DNA and cell biology最新文献

{"title":"Granzyme K, Regulated by the N6-Methyladenosine Methyltransferase Wilms' tumor 1-associate protein, Enhances Myocardial Infarction Injury.","authors":"Qing Lyu, Le Li","doi":"10.1089/dna.2025.0067","DOIUrl":"https://doi.org/10.1089/dna.2025.0067","url":null,"abstract":"<p><p>Myocardial infarction (MI) is a major contributor to death in contemporary society, and this mechanism involves n6-methyladenosine (m⁶A) modification. In this study, we studied the m⁶A mechanisms involved in MI. For this purpose, an H9C2 cell MI model and MI rat model were developed. Cell Counting Kit-8 was applied to determine the effect of granzyme K (GZMK) differential expression on cell survival. In addition, 2,3,5-triphenyl tetrazolium chloride, hematoxylin-eosin, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, and enzyme-linked immunosorbent assay were performed to determine the effect of GZMK differential expression on myocardial injury markers, apoptosis, and inflammatory factors. The m⁶A-modification effect between Wilms' tumor 1-associate protein (WTAP) and GZMK was detected via methylated RNA immunoprecipitation. The expression of WTAP and GZMK in MI model cardiomyocytes was measured by quantitative reverse transcription polymerase chain reaction and western blotting. WTAP and GZMK were found to be highly expressed in MI H9C2 cells. Moreover, GZMK knockdown boosted cardiomyocyte proliferation, dampened the markers of myocardial injury and inflammation, and injured apoptosis in the MI model, whereas GZMK overexpression aggravated cardiomyocyte MI injury. GZMK was positively mediated by WTAP in cardiomyocytes and was subjected to WTAP-mediated m⁶A modification. The low expression of GZMK reduced the MI area, attenuated myocardial tissue damage and inflammation, and arrested cardiomyocyte apoptosis in the MI rats. Thus, for the first time, we demonstrated that GZMK was modified by WTAP via m⁶A modification, which promoted its expression in MI, thereby aggravating MI-induced myocardial injury.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertilization Initiates Seed Nutrition via Phloem End by a Callose Degradation Enzyme.","authors":"Ryushiro D Kasahara","doi":"10.1089/dna.2025.0106","DOIUrl":"https://doi.org/10.1089/dna.2025.0106","url":null,"abstract":"<p><p>Why plants need fertilization to produce seeds has long been discussed. We recently identified a new specialized tissue required for seed formation at the ovule's chalazal end, showing the final form of the phloem end and supporting its transport function; however, it is blocked by callose deposition. Callose is removed after central cell fertilization (open state), allowing nutrients to be transported to the seed. However, if fertilization fails, callose deposition persists (closed state), preventing the tissue from transporting nutrients. A β-1,3-glucanase gene, AtBG_ppap, was identified, and the AtBG_ppap mutant showed the closed state, producing smaller seeds due to incomplete callose degradation. Contrarily, the AtBG_ppap overexpression line produced larger seeds due to continuous callose degradation, showing that the tissue is the \"gateway\" for the seed nutrients.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Active Ingredients of Herbs Targeting Long Noncoding RNA: A Potential Alternative to Treat Parenchymal Organ Inflammation and Fibrosis in the Future.","authors":"Min Zhou, Biyu Tan, Jian Liu, Qiong Zhang, Li Wang, Qiongdan Hu","doi":"10.1089/dna.2025.0058","DOIUrl":"https://doi.org/10.1089/dna.2025.0058","url":null,"abstract":"<p><p>We review current studies on the anti-inflammatory and antifibrotic effects of herbal medicines and their active ingredients. To explore how these active ingredients target long noncoding RNA to exert their effects, we searched PubMed and Chinese National Knowledge Infrastructure databases for preclinical and clinical studies of long noncoding RNAs (lncRNA), herbal medicine, inflammation, and fibrosis. The active ingredients of herbal medicines were able to target lncRNAs. These interactions can have anti-inflammatory and antifibrotic effects on various diseases. The current studies provide preliminary insights but are not comprehensive. Targeting lncRNAs with herbal medicine ingredients is a promising direction for further research. This approach could lead to new alternative treatments for inflammation and fibrosis-related diseases.