"The Antioxidant Defense System of Tomato (Solanum lycopersicum L.) Varieties under Drought Stress and upon Post-Drought Rewatering","authors":"Naima N. Niyazova,&nbsp;Irada M. Huseynova","doi":"10.1134/S0006297924060130","DOIUrl":"10.1134/S0006297924060130","url":null,"abstract":"<p>Water shortage induces physiological, biochemical, and molecular alterations in plant leaves that play an essential role in plant adaptive response. The effects of drought and post-drought rewatering on the activity of antioxidant enzymes and levels of H₂O₂, phenolic compounds, ascorbic acid, and proline were studied in six local tomato (<i>Solanum lycopersicum</i> L.) varieties. The contents of H₂O₂ and ascorbic acid increased in all drought-exposed tomato plants and then decreased upon rewatering. The level of phenolic compounds also decreased in response to water shortage and then recovered upon rehydration, although the extent of this response was different in different varieties. The activities of ascorbate peroxidase (APX) and guaiacol peroxidase (POX) and the content of proline significantly increased in the drought-stressed plants and then decreased when the plants were rewatered. The activities of 8 constitutive APX isoforms and 2 constitutive POX isoforms varied upon exposure to drought and were observed after rewatering in all studied varieties. The information on the response of tomato plants to drought and subsequent rewatering is of great importance for screening and selection of drought-tolerant varieties, as well as for development of strategies for increasing plant productivity under adverse environmental conditions.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 6","pages":"1146 - 1157"},"PeriodicalIF":2.3,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141550442","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":"Activity of DNA Repair Systems in the Cells of Long-Lived Rodents and Bats","authors":"Aleksei A. Popov,&nbsp;Irina O. Petruseva,&nbsp;Olga I. Lavrik","doi":"10.1134/S0006297924060038","DOIUrl":"10.1134/S0006297924060038","url":null,"abstract":"<p>Damages of various origin accumulated in the genomic DNA can lead to the breach of genome stability, and are considered to be one of the main factors involved in cellular senescence. DNA repair systems in mammalian cells ensure effective damage removal and repair of the genome structure, therefore, activity of these systems is expected to be correlated with high maximum lifespan observed in the long-lived mammals. This review discusses current results of the studies focused on determination of the DNA repair system activity and investigation of the properties of its key regulatory proteins in the cells of long-lived rodents and bats. Based on the works discussed in the review, it could be concluded that the long-lived rodents and bats in general demonstrate high efficiency in functioning and regulation of DNA repair systems. Nevertheless, a number of questions around the study of DNA repair in the cells of long-lived rodents and bats remain poorly understood, answers to which could open up new avenues for further research.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 6","pages":"1014 - 1023"},"PeriodicalIF":2.3,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297924060038.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141550532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gypenoside A Protects Human Myocardial Cells from Ischemia/Reperfusion Injury via the circ_0010729/miR-370-3p/RUNX1 Axis","authors":"Hailiang Ma,&nbsp;Yuanben Lu,&nbsp;Dewen Zhu,&nbsp;Zhenhua Jiang,&nbsp;FanZhi Zhang,&nbsp;Jun Peng,&nbsp;Li Wang","doi":"10.1134/S000629792405016X","DOIUrl":"10.1134/S000629792405016X","url":null,"abstract":"<p>Ischemia/reperfusion (I/R) injury is one of the major causes of cardiovascular disease. Gypenoside A (GP), the main active component of <i>Gynostemma pentaphyllum</i>, alleviates myocardial I/R injury. Circular RNAs (circRNAs) and microRNAs (miRNAs) are involved in the I/R injury. We explored the protective effect of GP on human cardiomyocytes (HCMs) via the circ_0010729/miR-370-3p/RUNX1 axis. Overexpression of circ_0010729 abolished the effects of GP on HMC, such as suppression of apoptosis and increase in cell viability and proliferation. Overexpression of miR-370-3p reversed the effect of circ_0010729 overexpression, resulting in the stimulation of HMC viability and proliferation and inhibition of apoptosis. The knockdown of miR-370-3p suppressed the effects of GP in HCMs. RUNX1 silencing counteracted the effect of miR-370-3p knockdown and maintained GP-induced suppression of apoptosis and stimulation of HMC viability and proliferation. The levels of RUNX1 mRNA and protein were reduced in cells expressing miR-370-3p. In conclusion, this study confirmed that GP alleviated the I/R injury of myocardial cell via the circ_0010729/miR-370-3p/RUNX1 axis.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 5","pages":"973 - 986"},"PeriodicalIF":2.