Molecular Biology最新文献

New Epigenetic Markers of Age-Dependent Changes in the Cardiovascular System 心血管系统随年龄变化的新表观遗传标记

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-09-11 DOI: 10.1134/s002689332470064x

L. M. Ermakova, E. A. Davydova, E. V. Kondakova, K. V. Kuchin, M. V. Vedunova

{"title":"New Epigenetic Markers of Age-Dependent Changes in the Cardiovascular System","authors":"L. M. Ermakova, E. A. Davydova, E. V. Kondakova, K. V. Kuchin, M. V. Vedunova","doi":"10.1134/s002689332470064x","DOIUrl":"https://doi.org/10.1134/s002689332470064x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Cardiovascular diseases remain a predominant global cause of mortality, with a noteworthy rise in the risk of morbidity with advancing age. Besides, it accompanied by a phenomenon of disease rejuvenation in the circulatory system. Currently, epigenetic modifications play a key role in the genesis of cardiovascular diseases (CVD), influencing the complex interaction between genotype and phenotype variability. Consequently, delving into the realm of epigenetic markers offers a promising avenue to unravel the molecular underpinnings of cardiovascular disease pathogenesis. This study endeavors to pinpoint epigenetic markers intricately linked with age-related transformations in the cardiovascular system. The study revealed a robust correlation with age for two cardiological parameters: R wave tension in the augmented left arm lead (RaVL) and carotid-femoral pulse wave velocity (cfPWV). Moreover, these parameters exhibited a strong correlation with the DNA methylation level of 21 CpG-sites (CpGs) examined through the Illumina EPIC array. Notably, the majority of these identified CpG-sites are affiliated with genes involved in the development of pathologies of the cardiovascular system.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201114","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

Silencing of the S-Phase Kinase-Associated Protein 2 Gene (SKP2) Inhibits Proliferation and Migration of Hepatocellular Carcinoma Cells 抑制 S 期激酶相关蛋白 2 基因 (SKP2) 可抑制肝细胞癌细胞的增殖和迁移

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-09-11 DOI: 10.1134/s0026893324700651

Y. Y. Zhao, Z. X. Gao, S. D. Wei, W. Song

{"title":"Silencing of the S-Phase Kinase-Associated Protein 2 Gene (SKP2) Inhibits Proliferation and Migration of Hepatocellular Carcinoma Cells","authors":"Y. Y. Zhao, Z. X. Gao, S. D. Wei, W. Song","doi":"10.1134/s0026893324700651","DOIUrl":"https://doi.org/10.1134/s0026893324700651","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><i>SKP2</i> gene is an independent prognostic factor in some diseases and a potential oncogene. The molecular mechanism underlying the occurrence and development of hepatoma, and the involvement of the <i>SKP2</i> in this process remain unclear. Here, in order to study the effect of SKP2 on proliferation, apoptosis and migration of hepatoma cells, we utilized lentivirus-mediated RNA interference technology using short hairpin RNAs (shRNAs) specific for <i>SKP2</i>. It was demonstrated that <i>SKP2</i> expression was significantly upregulated in 809 hepatocarcinoma tissues compared to 379 normal liver tissues. The survival time of patients with high levels of SKP2 mRNA was shorter than those with low levels, and <i>SKP2</i> expression was maximal in stage III hepatocellular carcinoma tissues. The effects of <i>SKP2</i> silencing on proliferation, apoptosis, cell cycle, migration, and the expression of apoptosis proteins in Huh7 and HepG2 cells were evaluated by MTT assay, flow cytometry, colony formation assay, Transwell, and Western blot analysis. <i>SKP2</i> expression was significantly reduced in stably transfected Huh7 and HepG2 cells, with knockout efficiencies of 95.7 and 85.8%, respectively. The viability, proliferation, and migration of transfected cancer cells were reduced. In these cells, the apoptosis rate was increased, and the cell cycle was arrested in the G2/M phase. The expression of the apoptosis-associated BCL-2/BAX proteins was decreased, while p53 was upregulated. Thus, we have shown that inhibiting the expression of <i>SKP2</i> can significantly impede cancer cell proliferation and migration, halt the cell cycle, and induce apoptosis.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201113","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

