DNA and cell biology最新文献

{"title":"Targeting p97/Valosin-Containing Protein Promotes Hepatic Stellate Cell Senescence and Mitigates Liver Fibrosis.","authors":"Ying Yang, Yuwei Zhang, Lu Wang, Guanyi He, Xue Yang, Jie Qing","doi":"10.1089/dna.2024.0198","DOIUrl":"10.1089/dna.2024.0198","url":null,"abstract":"<p><p>Liver fibrosis, one of the main histological determinants of various chronic liver diseases, currently lacks effective treatment. Hepatic stellate cells (HSCs) are pivotal in the production of extracellular matrix and amplify the fibrogenic response. Inhibiting the activation of HSCs or promoting the senescence of activated HSCs is crucial for the regression of liver fibrosis. The ATPase p97, also known as valosin-containing protein (VCP), is a central component of the ubiquitin-proteasome system, and it regulates numerous cellular processes by influencing protein homeostasis. In this study, we observed an upregulation of p97 expression around regions exhibiting fibrosis in a diet- and chemical-induced nonalcoholic steatohepatitis and fibrosis murine model. Intervention with the p97 antagonist CB-5083 or the knockdown of p97 reduced the expression of alpha-smooth muscle actin and collagen-I in both mouse or human HSCs. The administration of CB-5083 induced HSC senescence and resulted in the upregulation of senescence markers, including p21, p53, GPX4, and senescence-associated β-galactosidase. Furthermore, CB-5083 treatment also inhibited the expression of Yes-associated protein (YAP), which is also a senescence-related regulatory protein and has a profibrotic function. We used CB-5083 to treat fibrotic mice and found that the activation of HSCs was inhibited, and the liver fibrosis was attenuated. In addition, <i>in vivo</i> experiments confirmed that CB-5083 facilitated HSC senescence and reduced YAP expression. These findings underscore the potential of pharmacological targeting p97/VCP to induce HSC senescence and alleviate liver fibrosis.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"132-143"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960465","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":"A Long-Term Follow-Up Study of Serum NFATc3 Levels in Pediatric Patients with Bronchial Asthma: A Prospective Observational Case-Control Investigation.","authors":"Xi Zhang, Xiaojun Duan, Yuan Chen, Lili Wang, Yanping Chen","doi":"10.1089/dna.2024.0146","DOIUrl":"10.1089/dna.2024.0146","url":null,"abstract":"<p><p>The early and precise diagnosis of asthma significantly impacts the long-term health outcomes of pediatric patients. The sensitivity and specificity of current biomarkers, however, are frequently limited. Our study aimed to evaluate the clinical significance of nuclear factor of activated T cells, cytoplasmic 3 (NFATc3), in pediatric bronchial asthma, focusing on its diagnostic and prognostic value for disease severity and recurrence. This observational, prospective case-control study involved 200 pediatric patients with bronchial asthma and 200 age- and sex-matched healthy controls, from January 2020 to January 2023. Follow-up varied from 1 to 3 years. We measured levels of NFATc3 and inflammatory cytokines interleukin-1β (IL-1β), IL-6, and TNF-α via enzyme-linked immunosorbent assay. NFATc3 and IL-1β levels at enrollment were markedly higher in patients with acute exacerbations and those classified as severe, compared with their less severe counterparts. Throughout the study, NFATc3, IL-1β, and IL-6 levels significantly increased in severe or acutely exacerbating cases. The diagnostic value of NFATc3 was assessed through receiver operating characteristic curve analysis, which showed its potential in diagnosing bronchial asthma and identifying severe cases. Spearman's analysis confirmed positive associations between peak NFATc3 and cytokine levels. Importantly, disease type, NFATc3 values at enrollment, as well as peak IL-6 levels were identified as independent risk factors for severe bronchial asthma. Elevated NFATc3 is linked with the severity of pediatric bronchial asthma and serves as a potential biomarker for diagnosis and severity prediction, emphasizing its role in guiding treatment strategies.