Tandutinib

This investigation aims to screen ischemic stroke (IS)-related hub genes of central post-stroke pain (CPSP) from public databases and predict their potential roles through bioinformatics analysis to better interpret CPSP in IS. First, based on differential analysis, Venn analysis, and enrichment analyses, we identified 13 differently expressed genes in CPSP (CPSP-DEGs) related to the TNF signaling pathway, Vascular smooth muscle contraction, and IL-17 signaling pathway. Subsequently, through screening and analysis of the PPI network constructed by the Search Tool for the Retrieval of Interacting Genes (STRING) database, we obtained 3 CPSP-related hub genes (CD163, MMP9, and ARG1). They were all highly expressed in the IS group, exhibiting good diagnostic performance, with area under curve (AUC) value > 0.85. The immune-related analysis demonstrated that the infiltration levels of various immune cells in the IS group and the normal group were substantially different. In addition, by utilizing some online websites, we not only predicted some microRNAs (miRNAs) and transcription factors (TFs) that may target hub genes but also mined small molecular drugs that may target differentially expressed genes (DEGs) in IS. In conclusion, this project first investigated the role of CPSP-related genes in IS and identified 3 hub genes. At the same time, we predicted some miRNAs, TFs, and candidate drugs that may target hub genes. Our research uncovered the potential mechanism of CPSP-related genes in IS from multiple perspectives. Furthermore, it also laid a research foundation for the future study of the mechanisms of IS disease.

Keloids are a skin fibrosis disease characterized by troublesome symptoms, a varying degree of recurrence and inevitable side effects from treatments. Thus, identifying their drug targets is necessary. A 2-sample Mendelian randomization analysis was conducted using proteins from the intersection of the deCODE database and "The Druggable Genome and Support for Target Identification and Validation in Drug Development" as the exposure variable. The outcome variable was based on recently published GWAS of keloids. Summary data-based Mendelian randomization and colocalization analysis was employed to distinguish pleiotropy from linkage. Candidate targets underwent drug target analysis. The primary findings were validated through single-cell RNA-sequencing data, Western Blot and immunofluorescence staining on keloids. Seven proteins were identified as potential drug targets for keloids. Among these proteins, Hedgehog-interacting protein, neurotrimin [NTM], KLKB1, and CRIPTO showed positive correlations with keloids, while PLXNC1, SCG3 and PDGFD exhibited negative correlations. Combined with the single-cell RNA-sequencing data, NTM, PLXNC1, and PDGFD were found highly expressed in the fibroblasts. NTM showed a significant increase in keloids as compared to normal scars. In accordance with the analysis, higher levels of protein expression of NTM in keloids compared to normal skin was observed. The identified proteins may be appealing drug targets for keloids treatment with a special emphasis on NTM.