Genes & Diseases最新文献

{"title":"Multiomic insights into the MPO-mediated NET formation pathway in alcohol-induced epilepsy risk","authors":"Ningning Zhang ,&nbsp;Sirui Chen ,&nbsp;Jialing Jiang ,&nbsp;Hong Jiang ,&nbsp;Qing Wang ,&nbsp;Srikrishnan Raju ,&nbsp;Jackson G. Schumacher ,&nbsp;Jiliang Lu ,&nbsp;Yihe Lian ,&nbsp;Yuansong Zhang ,&nbsp;Yuanhang Xu ,&nbsp;Lan Zhang ,&nbsp;Yaqing Liu ,&nbsp;Junqiang Li ,&nbsp;Yiru Zhang ,&nbsp;Yuxuan Wang ,&nbsp;Yixue Gu ,&nbsp;Tiancheng Wang ,&nbsp;Xin Tian","doi":"10.1016/j.gendis.2025.101917","DOIUrl":"10.1016/j.gendis.2025.101917","url":null,"abstract":"<div><div>Epilepsy is a highly prevalent chronic central nervous system disorder that imposes substantial societal and economic burdens. Inconsistent associations of alcohol consumption, identified as a major global health risk factor, with epilepsy risk have been reported. The aim of the present study was to assess the relationship between alcohol use and epilepsy and to identify potential underlying mechanisms, with a particular focus on the role of neutrophil extracellular traps (NETs), using an integrated multiomic approach. We assessed the global risk of alcohol consumption for epilepsy using data from the Global Burden of Disease Study 2021, and we conducted a Mendelian randomization (MR) analysis to evaluate causality. Additionally, we employed machine learning algorithms and protein–protein interaction networks to identify key genes. Our results indicate that alcohol consumption significantly contributes to the risk of epilepsy, as confirmed by MR analysis (odds ratio = 1.30, 95% confidence interval 1.06–1.60; <em>p</em> = 0.011). Functional enrichment analysis revealed pathways related to NET formation, whereas machine learning identified key genes such as myeloperoxidase (MPO) and neutrophil elastase. Animal and molecular experiments confirmed that acute alcohol exposure increases the susceptibility to epileptic seizures, whereas the MPO inhibitor 4-aminobenzoic acid hydrazide showed therapeutic potential for alcohol-induced epilepsy. This study provides novel insights into the role of NETs in alcohol-induced epilepsy and highlights potential therapeutic targets, thereby contributing to the development of innovative treatment strategies for epilepsy prevention and management.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101917"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting SUMOylation in glioblastoma: A novel avenue for therapy and biomarker discovery","authors":"Wiktoria Dubanosow,&nbsp;Bartosz Lenda,&nbsp;Marta Żebrowska-Nawrocka,&nbsp;Dagmara Szmajda-Krygier,&nbsp;Rafał Świechowski,&nbsp;Ewa Balcerczak","doi":"10.1016/j.gendis.2025.101841","DOIUrl":"10.1016/j.gendis.2025.101841","url":null,"abstract":"<div><div>SUMOylation, a post-translational protein modification, plays a crucial role in regulating various biological processes. Dysregulation of SUMOylation has been linked to glioblastoma progression, impacting key signaling pathways. This review summarizes the current knowledge on SUMOylation's role in glioma malignancy, highlighting its influence on cell cycle regulation, PKB/AKT signaling pathway, and microRNA expression. Our work identifies Ubc9 as a promising therapeutic target due to its role in enhancing SUMOylation, promoting glioblastoma aggressiveness, and facilitating tumor proliferation. Additionally, SAE1 correlates with glioblastoma grade and affects cell cycle regulators, while SUMOylation stabilizes CDK6, driving the G1/S transition. Targeting these pathways with inhibitors, such as topotecan and chlorogenic acid, may provide novel treatment strategies. Furthermore, SUMOylation-driven alterations in transcription factors and DNA repair mechanisms contribute to therapy resistance. Understanding these mechanisms could pave the way for innovative interventions in glioblastoma management.