Genes & Diseases基因与疾病
Genes & Diseases(英文缩写 GENES DIS),ISSN 2352-4820,eISSN 2352-3042,中文译名:基因与疾病 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 7.376 | Q1 |
| 2022 | 6.800 | Q1 |
| 2023 | 6.900 | Q1 |
| 2024 | 9.400 | Q1 |
| 2025 | 14.600 | Q1 |
Genes & Diseases 最新收录文献
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1. ZO-2 blocks the localization of PGAM5 protein to the mitochondrial membrane and suppresses pancreatic cancer malignancy through metabolic reprogramming.
1. ZO-2阻断PGAM5蛋白向线粒体膜的定位并通过代谢重编程抑制胰腺癌恶性程度PMID:日期:2026-06-24[中文摘要] 胰腺导管腺癌（PDAC）是癌症相关死亡的主要原因之一，治疗选择有限，亟需开发有效的治疗策略。闭锁小带蛋白-2（ZO-2）是紧密连接蛋白家族成员，其在PDAC中的功能及潜在作用机制尚不清楚。研究采用免疫组化和生物信息学方法分析基因表达及其与PDAC患者临床病理特征的关系，并利用小鼠模型进行功能验证。通过功能获得和功能缺失实验及分子生物学方法检测蛋白表达和蛋白调控。结果显示，ZO-2在PDAC中表达降低，且与侵袭性病理特征及患者预后高度相关。ZO-2表达升高可抑制PDAC细胞的增殖、迁移和集落形成，并抑制PDAC肿瘤生长和肝转移。机制上，ZO-2与线粒体膜蛋白磷酸甘油酸变位酶5（PGAM5）结合并将其滞留于细胞质中。ZO-2表达降低导致PGAM5线粒体定位增加，从而激活线粒体功能并增加细胞内活性氧和ATP水平，进而促进PDAC恶性进展，而ZO-2表达升高则产生相反效应。ZO-2表达还与PDAC中免疫细胞浸润和免疫信号直接相关。ZO-2下调导致PGAM5向线粒体膜定位增加，并通过代谢重编程促进PDAC恶性进展。ZO-2与PDAC免疫微环境相关。ZO-2-PGAM5轴可能作为PDAC的潜在治疗靶点。
[英文摘要] Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death with limited treatment options, and there is an urgent need to develop effective therapeutic strategies. The zonula occludens-2 (ZO-2) protein is a member of the tight junction protein family, and its function and underlying mechanisms of action in PDAC are unknown. Gene expression and its association with the clinicopathologic characteristics of patients with PDAC were analyzed using immunohistochemistry and bioinformatics and functionally validated by using and mouse models. Protein expression and protein regulation were measured by using gain- and loss-of-function assays and molecular biology methods. The expression level of ZO-2 decreased in PDAC and was highly correlated with aggressive pathological features and the prognosis of patients. Increased expression of ZO-2 inhibited the proliferation, migration and colony formation of PDAC cells and inhibited PDAC tumor growth and liver metastasis . Mechanistically, ZO-2 bound to the mitochondrial membrane protein phosphoglycerate mutase 5 (PGAM5) and trapped it in the cytosol. Reduced expression of ZO-2 caused increased mitochondrial localization of PGAM5, leading to activated mitochondrial function and increased intracellular reactive oxygen species and ATP levels, thereby promoting PDAC malignancy, whereas increased ZO-2 expression did the opposite. ZO-2 expression also correlated directly with immune cell infiltration and immune signaling in PDAC. Downregulation of ZO-2 caused increased localization of PGAM5 to the mitochondrial membrane and promoted PDAC malignancy through metabolic reprogramming. ZO-2 is associated with the PDAC immune microenvironment. The ZO-2-PGAM5 axis could serve as a potential therapeutic target in PDAC.
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2. ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.
