Biochemistry (Moscow)最新文献

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STAT3/Snail Signaling and Progression of Hypoxia Tolerance in Breast Cancer Cells STAT3/蜗牛信号传导与乳腺癌细胞缺氧耐受的进展
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S0006297925601315
Olga E. Andreeva, Danila V. Sorokin, Alexander M. Scherbakov, Svetlana V. Vinokurova, Pavel B. Kopnin, Nadezhda V. Elkina, Maria D. Fedorova, Alexey N. Katargin, Danila S. Elkin, Mikhail A. Krasil’nikov
{"title":"STAT3/Snail Signaling and Progression of Hypoxia Tolerance in Breast Cancer Cells","authors":"Olga E. Andreeva,&nbsp;Danila V. Sorokin,&nbsp;Alexander M. Scherbakov,&nbsp;Svetlana V. Vinokurova,&nbsp;Pavel B. Kopnin,&nbsp;Nadezhda V. Elkina,&nbsp;Maria D. Fedorova,&nbsp;Alexey N. Katargin,&nbsp;Danila S. Elkin,&nbsp;Mikhail A. Krasil’nikov","doi":"10.1134/S0006297925601315","DOIUrl":"10.1134/S0006297925601315","url":null,"abstract":"<p>One of the hallmarks of malignant neoplasms is their ability to sustain growth under hypoxic conditions resulting from insufficient oxygenation of tumor tissues. Prolonged hypoxia is associated with the gradual adaptation of tumor cells to low oxygen levels, leading to the enhanced survival, increased metastatic potential, and development of resistance to anticancer therapies. The aim of this study was to investigate the mechanisms underlying adaptation of breast cancer cell to prolonged hypoxia and maintenance of the hypoxia-tolerant phenotype. Using long-term culturing under low oxygen conditions (1% O<sub>2</sub>), we established hypoxia-adapted sublines of luminal (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells, characterized by a stable growth in a hypoxic environment. The acquisition of hypoxia tolerance was accompanied by the activation of the HIF-1α-dependent transcription factor STAT3 and persistent overexpression of Snail, a key downstream effector of STAT3. The maintenance and stabilization of hypoxia-tolerant phenotype are mediated by miR-181a-2, which targets the STAT3/Snail signaling axis in the resistant cells. Analysis of DNA methylation status revealed no significant changes in the expression or activity of DNA methyltransferases (DNMTs) in the hypoxia-adapted cells. However, pharmacological inhibition of DNMTs using decitabine, as well as DNMT knockdown, increased cell sensitivity to hypoxia and partially reversed the hypoxia-resistant phenotype, which was accompanied by the activation of pro-apoptotic p53 signaling. In conclusion, our findings suggest that the acquired hypoxia tolerance in breast cancer cells is mediated, at least in part, by the activation of the miR-181a-2/STAT3/Snail signaling pathway. Furthermore, the use of demethylating agents may represent a promising therapeutic approach to targeting hypoxia-tolerant cancer cell populations.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"1064 - 1076"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918290","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}
引用次数: 0
Role of Autophagy in the Mechanisms of Chemoresistance of Tumor Cells Induced by the Use of Anthracycline Antibiotics 自噬在蒽环类抗生素诱导肿瘤细胞化疗耐药机制中的作用
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S0006297925601005
Nadezhda A. Persiyantseva, Ekaterina S. Ivanova, Maria A. Zamkova
{"title":"Role of Autophagy in the Mechanisms of Chemoresistance of Tumor Cells Induced by the Use of Anthracycline Antibiotics","authors":"Nadezhda A. Persiyantseva,&nbsp;Ekaterina S. Ivanova,&nbsp;Maria A. Zamkova","doi":"10.1134/S0006297925601005","DOIUrl":"10.1134/S0006297925601005","url":null,"abstract":"<p>Autophagy not only helps eliminate damaged, mutated, or genomically unstable cells, but also increases the chances of tumor cells overcoming the consequences of damage caused by chemotherapy. Autophagy induced by anthracyclines is cytoprotective in most tumor cell lines. Pharmacological or genetic blocking of autophagy in this case sensitizes tumor cells to therapy. Activation of cytoprotective autophagy can lead to chemoresistance, and with excessive enhancement, it can lead to energy depletion and trigger autophagic death. In some cases, cytotoxic autophagy develops under the action of anthracyclines, and its blocking increases cell survival. Activation of cytotoxic autophagy, on the contrary, triggers the process of “self-eating.” Modulation of autophagy in response to chemotherapeutic agents can be a double-edged sword for tumor cells, leading to both death and survival.