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"46-53"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590921","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":"Uncovering ASO-Targetable Deep Intronic <i>AIRE</i> Variants: Insights and Therapeutic Implications.","authors":"Sebastian Ochoa, Michail S Lionakis","doi":"10.1089/dna.2024.0223","DOIUrl":"10.1089/dna.2024.0223","url":null,"abstract":"<p><p>High-throughput DNA sequencing has accelerated the discovery of disease-causing genetic variants, yet only in 10-40% of cases yield a genetic diagnosis. Increased implementation of genome sequencing has enabled a deeper exploration of the noncoding genome and recognition of noncoding variants as major contributors to disease. In a recent study, we identified a deep intronic variant in the AutoImmune REgulator (<i>AIRE</i>) gene (c.1504-818 G>A) as the cause of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a life-threatening monogenic autoimmune disorder most often caused by biallelic <i>AIRE</i> defects. This deep intronic variant disrupts normal splicing <i>AIRE</i> , causing pseudoexon inclusion and altered protein function. By developing an antisense oligonucleotide (ASO) targeting the pseudoexon sequence, we restored normal <i>AIRE</i> transcript <i>in vitro</i>, thereby revealing a potential genotype-specific candidate treatment. Our study illustrates key aspects of intronic variant detection, validation, and candidate ASO development. Herein, we briefly highlight the growing potential of ASO-based therapies for deep intronic variants, addressing the unmet need of personalized, genotype-specific therapies in diseases lacking curative options.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Role of Pleural Macrophages in Influenza Defense.","authors":"Roksana Shirazi, Juliet Morrison","doi":"10.1089/dna.2024.0283","DOIUrl":"10.1089/dna.2024.0283","url":null,"abstract":"<p><p>The pleural cavity is gaining recognition as an important player in lung infections. Our recent research revealed that pleural macrophages (PMs) migrate from the pleural cavity into the lung during influenza virus infection, contributing to improved disease outcomes. This summary highlights key findings on the role of PMs in influencing viral lung infection outcomes and explores the potential directions for advancing this emerging field of study.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"127-131"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049154","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":"A Comprehensive Study on the Distribution of Integrons and Their Gene Cassettes in Clinical Isolates.","authors":"Fatemeh Sarina Abdinia, Kasra Javadi, Mehdi Rajabnia, Elaheh Ferdosi-Shahandashti","doi":"10.1089/dna.2024.0175","DOIUrl":"10.1089/dna.2024.0175","url":null,"abstract":"<p><p>Antibiotic resistance is a significant global health concern, leading to increased morbidity, mortality, and health care costs. Integrons are genetic elements that could acquire and express gene cassettes, including those that confer antibiotic resistance. This comprehensive study focused on the distribution of integrons and their gene cassettes in clinical isolates. This study explored the structure and classification of integrons with particular emphasis on Class I, II, III, and IV integrons. It also discussed the role of integrons in antibiotic resistance. The findings of this study contribute to a better understanding of the mechanisms underlying antibiotic resistance and provide valuable insights for developing strategies to combat this public health crisis.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"579-595"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483942","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":"Magnesium Lithospermate B Inhibits Colorectal Cancer Cell Progression Through JAK2-STAT3 Signaling.","authors":"Dan Huo, Jinpeng Zhang, Tengfei Ma, Yemao Liu, Jianqing Zhang, Bizhen Dong, Yanjun Lu, Anding Wu, Zhaoxia Jin, Yuping Li","doi":"10.1089/dna.2024.0071","DOIUrl":"10.1089/dna.2024.0071","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The discovery of new effective therapeutic drugs is always a priority. Magnesium lithospermate B (MLB), a native polyphenol acid, is the major component of the aqueous extracts from Danshen, a traditional Chinese medicine derived from the dry root and rhizome of <i>Salvia miltiorrhiza</i>. MLB has been reported to have antioxidant, anti-inflammatory, and ion channel-regulating activities in several diseases, including cardiovascular, renal, and neuronal diseases. However, the effect of MLB on cancer progression has not been reported. In this study, a series of cellular and molecular experiments were conducted on two CRC cell lines (HCT116 and SW480) to investigate the effects of. The results demonstrated that MLB exerted inhibitory effects on cell proliferation, migration, and invasion. The administration of 50 mg/kg MLB inhibited tumor growth in HCT116 cells in xenografted models. Importantly, we found that MLB treatment inhibited the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway, and activation of JAK2-STAT3 signaling with interleukin 6 or overexpression STAT3 significantly suppressed the inhibitory effect of MLB. These findings provide evidence that MLB could inhibit CRC cell progression <i>in vitro</i> and might serve as a potential therapeutic drug for the treatment of CRC.