Molecular Biology最新文献

{"title":"Synthesis of a Bisbenzoxazole Analogue of Hoechst 33258 as a Potential GC-Selective DNA Ligand","authors":"A. F. Arutuynyan, M. S. Aksenova, A. A. Kostyukov, A. A. Stomakhin, D. N. Kaluzhny, A. L. Zhuze","doi":"10.1134/s0026893324700171","DOIUrl":"https://doi.org/10.1134/s0026893324700171","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Using a computer modeling approach, we proposed a structure for a potential GC-specific DNA ligand, which could form a complex with DNA in the minor groove similar to that formed by Hoechst 33258 at DNA AT-enriched sites. According to this model, MBoz₂A, a bisbenzoxazole ligand, was synthesized. The results of spectrophotometric methods supported the complex formation of the compound under study with DNA differing in the nucleotide composition.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"68 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254014","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":"Recombinant VLP Vaccines Synthesized in Plant Expression Systems: Current Updates and Prospects","authors":"S. M. Rozov, E. V. Deineko","doi":"10.1134/s0026893324700043","DOIUrl":"https://doi.org/10.1134/s0026893324700043","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The development and creation of a new generation vaccines based on recombinant proteins that assemble into virus-like particles (VLPs), as well as recombinant proteins in the form of nanoparticles, are promising directions in modern biotechnology. Due to their large size (20–200 nm) and multiplicity of viral antigenic determinants on the surface, VLPs can stimulate strong humoral and cellular immune responses. The main types of VLPs, as well as the features and disadvantages of the main expression systems used for their biosynthesis, are considered in this review. The main focus was on plant expression systems that ensure the biosynthesis of a target recombinant protein from a DNA matrix integrated into the nuclear or chloroplast genomes of a plant (stable expression) or from a matrix for temporary production of the target product (transient expression). Various approaches for increasing the yield of VLP-forming recombinant proteins, including fusion with a transit peptide that directed the protein into the chloroplast, were discussed. The possibility of accumulation of recombinant proteins expressed in plants and intended for creation of VLP-vaccines in another type of nanoparticle, protein bodies, using specific signal sequences was also considered.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"52 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254260","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":"Cytoplasmic mRNA Transport: Adaptors of mRNA Binding to Microtubule Motor Proteins","authors":"Y. A. Vdovina, S. G. Georgieva, D. V. Kopytova","doi":"10.1134/s0026893324700018","DOIUrl":"https://doi.org/10.1134/s0026893324700018","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The process of mRNA localization in the cytoplasm involves the directed transport of mRNP particles using the microtubule system. This transport is mediated and regulated by specific factors—adaptors between mRNA molecules and microtubule motor proteins. Adaptors are a key link in the mechanism of mRNA transport, but to date their identity and functioning are mostly unknown. In this review, we examine the features and importance of adaptor proteins in mRNA transport during oogenesis and in neuronal function. This article summarizes recent data on mRNA binding adaptors in the cytoplasm and the mechanisms of their interaction with microtubule motor proteins.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"48 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254093","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":"ArdA Protein Specificity against Type I Restriction–Modification Systems","authors":"A. A. Kudryavtseva, A. V. Vlasov, E. V. Zinovev, D. D. Yanovskaya, A. A. Utkina, S. M. Rastorguev, I. V. Manukhov","doi":"10.1134/s0026893324700158","DOIUrl":"https://doi.org/10.1134/s0026893324700158","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The ArdA DNA-mimic antirestriction proteins inhibit type I restriction−modification (RMI) systems by binding instead of DNA to RMI. The ArdA specificity to DNA methylation sites recognized by RMI complexes remains poorly understood; i.e., it is unclear whether a particular DNA site is mimicked by ArdA. The <i>ardA</i> genes were cloned from three Gram-positive bacteria: <i>Agrobacterium tumefaciens</i>, <i>Pseudomonas monteilii,</i> and <i>Xanthomonas</i> sp<i>.