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"985 - 999"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918293","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}
引用次数: 0
DNA Supercoiling Alleviates Cold-Sensitivity of Promoter Melting by Extremophilic Deinococcus-Thermus RNA Polymerases DNA超卷曲减轻嗜极性热球菌RNA聚合酶融化启动子的冷敏感性
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S0006297924603411
Andrey V. Kulbachinskiy
{"title":"DNA Supercoiling Alleviates Cold-Sensitivity of Promoter Melting by Extremophilic Deinococcus-Thermus RNA Polymerases","authors":"Andrey V. Kulbachinskiy","doi":"10.1134/S0006297924603411","DOIUrl":"10.1134/S0006297924603411","url":null,"abstract":"<p>Melting of promoter DNA around the transcription start site (TSS) is a critical step of transcription required for initiation of RNA synthesis. In bacteria, promoter melting is mediated by the holoenzyme of RNA polymerase (RNAP) consisting of the catalytic core enzyme and the promoter recognition subunit, σ factor. Previously, we showed that RNAPs from thermophilic <i>Thermus aquaticus</i> and mesophilic <i>Deinococcus radiodurans</i> are unable to open promoters at ambient temperatures and require heating for DNA melting. These properties depend on their σ factors and are recapitulated in the hybrid holoenzymes including these σ factors and the core enzyme of <i>Escherichia coli</i>. Here, we show that DNA supercoiling alleviates the observed cold-sensitivity of promoter opening by the <i>Deinococcus-Thermus</i> RNAPs and by the hybrid holoenzymes and allows melting of the transcription start site at the same temperatures as in the case of <i>E. coli</i> RNAP. Supercoiling also suppresses salt sensitivity of the promoter complexes formed by these RNAPs. The results demonstrate that the RNAPs from <i>Deinococcus-Thermus</i> species are sensitive to DNA supercoiling and suggest that they can be rapidly switched-off or activated by the supercoiling state of the host genomes.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"1088 - 1098"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918294","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}
引用次数: 0
Leptin Potentiates the Inflammatory Effect of Interleukin-1 Beta on Synoviocytes. Potential Preventive Role of DHA and EPA in Osteoarthritis Cell Model 瘦素增强白细胞介素-1 β对滑膜细胞的炎症作用。DHA和EPA在骨关节炎细胞模型中的潜在预防作用
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S0006297925600863
Atitaya Wayupat, Prachya Kongtawelert, Peraphan Pothacharoen, Thuzar Hla Shwe, Thanyaluck Phitak
{"title":"Leptin Potentiates the Inflammatory Effect of Interleukin-1 Beta on Synoviocytes. Potential Preventive Role of DHA and EPA in Osteoarthritis Cell Model","authors":"Atitaya Wayupat,&nbsp;Prachya Kongtawelert,&nbsp;Peraphan Pothacharoen,&nbsp;Thuzar Hla Shwe,&nbsp;Thanyaluck Phitak","doi":"10.1134/S0006297925600863","DOIUrl":"10.1134/S0006297925600863","url":null,"abstract":"<p>A growing body of evidence indicates a high incidence of osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints in obese patients. The levels of leptin in the synovial fluid of obese patients with OA are elevated compared to healthy people, suggesting that leptin may be a key factor of OA in obese individuals. Synovitis can occur at all stages of OA development, causing diseases progression. We examined the effect of leptin on the inflammation in synoviocytes and demonstrated that leptin at its physiological concentration (1 ng/mL) promoted expressions of interleukin-6 (IL-6) and IL-8 in SW982 cells by activating p65, p38, JNK, STAT1, and