Genes & Diseases最新文献

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Network pharmacology reveals that Yanghe Decoction inhibits osteosarcoma progression via ROS-induced mitochondrial dysfunction and enhances cisplatin sensitivity 网络药理学研究表明，洋河汤通过ros诱导的线粒体功能障碍抑制骨肉瘤进展，并增强顺铂敏感性

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-09-20 DOI: 10.1016/j.gendis.2025.101862

Yanran Huang , Dagang Tang , Runhan Zhao , Jun Zhang , Xiao Qu , Ningdao Li , Yi Ren , Xiaoji Luo

Osteosarcoma (OS) is a highly aggressive bone malignancy with limited treatment options and frequent chemoresistance. Yanghe Decoction (YHD), a traditional Chinese medicine formula, has demonstrated anti-tumor potential, but its mechanisms in OS remain unclear. In this study, we employed a network pharmacology approach to identify 67 active components and 101 OS-related targets of YHD, with core targets including AKT1, TP53, MAPK14, and CASP3, mainly enriched in the PI3K/AKT and MAPK signaling pathways. Molecular docking confirmed strong binding affinities between representative compounds and these targets. Functional experiments revealed that YHD inhibited OS cell proliferation, migration, and invasion, and promoted apoptosis by elevating intracellular reactive oxygen species levels and inducing mitochondrial dysfunction. Mechanistically, YHD suppressed the PI3K/AKT pathway while activating p38 MAPK signaling. Importantly, YHD enhanced the sensitivity of OS cells to cisplatin, demonstrating a synergistic inhibitory effect in vitro and in an orthotopic OS mouse model. These findings suggest that YHD exerts its anti-osteosarcoma effects via reactive oxygen species-mediated mitochondrial disruption and pathway modulation, and may serve as a promising adjuvant to conventional chemotherapy.

骨肉瘤（OS）是一种高度侵袭性的骨恶性肿瘤，治疗选择有限，经常出现化疗耐药。中药洋河汤（YHD）具有抗肿瘤的潜力，但其在OS中的作用机制尚不清楚。在本研究中，我们采用网络药理学方法鉴定了YHD的67个有效成分和101个os相关靶点，核心靶点包括AKT1、TP53、MAPK14和CASP3，主要富集于PI3K/AKT和MAPK信号通路。分子对接证实了代表性化合物与这些靶标之间的强结合亲和力。功能实验显示，YHD通过提高细胞内活性氧水平和诱导线粒体功能障碍，抑制OS细胞增殖、迁移和侵袭，促进细胞凋亡。在机制上，YHD抑制PI3K/AKT通路，同时激活p38 MAPK信号。重要的是，YHD增强了OS细胞对顺铂的敏感性，在体外和原位OS小鼠模型中显示出协同抑制作用。这些发现表明，YHD通过活性氧介导的线粒体破坏和途径调节发挥其抗骨肉瘤作用，并可能作为传统化疗的一种有希望的辅助药物。

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引用次数: 0

Identification and analysis of extrachromosomal circular DNAs in pancreatic islets during the early and late stages of T2DM mice T2DM小鼠早期和晚期胰岛染色体外环状dna的鉴定和分析

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-10-31 DOI: 10.1016/j.gendis.2025.101914

Zhichao Li , Yue Sun , Shujun Wan , Hongwen Chu , Deguo Wang , Kun Lv , Xiang Kong , Xinming Yao

引用次数: 0

Leveraging a chromosomal instability-based signature to predict the prognosis and immune landscape of breast cancer 利用基于染色体不稳定性的特征来预测乳腺癌的预后和免疫景观。

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-11-06 DOI: 10.1016/j.gendis.2025.101924

Huiling Wang , Huijuan Dai , Yaohui Wang, Qiong Wu, Mingxi Zhu, Wenjin Yin, Jinsong Lu

Chromosomal instability (CIN) significantly impacts the tumor progression and tumor immune microenvironment (TIME). However, few researchers have focused on CIN variables in predicting prognosis and the immune landscape of breast cancer. Through unsupervised consensus clustering, the TCGA-BRCA cohort was categorized into two clusters based on the CIN25 gene signature. After identifying the two clusters’ differentially expressed genes, we sequentially performed univariate Cox, LASSO, and multivariate Cox regression analyses to construct a 13-gene signature, termed “CIN score”. Then, the breast cancer patients were divided into low- and high-CIN score groups. The differences in survival outcome, clinicopathological parameters, TIME, and drug sensitivity between the two groups were further investigated. The high-CIN score group had unfavorable clinicopathological features and overall survival. TIME analysis indicated that the low-CIN score group had increased expression of immune checkpoint genes and infiltration of immune cells, suggesting that immunotherapy was more likely to benefit the low-CIN score group. Additionally, drug sensitivity analysis indicated the high-CIN score group has lower sensitivity to several commonly used chemotherapeutic, endocrine, and targeted agents than the low-CIN score group. The novel gene signature, CIN score, identified in our research, offers a novel tool to predict the prognosis, TIME, and drug responsiveness in breast cancer, thus providing insights into immunotherapy decision-making and contributing to the precision treatment in breast cancer.

