Project description:Evodiamine (Evo), a kind of alkaloid mostly extracted from Tetradium ruticarpum, which has many pharmacological functions, such as antidiarrheal, antiemetic, and antiulcer effects. In this study, the effects of Evo were investigated in DSS-induced ulcerative colitis (UC) mice and C57BL/6-ApcMinC/Gpt mice with colorectal cancer (CRC). The results showed Evo not only sup-pressed the weight loss and the shorthen of colon, decreased disease activity index (DAI) and ameliorated the pathological alteration of colon in UC mice, but also inhibited the numbers and sizes of colonic tumor of ApcMinC/Gpt mice. Meanwhiles, Evo regulated nuclear factor-kappa B (NF-κB) related signal pathways to mediate various cytokines such as interleukins (Ils), tumor necrosis factor-α (TNF-α) to achieve anti-inflammatory and anti-tumor effects. In SW480 and Caco cells, Evo reduced the cell viabilities, promoted the mitochondrial membrane potential (MMP) and caused the over-accumulation of intracellular reactive oxygen species (ROS). Theoretical evi-dences indicated Evo binding NF-κB may be useful to contain ordered domain (α helix) in NF-κB, which can induce NF-κB to perform its function. Our results provide experimental and theoretical evidence that Evo might be promising and effective treatments in clinics for UC and CRC.
Project description:Polyglutamine expansion is associated with pathogenic protein aggregation in neurodegenerative disorders. However, long polyglutamine tracts are also found in many transcription factors (TFs), such as FOXP2, a TF implicated in human speech. Here, we explore how FOXP2 and other glutamine-rich TFs avoid unscheduled assembly. Throughout interphase, DNA binding, irrespective of sequence specificity, has a solubilizing effect. During mitosis, multiple phosphorylation events promote FOXP2’s eviction from chromatin and supplant the solubilizing function of DNA. Further, human-specific amino-acid substitutions linked to the evolution of speech map to a mitotic phospho-patch, the ‘EVO patch’, and reduce the propensity of the human FOXP2 to assemble. Fusing the pathogenic form of Huntingtin to either a DNA binding domain, a phospho-mimetic variant of this ‘EVO patch’ or a negatively charged peptide is sufficient to diminish assembly formation, suggesting that hijacking mechanisms governing solubility of glutamine-rich TFs may offer new strategies for treatment of polyQ expansion diseases.
Project description:Transcription profiling of X.laevis development. The experiment were perfomed as a part of our Vertebrate Evo-Devo project. The aim of the project is to compare transcription profiles of normal (unmanipulated, wild-type, whole embryo) vertebrate embryos.
Project description:Transcription profiling of mouse development The experiment were perfomed as a part of our Vertebrate Evo-Devo project. The aim of the project is to compare transcription profiles of normal (unmanipulated, wild-type, whole embryo) vertebrate embryos.