STAT3. Moreover, the lowest pathological concentration of leptin potentiated the effect of IL-1β (main cytokine involved in OA pathogenesis) via activation of p65 and STAT3, leading to a significant upregulation of the IL-6 and IL-8 production. Pretreatment with omega-3 polyunsaturated fatty acids DHA and EPA suppressed the action of leptin and inhibited the IL-1β-mediated stimulation of synovitis by lowering the extent of p65 and STAT3 activation. According to our research, leptin may play a significant role in the development of OA in the joints of obese patients by promoting inflammation of synoviocytes through the activation of p65 and STAT3, while DHA and EPA, which inhibit activation of p65 and STAT3, can suppress the inflammation. Therefore, compounds that downregulate the activity of p65 and STAT3 may be the candidates for synovitis prevention and management in obese patients.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"1153 - 1167"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918361","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}
引用次数: 0
Autoregulation of YB-1 Synthesis in Cells 细胞中YB-1合成的自动调节
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S0006297925601571
Valeria S. Kachan, Irina A. Eliseeva, Andrey I. Buyan, Dmitry N. Lyabin
{"title":"Autoregulation of YB-1 Synthesis in Cells","authors":"Valeria S. Kachan,&nbsp;Irina A. Eliseeva,&nbsp;Andrey I. Buyan,&nbsp;Dmitry N. Lyabin","doi":"10.1134/S0006297925601571","DOIUrl":"10.1134/S0006297925601571","url":null,"abstract":"<p>The Y-box binding protein 1 (YB-1) plays a crucial role in regulating essential cell functions, including transcription, translation, and DNA repair, through its interactions with nucleic acids and multiple protein partners. The multifunctionality of YB-1 makes the control of its levels critical for cellular homeostasis and adaptation to stress. The synthesis of YB-1 is regulated by gene transcription, protein stability (mediated by long non-coding RNAs), and translation of its mRNA. Autoregulation of <i>YB-1</i> mRNA translation remains the topic of ongoing debate. Some earlier <i>in vitro</i> studies suggested a role of the 5′ untranslated region (UTR) in inhibiting protein synthesis, while others demonstrated the importance of YB-1 binding to the 3′ UTR for reducing translation. This disagreement has been further complicated by the absence of evidence for these mechanisms in living cells. Here, we provide the first direct evidence that YB-1 represses its synthesis in cultured human cells. Using metabolic protein labeling and immunoprecipitation, we confirmed the effect of YB-1 on the translation of its mRNA. Experiments with reporter constructs showed that both UTRs of the <i>YB-1</i> mRNA are involved in autoregulation, thus resolving the contradiction in the literature. These results highlight a sophisticated mechanism for controlling YB-1 levels, which requires both 5′ and 3′ UTRs of the <i>YB-1</i> mRNA, and confirm their role in fine-tuning YB-1 synthesis.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"1077 - 1087"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S0006297925601571.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918485","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}
引用次数: 0
Immortalization of Cultured Cells in Regenerative Biomedicine: Approaches, Opportunities, and Limitations 再生生物医学中培养细胞的永生化:方法、机会和限制
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S0006297925601698
Alexandra L. Primak, Liliya N. Shkarina, Maria E. Illarionova, Ivan V. Plyushchiy, Alina V. Zakharova, Vsevolod A. Tkachuk, Maksim N. Karagyaur