</i> Antirestriction activities of their products were tested against three <i>Escherichia coli</i> RMI systems differing in DNA recognition/methylation sites. Although similar structures were predicted for the ArdA proteins, the strong specificity to three RMI systems was observed. The results indicate that specific DNA sites may be imitated by DNA mimic ArdA proteins.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"15 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254258","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":"Development of Biological Microchips on an Aluminum Support with Cells Made of Brush Polymers","authors":"I. Yu. Shishkin, G. F. Shtylev, V. E. Barsky, S. A. Lapa, O. A. Zasedateleva, V. E. Kuznetsova, V. E. Shershov, V. A. Vasiliskov, S. A. Polyakov, A. S. Zasedatelev, A. V. Chudinov","doi":"10.1134/s002689332470016x","DOIUrl":"https://doi.org/10.1134/s002689332470016x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>A method has been developed for manufacturing biological microchips on an aluminum substrate with hydrophilic cells from brush copolymers with the formation of a matrix of cells using photolithography. The surface of aluminum substrates was previously coated with a thin, durable, moderately hydrophobic layer of cross-linked polymer to prevent contact with the aluminum surface of the components used in the analysis of nucleic acids. Aluminum biochip substrates have high thermal conductivity and low heat capacity, which is important for the development of methods for multiplex PCR analysis on a chip. Oligonucleotide probes were covalently immobilized in the cells of the biochip. The preservation of the hybridization activity of the immobilized DNA probes was demonstrated in a hybridization analysis with a synthetic DNA target representing a section of the sequence of the seventh exon of the human <i>ABO</i> gene. The methods developed can be used in the development of a technology for parallel multiple rapid microanalysis of nucleic acids “lab on a chip” for the detection of human somatic and infectious diseases.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"106 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254360","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":"DNA Methylation Profiling in Aneurysm and Comorbid Atherosclerosis of the Ascending Aorta","authors":"I. A. Goncharova, A. A. Zarubin, S. A. Shipulina, Iu. A. Koroleva, D. S. Panfilov, B. N. Kozlov, M. S. Nazarenko","doi":"10.1134/s0026893324700079","DOIUrl":"https://doi.org/10.1134/s0026893324700079","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Atherosclerosis and aneurysm of the aorta are relatively common pathological conditions that remain asymptomatic for a long period of time and have life-threatening and disabling complications. DNA methylation profiling in several regions (a dilated area, a nondilated area, and an atherosclerotic plaque) of the ascending aorta was carried out in patients with aortic aneurysm. DNA methylation was analyzed by reduced representation bisulfite sequencing (RRBS). Differences in methylation level between dilated and normal aortic tissues were detected for two CpG sites of the <i>NR2F1-AS1</i> gene (|Δβ| ≥ 0.2 and <i>FDR</i> &lt; 0.05). In total, 586/480 differentially methylated CpG sites (DMSs) were identified by comparing atherosclerotic plaque samples with dilated/normal aortic tissues; 323/234 of the DMSs were hypermethylated and 263/246 were hypomethylated in atherosclerotic plaques. Most DMSs were in introns and intergenic regions; 88.2% of the DMSs were in the binding sites of transcription factors, among which ZNf263, ZFP148, PATZ1, NRF1, TCF12, and EGR1 play a role in the pathogenesis of atherosclerosis of various arteries and ELK1, ETS1, and KLF15 play a role in aortic aneurysms. Sixteen DMSs were found in the regions of the genes <i>CMIP</i>, <i>RPH3AL</i>, <i>XRCC1</i>, <i>GATA5</i>, <i>EXD3</i>, <i>KCNC2</i>, <i>HIVEP3</i>, <i>ADCY9</i>, <i>CDCP2</i>, <i>FOLR1</i>, <i>WT1</i>, <i>MGMT</i>, <i>GAS2</i>, <i>CA1</i>, <i>PRSS16</i>, and <i>ANK3</i>, whose protein products are involved in both aortic dissection and atherosclerosis in various arterial circulation regions. The protein products of the genes are involved in a wide range of biological processes, including mesenchyme development (GO:0060485; <i>FOLR1</i>, <i>WT1</i>, <i>GATA5</i>, <i>HIVEP3</i>, and <i>KCNC2</i>) and positive regulation of DNA metabolic processes (GO:0051054; <i>MGMT</i>, <i>WT1</i>, and <i>XRCC1</i>).