Triosephosphate Isomerase Inhibition by Resveratrol: A New Mechanism of Anti-Glycolysis in Breast Cancer 白藜芦醇对磷酸三糖异构酶的抑制：乳腺癌抗糖酵解的新机制

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-09-11 DOI: 10.1134/s0026893324700663

G. Tuna, O. Akgün, F. Arı

{"title":"Triosephosphate Isomerase Inhibition by Resveratrol: A New Mechanism of Anti-Glycolysis in Breast Cancer","authors":"G. Tuna, O. Akgün, F. Arı","doi":"10.1134/s0026893324700663","DOIUrl":"https://doi.org/10.1134/s0026893324700663","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Breast cancer cells undergo a process of reprogramming their metabolism for rapid growth and proliferation. One of the most common metabolic changes is aerobic glycolysis (Warburg effect), which leads to increased lactate generation and glucose uptake capacity. Triosephosphate isomerase (TPI) is a key enzyme in glycolysis. The effect of Resveratrol (RES), a natural plant compound with known anti-cancer properties, on the TPI enzyme is unknown. The purpose of this study is to examine how RES relates to TPI in breast cancer. TPI levels were examined by ELISA and western-blotting methods in MCF-7 and MDA-MB-231 cells. The changes in lactate dehydrogenase (LDH) activity, methylglyoxal (MGO) formation, nitric oxide synthase (eNOS and iNOS) levels, and MAPK signaling pathway were investigated by colorimetric assays and western-blotting. It was shown for the first time that RES induced a significant decrease in TPI in a dose-dependent manner, with a concomitant increase in levels of MGO, a toxic intermediate. Furthermore, RES treatment decreased LDH activity, and the expression of MAPK, ERK1/2, and JNK, while increasing the expression of eNOS and iNOS levels. The results sign a potential cytotoxic effect of RES due to increased MGO levels resulting from TPI inhibition. The effect of RES on TPI function and glycolysis may be related to NOS induction and the MAPK pathway. These findings are the first data showing the effect of RES treatment on TPI, suggesting that TPI may be a target for energy metabolism in breast cancer.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200847","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

Molecular Ion Channel Blockers of Influenza A and SARS-CoV-2 Viruses 甲型流感和 SARS-CoV-2 病毒的分子离子通道阻断剂

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-08-07 DOI: 10.1134/s0026893324700353

Yu. N. Vorobjev

引用次数: 0

Methods to Increase the Efficiency of Knock-in of a Construct Encoding the HIV-1 Fusion Inhibitor, MT-C34 Peptide, into the CXCR4 Locus in the CEM/R5 T Cell Line 提高将编码 HIV-1 融合抑制剂 MT-C34 肽的构建基因敲入 CEM/R5 T 细胞系 CXCR4 基因座的效率的方法

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-08-07 DOI: 10.1134/s0026893324700249

D. S. Golubev, D. S. Komkov, M. V. Shepelev, D. V. Mazurov, N. A. Kruglova

{"title":"Methods to Increase the Efficiency of Knock-in of a Construct Encoding the HIV-1 Fusion Inhibitor, MT-C34 Peptide, into the CXCR4 Locus in the CEM/R5 T Cell Line","authors":"D. S. Golubev, D. S. Komkov, M. V. Shepelev, D. V. Mazurov, N. A. Kruglova","doi":"10.1134/s0026893324700249","DOIUrl":"https://doi.org/10.1134/s0026893324700249","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The low knock-in efficiency, especially in primary human cells, limits the use of the genome editing technology for therapeutic purposes, rendering it important to develop approaches for increasing the knock-in levels. In this work, the efficiencies of several approaches were studied using a model of knock-in of a construct coding for the peptide HIV fusion inhibitor MT-C34 into the human <i>CXCR4</i> locus in the CEM/R5 T cell line. First, donor DNA modification was evaluated as a means to improve the efficiency of plasmid transport into the nucleus. The donor plasmid was modified to include the simian virus 40 (SV40) DNA nuclear targeting sequence (DTS) or binding sites for the transcription factor NF-κB, whose effects on the knock-in levels have not been described. The modification was ineffective in the model of MT-C34 knock-in into the <i>CXCR4</i> locus. A second approach consisted in modification of Cas9 nuclease by introducing two additional nuclear localization signals (NLSs) and increased the knock-in level by 30%. Finally, blocking DNA repair via the nonhomologous end joining (NHEJ) pathway with DNA-dependent protein kinase inhibitors caused a 1.8-fold increase in knock-in. A combination of the last two approaches caused an additive effect. Thus, increasing the number of NLSs in the Cas9 protein and inhibiting DNA repair via the NHEJ pathway significantly increased the level of knock-in of the HIV-1 fusion inhibitory peptide into the clinically relevant locus <i>CXCR4.</i> The finding can be used to develop effective gene therapy approaches for treating HIV infection.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141969132","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

