The changes in the tau protein phosphorylation and expression of bcl-2, and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion (I/R) were explored, and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease. The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method. The level of tau protein phosphorylation at Ser396, Ser404, Tyr231, Ser199/202 sites and the expression of bcl-2, bax and total tau 5 in rat parietal cortex during focal cerebral ischemia/reperfusion were detected by Western blot. The relationship between the tau protein phosphorylation and the expression of bax, or apoptosis was examined by TUNEL method and double-labeling immunofluorenscence method. The results showed that the level of tau hyperphosphorylation at Ser199 / 202, Ser396, Ser404, Tyr231 sites and the expression levels of bcl-2, and bax were significantly higher in I/R group than in the sham group, but the ratio of bcl-2/bax was decreased. Neuronal apoptosis, bax expression and the tau protein hyperphosphorylation were co-localized. It is suggested that Alzheimer's disease-like pathological changes occur after cerebral I/R. The highly abnormal phosphorylation of tau protein plays a key role in cerebral I/R-induced apoptosis. The cerebral infarction may contribute to Alzheimer's disease occurrence and development.

Objective : To investigate the combined effects of triclosan（TCS）and PCB153 on the activity of superoxide dismutase（SOD）and the concentration of malondialdehyde（MDA）in zebrafish liver. Methods : Adult zebrafish were exposed to a series of concentrations of TCS,and the mortality in each group was observed and recorded during the acute toxicity test process. The concentrations in subsequent combined exposure experiments were arranged on the basis of the 96 h-LC50. The factorial design was used to determine the concentrations of combined exposure groups between TCS（0,0.125,0.5 μmol/L）and PCB153（0,0.05,0.2 μmol/L）. After 5,10 and 14 days of exposure,the zebrafish livers were dissected and frozen in each group. The potential interactions of these two compounds were analyzed according to the results of the SOD and MDA. Results : The 96 h-LC50 of TCS exposed to adult zebrafish was 2.64 μmol/L（95%CI：2.37-2.89 μmol/L）. After 5 days of exposure,combined exposure to 0.5 μmol/L TCS+0.2 μmol/L PCB153 caused lower liver SOD activities than single exposure groups and the control group（P<0.05）. After 10 days of exposure,combined exposure to 0.125 μmol/L TCS+0.05 μmol/L PCB153,0.5 μmol/L TCS+0.05 μmol/L PCB153 caused lower liver SOD activities than single exposure groups and the control group（P<0.05）. After 14 days of exposure,combined exposure to 0.5 μmol/L TCS+0.05 μmol/L PCB153,0.5 μmol/L TCS+0.2 μmol/L PCB153 caused higher liver SOD activities than single exposure groups and the control group（P<0.05）. There was an interactive effect between TCS and PCB153 on the liver SOD activity in zebrafish（P<0.05）. There was no significant effect of MDA content in each group. Conclusion Combined exposure to TCS and PCB153 could enhance （inhibit first） the liver SOD activities in zebrafish,and the interaction was synergistic.

The changes in the tau protein phosphorylation and expression of bcl-2,and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion(I/R)were explored,and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease.The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.The level of tau protein phosphorylation at Ser396,Ser404,Tyr231,Ser199/202 sites and the expression of bcl-2,bax and total tau 5 in rat parietal cortex during focal cerebral ischemia/reperfusion were detected by Western blot.The relationship between the tau protein phosphorylation and the expression of bax,or apoptosis was examined by TUNEL method and double-labeling immunofluorenscence method.The results showed that the level of tau hyperphosphorylation at Ser199/202,Ser396,Ser404,Tyr231 sites and the expression levels of bcl-2,and bax were significantly higher in I/R group than in the sham group,bat the ratio of bcl-2/bax was decreased.Neuronal apoptosis,bax expression and the tau protein hyperphosphorylation were co-localized.It is suggested that Alzheimer's disease-like pathological changes occur after cerebral I/R.The highly abnormal phosphorylation of tau protein plays a key role in cerebral I/R-induced apoptosis.The cerebral infarction may contribute to Alzheimer's disease occurrence and development.

Objective:To investigate the changes in interaction proteome of NUS1 mutant R290C and their relations with pathogenicity of Lennox Gastaut syndrome (LGS). Methods:The wild-type and mutant NUS1(R290C) plasmids were constructed and transfected into human embryonic kidney HEK293T cells; 48 h after that, NUS1 protein expression in HEK293T cells was detected by Western blotting. Co-immunoprecipitation, silver nitrate staining, and proteomic analysis were used to analyze the proteins interacted with wild-type or mutant NUS1 and identify the differential interacting proteins. Enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to annotate the molecular function and signaling pathways involved in the differential proteins. DisGeNet database was used to analyze the association between differential proteins and human diseases. Protein-protein interaction (PPI) was used to analyze the interaction network of NUS1 with protein folding regulatory proteins (RTN4 and DHDDS) and developmental epileptic encephalopathy related proteins.Results:(1) There was no significant difference in NUS1 protein expression between the wild-type and mutant NUS1 transfected HEK293T cells ( t=0.536, P=0.620). (2) Compared with that with wild-type NUS1 plasmid, number of proteins interacting with mutant NUS1 plasmid was significantly reduced in the transfected cells; 310 differential interacting proteins were screened in the mutant NUS1. (3) GO and KEGG enrichment analyses showed that the differential proteins were mainly involved in protein folding reaction and translation regulation. (4) DisGeNet association analysis showed that the two most relevant proteins in the differential interacting proteins were associated with frontotemporal dementia and developmental epileptic encephalopathy. (5) PPI analysis showed that NUS1 may be involved in occurrence of neurological diseases such as LGS by affecting protein folding signaling pathways. Conclusion:NUS1 mutant R290C alters its interacting protein lineage and mediates the development of LGS and other neurological diseases probably by regulating protein folding-related signaling.