MMP-2-mediated Scube2 degradation promotes blood-brain barrier disruption by blocking the interaction between astrocytes and endothelial cells via inhibiting Sonic hedgehog pathway during early cerebral ischemia.

We have previously demonstrated a rapid secretion of matrix metalloproteinase-2 (MMP-2) in the ischemic brain. Since Scube2 can interact with Sonic hedgehog (Shh) to maintain blood-brain barrier (BBB) integrity via regulating the interaction between brain capillary endothelial cells (ECs) and perivascular astrocytes, and it is also a substrate of MMP-2, we hypothesized that the secreted MMP-2 could degrade Scube2 and contribute to ischemic BBB disruption. Using an in vitro ischemic model of 90-min oxygen-glucose deprivation/3-h reoxygenation (OGD/R) and an in vivo mouse stroke model of 90-min middle cerebral artery occlusion (MCAO) with 3-h reperfusion, we established an important role of MMP-2-mediated Scube2 degradation in early ischemic BBB disruption.

Activation of Swell1 in microglia suppresses neuroinflammation and reduces brain damage in ischemic stroke.

Cl movement and Cl-sensitive signal pathways contributes to the survival and switch of inflammatory phenotype of microglia and are believed to play a key role in the inflammatory brain injury after ischemic stroke. Here, we demonstrated an important role of Cl transmembrane transporter Swell1, in the survival and M2-like polarization of microglia in ischemic stroke. Knockdown or overexpression of Swell1 in cultured microglia inhibited or increased hypotonic-activated Cl currents, respectively, and these changes were completely blocked by the volume-regulated anion channels (VRACs) inhibitor DCPIB.

The Function of Selenium in Central Nervous System: Lessons from MsrB1 Knockout Mouse Models.

MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in , which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3.

Loss of MsrB1 perturbs spatial learning and long-term potentiation/long-term depression in mice.

MsrB1 belongs to the methionine sulfoxide reductase family, it is also known as selenoprotein R for the sake of possessing a selenocysteine residue. It has been reported that MsrB1 could interact with actin, TRPM6, clusterin, and amyloid-beta in vitro. Thus, we presumed that MsrB1 may play an important role in central nervous system.

Whole Body Vibration Improves Insulin Resistance in db/db Mice: Amelioration of Lipid Accumulation and Oxidative Stress.

Insulin resistance (IR) is the hallmark of type 2 diabetes mellitus (T2DM), which is one of the most important chronic noncommunicable diseases. Effective and feasible strategies to treat IR are still urgently needed. Previous research studies reported that whole body vibration (WBV) was beneficial for IR in clinical; however, its underlying mechanisms remains unknown.

ROS-dependent mitochondria molecular mechanisms underlying antitumor activity of Pleurotus abalonus acidic polysaccharides in human breast cancer MCF-7 cells.

Background: A greater reduction in cancer risk associated with mushroom diet rich in fungus polysaccharides is generally accepted. Meanwhile, edible Pleurotus abalonus as a member of Abalone mushroom family is a popular nutritional supplement that purportedly prevents cancer occurrence. However, these anecdotal claims are supported by limited studies describing tumor-inhibitory responses to the promising polysaccharides, and the molecular mechanisms underlying these properties have not yet been elucidated.