RESUMO
ELF4 (E74-like factor 4) is a transcription factor, dysregulation of which has been associated with carcinogenesis and cancer development. Nevertheless, the precise role of ELF4 in glioma pathology and its impact on clinical outcomes remains to be investigated. In the present research, comprehensive analyses demonstrated that elevated expression of ELF4 in glioma tissues correlates with malignant phenotypes and adverse clinical outcomes. Multivariate Cox regression analysis determined that ELF4 expression could serve as a reliable predictor of glioma outcomes. (CGGA, hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.09-1.34, p<0.001; TCGA, HR: 1.19, 95%CI: 1.01-1.41, p=0.043; and Gravendeel, HR: 1.44, 95%CI: 1.15-1.80, p=0.002). Knockdown of ELF4 reduced the cell viability and migration capacity of glioma cells in vitro. In addition to the tumor invasive role, enrichment analysis revealed the overexpressed ELF4 was involved in the immune regulation, characterized by the elevated activity of Il6/Jak/Stat3 signaling, interferon alpha (IFN-α) response, and IL2/Stat5 signaling. Single-cell RNA sequencing (scRNA)-seq and spatial transcriptome (ST)-seq analyses revealed that ELF4 could induce reprogramming of tumor-associated monocytes/macrophages (TAMMs). Molecular docking analysis revealed ELF4 might be targeted by drugs/compounds, including Veliparib (ABT-888), Motesanib (AMG 706), and EHT 1864. Genomic analysis revealed that, in LGG, in the low ELF4 expression subgroup, IDH1 demonstrated a higher mutation rate, and TP53 and ATRX Chromatin Remodeler (ATRX) displayed the lower mutation rates, than the high ELF4 expression group. Conclusion: Our research suggests that ELF4 may contribute to the prognostic assessment of glioma and personalized medicine.
RESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by continuous and selective degeneration or death of dopamine neurons in the midbrain, leading to dysfunction of the nigrostriatal neural circuits. Current clinical treatments for PD include drug treatment and surgery, which provide short-term relief of symptoms but are associated with many side effects and cannot reverse the progression of PD. Pluripotent/multipotent stem cells possess a self-renewal capacity and the potential to differentiate into dopaminergic neurons. Transplantation of pluripotent/multipotent stem cells or dopaminergic neurons derived from these cells is a promising strategy for the complete repair of damaged neural circuits in PD. This article reviews and summarizes the current preclinical/clinical treatments for PD, their efficacies, and the advantages/disadvantages of various stem cells, including pluripotent and multipotent stem cells, to provide a detailed overview of how these cells can be applied in the treatment of PD, as well as the challenges and bottlenecks that need to be overcome in future translational studies.