{"title":"Immortalization of Cultured Cells in Regenerative Biomedicine: Approaches, Opportunities, and Limitations","authors":"Alexandra L. Primak,&nbsp;Liliya N. Shkarina,&nbsp;Maria E. Illarionova,&nbsp;Ivan V. Plyushchiy,&nbsp;Alina V. Zakharova,&nbsp;Vsevolod A. Tkachuk,&nbsp;Maksim N. Karagyaur","doi":"10.1134/S0006297925601698","DOIUrl":"10.1134/S0006297925601698","url":null,"abstract":"<p>Primary cell cultures are one of the main research objects and promising tools in regenerative biomedicine. However, their application is significantly limited by the short lifespan and rapid aging. Existing approaches to prolong the “youth” of cultured cells inevitably alter their properties, which raises questions about their applicability in regenerative biomedicine. Our review examines the main mechanisms of aging of cultured cells, existing methods used to overcome it, and safety issues associated with the produced cultures. We analyzed the data on cell immortalization and its connection with tumor transformation. Among the methods for prolonging the proliferative activity of cells are spontaneous immortalization and immortalization induced by overexpression of the catalytic subunit of telomerase (TERT), viral oncogenes (T antigens of the polyomavirus SV40, proteins E6/E7 of human papillomavirus type 16, and adenoviral proteins E1A and E1B of adenoviruses), and cellular transcription factors, such as proto-oncogenes (c-MYC, BMI1). The accumulated data suggest that increasing the expression of the gene encoding TERT is one of the relatively safe approaches to prolonging the proliferative activity of a cell line, which does not lead to the tumor transformation of cell line. Based on the analyzed data, an attempt was made to identify the “boundary” between the permissible prolongation of cell culture life and its tumor transformation.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"1000 - 1017"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918286","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}
引用次数: 0
Cells Dying via the AP-3 Complex-Dependent Regulated Death Pathway Support the Surviving Cells under Amino Acid Deficiency Conditions 在氨基酸缺乏条件下,通过AP-3复合物依赖的调节死亡途径死亡的细胞支持存活细胞
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S0006297924604386
Svyatoslav S. Sokolov, Ekaterina A. Smirnova, Natalia A. Kireeva, Alexandr L. Ksenofontov, Vadim N. Tashlitsky, Fedor F. Severin
{"title":"Cells Dying via the AP-3 Complex-Dependent Regulated Death Pathway Support the Surviving Cells under Amino Acid Deficiency Conditions","authors":"Svyatoslav S. Sokolov,&nbsp;Ekaterina A. Smirnova,&nbsp;Natalia A. Kireeva,&nbsp;Alexandr L. Ksenofontov,&nbsp;Vadim N. Tashlitsky,&nbsp;Fedor F. Severin","doi":"10.1134/S0006297924604386","DOIUrl":"10.1134/S0006297924604386","url":null,"abstract":"<p>Starvation can initiate a programmed death in unicellular organisms. It is believed that cells committing suicide via this mechanism support surviving cells with their nutrients. It was recently discovered that heating <i>Saccharomyces cerevisiae</i> yeast cells to 51°C kills the cells though a special pathway that starts with the decomposition of the lysosomal membrane followed by the loss of the plasma membrane integrity a few hours later. Since lysosomes contain hydrolases of nitrogen-containing biopolymers, this programmed death pathway could help the survivors during nitrogen starvation. The loss of the plasma membrane integrity significantly alters the water/salt composition of the cytosol, which in turn can lead to the aggregation of nitrogen-containing macromolecules (proteins and nucleic acids). The pores of the yeast cell wall are too small to let such aggregates through. We showed that cells killed by heating at 52°C stimulated the growth of living cells under conditions of amino acid deficiency, while mutant cells deficient by the AP-3 complex, which were unable to destroy the lysosomal membrane, lacked this ability. Yeast cells killed by boiling also did not support the growth of surviving cells under amino acid deficiency conditions. Unexpectedly, the medium from the cells killed by boiling contained, on average, higher amounts of each amino acid than the medium from the cells killed by heating to 52°C. At the same time, according spectrophotometry and mass spectrometry analysis, the medium obtained by cell heating to 52°C contained higher amount of substances absorbing in a short-wavelength range. We speculate that the compounds supporting the growth of surviving cells under the nitrogen deficiency conditions are generated by hydrolysis of nucleic acids.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"1027 - 1036"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918291","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}