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101841"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of glutamine metabolism in stromal components of the tumor microenvironment and potential anti-tumor therapies","authors":"Zizhuo Li ,&nbsp;Jiapeng Deng ,&nbsp;Hai Wang ,&nbsp;Tao Liu ,&nbsp;Yuyang Zhou ,&nbsp;Pei Ouyang ,&nbsp;Xuan Liang ,&nbsp;Xian Zhang ,&nbsp;Songtao Qi ,&nbsp;Yaomin Li","doi":"10.1016/j.gendis.2025.101834","DOIUrl":"10.1016/j.gendis.2025.101834","url":null,"abstract":"<div><div>As a critical metabolite in the tumor microenvironment, glutamine plays a crucial role in tumor progression, and its dual effects on promoting and inhibiting tumors have garnered increasing attention in recent years. Glutamine metabolism in tumor cells has been extensively studied; however, there is currently a lack of a comprehensive description of how it interacts with tumor stromal components in the tumor microenvironment. This review focuses on the interaction of glutamine metabolism and a range of tumor stromal components, such as macrophages, dendritic cells, T cells, fibroblasts, collagen, and blood vessels in the tumor microenvironment, as well as a summary of current prospective anti-tumor therapeutics targeting glutamine metabolism. Furthermore, this study discusses the shortcomings of mechanism research, metabolic complexity, and metabolic therapy for glutamine metabolism and proposes future research directions that are expected to provide a theoretical foundation for clinical cancer treatment strategies.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101834"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sox11 deficiency induces paravertebral muscle injury and scoliosis via Mlxipl upregulation","authors":"Ruohao Wu ,&nbsp;Wenting Tang ,&nbsp;Yu Li ,&nbsp;Zihao Deng ,&nbsp;Jing Zhang ,&nbsp;Xiaojuan Li ,&nbsp;Chunwei Cao ,&nbsp;Liyang Liang","doi":"10.1016/j.gendis.2025.101970","DOIUrl":"10.1016/j.gendis.2025.101970","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101970"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic variation in human DNA damage repair genes was originated from the evolutionary process of modern humans","authors":"Jiaheng Li ,&nbsp;Bojin Zhao ,&nbsp;Zixin Qin ,&nbsp;Si Hoi Kou ,&nbsp;Jia Sheng Chian ,&nbsp;Fengxia Xiao ,&nbsp;Huijun Lei ,&nbsp;Stephanie Andaluz ,&nbsp;Jun He ,&nbsp;Siddharth Sinha ,&nbsp;Xiaowei Mao ,&nbsp;San Ming Wang","doi":"10.1016/j.gendis.2025.101916","DOIUrl":"10.1016/j.gendis.2025.101916","url":null,"abstract":"<div><div>DNA damage repair (DDR) genes play critical roles in maintaining genome stability. However, they are prone to genetic variation, of which pathogenic variation (PV) is a predisposing factor for high risk of cancer development in modern humans. Knowing the origin of DDR PV is critical for understanding the genetic basis and developing strategies against cancer risk for modern humans. So far, there is no consensus on the original sources of DDR PV in modern humans. We performed phylogenic analysis, and the results ruled out non-human species as the original source for the PV in modern humans through evolutionary conservation. We performed anthropological analyses by tracing the PV from modern humans in over 5000 ancient humans spanning the past 40,000 years. We observed a widespread distribution of DDR PV shared between modern and ancient humans. The shared DDR PV was predominantly found in modern non-Africans within the past 10,000 years rather than in modern Africans, highlighting that the arising time should be post the latest Out-of-Africa human migration. We also observed the rich distribution of Portuguese <em>BRCA</em> founder PV in Brazilian, highlighting that human admixture facilitated DDR PV transmission globally between ethnic human populations. The shorter arising time of DDR PV was further supported by the haplotyping results of DDR founder PV in multiple DDR genes and the predominant heterozygotic nature of DDR PV. Our comprehensive investigation reveals that DDR PV was mainly originated from the recent evolutionary history of modern humans, and highlights that the high cancer risk caused by DDR PV in modern humans is a by-product of the human evolution process.