2. ONC201/dordaviprone用于H3 K27M突变肿瘤：发现、机制、治疗潜力及未来方向PMID:日期:2026-06-24[中文摘要] ONC201（多伐匹隆）近期获得加速批准，用于治疗复发性H3 K27M突变型弥漫性中线胶质瘤。ONC201最初被鉴定为TRAIL诱导化合物10（TIC10），是一种首创性小分子药物，具有独特的药理学特征。它通过多种汇聚机制促进细胞凋亡，包括上调TRAIL、激活整合应激反应（ISR）、直接变构激活线粒体蛋白酶ClpP以及拮抗多巴胺受体D2（DRD2）。这些通路汇聚后同时启动外源性和内源性凋亡程序，破坏线粒体生物能量学，并重编程生存信号，使ONC201区别于传统细胞毒性药物和靶向药物。临床前研究已在多种癌症模型中证实其广泛的抗肿瘤疗效。在临床方面，ONC201已快速推进通过早期试验，确立了良好的安全性和药代动力学特征，具有持续的生物学活性和每周口服给药方案。在H3 K27M突变型弥漫性中线胶质瘤中开展的关键性试验显示了有意义的临床获益，促使其获得加速监管批准，并成为首个针对这一毁灭性疾病获得此类批准的治疗药物。正在进行的研究正在将ONC201的临床应用扩展至血液系统恶性肿瘤和妇科肿瘤，以及联合治疗方案。尽管取得了这些进展，新出现的耐药机制，包括ClpP突变以及EGFR和MAPK/AKT通路的适应性激活，凸显了生物标志物开发和合理联合策略的必要性。总之，这些见解使ONC201既成为一个治疗里程碑，也成为未来转化肿瘤学创新的平台。
[英文摘要] ONC201 (dordaviprone) has recently received accelerated approval for the treatment of recurrent H3 K27M-mutant diffuse midline glioma. Originally identified as TRAIL-inducing compound 10 (TIC10), ONC201 is a first-in-class small molecule distinguished by a unique pharmacologic profile. It promotes apoptosis through multiple convergent mechanisms, including upregulation of TRAIL, activation of the integrated stress response (ISR), direct allosteric activation of the mitochondrial protease ClpP, and antagonism of dopamine receptor D2 (DRD2). These pathways converge to engage both extrinsic and intrinsic apoptotic programs, disrupt mitochondrial bioenergetics, and reprogram survival signaling, distinguishing ONC201 from conventional cytotoxic and targeted agents. Preclinical studies have demonstrated broad antitumor efficacy across diverse cancer models. Clinically, ONC201 has progressed rapidly through early-phase trials, establishing a favorable safety and pharmacokinetic profile, with sustained biological activity and weekly oral dosing. Pivotal trials in H3 K27M-mutant diffuse midline glioma demonstrated meaningful clinical benefit, leading to accelerated regulatory approval and making it the first therapy to receive such approval for this devastating disease. Ongoing studies are expanding ONC201's clinical applications to hematologic malignancies and gynecologic cancers, as well as to combination regimens. Despite these advances, emerging resistance mechanisms, including ClpP mutations and adaptive activation of the EGFR and MAPK/AKT pathways, highlight the need for biomarker development and rational combination strategies. Together, these insights position ONC201 as both a therapeutic milestone and a platform for future translational oncology innovation.
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3. {"_":" pathogenic variant uncovers a novel autoantigen in membranous nephropathy.","i":["LAMA5"]}
PMID:日期:2026-06-13Membranous nephropathy is a leading cause of nephrotic syndrome, driven by autoantibodies targeting podocyte antigens. Although antibodies against PLAR and THSD7A account for the majority of cases, a substantial fraction of patients remain seronegative, implying the existence of additional, unidentified autoantigens. Here, we report the identification of two novel compound heterozygous mutations in encoding Laminin α5, in a pediatric patient with severe nephrotic syndrome. Whole-exome sequencing revealed c.1355A>T (p.N452I) and c.9770A>G (p.N3257S) variants, with structural modeling indicating that p.N452I induces a conformational change in Laminin α5. This altered conformation enhanced its binding to Collagen IV networks, resulting in thickening of the glomerular basement membrane and the creation of a neo-epitope recognized by conformation-specific IgG1/IgG3 autoantibodies. These autoantibodies activated the classical complement pathway, triggering podocyte injury. A knock-in mouse model harboring the mutation recapitulated the human phenotype, exhibiting proteinuria, glomerular basement membrane thickening, and glomerular IgG deposits. Notably, rituximab treatment in the patient led to the disappearance of anti-Laminin α5 autoantibodies and sustained clinical remission. Our findings establish Laminin α5 as a novel genetic autoantigen in membranous nephropathy and suggest that screening for anti-Laminin α5 antibodies may help identify patients who could benefit from B-cell-targeted therapies.
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5. Epigenetic insights into cancer metastasis via lineage trans-differentiation.
PMID:日期:2026-06-06该文献暂无摘要。
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6. A novel adenoma-carcinoma sequence- and disulfidptosis-associated gene signature for prognostic prediction and mechanistic insights in colorectal cancer.
6. 一种新型腺瘤-癌序列和二硫死亡相关基因特征用于结直肠癌的预后预测和机制研究PMID:日期:2026-06-03该文献暂无摘要。
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7. Differential contribution of elastin and fibrillin-1 to the cardiovascular phenotype of a double heterozygous Marfan and Williams-Beuren syndrome mouse model.