</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"35 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141254088","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":"Methylation of Long Noncoding RNA Genes SNHG6, SNHG12, and TINCR in Ovarian Cancer","authors":"S. S. Lukina, A. M. Burdennyy, E. A. Filippova, L. A. Uroshlev, I. V. Pronina, N. A. Ivanova, M. V. Fridman, K. I. Zhordania, T. P. Kazubskaya, N. E. Kushlinskii, V. I. Loginov, E. A. Braga","doi":"10.1134/s0026893324700067","DOIUrl":"https://doi.org/10.1134/s0026893324700067","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Ovarian cancer (OC) develops asymptomatically and escapes diagnosis until advanced stages, the feature contributing to a higher mortality rate. New prospects of OC diagnosis and treatment have been opened in studies of the gene regulation mechanisms that involve long noncoding RNAs (lncRNAs) and identification of the lncRNA genes that are inhibited via methylation of the promoter region. A set of 122 samples of primary OC tumors was examined by methylation specific real-time PCR to assess the methylation level of the lncRNA genes <i>PLUT</i>, <i>SNHG1</i>, <i>SNHG6</i>, <i>SNHG12,</i> and <i>TINCR</i>. A significant increase in their methylation levels was observed in OC (<i>p</i> &lt; 0.001 by the nonparametric Mann–Whitney test). The methylation levels of <i>SNHG6</i>, <i>SNHG12</i>, and <i>TINCR</i> were found to correlate significantly (<i>p</i> &lt; 0.05) with the stage of the tumor process, the histological grade, and metastasis. Downregulation of <i>SNHG6</i>, <i>SNHG12</i>, and <i>TINCR</i> was detected by real-time RT–qPCR, and a significant correlation between methylation and expression was demonstrated for <i>SNHG6</i> and <i>TINCR</i> (<i>r</i>_s ≤ –0.5, <i>p</i> &lt; 0.001). The respective lncRNA genes were assumed to provide potential epigenetic markers of OC.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"27 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259723","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":"SMURF1-Interference Effects Autophagy and Pulmonary Fibrosis through SMAD7 and the TGF-β1/SMAD Pathway","authors":"L. Lin, D. Xue, L.-M. Chen, Q.-Y. Wei, J.-H. Chen, Y. Li, X.-L. Ye, Z.-H. Huang","doi":"10.1134/s002689332470033x","DOIUrl":"https://doi.org/10.1134/s002689332470033x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>SMAD-specific E3 ubiquitin proten ligase 1 (SMURF1) is involved in transforming growth factor (TGF)-β1/Smad pathway-mediated tissue fibrosis. However, its role in pulmonary fibrosis and the related molecular mechanisms are still unclear. This study aims to investigate whether SMURF1 inhibits autophagy and promotes pulmonary fibrosis via SMAD family member 7 (SMAD7) and TGF-β1/SMAD signal pathway. MRC-5 cells were treated with TGF-β1 followed by <i>MURF1-</i>interference. The rate of cell migration was assessed using the cell scratch test. Autophagosomes were analyzed using a transmission electron microscope. mRNA levels of SMURF1, SMAD7, TGF-β1, phosphorylated (p)-SMAD1, p-SMAD3, α-smooth muscle actin (α-SMA), matrix metallopeptidase 7 (MMP7), microtubule-associated protein light chain 3 (LC3 ) and Beclin1 were evaluated by quantitative real-time PCR (qPCR), Western blotting, and immunofluorescence. The interaction between SMURF1 and SMAD7 was investigated in a co-immunoprecipitation (Co-IP) experiment. We found that after TGF-β1 treatment, the mRNA levels of SMURF1, α-SMA, MMP7, and p-Smad1/3 were increased, and the levels of Beclin1 and LC3 were decreased. Apart from these, cell autophagy was decreased, while the migration ability was increased. After SMURF1-interference, SMURF1, α-SMA and MMP7 mRNA levels were significantly decreased, p-SMAD1 was slightly reduced, and p-Smad3 was not changed. As for Beclin1 and LC3, their transcription increased, cell autophagy increased, and migratory ability decreased. The interaction between SMURF1 and Smad7 was confirmed by Co-IP. In conclusion, SMURF1 may inhibit autophagy and promote lung fibrosis by downregulating <i>SMAD7</i> and activating the TGF-β1/SMAD pathway. These results may serve as a basis for the development of new therapeutic targets in the pulmonary fibrosis clinic.