ABSTRACT
Cerebral hemorrhage is a fatal disease that causes severe damage to local nerve function. The purpose of this research is to analyze the effect of kurarinone on hemin-induced neuroinflammation and neurotoxicity. In our study, according to the results of bioinformatics analysis, we hypothesized that kurarinone might modulate cerebral hemorrhage advancement via the insulin-like growth factor 1/phosphoinositide 3-kinase/protein kinase B (IGF1/PI3K/Akt) signaling. Kurarinone promoted M2 microglia polarization, and curbed M1 polarization and inflammation in human microglial cells (HMC3) cells with hemin treatment. Besides, kurarinone upregulated IGF1 expression and activated the PI3K/Akt signaling pathway in hemin-treated HMC3 cells. In addition, downregulation of IGF1 or inhibition of the PI3K/Akt signaling weakened the effects of kurarinone on microglia polarization and inflammation in HMC3 cells with hemin treatment. Kurarinone alleviated apoptosis and oxidative damage of SH-SY5Y cells co-cultured with hemin-treated HMC3 cells. In conclusion, kurarinone lessened hemin-induced neuroinflammation and microglia-mediated neurotoxicity by regulating microglial polarization through modulating the IGF1/PI3K/Akt signaling. These results delivered a new prospective therapeutic drug for the treatment of cerebral hemorrhage.
Subject(s)
Microglia , Neuroblastoma , Humans , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Hemin/pharmacology , Hemin/metabolism , Insulin-Like Growth Factor I/metabolism , Neuroinflammatory Diseases , Neuroblastoma/metabolism , Signal Transduction , Inflammation/drug therapy , Inflammation/metabolism , Cerebral Hemorrhage/metabolismABSTRACT
CuInP2S6 (CIPS) is a novel two-dimensional (2D) van der Waals (vdW) ferroelectric layered material with a Curie temperature of TC~315 K, making it promising for great potential applications in electronic and photoelectric devices. Herein, the ferroelectric and electric properties of CIPS at different thicknesses are carefully evaluated by scanning probe microscopy techniques. Some defects in some local regions due to Cu deficiency lead to a CuInP2S6-In4/3P2S6 (CIPS-IPS) paraelectric phase coexisting with the CIPS ferroelectric phase. An electrochemical strain microscopy (ESM) study reveals that the relaxation times corresponding to the Cu ions and the IPS ionospheres are not the same, with a significant difference in their response to DC voltage, related to the rectification effect of the ferroelectric tunnel junction (FTJ). The electric properties of the FTJ indicate Cu+ ion migration and propose that the current flow and device performance are dynamically controlled by an interfacial Schottky barrier. The addition of the ferroelectricity of CIPS opens up applications in memories and sensors, actuators, and even spin-orbit devices based on 2D vdW heterostructures.