The Drosophila Zinc Finger Proteins Aef1 and CG10543 Are Co-Localized with SAGA, SWI/SNF, and ORC Complexes on Gene Promoters and Involved in Transcription Regulation 果蝇锌指蛋白 Aef1 和 CG10543 与基因启动子上的 SAGA、SWI/SNF 和 ORC 复合物共定位并参与转录调控

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-08-07 DOI: 10.1134/s0026893324700286

J. V. Nikolenko, M. M. Kurshakova, D. V. Kopytova, Y. A. Vdovina, N. E. Vorobyova, A. N. Krasnov

引用次数: 0

Metabolic Profile of Gut Microbiota and Levels of Trefoil Factors in Adults with Different Metabolic Phenotypes of Obesity 不同代谢表型肥胖成人的肠道微生物群代谢谱和三叶草因子水平

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-08-07 DOI: 10.1134/s0026893324700316

I. M. Kolesnikova, L. A. Ganenko, I. Yu. Vasilyev, T. V. Grigoryeva, N. I. Volkova, S. A. Roumiantsev, A. V. Shestopalov

{"title":"Metabolic Profile of Gut Microbiota and Levels of Trefoil Factors in Adults with Different Metabolic Phenotypes of Obesity","authors":"I. M. Kolesnikova, L. A. Ganenko, I. Yu. Vasilyev, T. V. Grigoryeva, N. I. Volkova, S. A. Roumiantsev, A. V. Shestopalov","doi":"10.1134/s0026893324700316","DOIUrl":"https://doi.org/10.1134/s0026893324700316","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Obesity is associated with changes in the gut microbiota, as well as with increased permeability of the intestinal wall. In 130 non-obese volunteers, 57 patients with metabolically healthy obesity (MHO), and 76 patients with metabolically unhealthy obesity (MUHO), bacterial DNA was isolated from stool samples, and the 16S rRNA gene was sequenced. The metabolic profile of the microbiota predicted by PICRUSt2 (https://huttenhower.sph.harvard.edu/picrust/) was more altered in patients with MUHO than MHO. Obesity, especially MUHO, was accompanied by an increase in the ability of the gut microbiota to degrade energy substrates, produce energy through oxidative phosphorylation, synthesize water-soluble vitamins (B1, B6, B7), nucleotides, heme, aromatic amino acids, and protective structural components of cells. Such changes may be a consequence of the microbiota adaptation to the MUHO-specific conditions. Thus, a vicious circle is formed, when MUHO promotes the depletion of the gut microbiome, and further degeneration of the latter contributes to the pathogenesis of metabolic disorders. The concentration of the trefoil factor family (TFF) in the serum of the participants was also determined. In MHO and MUHO patients, the TFF2 and TFF3 levels were increased, but we did not find significant associations of these changes with the metabolic profile of the gut microbiota.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941178","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

How to Shift the Equilibrium of DNA Break Repair in Favor of Homologous Recombination 如何使 DNA 断裂修复的平衡有利于同源重组

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-08-07 DOI: 10.1134/s0026893324700201

