Cardioprotective Effects of Salvianolic Acid A on Myocardial Ischemia-Reperfusion Injury In Vivo and In Vitro

Salvianolic acid A (SAA), one of the major active components of Danshen that is a traditional Chinese medicine, has been reported to possess protective effect in cardiac diseases and antioxidative activity. This study aims to investigate the cardioprotection of SAA in vivo and in vitro using the model of myocardial ischemia-reperfusion in rat and hydrogen peroxide (H2O2)-induced H9c2 rat cardiomyoblasts apoptosis. It was found that SAA significantly limited infarct size of ischemic myocardium when given immediately prior to reperfusion. SAA also significantly suppressed cellular injury and apoptotic cell death. Additionally, the results of western blot and phospho-specific antibody microarray analysis showed that SAA could up-regulate Bcl-2 expression and increase the phosphorylation of proteins such as Akt, p42/p44 extracellular signal-related kinases (Erk1/2), and their related effectors. The phosphorylation of those points was related to suppress apoptosis. In summary, SAA possesses marked protective effect on myocardial ischemia-reperfusion injury, which is related to its ability to reduce myocardial cell apoptosis and damage induced by oxidative stress. The protection is achieved via up-regulation of Bcl-2 expression and affecting protein phosphorylation. These findings indicate that SAA may be of value in cardioprotection during myocardial ischemia-reperfusion injury, which provide pharmacological evidence for clinical application

Teleconnections among tipping elements in the Earth system

Tipping elements are components of the Earth system that may shift abruptly and irreversibly from one state to another at specific thresholds. It is not well understood to what degree tipping of one system can influence other regions or tipping elements. Here, we propose a climate network approach to analyse the global impacts of a prominent tipping element, the Amazon Rainforest Area (ARA). We find that the ARA exhibits strong correlations with regions such as the Tibetan Plateau (TP) and West Antarctic ice sheet. Models show that the identified teleconnection propagation path between the ARA and the TP is robust under climate change. In addition, we detect that TP snow cover extent has been losing stability since 2008. We further uncover that various climate extremes between the ARA and the TP are synchronized under climate change. Our framework highlights that tipping elements can be linked and also the potential predictability of cascading tipping dynamics

Teleconnections among tipping elements in the Earth system

Tipping elements are components of the Earth system that may shift abruptly and irreversibly from one state to another at specific thresholds. It is not well understood to what degree tipping of one system can influence other regions or tipping elements. Here, we propose a climate network approach to analyse the global impacts of a prominent tipping element, the Amazon Rainforest Area (ARA). We find that the ARA exhibits strong correlations with regions such as the Tibetan Plateau (TP) and West Antarctic ice sheet. Models show that the identified teleconnection propagation path between the ARA and the TP is robust under climate change. In addition, we detect that TP snow cover extent has been losing stability since 2008. We further uncover that various climate extremes between the ARA and the TP are synchronized under climate change. Our framework highlights that tipping elements can be linked and also the potential predictability of cascading tipping dynamics.Peer reviewe

Carnosic Acid Mitigates Early Brain Injury After Subarachnoid Hemorrhage: Possible Involvement of the SIRT1/p66shc Signaling Pathway

Carnosic acid (CA) has been reported to exhibit a variety of bioactivities including antioxidation, neuroprotection, and anti-inflammation; however, the impact of CA on subarachnoid hemorrhage (SAH) has never been elucidated. The current study was undertaken to explore the role of CA in early brain injury (EBI) secondary to SAH and the underlying mechanisms. Adult male Sprague-Dawley rats were perforated to mimic a clinical aneurysm with SAH. CA or vehicle was administered intravenously immediately after the SAH occurred. Mortality, SAH grade, neurologic function scores, brain water content, Evans blue extravasation, and the levels of reactive oxygen species (ROS) levels in the ipsilateral cortex were determined 24 h after the SAH occurred. Western blot, immunofluorescence, Fluoro-Jade C (FJC) and TUNEL staining were also performed. Our results showed that CA decreased ROS levels, alleviated brain edema and blood-brain barrier permeability, reduced neuronal cell death, and promoted neurologic function improvement. To probe into the potential mechanisms. We showed that CA increased SIRT1, MnSOD, and Bcl-2 expression, as well as decreased p66shc, Bax, and cleaved caspase-3 expression. Interestingly, sirtinol, a selective inhibitor of SIRT1, abolished the anti-apoptotic effects of CA. Taken together, these data revealed that CA has a neuroprotective role in EBI secondary to SAH. The potential mechanism may involve suppression of neuronal apoptosis through the SIRT1/p66shc signaling pathway. CA may provide a promising therapeutic regimen for management of SAH