Resolvin D1 Induces mTOR-independent and ATG5-dependent Autophagy in BV-2 Microglial Cells

Objective The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation.Autophagy is a catabolic process responsible for maintaining cellular homeostasis.In recent years,autophagy has been demonstrated to play an important role in neuroinflammation.Resolvin D1(RvD1)is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities.However,whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation.The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways.Methods Mouse microglial cells(BV-2)were cultured,treated with RvD1,and examined by Western blotting,confocal immunofluorescence microscopy,transmission electron microscopy,and flow cytometry.Results RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes.Importantly,RvD1 had no significant effect on the activation of mammalian target of rapamycin(mTOR)signaling.Furthermore,RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II(CaMK II)activation.Moreover,by downregulating ATG5,the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy.Conclusion The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy,highlighting its therapeutic potential against neuroinflammation.

Overview of point-of-care ultrasound in diagnosing intestinal obstruction

Intestinal obstruction(IO),which refers to a partial or complete blockage of the intestine,is an emergency gastrointestinal disorder commonly seen in the intensive care unit(ICU)and emergency department and associated with high morbidity and mortality.[1,2]Common etiologies of IO include adhesions,hernias,intussusception,foreign bodies,ischemia,tumors,etc.Delay in the diagnosis and management of IO is associated with higher mortality due to complications such as bowel necrosis,perforation,sepsis,and septic shock.[3]IO can be divided into small bowel obstruction(SBO)and colonic obstruction(CO).In SBO,74%of cases are caused by adhesions,which may respond to conservative management.It is critical to identify which of those cases may progress and require emergent surgical intervention with the help of the diagnostic and assessment tools.In contrast to SBO,most cases of CO demand surgery.In this instance,appropriate assessment tools are required to define the location of the obstruction,which will assist in the proper surgical procedure.[4]