Yangyang Lu

Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata, is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.

INPLASY202250145 The Efficacy and Safety of Employed Treatments for Ischemic Stroke: An Umbrella Review Keywords: ischemic stroke; clinical trial; systematic review; umbrella review; neurological f…

A capacitor pre‐charge technique based CMOS relaxation oscillator is proposed to improve its linearity adaptively. The effect of comparator offset and delay variation across PVT will be counteracted by the pre‐charge process because it is included both in the effective charge process and the pre‐charge process. Then, the non‐linearity of the oscillator caused by the delay of the control circuit and the offset voltage of the comparator can be eliminated. The proposed relaxation oscillator with a typical frequency of 100 kHz is implemented in 0.5 μm Bipolar‐CMOS‐DMOS process. Measured results show that <0.54% non‐linearity in the current–frequency transfer function from 0 to 5 MHz without trimming.