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Efficacy of Melatonin and Flutamide Combination in Safety for Prostate Cancer: An <i>In Vitro</i> Study.","authors":"Reza Omid, Fatemeh Khatami, Ramin Rahimnia, Diana Taheri, Rahil Mashhadi, Akram Mirzaei, Seyedeh Fatemeh Hosseini, Seyedeh Negin Hashemi Dougaheh, Leonardo Oliveira Reis, Seyed Mohammad Kazem Aghamir","doi":"10.1089/dna.2025.0018","DOIUrl":"https://doi.org/10.1089/dna.2025.0018","url":null,"abstract":"<p><p>The side effects associated with flutamide as a first-line drug treating prostate cancer, including hepatotoxicity, the aim of this research was to use melatonin as an anticancer candidate to reduce the dose of flutamide and reduce its side effects. We evaluated the effect of melatonin, flutamide, and melatonin-flutamide combination therapy in LNCaP, DU145, and PC3 cell lines. The assessment includes Hoechst dye staining, scratch-wound assay, colony formation assay, flow cytometric analysis of apoptosis and DNA cell cycle, real-time PCR (<i>BAX [BCL2 Associated X]/B-cell lymphoma-2 [BCL2]</i>, <i>E-cadherin</i>, Zinc finger protein SNAI2 [<i>SNAIL]</i>, Hypoxia Inducible Factor 1 Subunit Alpha [<i>HIF1α]</i>, Vascular Endothelial Growth Factor C [<i>VEGFC]</i>, and <i>kallikrein-related peptidase 3</i> [<i>KLK3</i>] genes). To determine Half maximal inhibitory concentration (IC50) levels, cell lines were exposed to different concentrations of the drugs. Our data indicated that IC50 values for melatonin (75 µM) and three cell lines and flutamide (12 and 10 µM) for PC3 and LNCaP/DU145, respectively, with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide were approved by flow cytometry in a dose and time-dependent manner which was as a consequence of cell cycle arrest at G0/G1 phase. Due to the efficacy of melatonin in combination with flutamide, we used 75 µM melatonin, and 5 µM flutamide instead of 12 µM in DU145, and 6 µM in PC3 and LNCaP, respectively. The combination of melatonin and flutamide significantly upregulated the expression of <i>BAX/BCL2</i> ratio in all three cell lines (<i>p</i> < 0.0001) and downregulated the expression of <i>KLK3</i> (<i>p</i> < 0.01), <i>HIF1α</i> (<i>p</i> < 0.01), <i>VEGFC</i> (<i>p</i> < 0.001), and epithelial-mesenchymal transition pathway genes in PC3 and LNCaP (<i>p</i> < 0.01). Melatonin in combination with flutamide reduced its dose and increased the sensitivity of prostate cancer cells to treatment.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Vitro</i> Reconstitution of SPO11-Mediated DNA Cleavage Sheds New Light on the Initiation of Meiotic Recombination.","authors":"Cédric Oger, Corentin Claeys Bouuaert","doi":"10.1089/dna.2025.0091","DOIUrl":"https://doi.org/10.1089/dna.2025.0091","url":null,"abstract":"<p><p>Three recent studies report the first biochemical reconstitution of DNA double-strand break (DSB) formation by SPO11, the topoisomerase-derived transesterase that initiates meiotic recombination in sexually reproducing organisms. A central conclusion of these studies is that SPO11 is sufficient to catalyze DSBs <i>in vitro</i>, but cleavage is limited by the poor propensity of SPO11 to dimerize, thereby providing an effective mechanism to prevent uncontrolled breaks. The studies yield new insights into the mechanism of DNA DSB formation and raise new questions regarding the functions of SPO11 partners, the impact of the DNA substrate, the coordination between cleavage events, and the reversibility of the reaction.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Cuproptosis Pathway Genes (DLAT, FDX1) and Antioxidant Enzyme Activities in Obese Mice in Response to Quercetin and Calorie Restriction.","authors":"Nima Mahdei Nasirmahalleh, Mina Hemmati, Negin Parsamanesh, Mohammad Borji","doi":"10.1089/dna.2025.0005","DOIUrl":"https://doi.org/10.1089/dna.2025.0005","url":null,"abstract":"<p><p>Cuproptosis is a new mode of cell death that is closely related to mitochondrial stress. The purpose of this study is to investigate the amount of copper, copper-associated genes DLAT and FDX1 oxidative stress (OS) status in obesity. Since there is a close relationship between OS and cuproptosis, evaluating the effect