A phospholipase D2 inhibitor, CAY10594, ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3 beta/JNK axis

We examined the role of phospholipase D2 (PLD2) on acetaminophen (APAP)-induced acute liver injury using a PLD2 inhibitor (CAY10594). 500 mg/kg of APAP challenge caused acute liver damage. CAY10594 administration markedly blocked the acute liver injury in a dose-dependent manner, showing almost complete inhibition with 8 mg/kg of CAY10594. During the pathological progress of acute liver injury, GSH levels are decreased, and this is significantly recovered upon the administration of CAY10594 at 6 hours post APAP challenge. GSK-3 beta (Serine 9)/JNK phosphorylation is mainly involved in APAPinduced liver injury. CAY10594 administration strongly blocked GSK-3 beta (Serine 9)/JNK phosphorylation in the APAP-induced acute liver injury model. Consistently, sustained JNK activation in the cytosol and mitochondria from hepatocytes were also decreased in CAY10594-treated mice. Many types of immune cells are also implicated in APAP-induced liver injury. However, neutrophil and monocyte populations were not different between vehicle- and CAY10594-administered mice which are challenged with APAP. Therapeutic administration of CAY10594 also significantly attenuated liver damage caused by the APAP challenge, eliciting an enhanced survival rate. Taken together, these results indicate that PLD2 is involved in the intrinsic response pathway of hepatocytes driving the pathogenesis of APAP-induced acute liver injury, and PLD2 may therefore represent an important therapeutic target for patients with drug-induced liver injury.11Ysciescopu

Surface figure metrology based on geometric phase components

A geometric phase component is very attractive in optical metrology because its meta-surface characteristic enables traditional optical systems to be more compact and multi-functional. In this presentation, we introduce two types of geometric phase components, i.e. a geometric phase lens and a polarization grating in surface figure metrology. Their features of polarized beam splitting and phase retardation play a role of wavefront shearing device, and simple shearing interferometers can be designed. We focus on the instrumentation of a radial shearing interferometer using a geometric phase lens and a lateral shearing interferometer based on a polarization grating. With the aid of a polarization pixelated CMOS camera, each interferometer can provide the phase map corresponding to the sheared wavefront as a snapshot measurement. In the experiment, various wavefronts generated by a deformable mirror and shapes of several mirrors were measured and compared with other commercial devices. © 2022 SPIEImmediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]