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"619-629"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523909","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":"Histone Lactylation-Driven GPD2 Mediates M2 Macrophage Polarization to Promote Malignant Transformation of Cervical Cancer Progression.","authors":"Chenlingzi Huang, Lujiadai Xue, Xinzi Lin, Yuan Shen, Xiaoyu Wang","doi":"10.1089/dna.2024.0122","DOIUrl":"10.1089/dna.2024.0122","url":null,"abstract":"<p><p>Cervical cancer (CC) is the most common cancer in women. This study aims to explore the molecular mechanism of lactate secreted by CC cells modulating macrophage polarization in CC via histone lactylation. Normal cervical epithelium (NCE), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and cervical squamous cell carcinoma (CESC) were collected to assess H3K18la level and macrophage infiltration. Macrophages were incubated with SiHa cell-derived conditioned medium to detect M1 and M2 markers. NCE, HSIL, and CESC samples were used for ChIP-seq of H3K18la. Histone lactylation-dirven <i>GPD2</i> was knocked down in macrophages. Compared to NCE, H3K18la level and M2 macrophage abundance were increased in LSIL, HSIL, and CESC. Lactate secreted by CC cells upregulated H3K18la and M2 markers but downregulated M1 markers in macrophages. ChIP-seq revealed that upregulated pathways in HSIL vs. NCE and CESC vs. HSIL were commonly enriched in lipid metabolism. Notably, lactate upregulated H3K18la-modified <i>GPD2</i> expression in macrophages, and <i>GPD2</i> knockdown reversed lactate induction to M2 macrophages. Collectively, lactate secreted by CC cells upregulates <i>GPD2</i> via histone lactylation, thereby promoting M2 macrophage polarization in CC. This study provides new insights into the role of histone lactylation in macrophage polarization in the malignant transformation of CC.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"605-618"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585296","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":"Hypertension Control Is Associated with Telomere Length in Older Adults.","authors":"Kenneth Rubio-Carrasco, Paola García de la Torre, José D Martínez-Ezquerro, Sergio Sánchez-García, Elisa García-Vences, Ignacio Camacho-Arroyo, Mauricio Rodríguez-Dorantes, Vanessa González-Covarrubias","doi":"10.1089/dna.2024.0173","DOIUrl":"10.1089/dna.2024.0173","url":null,"abstract":"<p><p>Hypertension is the leading risk for cardiovascular disease and worldwide mortality. Uncontrolled blood pressure worsens with age and its control is part of public health strategies especially for older adults. Telomere length (TL) has been associated with hypertension, with age and sex as relevant confounding factors, but it is not clear whether hypertension control in older adults impacts on TL and if this relationship is consistently age and sex dependent. TL was assessed in leukocytes of 369 hypertensive patients. Individuals were >60 years male (169) and female (200) and have been diagnosed and treated for hypertension for at least four years. TL was measured by RT-PCR using a commercial probe. Regression models were developed considering systolic and diastolic blood pressure control as dependent variables and age, sex, glucose, and lipid levels as confounding factors. TL showed a mean of 7.5 ± 5.1 Kb, and no difference between males and females was observed. We identified a significant association between systolic blood pressure control and TL (<i>p</i> value = 0.039) and a trend for diastolic blood pressure (<i>p</i> value = 0.061). These observations confirm and expand previous reports showing that hypertension control can have an impact on TL and consequently on other factors of healthy aging.