of various strategies to reduce OS, including quercetin (QUER) and caloric restriction (CR), is another goal of this study. In this study, 30 male BALB-C mice aged 8 weeks and weighing 25 g, including the groups receiving normal diet (ND), ND with QUER (15 mg/kg, IP) and CR, a high-fat diet (HFD) with the QUER, CR or a combination of both were used. The activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione reductase (GR), amount of copper in the liver and kidney tissues, and expression of DLAT and FDX1 genes were measured in all studied groups. The amount of copper in the liver and kidney tissue as well as the expression of FDX1 and DLAT in the HFD group increased significantly compared with the ND group. QUER, CR or their combination could significantly reduce the amount of copper as well as the expression of FDX1 and DLAT in liver and kidney tissues. QUER and CR, also significantly increased the activity of GR, SOD and GPX in serum, liver, and kidney tissues. Based on the results, QUER, CR and especially the simultaneous use of both, was able to reduce the amount of copper and its related cuproptosis. These effects may reduce cuproptosis-associated cell death. Therefore, the use of antioxidants and CR may be a promising solution to protect the human body against the effects of cuproptosis in conditions like obesity.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>STING</i> rs7380824 Polymorphism Contributes to the Susceptibility of Colorectal Cancer in Chinese Population.","authors":"Xiufeng Zhang, WenLong Wu, Hongyan Li, Ying Jian, Ang Li, Zhi Zhang, Xuemei Zhang","doi":"10.1089/dna.2025.0020","DOIUrl":"https://doi.org/10.1089/dna.2025.0020","url":null,"abstract":"<p><p><i>STING</i>, an endoplasmic reticulum-localized protein with multiple transmembrane domains, has been implicated in colorectal cancer (CRC) development. This study investigated the association between <i>STING</i> rs7380824 polymorphism and CRC susceptibility using both bioinformatics analysis and a case-control study. Bioinformatics predictions from SIFT and PolyPhen indicated that the rs7380824 variant, which results in an amino acid substitution from arginine (R) to glutamine (Q) at position 293, is likely to be deleterious, with a SIFT score of 0.000 and a PolyPhen score of 0.999. A total of 870 CRC patients and 870 healthy controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression analysis demonstrated that individuals carrying the CT and TT genotypes had an increased risk of CRC with OR (95% CI) of 1.564 (1.115-2.192) and 1.551 (1.271-1.893), respectively. Stratified analysis showed that the rs7380824 C > T variant increased CRC risk in all age and gender groups. Furthermore, non-smokers with the CT or TT genotype had a higher CRC risk (OR = 1.661, 95% CI: 1.333-2.071, <i>p</i> < 0.001), while no significant association was observed among smokers (<i>p</i> = 0.238). Similarly, non-drinkers carrying the CT or TT genotype showed an increased CRC risk (OR = 1.746, 95% CI: 1.395-2.185, <i>p</i> < 0.001), whereas no significant difference was detected among drinkers (<i>p</i> = 0.265). This study identifies <i>STING</i> rs7380824 polymorphism as a significant contributor to CRC susceptibility, with bioinformatics predictions and case-control analysis confirming its deleterious impact and the association with increased CRC risk. In addition, these findings underscore the interplay between genetic and environmental factors in CRC development, highlighting <i>STING</i>'s potential as a genetic biomarker for CRC risk assessment in the Chinese population.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Therapeutic Potential of Extracellular Vesicles in Sepsis Management.","authors":"Laifa Kong, Qigang Huang, Jianghua Cheng, Yingwei Ding, Baodi Wang","doi":"10.1089/dna.2025.0009","DOIUrl":"10.1089/dna.2025.0009","url":null,"abstract":"<p><p>Sepsis is a serious systemic inflammatory condition triggered by a variety of pathogens, including bacteria and viruses, that can result in multiple organ failure and a life-threatening situation. Despite advances in medical care, the mortality rate for sepsis remains high even with aggressive treatment strategies such as antibiotic therapy, fluid resuscitation, and respiratory and circulatory support. Extracellular vesicles (EVs), as a novel nanoscale biocarrier, exhibit diverse biological functions including immune modulation and tissue regeneration, suggesting promising applications in the field. This article provides an overview of the diverse therapeutic effects of EVs derived from various sources in the management of sepsis. Furthermore, EVs not only possess intrinsic therapeutic properties, such as immune modulation, but also function as targeted delivery vehicles for a variety of drug molecules, leading to synergistic therapeutic outcomes. In conclusion, extracellular vesicle therapy is poised to emerge as a dynamic and innovative force driving advancements in sepsis treatment.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin Shearing in Suspension Cell Line: A Guide for Optimization.","authors":"Ambika Chamoli, Priyanka Patel Vatsa, Vinal Upadhyay, Amit Mandoli","doi":"10.1089/dna.2024.0284","DOIUrl":"https://doi.org/10.1089/dna.2024.0284","url":null,"abstract":"<p><p>Chromatin immunoprecipitation (ChIP) assesses DNA-proteins interactions and hence helps to generate intricate relationships and vital information. ChIP determines the genomic location of specific proteins or post-translational modifications at an individual locus or genome-wide. The protocol endures complexity; hence it is of utmost importance to identify the variable responsible for experimental erraticism. The most sensitive and critical step involves the chromatin fragmentation step. In the current study, the parameters required for chromatin shearing in the Kasumi-1 cell line have been optimized. To address this, the protocol includes the fixation of cells with formaldehyde followed by cell lysis and nuclei isolation. Further chromatin shearing using various sonication buffers and sonicator parameters was performed. Successful sonication was observed at the following settings: peak incident power of 150 W, duty factor 7.0%, cycles per burst 200, and water fill level 8 generating fragments of ∼250-600 bp in 7 min. To analyze enriched DNA sequences that are associated with the target protein ChIP coupled with quantitative PCR was performed. With this study, the optimal procedure has been standardized for a percentage of detergents, SDS (0.15%), DOC (0.05%) in the sonication buffer, and duration of sonication to achieve the desired fragmentation pattern. The quality of shearing determines the success of the experiment.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing Long-Read Sequencing for Haplotype Construction and Prevention of Autosomal Dominant Polycystic Kidney Disease Transmission in Mosaicism Family.","authors":"Wu Zubo, Jie Liu, Yi Liu, Xiaoli Wang, Defeng Shu","doi":"10.1089/dna.2024.0280","DOIUrl":"10.1089/dna.2024.0280","url":null,"abstract":"<p><p>This study presents a case of autosomal dominant polycystic kidney disease (ADPKD) involving a mosaic microdeletion in the <i>PKD1</i> gene and explores the application of long-read sequencing technologies for haplotype construction and preimplantation genetic testing (PGT). We report on a family where the proband was clinically diagnosed with PKD and found to have a partial deletion of the <i>PKD1</i> gene because of the mosaic deletion mutation of <i>PKD1</i> in the mother of the proband. Utilizing Oxford Nanopore long-read sequencing, we successfully constructed the haplotype of the deleted fragment region and identified an unaffected embryo for transplantation, resulting in a successful pregnancy. The prenatal genetic diagnosis confirmed the absence of deletion abnormalities in the fetus. Our findings underscore the significance of integrating advanced genomic technologies into clinical practice for PGT in ADPKD, particularly in cases involving partial deletion of X chromosome mosaic embryo transferred or complex structural variants. This approach not only prevents the transmission of ADPKD but also demonstrates the utility of long-read sequencing in overcoming the limitations of traditional PGT methods. Further research is warranted to evaluate the broader application of long-read sequencing for other monogenic disorders and to refine these techniques for enhanced diagnostic precision and clinical outcomes.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"238-248"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}