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- The early detection and diagnosis of head and neck squamous cell carcinoma (HNSCC) pose significant challenges. - Source: PubMed
Publication date: 2026/04/24
Xia YichaoLou HuiquanShao ShengjieLiu XiangLi Yongsheng - Erythroid acute myeloid leukemia (AML) cell line OCI-M2 expresses a particular oncogenic network: IRF6, in concert with ETV2 and HEY1, aberrantly activates NKL homeobox gene NKX2-4, which in turn represses megakaryocytic lineage factor FLI1. Interestingly, in keratinocytes, IRF6 is able to bind glucose which promotes IRF6-dimerization and thus alters its binding site selection. Here, we used OCI-M2 as a model to investigate the role of glucose level and IRF6 in leukemogenesis. Treatment of OCI-M2 with high glucose or 2-deoxy-glucose resulted in the downregulation of IRF6 and NKX2-4, and the upregulation of FLI1, indicating that glucose-mediated dimerization of IRF6 altered its reported autoactivation. The screening of this cell line for genes encoding glycolytic enzymes identified aberrant overexpression of glucose-6-phosphate isomerase (GPI) and phosphofructokinase L (PFKL), which were targeted by genomic amplification and chromothripsis-like alterations, respectively. Furthermore, GPI was activated by NKX2-4 and ETV2, and PFKL by ETV2. Finally, siRNA-mediated downregulation of PFKL resulted in elevated glucose levels, suppressed expression of IRF6 and NKX2-4, and activated FLI1. Thus, we connected an oncogenic regulatory network with deregulated glycolytic enzymes and glucose metabolism, thereby establishing a new in vitro model to develop novel therapeutic avenues in AML subsets. - Source: PubMed
Publication date: 2026/03/23
Nagel StefanMeyer CorinnaPommerenke Claudia - Attention-deficit/hyperactivity disorder (ADHD) is a common heritable neurodevelopmental disorder, affecting ~7 million children (11.4%) in the U.S. However, ADHD's underlying genetic architecture remains largely unknown. Transcriptome-wide association studies (TWAS), which integrate expression quantitative trait loci (eQTL) and GWAS summary data, can identify differentially expressed risk genes underlying complex phenotypes. Here we conduct a TWAS of ADHD using expression data from multiple brain tissues to improve understanding of the complex genetic architecture underlying this psychopathology. - Source: PubMed
Publication date: 2026/02/22
Abrishamcar SarinaDai QileYang JingjingHüls AnkeEpstein Michael P - Sleep deprivation is a growing public health burden linked to neuroinflammation, oxidative stress, and neurodegeneration. While conventional hypnotics provide transient relief, their long-term use is limited by tolerance and adverse effects. Guhan Yangsheng Jing (GHYSJ), a classical multi-herbal prescription from traditional Chinese medicine, has been clinically used to relieve insomnia and fatigue, yet its neuroprotective mechanisms remain unclear. - Source: PubMed
Publication date: 2026/01/13
Fu XinyingLong QingyingWang ZhibinYan SiyangLi LingLiu LumeiHu ZongrenZeng XiaokeZhu XinhuaJiang JinYang RenyiZhang WeiHe Qinghu - Bladder urothelial carcinoma (BLCA) is a common malignant tumor with high invasiveness and recurrence rates, underscoring the need for early diagnosis and effective monitoring. Current diagnostic methods, such as invasive cystoscopy and low-sensitivity urine cytology, have limitations. Oncogene hypermethylation plays a key role in tumorigenesis and progression. However, DNA methylation in BLCA remain underexplored. Identifying and validating new DNA methylation markers in urine samples is crucial to enhance early detection accuracy. In this study, we identified three novel BLCA DNA methylation biomarkers (HIST1H3J, NKX2-4, and YBX3P1 genes), and compared with six known markers (ONECUT2, OTX1, POU4F2, SOX1, TWIST1, VIM). Real-time quantitative methylation-specific PCR (qMSP) was used to detect the methylation levels of biomarkers in 319 urine samples from patients with suspected BLCA. The individual biomarkers of HIST1H3J, NKX2-4, and YBX3P1 achieved Areas Under the Curve (AUCs) of 0.892, 0.914 and 0.871, with accuracies of 84.80%, 85.38% and 81.29%, respectively. In comparison, the six known markers exhibited AUCs ranging from 0.850 to 0.939 and the accuracies of 81.87%-88.30%. These methylation markers can not only identify high-grade BLCA but also low-grade BLCA, highlighting their potential clinical utility. Notably, a four-gene panel (ONECUT2, SOX1, TWIST1 and NKX2-4) significantly improved the detection performance, with an AUC of 0.971 and an accuracy of 92.39%. Our results provide three new DNA methylation markers for BLCA and propose a urine-based DNA methylation detection panel for non-invasive clinical diagnosis. - Source: PubMed
Publication date: 2025/12/19
Shi CongXu JiangleiChen QinyuGao XuejuanChen LinJin ChunyuYu ZhixianDou Xiaobing