Cannabinoid receptor 2 protects against acute experimental sepsis in mice.

The systemic inflammatory response syndrome can be self-limited or can progress to severe sepsis and septic shock. Despite significant advances in the understanding of the molecular and cellular mechanisms of septic shock, it is still one of the most frequent and serious problems confronting clinicians in the treatments. And the effects of cannabinoid receptor 2 (CB2R) on the sepsis still remain undefined. The present study was aimed to explore the role and mechanism of CB2R in acute sepsis model of mice. Here, we found that mice were more vulnerable for lipopolysaccharide- (LPS-) induced death and inflammation after CB2R deletion (CB2R(-/-)). CB2R agonist, GW405833, could significantly extend the survival rate and decrease serum proinflammatory cytokines in LPS-treated mice. GW405833 dose-dependently inhibits proinflammatory cytokines release in splenocytes and peritoneal macrophages as well as splenocytes proliferation, and these effects were partly abolished in CB2R(-/-) splenocytes but completely abolished in CB2R(-/-) peritoneal macrophages. Further studies showed that GW405833 inhibits LPS-induced phosphorylation of ERK1/2 and STAT3 and blocks I κ B α degradation and NF- κB p65 nuclear translocation in macrophages. All data together showed that CB2R provides a protection and is a potential therapeutic target for the sepsis.

Estrogen weakens muscle endurance via estrogen receptor-p38 MAPK-mediated orosomucoid (ORM) suppression.

Gender differences in fatigue manifest as females being more prone to feel exhaustion and having lower muscle endurance. However, the mechanisms of these effects remain unclear. We investigated whether orosomucoid, an endogenous anti-fatigue protein that enhances muscle endurance, is involved in this regulation. Female rats exhibited lower muscle endurance, and this gender difference disappeared in orosomucoid-1-deficient mice. Female rats also exhibited weaker orosomucoid induction in serum, liver and muscle in response to fatigue compared with male rats. Ovariectomy elevated orosomucoid levels and increased swimming time, and estrogen replenishment reversed these effects. Exogenous estrogen treatment in male and female mice produced opposite effects. Estrogen decreased orosomucoid expression and its promoter activity in C2C12 muscle and Chang liver cells in vitro, and estrogen receptor or p38 mitogen-activated protein kinase blockade abolished this effect. Therefore, estrogen negatively regulates orosomucoid expression that is responsible for the weaker muscle endurance in females.

An updated role of microRNA-124 in central nervous system disorders: a review.

MicroRNA-124 (miR-124) is the most abundant miRNA in the brain. Biogenesis of miR-124 displays specific temporal and spatial profiles in various cell and tissue types and affects a broad spectrum of biological functions in the central nervous system (CNS). Recently, the link between dysregulation of miR-124 and CNS disorders, such as neurodegeneration, CNS stress, neuroimmune disorders, stroke, and brain tumors, has become evident. Here, we provide an overview of the specific molecular function of miR-124 in the CNS and a revealing insight for the therapeutic potential of miR-124 in the treatment of human CNS diseases.

MicroRNA-124 protects neurons against apoptosis in cerebral ischemic stroke.

AIMS: To explore the role and underlying mechanism of miR-124 in stroke. METHODS: miR-124 expression was determined by real-time PCR. The effect of miR-124 on infarct area was assessed in middle cerebral artery occlusion (MCAO) mice. The influence of miR-124 on oxygen and glucose deprivation (OGD) induced neuron apoptosis and death was examined by immunofluorescence. The effect of miR-124 on apoptosis-related proteins was determined by Western blot. RESULTS: The level of miR-124 is significantly increased in ischemic penumbra as compared with that in nonischemic area of MACO mice. Brain tissue of stroke-prone spontaneously hypertensive rats (SHR-SP) also showed higher level of miR-124 as compared with that of spontaneously hypertensive rats (SHR). Consistently, OGD treatment obviously increased miR-124 level in primary neurons. In vivo, miR-124 overexpression significantly decreased, while miR-124 knockdown significantly increased, the infarct area of MCAO mice. In vitro, gain or loss of miR-124 function resulted in reduced or increased neuron apoptosis and death induced by OGD, and increased or reduced antiapoptosis protein, Bcl-2 and Bcl-xl, respectively. CONCLUSIONS: miR-124 plays a neurons-protective role via apoptosis-inhibiting pathway in ischemic stroke.