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141190974","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":"Tumor-Associated Senescent Macrophages, Their Markers, and Their Role in Tumor Microenvironment","authors":"Tamara V. Pukhalskaia,&nbsp;Taisiya R. Yurakova,&nbsp;Daria A. Bogdanova,&nbsp;Oleg N. Demidov","doi":"10.1134/S0006297924050055","DOIUrl":"10.1134/S0006297924050055","url":null,"abstract":"<p>Tumor-associated macrophages (TAMs) are an important component of the tumor microenvironment (TME) and the most abundant population of immune cells infiltrating a tumor. TAMs can largely determine direction of anti-tumor immune response by promoting it or, conversely, contribute to formation of an immunosuppressive TME that allows tumors to evade immune control. Through interactions with tumor cells or other cells in the microenvironment and, as a result of action of anti-cancer therapy, macrophages can enter senescence. In this review, we have attempted to summarize information available in the literature on the role of senescent macrophages in tumors. With the recent development of senolytic therapeutic strategies aimed at removing senescent cells from an organism, it seems important to discuss functions of the senescent macrophages and potential role of the senolytic drugs in reprogramming TAMs to enhance anti-tumor immune response and improve efficacy of cancer treatment.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 5","pages":"839 - 852"},"PeriodicalIF":2.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191286","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":"Dysregulation of Immune Tolerance to Autologous iPSCs and Their Differentiated Derivatives","authors":"Margarita E. Bogomiakova,&nbsp;Alexandra N. Bogomazova,&nbsp;Maria A. Lagarkova","doi":"10.1134/S0006297924050031","DOIUrl":"10.1134/S0006297924050031","url":null,"abstract":"<p>Induced pluripotent stem cells (iPSCs), capable of differentiating into any cell type, are a promising tool for solving the problem of donor organ shortage. In addition, reprogramming technology makes it possible to obtain a personalized, i.e., patient-specific, cell product transplantation of which should not cause problems related to histocompatibility of the transplanted tissues and organs. At the same time, inconsistent information about the main advantage of autologous iPSC-derivatives – lack of immunogenicity – still casts doubt on the possibility of using such cells beyond immunosuppressive therapy protocols. This review is devoted to immunogenic properties of the syngeneic and autologous iPSCs and their derivatives, as well as to the reasons for dysregulation of their immune tolerance.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 5","pages":"799 - 816"},"PeriodicalIF":2.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141190903","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":"Microglia and Dendritic Cells as a Source of IL-6 in a Mouse Model of Multiple Sclerosis","authors":"Violetta S. Gogoleva,&nbsp;Quynh Chi Nguyen,&nbsp;Marina S. Drutskaya","doi":"10.1134/S0006297924050109","DOIUrl":"10.1134/S0006297924050109","url":null,"abstract":"<p>Multiple sclerosis (MS) is a complex autoimmune disease of central nervous system (CNS) characterized by the myelin sheath destruction and compromised nerve signal transmission. Understanding molecular mechanisms driving MS development is critical due to its early onset, chronic course, and therapeutic approaches based only on symptomatic treatment. Cytokines are known to play a pivotal role in the MS pathogenesis with interleukin-6 (IL-6) being one of the key mediators. This study investigates contribution of IL-6 produced by microglia and dendritic cells to the development of experimental autoimmune encephalomyelitis (EAE), a widely used mouse model of MS. Mice with conditional inactivation of IL-6 in the CX₃CR1⁺ cells, including microglia, or CD11c⁺ dendritic cells, displayed less severe symptoms as compared to their wild-type counterparts. Mice with microglial IL-6 deletion exhibited an elevated proportion of regulatory T cells and reduced percentage of pathogenic IFNγ-producing CD4⁺ T cells, accompanied by the decrease in pro-inflammatory monocytes in the CNS at the peak of EAE. At the same time, deletion of IL-6 from microglia resulted in the increase of CCR6⁺ T cells and GM-CSF-producing T cells. Conversely, mice with IL-6 deficiency in the dendritic cells showed not only the previously described increase in the proportion of regulatory T cells and decrease in the proportion of T_H17 cells, but also reduction in the production of GM-CSF and IFNγ in the secondary lymphoid organs. In summary, IL-6 functions during EAE depend on both the source and localization of immune response: the microglial IL-6 exerts both pathogenic and protective functions specifically in the CNS, whereas the dendritic cell-derived IL-6, in addition to being critically involved in the balance of regulatory T cells and T_H17 cells, may stimulate production of cytokines associated with pathogenic functions of T cells.