7. 弹性蛋白和纤维蛋白-1对马凡综合征和威廉姆斯-贝伦综合征双杂合小鼠模型心血管表型的差异性贡献PMID:日期:2026-06-01该文献暂无摘要。
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8. VCP at the crossroads of UPS and autophagy in cancer.
8. VCP在癌症中处于UPS与自噬的交叉路口PMID:日期:2026-05-28[中文摘要] 蛋白质稳态由泛素-蛋白酶体系统（UPS）与自噬-溶酶体途径的协同作用维持。含缬酪肽蛋白（VCP/p97）是一种AAA+去折叠酶，通过提取泛素化底物并组装决定底物命运的辅因子限定性复合物，处于上述两条通路的交汇点。在癌症中，VCP上调及辅因子募集改变重塑了这些泛素依赖性分选决策。通过募集重塑K48和K63连接泛素链的E3连接酶和去泛素化酶，VCP使底物偏向Ufd1-Npl4偶联的蛋白酶体降解或自噬相关清除，从而实现癌基因稳定或抑癌基因缺失。这些原则体现在调控自噬流、侵袭与转移、PI3K/AKT/mTOR信号传导及免疫逃逸的癌症轴中。抑癌蛋白p53以状态依赖性结局说明了这种复杂性：VCP通过经典Ufd1-Npl4复合物促进野生型p53的蛋白酶体降解，而以伴侣/保持酶样方式稳定R273H热点突变体，延长功能获得性表型。对立的调控因子进一步控制VCP功能：PLAC8增强VCP-Ufd1-Npl4活性，并与野生型p53降解、PI3K/AKT/mTOR激活及情境依赖性自噬效应相关。相反，SVIP可竞争性取代其他VCP辅因子，并通过酰化依赖性膜靶向将VCP重定向至溶酶体相关功能，主要产生抑瘤效应。总体而言，这一框架推动了通过调节VCP-辅因子相互作用来调控底物降解命运的治疗策略。相关方法包括破坏Ufd1-Npl4轴、使VCP从UPS偏向自噬、改变亚细胞定位以及重编程VCP用于靶向蛋白降解，对癌症、纤维化、神经退行性疾病及多系统蛋白病具有重要意义。
[英文摘要] Proteostasis is maintained by the coordinated action of the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathways. Valosin-containing protein (VCP/p97), an AAA + unfoldase, sits at its intersection by extracting ubiquitinated clients and assembling cofactor-defined complexes that determine substrate fate. In cancer, VCP up-regulation and altered cofactor recruitment rewire these ubiquitin-dependent routing decisions. By recruiting E3 ligases and deubiquitinases that remodel K48- and K63-linked ubiquitin chains, VCP biases substrates toward Ufd1-Npl4-coupled proteasomal turnover or autophagy-linked clearance, enabling oncogene stabilization or tumor suppressor loss. These principles are reflected in cancer axes that modulate autophagy flux, invasion and metastasis, PI3K/AKT/mTOR signaling, and immune evasion. The tumor suppressor p53 illustrates this complexity with state-dependent outcomes: VCP promotes proteasomal turnover of wild-type p53 through the canonical Ufd1-Npl4 complex, whereas it can stabilize the R273H hotspot mutant in a chaperone/holdase-like manner, prolonging gain-of-function phenotypes. Opposing regulators further control VCP function: PLAC8 enhances VCP-Ufd1-Npl4 activity and is linked to wild-type p53 turnover, PI3K/AKT/mTOR activation, and context-dependent autophagy effects. In contrast, SVIP can outcompete other VCP cofactors and, via acylation-dependent membrane targeting, redirect VCP toward lysosome-associated functions with predominantly tumor-suppressive effects. Collectively, this framework motivates therapeutic strategies that modulate VCP-cofactor interactions to regulate substrate degradative fate. Approaches include disrupting the Ufd1-Npl4 axis, biasing VCP from UPS to autophagy, altering subcellular localization, and reprogramming VCP for targeted proteolysis, with implications for cancer, fibrosis, neurodegeneration, and multisystem proteinopathy.
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9. Endothelial-specific RIPK1 K376 mutation triggers kinase hyperactivation and embryonic lethality.
PMID:日期:2026-05-27该文献暂无摘要。
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10. An antibiotic-free plasmid vector platform for non-viral DNA delivery.
10. 一种用于非病毒DNA递送的无抗生素质粒载体平台PMID:日期:2026-05-23该文献暂无摘要。