染色体不稳定性（CIN）显著影响肿瘤进展和肿瘤免疫微环境（TIME）。然而，很少有研究者关注CIN变量在预测乳腺癌预后和免疫景观中的作用。通过无监督共识聚类，根据CIN25基因特征将TCGA-BRCA队列分为两类。在确定了两个集群的差异表达基因后，我们依次进行单变量Cox、LASSO和多变量Cox回归分析，构建了一个13个基因的特征，称为“CIN评分”。然后将乳腺癌患者分为cin评分低组和高组。进一步观察两组患者在生存结局、临床病理参数、时间、药物敏感性等方面的差异。cin高评分组的临床病理特征和总生存期均较差。TIME分析提示低cin评分组免疫检查点基因表达增加，免疫细胞浸润增加，提示免疫治疗更可能使低cin评分组获益。此外，药物敏感性分析显示，高cin评分组对几种常用化疗药物、内分泌药物和靶向药物的敏感性低于低cin评分组。我们的研究发现了一种新的基因标记，CIN评分，为预测乳腺癌的预后、时间和药物反应性提供了一种新的工具，从而为免疫治疗决策提供了见解，有助于乳腺癌的精确治疗。

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引用次数: 0

Targeting MDK alleviates bone loss via dual regulation of osteogenic differentiation and inflammatory cytokine expression 以MDK为靶点，通过调控成骨分化和炎性细胞因子表达来缓解骨质流失。

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-11-10 DOI: 10.1016/j.gendis.2025.101931

Xieyidai Ruze , Yutong Hu , Xiongyi Wang , Houfu Lai , Ruizhi Zhang , Sheng Pan , Jiajun Zhang , Yike Wang , Simin Yun , Ying Xu , Junjie Li , Youjia Xu

Growth factors are bioactive molecules that play crucial roles in regulating growth, development, and disease processes, both locally and systemically. Identifying growth factors involved in bone homeostasis and targeting them is a key strategy for treating bone metabolic diseases. In this study, we observed significantly elevated serum levels of midkine (MDK) in patients with postmenopausal osteoporosis and in ovariectomized mice, based on clinical data and animal experiments. We also identified a negative correlation between MDK levels and bone mineral density. The small molecule inhibitor of MDK, iMDK, effectively mitigated estrogen deficiency-induced bone loss by promoting bone formation and inhibiting inflammatory factors. Our in vitro experiments further revealed that recombinant MDK protein dose-dependently inhibited osteogenic differentiation. Transcriptome analysis showed that recombinant MDK protein affected osteogenic differentiation through the PI3K/AKT signaling pathway. Additionally, it increased the expression of inflammatory cytokines, including IL-6, TNF-α, and IL-1β, via the NF-κB signaling pathway. These findings suggest that MDK could serve as a novel therapeutic target for postmenopausal osteoporosis, and that iMDK may be a promising therapeutic candidate.

生长因子是一种生物活性分子，在局部和全身调节生长、发育和疾病过程中起着至关重要的作用。识别与骨稳态相关的生长因子并靶向它们是治疗骨代谢疾病的关键策略。在本研究中，基于临床数据和动物实验，我们观察到绝经后骨质疏松症患者和去卵巢小鼠的血清midkine （MDK）水平显著升高。我们还发现MDK水平与骨密度呈负相关。MDK的小分子抑制剂iMDK通过促进骨形成和抑制炎症因子有效减轻雌激素缺乏引起的骨质流失。我们的体外实验进一步揭示了重组MDK蛋白的剂量依赖性抑制成骨分化。转录组分析显示重组MDK蛋白通过PI3K/AKT信号通路影响成骨分化。此外，它通过NF-κB信号通路增加炎症因子IL-6、TNF-α、IL-1β的表达。这些发现表明MDK可以作为绝经后骨质疏松症的新治疗靶点，而iMDK可能是一个有希望的治疗候选者。

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引用次数: 0

A novel truncating variant in PRDM16 causes severe familial cardiomyopathy with variable clinical presentations 一种新的截断型PRDM16导致严重的家族性心肌病，具有不同的临床表现

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-10-13 DOI: 10.1016/j.gendis.2025.101879

Yuan Che , Lindsey Walker , Lillian Sau , Tingting Tang , Wei Li , Chao Shen , Nick Shillingford , Ramzi Bawab , Jianjun Chen , Miao Sun

引用次数: 0

In vivo CRISPR/Cas9-mediated gene integration corrects mucopolysaccharidosis type II in mice 体内CRISPR/ cas9介导的基因整合可纠正小鼠II型粘多糖病

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-11-08 DOI: 10.1016/j.gendis.2025.101928

Hanfei Yu , Qian Qin , Shiyu Cui , Yujuan Wa , Kexian Dong , Wei Ji , Xueyuan Jia , Songbin Fu , Jie Wu , Wenjing Sun

引用次数: 0

PI3Kα-RAS interface disruption as a new therapeutic strategy 破坏PI3Kα-RAS界面作为新的治疗策略

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-10-27 DOI: 10.1016/j.gendis.2025.101905

Abdelhalim Azzi

引用次数: 0

HSF5: A novel switch for meiotic pachynema progression in male germ cells HSF5：男性生殖细胞减数分裂厚壁瘤进展的新开关

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-09-23 DOI: 10.1016/j.gendis.2025.101868

Chunhai Luo, Ziqi Yu, Dalin Liu, Haoran Xu, Junfeng Zhan, Fei Sun

引用次数: 0

SPP1 expression serves as a potential peripheral circulating biomarker for lung cancer prognostics and drives tumorigenesis SPP1表达可作为肺癌预后的潜在外周循环生物标志物，并可驱动肿瘤发生

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-12-23 DOI: 10.1016/j.gendis.2025.101994

Xu-Ran Zhang , Fan-Li Sun , Bing Wei , Bing-Hua Jiang

引用次数: 0

Identification and functional characterization of a novel nonsense mutation of CASR gene in a familial hypocalciuric hypercalcemia pedigree 家族性低钙高钙血症家系中CASR基因新无义突变的鉴定和功能表征

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-07-25 DOI: 10.1016/j.gendis.2025.101781

Yang Tian , Bingyang Liu , Yang Xudan , Ruojun Qiu , Zhang Shaojun , Huang Haoshu , Wu Fang , Fenping Zheng

引用次数: 0

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