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101916"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variability in the PLIN4 gene: A new sequence duplication causing autophagic vacuolar myopathy","authors":"Alessandra Carnazzi ,&nbsp;Eliana Iannibelli ,&nbsp;Sara Gibertini ,&nbsp;Lucia Nicolini De Gaetano ,&nbsp;Giorgia Riolo ,&nbsp;Franco Salerno ,&nbsp;Andrea Legati ,&nbsp;Daniele Ghezzi ,&nbsp;Lorenzo Maggi ,&nbsp;Alessandra Ruggieri","doi":"10.1016/j.gendis.2025.101849","DOIUrl":"10.1016/j.gendis.2025.101849","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101849"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-mode aptamer-driven biosensing platform for ultrasensitive and mutation-resilient detection of the SARS-CoV-2 nucleocapsid protein","authors":"Shu Zhou ,&nbsp;Yuxi Xu ,&nbsp;Huan Liao ,&nbsp;Hailong Ou ,&nbsp;Dan Qi ,&nbsp;Yatao Wu ,&nbsp;Yunyi Liu ,&nbsp;Juan Li ,&nbsp;Jiaxuan Li ,&nbsp;Bi Shi ,&nbsp;Fei Zhu ,&nbsp;Siran Zhang ,&nbsp;Jason H. Huang ,&nbsp;Erxi Wu ,&nbsp;Xiaoxiao Hu","doi":"10.1016/j.gendis.2025.101943","DOIUrl":"10.1016/j.gendis.2025.101943","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a significant global health threat because of its rapid evolution and high mutation rate, which limits the performance of existing molecular diagnostics. This study presents a dual-mode, aptamer-based detection platform that combines high sensitivity with mutation resilience. Using a computer-assisted X-aptamer Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach, we identified NP14, a high-affinity, dual-target DNA aptamer that specifically binds to the SARS-CoV-2 nucleocapsid (N) protein at its N-terminal domain. Analyses via molecular docking, aptamer truncation, and targeted mutagenesis revealed that NP14 interacted with both SARS-CoV-2 and SARS-CoV N proteins and identified key nucleotides C24 and G27 of the P1 region and structural determinants critical for its high-affinity binding. Building on this discovery, we engineered a dual-mode biosensing system by integrating NP14 into a multicolor dynamic light scattering-enhanced enzyme-linked aptamer-antibody assay (MD ELAAA). MD ELAAA synergistically combines two complementary detection strategies: i) non-aggregative plasmonic colorimetry for visual signal detection and ii) dynamic light scattering for ultrasensitive quantitative analysis, in which Au/Ag nanomaterials are used to amplify optical and scattering signals. This system achieves a sensitivity of 0.43 TCID₅₀/mL, representing a 47-fold improvement over standard methods. By integrating high sensitivity, specificity, variant recognition, and dual-mode signal output, the MD ELAAA platform enables reliable detection of low-abundance SARS-CoV-2 antigens. Its robust performance supports early-stage diagnostics and high-throughput variant monitoring, establishing MD ELAAA as a robust platform for next-generation viral detection and surveillance.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101943"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic insights into minimal residual disease detection in cancer","authors":"Lingao Ju ,&nbsp;Gang Wang ,&nbsp;Zilin Xu ,&nbsp;Wan Xiang ,&nbsp;Hongwei Peng ,&nbsp;Mengxue Yu ,&nbsp;Shenjuan Li ,&nbsp;Yi Zhang ,&nbsp;Kaiyu Qian ,&nbsp;Yu Xiao","doi":"10.1016/j.gendis.2025.101830","DOIUrl":"10.1016/j.gendis.2025.101830","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101830"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in human papillomavirus vaccines and therapeutic strategies: Combating cervical and non-cervical cancers","authors":"Md Rezaul Islam ,&nbsp;Abdur Rauf ,&nbsp;Most Nazmin Aktar ,&nbsp;Md