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"571-578"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483943","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":"Impact of Chondroitin Sulfate Proteoglycan 4 Pseudogene 12 Genetic Variants on Colorectal Cancer Risk: A Case-Control Study.","authors":"Xianlei Zhou, Liwen Guo, Zhenbang Yang, Hongxue Xu, Zhi Zhang, Xuemei Zhang","doi":"10.1089/dna.2024.0174","DOIUrl":"10.1089/dna.2024.0174","url":null,"abstract":"<p><p>This study aims to investigate the correlation between the chondroitin sulfate proteoglycan 4 pseudogene 12 (<i>CSPG4P12</i>) polymorphism and the risk of colorectal cancer (CRC). This case-control study involved 850 patients with CRC and 850 health controls. The genotypes of <i>CSPG4P12</i> (rs2880765, rs6496932, and rs8040855) were determined by the TaqMan-MGB probe method. Logistic regression model was employed to evaluate the association of <i>CSPG4P12</i> single-nucleotide polymorphisms (SNPs) with the risk of CRC by calculating the odds ratio (OR) and 95% confidence interval (CI). The <i>CSPG4P12</i> exhibited lower expression in CRC tissues. Our data showed that the rs6496932 variant increased CRC risk (CA vs. CC: <i>p</i> = 0.006; CA + AA vs. CC: <i>p</i> = 0.005). In contrast, the rs8040855 variant reduced the risk of CRC (CG vs. CC: <i>p</i> < 0.001; CG + GG vs. CC: <i>p</i> < 0.001). Stratification by gender and age revealed that the rs8040855 variant decreased CRC risk; however, the rs6496932 variant increased CRC risk among males (CA vs. CC: <i>p</i> = 0.024; CA + AA vs. CC: <i>p</i> = 0.014) and younger individuals (CA vs. CC: <i>p</i> = 0.004; CA + AA vs. CC: <i>p</i> = 0.010). When stratified by smoking and drinking status, the rs8040855 variant decreased CRC risk among nonsmokers (CG vs. CC: <i>p</i> < 0.001; CG + GG vs. CC: <i>p</i> < 0.001) and nondrinkers (CA vs. CC: <i>p</i> = 0.002; CA + AA vs. CC: <i>p</i> = 0.004). The rs6496932 variant increased CRC risk among nonsmokers (CA vs. CC: <i>p</i> = 0.016; CA + AA vs. CC: <i>p</i> = 0.036) and nondrinkers (CG vs. CC: <i>p</i> < 0.001; CG + GG vs. CC: <i>p</i> < 0.001). Haplotype analysis showed that the <i>CSPG4P12</i> T_rs2880765C_rs6496932G_rs8040855 haplotype reduced the risk of CRC compared with the reference haplotype (<i>CSPG4P12</i> A_rs2880765C_rs6496932C_rs8040855) (OR = 0.46, 95% CI = 0.26-0.82, <i>p</i> = 0.049). These findings highlight the potential of these genetic variants as biomarkers for CRC susceptibility, offering insights into personalized prevention strategies.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"596-604"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483944","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":"SNORA71A Downregulation Enhances Gemcitabine Sensitivity in Gallbladder Cancer Cells by Inducing Ferroptosis Through Inhibiting the AKT/NRF2/GPX4 Pathway.","authors":"Yiyu Qin, Yang Zhou, Hongyan Wu, Haiming Lei, Tingyu Ding, Xinya Shen, Jian Li","doi":"10.1089/dna.2024.0107","DOIUrl":"10.1089/dna.2024.0107","url":null,"abstract":"<p><p>Previous findings have indicated a marked upregulation of SNORA71A in gallbladder cancer (GBC) tissues compared to normal samples. However, the precise role and molecular mechanisms of SNORA71A in GBC remain largely unknown. Moreover, gemcitabine (GEM) drug resistance has been found to lead to unfavorable outcomes and recurrence in GBC patients. Therefore, this study aims to investigate the impact of SNORA71A on GBC and explore its potential effects on the sensitivity of GBC cells to GEM. RT-qPCR was conducted to assess SNORA71A level in matched normal and GBC tissues. Cell proliferation was examined through CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays. Additionally, the expression of proteins in GBC cells was analyzed using western blot assay. The level of SNORA71A was notably higher in GBC tissues relative to normal tissues. SNORA71A overexpression led to increased GBC cell proliferation and invasion. Conversely, SNORA71A deficiency strongly suppressed GBC cell proliferation and invasion and triggered cell apoptosis and ferroptosis. Additionally, downregulation of SNORA71A obviously enhanced the antiproliferative and anti-invasive effects of GEM on GBC cells, whereas these changes were reversed by inhibiting ferroptosis. Furthermore, deficiency of SNORA71A further augmented the GEM-induced downregulation of p-Akt, Nrf2, and GPX4 in NOZ cells; however, these effects were reversed by ferroptosis inhibition. Collectively, these findings suggested that downregulation of SNORA71A may increase the sensitivity of GBC cells to GEM by triggering ferroptosis through inhibiting the AKT/NRF2/GPX4 signaling pathway.</p>","PeriodicalId":93981,"journal":{"name":"DNA and cell biology","volume":" ","pages":"559-569"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483945","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}