No abstract

Loss of energy supply to neurons during stroke induces a rapid loss of membrane potential that is called the anoxic depolarization. Anoxic depolarizations result in tremendous physiological stress on the neurons because of the dysregulation of ionic fluxes and the loss of ATP to drive ion pumps that maintain electrochemical gradients. In this review, we present an overview of some of the ionotropic receptors and ion channels that are thought to contribute to the anoxic depolarization of neurons and subsequently, to cell death. The ionotropic receptors for glutamate and ATP that function as ligand-gated cation channels are critical in the death and dysfunction of neurons. Interestingly, two of these receptors (P2X7 and NMDAR) have been shown to couple to the pannexin-1 (Panx1) ion channel. We also discuss the important roles of transient receptor potential (TRP) channels and acid-sensing ion channels (ASICs) in responses to ischemia. The central challenge that emerges from our current understanding of the anoxic depolarization is the need to elucidate the mechanistic and temporal interrelations of these ion channels to fully appreciate their impact on neurons during stroke.

No abstract

Pancreatic adenocarcinoma (PDAC) and extrahepatic cholangiocarcinoma (ECC) are highly lethal malignancies with limited treatment options. Both a small subpopulation of cancer stem cells (CSC) and the deregulation of the notch pathway have been considered potential sources of tumor formation. In this study, flow cytometry (FCM) was conducted to identify the CSC population and Notch-associated proteins in ECC and PDAC cell lines. Additionally, the treatment effect of Gemcitabine and the specific notch-inhibitor DAPT on ECC and PDAC cell lines was evaluated. Our results show that the amount of SP cells in ECC cell lines is significantly higher than in PDAC cell lines, and that SP-ECC cells show a higher sensitivity to therapy. In conclusion, inhibition of Notch signaling with DAPT may be of therapeutic value in ECC, but seems to show no effect on more aggressive PDAC. As it could be essential for the improvement in outcomes of the ECC patients, other trials are needed to determine the role of further Notch components.