A mini-review on ion fluxes that regulate NLRP3 inflammasome activation

The activation of NLR family pyrin domain containing 3(NLRP3)inflammasome can be induced by a wide spectrum of activators.This is unlikely achieved by the binding of different activators directly to the NLRP3 protein itself,as the activators found so far show different forms of chemical structures.Previous studies have shown that these activators can induce potassium ion(K+)and chloride ion(Cl?)efflux,calcium(Ca2+)and other ion mobilization,mitochondrial dysfunction,and lysosomal disruption,all of which are believed to cause NLRP3 inflammasome activation;how these events are induced by the activators and how they coordinate with each other in inducing the NLRP3 inflammasome activation are not fully understood.Increasing evidence suggests that the coordinated change of intracellular ion concentrations may be a common mechanism for the NLRP3 activation by different activators.In this mini-review,we present a brief summary of the current knowledge about how different ionic flows(including K+,sodium ion,Ca2+,magnesium ion,manganese ion,zinc ion,iron ion,and Cl?)are involved in regulating the NLRP3 inflammasome activation in macrophages.     

Ipriflavone as a non‐steroidal glucocorticoid receptor antagonist ameliorates diabetic cognitive impairment in mice

Diabetic cognitive impairment (DCI) is a common diabetic complication with hallmarks of loss of learning ability and disorders of memory and behavior. Glucocorticoid receptor (GR) dysfunction is a main reason for neuronal impairment in brain of diabetic patients. Here, we determined that ipriflavone (IP) a clinical anti‐osteoporosis drug functioned as a non‐steroidal GR antagonist and efficiently ameliorated learning and memory dysfunction in both type 1 and 2 diabetic mice. The underlying mechanism has been intensively investigated by assay against the diabetic mice with GR‐specific knockdown in the brain by injection of adeno‐associated virus (AAV)‐ePHP‐si‐GR. IP suppressed tau hyperphosphorylation through GR/PI3K/AKT/GSK3β pathway, alleviated neuronal inflammation through GR/NF‐κB/NLRP3/ASC/Caspase‐1 pathway, and protected against synaptic impairment through GR/CREB/BDNF pathway. To our knowledge, our work might be the first to expound the detailed mechanism underlying the amelioration of non‐steroidal GR antagonist on DCI‐like pathology in mice and report the potential of IP in treatment of DCI.     

Effect of Overexpression of Protective Genes on Mitochondrial Function of Stressed Astrocytes

Antiapoptotic members of the Bcl-2 family have been shown to reduce ischemic brain injury in vivo and in vitro. Understanding early changes in respiration are important in understanding the cells response to stress and the mechanisms of protection afforded by overexpression of protective genes. This mini-review summarizes current knowledge regarding early responses of astrocytes to ischemia-like stress and the effects of overexpression of protective Bcl-2 family genes on astrocyte mitochondrial function. Overexpression of Bcl-x(L) improves mitochondrial respiratory function, normalizes mitochondrial membrane potential, and reduces production of free radicals early after the imposition of a stress in primary cultured murine astrocytes.