ABSTRACT
OBJECTIVE To investigate the effects of pharmacological inhibition of STING by C-176,a STING selective inhibitor,in experimental model of Parkinson's disease.METHODS The acute and sub-acute mice mod-els of Parkinson's disease(PD)were established by in-traperitoneal injection of 1-methyl-4-(2′-methylphenyl)-1,2,3,6-tetrahydrophine(MPTP).The selective STING inhibitor C-176 was administered by intraperitoneal injec-tion.The potential neuroprotective effects of C-176 were evaluated by behavioral test,tyrosine hydroxylase(TH)immunostaining,Nissl staining,Western blotting,qPCR and immunofluorescence.For in vitro study,the effects of C-176 on LPS/MPP+-induced inflammatory responses in BV2 microglial cells were determined by real time RT-PCR and Western blotting analysis.RESULTS Our study revealed that C-176 significantly inhibited STING signaling activation,ameliorated MPTP-induced dopami-nergic neurotoxicity,motor deficit and associated neuroin-flammation.Furthermore,pharmacological inhibition of STING in BV2 microglia treated with LPS/MPP+ exhibited decreased inflammatory responses.More importantly,C176 also reduced NLRP3 inflammasome activation both in vitro and in vivo.CONCLUSION The results of our study suggest that pharmacologic inhibition of STING protects against neuroinflammation that may act at least in part through suppressing NLRP3 inflammasome acti-vation and thus ameliorated dopaminergic neurodegener-ation.STING signaling may holds great promise for the development of new treatment strategy for PD as an effective therapeutic target.
ABSTRACT
Objective To explore the postoperative psychological status of donors during pediatric living donor liver transplantation (LDLT) to elucidate the correlation between resilience,anxiety and depression.Methods Random sampling was employed for selecting 60 pediatric LDLT donors undergoing LDLT from September 2014 to February 2019.They were requested to answer a questionnaire.The questionnaire concluded general information,self-rating anxiety scale (SAS),selfrating depression scale (SDS) and Chinese version of Resilience Scale.Results The score of anxiety was (46.06 ± 10.06) and depression was (50.32 ± 11.49).Both values were higher than those of Chinese norm.The score of resilience was (59.55 ± 14.62).And the total score of resilience and the score of each dimension were negatively correlated with anxiety and depression (P＜0.01).Conclusions The postoperative anxiety and depression level of donors during LDLT are higher than the ordinary.Resilience is negatively correlated with the level of anxiety and depression.The lower level of resilience,the higher anxiety and depression of donors during LDLT.For clinicians,appropriate intervention measures should be taken for improving the resilience,reducing negative emotions and boosting the quality-of-life of donors during LDLT.