引用次数: 0
Nephroprotective Effects of Silymarin: A Systematic Review and Meta-Analysis 水飞蓟素的肾保护作用:系统综述和荟萃分析
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S0006297925600565
Negin Frounchi, Fariba Mahmoodpoor, Seyed Sina Zakavi, Kamala Eyvazova, Samira Yagubova, Mohammadreza Ardalan, Elham Ahmadian, Ilgiz Gareev, Ozal Beylerli, Sergey Roumiantsev
{"title":"Nephroprotective Effects of Silymarin: A Systematic Review and Meta-Analysis","authors":"Negin Frounchi,&nbsp;Fariba Mahmoodpoor,&nbsp;Seyed Sina Zakavi,&nbsp;Kamala Eyvazova,&nbsp;Samira Yagubova,&nbsp;Mohammadreza Ardalan,&nbsp;Elham Ahmadian,&nbsp;Ilgiz Gareev,&nbsp;Ozal Beylerli,&nbsp;Sergey Roumiantsev","doi":"10.1134/S0006297925600565","DOIUrl":"10.1134/S0006297925600565","url":null,"abstract":"<p>Kidney dysfunction could impose a heavy burden on patients and society by progressing to chronic kidney disease (CKD) and end-stage renal disease, which emphasizes the importance of a search for novel agents capable of slowing down kidney disease progression or ameliorating disease outcome in patients. One of the candidates for nephroprotective agents is silymarin, a flavonoid with the anti-oxidant and anti-inflammatory properties from the milk thistle plant. We performed a systematic review of articles from Scopus, PubMed, and Web of Science that compared the nephroprotective effects of silymarin in treated and control groups (studies conducted in animals or cells were excluded). We also performed a meta-analysis of changes in the serum creatinine level and ran a subgroup analysis on the silymarin dosage, treatment duration, patients’ age, and type of kidney disease. Quality assessment of the articles was performed with the ROB2 tool. We identified 10 relevant clinical trials; meta-analysis was performed on 7 studies and showed a significant effect of silymarin on the reduction of serum creatinine levels (Hedges’ g, −1.23; 95% CI, −2.02 to −0.43; <i>p</i> = 0.0024; <i>I</i><sup>2</sup> = 93.40%). Analysis of the subgroups revealed a significant creatinine reduction in patients with the drug-induced acute kidney injury (AKI) (<i>p</i> = 0.003), but not with CKD (<i>p</i> = 0.3065). The daily silymarin dose of 280 mg was ineffective (<i>p</i> = 0.2375) in reducing the creatinine levels. Despite the limitations, such as a small number of analyzed articles and their heterogeneity, we found that silymarin administration in the drug-induced AKI could provide a nephroprotective effect by lowering the serum levels of creatinine.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"1140 - 1152"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918450","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}
引用次数: 0
AP Site Does Not Introduce Significant Distortions into the DNA Structure in the Nucleosomes in vitro AP位点不会在体外核小体中引入显著的DNA结构扭曲
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S000629792560053X
Mikhail M. Kutuzov, Ekaterina A. Belousova, Valeria M. Dreiman, Olga I. Lavrik
{"title":"AP Site Does Not Introduce Significant Distortions into the DNA Structure in the Nucleosomes in vitro","authors":"Mikhail M. Kutuzov,&nbsp;Ekaterina A. Belousova,&nbsp;Valeria M. Dreiman,&nbsp;Olga I. Lavrik","doi":"10.1134/S000629792560053X","DOIUrl":"10.1134/S000629792560053X","url":null,"abstract":"<p>DNA damage results in distortion of the B-form structure of the DNA double helix. Recognition of such distortion by DNA repair proteins is an important stage in the process initiation. Nucleosome structure imposes restrictions on mobility and plasticity of DNA geometry. Under interaction of repair proteins with nucleosomal DNA, the main issue is the implementation