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 5","pages":"904 - 911"},"PeriodicalIF":2.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191014","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":"Molecular Changes in Immunological Characteristics of Bone Marrow Multipotent Mesenchymal Stromal Cells in Lymphoid Neoplasia","authors":"Nataliya A. Petinati,&nbsp;Aleksandra V. Sadovskaya,&nbsp;Natalia V. Sats,&nbsp;Nikolai M. Kapranov,&nbsp;Yulia O. Davydova,&nbsp;Ekaterina A. Fastova,&nbsp;Aminat U. Magomedova,&nbsp;Anastasia N. Vasilyeva,&nbsp;Olga A. Aleshina,&nbsp;Georgiy P. Arapidi,&nbsp;Viktoria O. Shender,&nbsp;Igor P. Smirnov,&nbsp;Olga V. Pobeguts,&nbsp;Maria A. Lagarkova,&nbsp;Nina I. Drize,&nbsp;Elena N. Parovichnikova","doi":"10.1134/S0006297924050092","DOIUrl":"10.1134/S0006297924050092","url":null,"abstract":"<p>Immune system and bone marrow stromal cells play an important role in maintaining normal hematopoiesis. Lymphoid neoplasia disturbs not only development of immune cells, but other immune response mechanisms as well. Multipotent mesenchymal stromal cells (MSCs) of the bone marrow are involved in immune response regulation through both intercellular interactions and secretion of various cytokines. In hematological malignancies, the bone marrow stromal microenvironment, including MSCs, is altered. Aim of this study was to describe the differences of MSCs’ immunological function in the patients with acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). In ALL, malignant cells arise from the early precursor cells localized in bone marrow, while in DLBCL they arise from more differentiated B-cells. In this study, only the DLBCL patients without bone marrow involvement were included. Growth parameters, surface marker expression, genes of interest expression, and secretion pattern of bone marrow MSCs from the patients with ALL and DLBCL at the onset of the disease and in remission were studied. MSCs from the healthy donors of corresponding ages were used as controls. It has been shown that concentration of MSCs in the bone marrow of the patients with ALL is reduced at the onset of the disease and is restored upon reaching remission; in the patients with DLBCL this parameter does not change. Proliferative capacity of MSCs did not change in the patients with ALL; however, the cells of the DLBCL patients both at the onset and in remission proliferated significantly faster than those from the donors. Expression of the membrane surface markers and expression of the genes important for differentiation, immunological status maintenance, and cytokine secretion differed significantly in the MSCs of the patients from those of the healthy donors and depended on nosology of the disease. Secretomes of the MSCs varied greatly; a number of proteins associated with immune response regulation, differentiation, and maintenance of hematopoietic stem cells were depleted in the secretomes of the cells from the patients. Lymphoid neoplasia leads to dramatic changes in the functional immunological status of MSCs.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 5","pages":"883 - 903"},"PeriodicalIF":2.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191289","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":"In vitro and in vivo Evaluation of Antifibrotic Properties of Verteporfin in a Composition of a Collagen Scaffold","authors":"Olga S. Rogovaya,&nbsp;Danila S. Abolin,&nbsp;Olga L. Cherkashina,&nbsp;Artem D. Smyslov,&nbsp;Ekaterina A. Vorotelyak,&nbsp;Ekaterina P. Kalabusheva","doi":"10.1134/S0006297924050146","DOIUrl":"10.1134/S0006297924050146","url":null,"abstract":"<p>Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel application as a wound dressing and fibroblast attractant with verteporfin as an antifibrotic agent was examined <i>in vivo</i> and <i>in vitro</i>. <i>In vitro</i> effects of verteporfin on viability and myofibroblast markers expression were evaluated using fibroblasts isolated from human scar tissue. <i>In vivo</i> the collagen gel and verteporfin (individually and in combination) were applied into the wound to investigate scarring during skin regeneration: deviations in skin layer thickness, collagen synthesis, and extracellular matrix fibers were characterized. The results indicate that verteporfin reduces fibrotic phenotype by suppressing expression of the contractile protein Sm22α without inducing cell death. However, administration of verteporfin in combination with the collagen gel disrupts its ability to direct wound healing in a scarless manner, which may be related to incompatibility of the mechanisms by which collagen and verteporfin control regeneration.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 5","pages":"942 - 957"},"PeriodicalIF":2.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141191331","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}