O. A. Averina, S. A. Kuznetsova, O. A. Permyakov, P. V. Sergiev

{"title":"How to Shift the Equilibrium of DNA Break Repair in Favor of Homologous Recombination","authors":"O. A. Averina, S. A. Kuznetsova, O. A. Permyakov, P. V. Sergiev","doi":"10.1134/s0026893324700201","DOIUrl":"https://doi.org/10.1134/s0026893324700201","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The CRISPR/Cas technology of targeted genome editing made it possible to carry out genetic engineering manipulations with eukaryotic genomes with a high efficiency. Targeted induction of site-specific DNA breaks is one of the key stages of the technology. The cell repairs the breaks via one of the two pathways, nonhomologous end joining (NHEJ) and homology-driven repair (HDR). The choice of the DNA repair pathway is determined by the architecture of the DNA break region formed as a result of terminal resection and depends on the cell cycle phase. NHEJ is the main pathway of double-strand break (DSB) repair in mammalian cells and involves a nonspecific ligation reaction. The reaction accuracy depends on the structure of break ends, and various insertions or deletions may arise as a result in the target genome region. Integration of a necessary sequence into the genome occurs via HDR, which requires a template with homology regions flanking a DSB. Introducing a genetic construct into a particular genomic locus is an important task, but is currently intricate and laborious to perform. However, the choice of the repair pathway can be of principal importance for basic research of gene functions and construction of animal models of human diseases to develop therapies. The review summarizes and systematizes the available information on strategies designed to increase the HDR efficiency. The strategies that most efficiently shift the balance towards HDR include use of NHEJ inhibitors, regulation of the key factors of homologous recombination, control of the cell cycle and chromatin status, and construction of HDR templates.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941264","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

Donor DNA Modification with Cas9 Targeting Sites Improves the Efficiency of MTC34 Knock-in into the CXCR4 Locus 用 Cas9 靶向位点修饰供体 DNA 可提高 MTC34 基因敲入 CXCR4 基因座的效率

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-08-07 DOI: 10.1134/s0026893324700250

M. V. Shepelev, D. S. Komkov, D. S. Golubev, S. E. Borovikova, D. V. Mazurov, N. A. Kruglova

{"title":"Donor DNA Modification with Cas9 Targeting Sites Improves the Efficiency of MTC34 Knock-in into the CXCR4 Locus","authors":"M. V. Shepelev, D. S. Komkov, D. S. Golubev, S. E. Borovikova, D. V. Mazurov, N. A. Kruglova","doi":"10.1134/s0026893324700250","DOIUrl":"https://doi.org/10.1134/s0026893324700250","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>To successfully apply the genome editing technology using the CRISPR/Cas9 system in the clinic, it is necessary to achieve a high efficiency of knock-in, which is insertion of a genetic construct into a given locus of the target cell genome. One of the approaches to increase the efficiency of knock-in is to modify donor DNA with the same Cas9 targeting sites (CTS) that are used to induce double-strand breaks (DSBs) in the cell genome (the double-cut donor method). Another approach is based on introducing truncated CTS (tCTS), including a PAM site and 16 proximal nucleotides, into the donor DNA. Presumably, tCTS sites do not induce cleavage of the donor plasmid, but can support its transport into the nucleus by Cas9. However, the exact mechanisms whereby these two donor DNA modifications increase the knock-in level are unknown. In this study, the modifications were tested for effect on the knock-in efficiency of the <i>MTC34</i> genetic construct encoding the HIV-1 fusion inhibitory peptide MT-C34 into the <i>CXCR4</i> locus of the CEM/R5 T-cell line. When full-length CTSs were introduced into the donor plasmid DNA, the knock-in level was doubled regardless of the CTS number or position relative to the donor sequence. Modifications with tCTSs did not affect the knock-in levels. In vitro, both CTS and tCTS were efficiently cleaved by Cas9. To understand the mechanism of action of these modifications in detail, it is necessary to evaluate their cleavage both in vitro and in vivo.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141941266","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

Virus-Like Particles Carrying HIV-1 Env with a Modulated Glycan Composition 携带HIV-1 Env的类病毒颗粒，其糖蛋白成分有所改变

IF 1.2 4区生物学

Molecular Biology Pub Date : 2024-08-07 DOI: 10.1134/s0026893324700341

G. A. Kaevitser, E. I. Samokhvalov, D. V. Scheblyakov, A. L. Gintsburg, A. N. Vzorov

引用次数: 0