ABSTRACT
Aim To investigate the effects of scutellarein on the macrophage foam cell formation and cholesterol efflux, and the underlying mechanism. Methods THP-1 cells were differentiated with PMA, and the cell viability was detected by MTT assays. The effects of scutellarein on the cholesterol efflux and macrophage foam cell formation were evaluated by using NBD-la-beled cholesterol and the cholesterol detection kit. The effects of scutellarein on the activation of PPARγ-LXRα-ABCA1 signaling pathway were determined by molecular docking, ELISA, dual-luciferase reporter and Western blot. The effects of PPARγ knowdown on scutellarein-induced cholesterol efflux and inhibiting macrophage foaming were analyzed by siRNA interference. Results Scutellarein dose-dependently inhibited oxLDL-induced cholesterol accumulation, accelerated cholesterol efflux and significantly increased the protein expression of LXRα and ABCA1. At the same time, scutellarein could bind PPARγ and initiate its downstream LXRa-ABCAl signaling pathway. In addition, gene silencing of PPARγ not only significantly inhibited scutellarein-induced LXRα-ABCA1 signaling pathway and cholesterol efflux, but also reversed the inhibitory effect of scutellarein on macrophage foaming. Conclusions Scutellarein could promote the cholesterol efflux by activating PPARγ and initiating the downstream LXR-ABCA1 signaling pathway, thereby prevent the macrophage foam cell formation.
ABSTRACT
Acute-on-chronic liver failure(ACLF) is the most severe form of acute decompensation that develops in patients with chronic liver disease or liver cirrhosis,and is always accompanied by one or more extrahepatic organ failure, and has an extremely poor short-term prognosis. The causes triggering ACLF are complex and diverse,and the clinical stage and the type and the definition of organ failure differ greatly from one another. Therefore, a universally accepted diagnostic criteria for ACLF is not to be defined, and the epidemiological data and patient outcomes on ACLF are not easy to predict and compare among different regions. Accumulating evidence has shown that liver transplantation(LT) plays a significant role in the surgical treatment of patients with ACLF,but its clinical value is still controversial. The specific management and treatment strategy after the admission of patients with ACLF has not yet formed a unified and standardized process or opinions, which includes the monitoring in the ICU,the support and maintenance of organ functions, the selection of the surgical indication and the timing for LT and so on. Moreover, there still exists many controversies concerning, for example, whether patients with ACLF should receive greater priority for organ allocation compared to other potential candidates on the waiting list. Besides, more prospective controlled studies are urgently needed to investigate the role of the artificial liver support system in the bridging therapy to LT. The aim of this article is to review the indication selection of patients with ACLF suitable for LT,the survival outcomes and prognostic factors after LT, the selection of timing, the organ allocation policy and the bridging therapy to LT, which intends to provide new direction for designing the future clinical studies on LT in patients with ACLF.