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.

Etomidate vs propofol in coronary heart disease patients undergoing major noncardiac surgery:A randomized clinical trial

BACKGROUND The ideal depth of general anesthesia should achieve the required levels of hypnosis,analgesia,and muscle relaxation while minimizing physiologic responses to awareness.The choice of anesthetic strategy in patients with coronary heart disease(CHD)undergoing major noncardiac surgery is becoming an increasingly important issue as the population ages.This is because general anesthesia is associated with a risk of perioperative cardiac complications and death,and this risk is much higher in people with CHD.AIM To compare hemodynamic function and cardiovascular event rate between etomidate-and propofol-based anesthesia in patients with CHD.METHODS This prospective study enrolled consecutive patients(American Society of Anesthesiologists grade II/III)with stable CHD(New York Heart Association class I/II)undergoing major noncardiac surgery.The patients were randomly allocated to receive either etomidate/remifentanil-based or propofol/remifentanil-based general anesthesia.Randomization was performed using a computer-generated random number table and sequentially numbered,opaque,sealed envelopes.Concealment was maintained until the patient had arrived in the operating theater,at which point the consulting anesthetist opened the envelope.All patients,data collectors,and data analyzers were blinded to the type of anesthesia used.The primary endpoints were the occurrence of cardiovascular events(bradycardia,tachycardia,hypotension,ST-T segment changes,and ventricular premature beats)during anesthesia and cardiac troponin I level at 24 h.The secondary endpoints were hemodynamic parameters,bispectral index,and use of vasopressors during anesthesia.RESULTS The final analysis included 40 patients in each of the propofol and etomidate groups.The incidences of bradycardia,hypotension,ST-T segment changes,and ventricular premature beats during anesthesia were significantly higher in the propofol group than in the etomidate group(P<0.05 for all).The incidence of tachycardia was similar between the two groups.Cardiac troponin I levels were comparable between the two groups both before the induction of anesthesia and at 24 h after surgery.When compared with the etomidate group,the propofol group had significantly lower heart rates at 3 min after the anesthetic was injected(T1)and immediately after tracheal intubation(T2),lower systolic blood pressure at T1,and lower diastolic blood pressure and mean arterial pressure at T1,T2,3 min after tracheal intubation,and 5 min after tracheal intubation(P<0.05 for all).Vasopressor use was significantly more in the propofol group than in the etomidate group during the induction and maintenance periods(P<0.001).CONCLUSION In patients with CHD undergoing noncardiac major surgery,etomidate-based anesthesia is associated with fewer cardiovascular events and smaller hemodynamic changes than propofol-based anesthesia.