of the DNA structure that characterizes the damage itself in a specific context. In addition, the DNA duplex in a nucleosome has a regular profile of contacts with histones corresponding to the pitch of DNA helix. Changes in the DNA structure could be assessed through the changes in this profile. This profile correlates with availability of the corresponding nucleotides for interaction with the DNA-binding proteins. In our work, it has been shown using footprinting assay that the presence of an AP site within the second or third turn from the 5′-end of the nucleosomal DNA does not significantly affect the profile of DNA contacts with histones.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"1116 - 1125"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918451","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}
引用次数: 0
Expression of Preselected Genes in Mononuclear Blood Cells Is Associated with the Extent of Coronary Artery Stenosis 预选择基因在单核血细胞中的表达与冠状动脉狭窄程度相关
IF 2.2 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-08-29 DOI: 10.1134/S0006297925600309
Alexander D. Dergunov, Elena V. Nosova, Alexandra V. Rozhkova, Veronika B. Baserova, Mikhail A. Popov, Margarita A. Vinogradina, Svetlana A. Limborska, Liudmila V. Dergunova
{"title":"Expression of Preselected Genes in Mononuclear Blood Cells Is Associated with the Extent of Coronary Artery Stenosis","authors":"Alexander D. Dergunov,&nbsp;Elena V. Nosova,&nbsp;Alexandra V. Rozhkova,&nbsp;Veronika B. Baserova,&nbsp;Mikhail A. Popov,&nbsp;Margarita A. Vinogradina,&nbsp;Svetlana A. Limborska,&nbsp;Liudmila V. Dergunova","doi":"10.1134/S0006297925600309","DOIUrl":"10.1134/S0006297925600309","url":null,"abstract":"<p>The goal of this study was examination of the association between the expression levels of the genes involved in high-density lipoprotein metabolism and atherogenesis and underlying metabolic pathways and the number of stenotic coronary arteries. Expression of 65 preselected genes in the peripheral blood mononuclear cells of the control patients (<i>n</i> = 63) and patients with coronary artery disease (CAD) with one or two (low stenosis group, <i>n</i> = 35) or three or four (high stenosis group, <i>n</i> = 41) stenotic vessels, confirmed by coronary angiography, was measured with real-time PCR. Functional enrichment analysis was applied for annotation of differentially expressed genes. Protein products of the differentially expressed genes (DEGs) in the CAD patients compared to the controls were associated with metabolic pathways related to assembly, remodeling, and clearance of plasma lipoproteins, as well as with signaling and regulation of expression of the genes involved in cholesterol transport and efflux. However, comparison of the gene expression profiles and associated metabolic pathways between the groups with high versus low stenosis revealed specific differences between these groups. Expression of the <i>CETP</i>, <i>PLTP</i>, <i>CD36</i>, <i>IL18</i>, <i>ITGB3</i>, <i>S100A8</i>, <i>S100A12</i>, and <i>VEGFA</i> genes increased with the increase of the number of stenotic vessels, which suggests involvement of these genes in stenosis expansion via lipoprotein metabolism, inflammation, angiogenesis, and innate immunity. The set of genes <i>ITGB3</i>, <i>VEGFA</i>, and <i>CETP</i> was selected as a new gene expression signature of expansion of the coronary artery stenosis, which was validated with the GSE12288 dataset from the Gene Expression Omnibus database, demonstrating an average odds ratio (OR) of 7.49 (95% CI, 2.21 to 25.43). Averaged expression levels of the <i>ITGB3</i>, <i>VEGFA</i>, and <i>CETP</i> genes could be used for diagnosis, prognosis evaluation, and treatment of coronary stenosis with strong predictive power.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 8","pages":"1037 - 1048"},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918289","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}
引用次数: 0
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