ABSTRACT
Objective To investigate the neuroprotective effect and its mechanism of local hypothermia combined with nicotinamide phosphoribosyltransferase (NAMPT) on cerebral ischemia-reperfusion injury in rats.Methods Fifty-four Sprague-Dawley rats were randomly divided into sham operation group,model group,NAMPT group,local hypothermia group,and combined treatment group (NAMPT + local hypothermia).A rat model of local cerebral ischemia-reperfusion was induced by suture method.Infarct volume and cerebral edema volume were assessed by 2,3,5-triphenyltetrazolium chloride staining after 2 h cerebral ischemia and 24 h reperfusion in rats.Evans blue staining was used to assess the extent of blood-brain barrier damage,and a 12-point scale was used to assess neurological deficits.Results The infarct volume in the local hypothermia group,NAMPT group,and combination treatment group was significantly lower than that in the model group (all P ＜0.05).The infarct volume in the combination treatment group was significantly lower than that in the NAMPT group (P ＜0.05).The infarct volume in the combination treatment group was lower than that in the local hypothermia group,but it did not reach statistical significance.The neurological function scores of the local hypothermia group,NAMPT group,and combination treatment group were significantly lower than those of the model group (all P ＜0.05).The score of the combined treatment group was significantly lower than that of the NAMPT group and the local hypothermia group (all P＜0.05).Evans blue leakage in the local hypothermia group,NAMPT group,and combination treatment group was lower than that in the model group (all P ＜0.05),but the differences between each treatment group were not statistically significant.Conclusion NAMPT and local hypothermia combination therapy showed better neuroprotective effects on cerebral ischemia-reperfusion injury,suggesting that the combination therapy had clinical transformation prospects.
ABSTRACT
Objective To study the role of human MutS homolog 2 (hMSH2), a newly identified protein ligand that was recognized by Vγ9δ2 T cells , in innate anti-gastric carcinoma immunity .Methods Flow cytometry and laser confocal microscopy were used to identify hMSH 2 that ectopically expressed on gas-tric carcinoma cell line 803.An anti-hMSH2 antibody was used to block hMSH2 to evaluate its effects on the cytotoxicity of Vγ9δ2 T cells and their cytokines secretion .Subcellular distribution of hMSH 2 in gastric car-cinoma tissues was examined by tissue microarray immunohistochemistry analysis .Results Ectopic mem-brane expression of hMSH 2 was observed on 803 cells at a relatively high level .Vγ9δ2 T cells blocked with specific anti-hMSH2 antibody showed a decreased cytotoxicity and a reduced IFN-γbut an increased TNF-αsecretion.Ectopic expression of hMSH2 was found in various types of gastric carcinoma tissues at different stages.Enhanced expression of hMSH2 was detected in specimens collected from patients with chronic super-ficial gastritis.Conclusion Ectopically expressed hMSH2 served as a stress-induced endogenous ligand which could promote the cytotoxicity of Vγ9δ2 T cells against gastric carcinoma cells and enhance their IFN-γsecretion.hMSH2 played an essential role in innate anti-gastric carcinoma immunity .