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"75 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885193","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":"Exploring the Potential Mechanism of Apoptosis Induced by MFSD8 in Endothelial Cells: an RNA Sequencing and Bioinformatics Analysis","authors":"Q. Xiang, Y. Liu, S. S. Jiang, Y. F. Chen, Y. X. Liu, D. W. Yang, L. Tang, J. M. Li","doi":"10.1134/s0026893324700225","DOIUrl":"https://doi.org/10.1134/s0026893324700225","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Neuronal ceroid lipofuscinoses (NCLs) belong to a group of inherited neurodegenerative disorders without effective treatments. Though loss-of-function in the <i>MFSD8</i> gene resulting in a variant late-infantile subtype of NCLs is well documented, its roles remain poorly explored and understood. The results showed an increased cell apoptosis rate after the <i>MFSD8</i> gene low expression in HUVECs by Flow cytometric analysis. RNA sequencing revealed 367 differentially expressed genes upon the <i>MFSD8</i> gene overexpression in HUVECs. Bioinformatics analyses revealed that the <i>MFSD8</i> gene overexpression might be involved in the PI3K/Akt signaling pathway, and interleukin-6 (<i>IL-6</i>), interleukin-1 beta (<i>IL-1B</i>), fibronectin 1 (<i>FN1</i>), fibroblast growth factor 2 (<i>FGF2</i>), toll-like receptor 4 (<i>TLR4</i>), tumor necrosis factor (<i>TNF</i>), and prostaglandin G/H synthase 2 (<i>PTGS2</i>) were the potential hub genes affected by the <i>MFSD8</i> gene. Gene set enrichment analysis and qRT-PCR assay validation also disclosed that the “Hallmark_Apoptosis” pathway was dramatically enriched in differentially expressed genes. The results revealed that the loss of functional MFSD8 protein indirectly or directly increased the apoptosis of HUVECs, indicating that the expression of the <i>MFSD8</i> gene was essential for cell survival. The hub genes, including <i>IL-6</i>, <i>IL-1B</i>, <i>FN1</i>, <i>FGF2</i>, <i>TLR4</i>, <i>TNF</i>, and <i>PTGS2</i>, might provide insight into the apoptosis induced by the <i>MFSD8</i> gene in NCLs. Although many experiments are required to validate these predictions, the results may help investigate the roles of the <i>MFSD8</i> gene on apoptosis and the corresponding mechanism.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"148 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885138","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":"Global Transcriptome Analysis Reveals Corresponding Genes and Key Pathways Involved in Oxidative Stress in Mouse Small Intestinal Cells","authors":"Y. He, C. P. Feng, J. L. Li, R. Du","doi":"10.1134/s0026893324700365","DOIUrl":"https://doi.org/10.1134/s0026893324700365","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Understanding the molecular mechanisms involved in the effects of oxidative stress in humans and animals is important to minimize the damage it causes, leading to various intestinal diseases. Our aim is to study the genes and pathways involved in oxidative stress in the gut using mouse small intestinal epithelial cells (MODE-K) as a model. The MODE-K cell line was divided into two different groups: one group was treated with hydrogen peroxide (H₂O₂) and the other group was not. To analyze the effects of H₂O₂ exposure, cell viability, apoptosis rate and reactive oxygen species (ROS) levels were determined. Next, transcriptome sequencing was performed, differentially expressed genes (DEGs) were identified and function annotation was performed, followed by a series of bioinformatics analyses. Real-time PCR was used to confirm the transcriptome data. Our results showed that H₂O₂-induced oxidative stress significantly increased ROS synthesis and promoted cell apoptosis in mouse small intestinal epithelial cells. During oxidative stress, 1207 DEGs (859 up-regulated, 348 down-regulated) were identified. According to GO analysis, DEGs are annotated into 51 different GO classifications including 22 biological processes, 15 cellular components and 14 molecular functions. In addition, using KEGG, PPI and correlation analysis, the two most significant subnetworks were identified. Ten correlated nodal DEGs of the first subnetwork correspond to MAPK, NF-kappa B and PI3K-AKT signaling pathways, and six correlated DEGs of the second subnetwork are associated with mitochondria. KDM6B was found to link these two subnetworks. The results suggest that oxidative stress affects epithelial growth, metabolism and apoptosis in a mouse model of intestinal cells through signaling pathways such as MAPK and PI3K/AKT/NF-kappa B, and mitochondria-related genes that are interconnected through the PTGS2-KDM6B-MT-ATP6 pathway.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":"22 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885487","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}