Naeem Hossain Fakir ,&nbsp;Sadiya Islam Trisha ,&nbsp;Asraful Islam Asif ,&nbsp;Md Harun Or Rashid ,&nbsp;Md Ibrahim Khalil Al-Imran ,&nbsp;Gazi Kaifeara Thufa ,&nbsp;Farhana Prodhan Emu ,&nbsp;Hassan A. Hemeg ,&nbsp;Hanan A. Ogaly ,&nbsp;Rekha Thiruvengadam ,&nbsp;Seung-Hyun Kim ,&nbsp;Muthu Thiruvengadam","doi":"10.1016/j.gendis.2025.101880","DOIUrl":"10.1016/j.gendis.2025.101880","url":null,"abstract":"<div><div>Human papillomaviruses (HPV) are a major cause of several cancers, particularly cervical cancer, and remain a serious public health challenge, particularly in low-resource countries. In addition to cervical cancer, HPV is linked to vulvar, vaginal, penile, anal, and oropharyngeal cancers, especially in men. The integration of HPV into the human genome plays a key role in cancer development. This review highlights the progress in HPV vaccination and new treatment approaches for non-cervical HPV-related cancers. Current vaccines provide strong protection against cervical cancer, and next-generation vaccines aim to protect against more types of cancer-causing HPV. New immunotherapy strategies, such as DNA-based vaccines and antigen-specific immunotherapy, are being developed to more effectively target HPV-driven cancers. Promising methods, such as CRISPR/Cas9 gene editing, therapeutic vaccines, and immune checkpoint inhibitors, have shown success in early research and clinical trials. Among these, DNA vaccines stand out as cost-effective and scalable solutions for treating HPV-related tumors. This review also explores the biology of HPV-related cancers, global trends, and the latest advances in prevention and treatment. To reduce the burden of HPV-related diseases, a combined approach involving vaccination, early detection, and personalized treatment is essential. Ongoing research on therapeutic vaccines, gene therapies, and immune-based treatments could greatly improve the management of HPV-related cancers, potentially lowering their global impact. Expanding these innovations in clinical practice may significantly reduce the global burden of HPV-related malignancies.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101880"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of long non-coding RNAs in NK cell biology and diseases","authors":"Dan Zhang ,&nbsp;Siqiao Wei ,&nbsp;Qianqiu Wei ,&nbsp;Zhansong Lin ,&nbsp;Xiaoming Sun","doi":"10.1016/j.gendis.2025.101833","DOIUrl":"10.1016/j.gendis.2025.101833","url":null,"abstract":"<div><div>Long non-coding RNAs (lncRNAs) are pivotal regulators of gene expression, increasingly recognized for their roles in immune responses and disease progression. Natural killer (NK) cells, essential cytotoxic lymphocytes of the innate immune system, orchestrate immune responses through cytokine secretion and direct cytotoxicity. This review elucidates the immunomodulatory functions of lncRNAs in NK cell biology and their implications in pathological conditions. LncRNAs intricately govern key NK cell processes, including development, differentiation, activation, recruitment, cytotoxic function, and immune infiltration within the tumor microenvironment. These regulatory effects are mediated through diverse mechanisms, such as transcriptional control of effector molecules, miRNA sponging, metabolic reprogramming, protein ubiquitination, and epigenetic modifications. Focusing on NK cell infiltration in tumors, we classify lncRNAs into mechanistically defined and uncharacterized groups, highlighting their roles in tumor-associated competing endogenous RNA (ceRNA) networks, epigenetic regulation, and cell death pathways. By integrating these perspectives, this review enhances our understanding of lncRNA-mediated immune regulation and underscores their potential as therapeutic targets for diseases involving NK cell dysfunction.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101833"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}