ABSTRACT
Alcoholic liver disease (ALD) is the major cause of chronic liver disease and a global health concern. ALD pathogenesis is initiated with liver steatosis, and ALD can progress to steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Salvianic acid A (SAA) is a phenolic acid component of Danshen, a Chinese herbal medicine with possible hepatoprotective properties. The purpose of this study was to investigate the effect of SAA on chronic alcoholic liver injury and its molecular mechanism. We found that SAA significantly inhibited alcohol-induced liver injury and ameliorated ethanol-induced hepatic inflammation. These protective effects of SAA were likely carried out through its suppression of the BRD4/HMGB1 signalling pathway, because SAA treatment largely diminished alcohol-induced BRD4 expression and HMGB1 nuclear translocation and release. Importantly, BRD4 knockdown prevented ethanol-induced HMGB1 release and inflammatory cytokine production in AML-12 cells. Similarly, alcohol-induced pro-inflammatory cytokines were blocked by HMGB1 siRNA. Collectively, our results reveal that activation of the BRD4/HMGB1 pathway is involved in ALD pathogenesis. Therefore, manipulation of the BRD4/HMGB1 pathway through strategies such as SAA treatment holds great therapeutic potential for chronic alcoholic liver disease therapy.
Subject(s)
Down-Regulation/drug effects , HMGB1 Protein/metabolism , Lactates/pharmacology , Liver Diseases, Alcoholic/drug therapy , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Animals , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cells, Cultured , Cytokines/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Liver/drug effects , Liver/metabolism , Liver Diseases, Alcoholic/metabolism , Male , Mice , Protective Agents/pharmacology , Rats , Rats, Wistar , Signal Transduction/drug effectsABSTRACT
This paper studies a multi-user network model based on sparse code multiple access (SCMA), where both unicast and multicast services are considered. In the direct transmission scheme, the communication between the base station (BS) and the users is completed with one stage, in which the relay is inexistent. In the two-stage cooperative transmission scheme, any number of relays are placed to improve the reliability of wireless communication system. The BS broadcasts the requested message to users and relays in the first stage, and the successful relays forward the message to unsuccessful users in the second stage. To characterize the performance of these two schemes, we derive the exact and approximate expressions of average outage probability. Furthermore, to take full advantage of the cooperative diversity, an optimal power allocation and relay location strategy in the high signal-to-noise ratio (SNR) regime is studied. The outage probability reaches the minimum value when the first stage occupies half of the total energy consumed. Simulation and analysis results are presented to demonstrate the performance of these two schemes. The results show that the two-stage cooperative scheme effectively reduce the average outage probability in SCMA network, especially in the high SNR region.
