Acute cerebral ischemia-induced down-regulation of Sirt3 protein expression contributes to neuronal injury via damaging mitochondrial function / 生理学报

This study was aimed to determine the effect of acute cerebral ischemia on the protein expression level of silent mating type information regulator 2 homolog 3 (Sirt3) in the neurons and clarify the pathological role of Sirt3 in acute cerebral ischemia. The mice with middle cerebral artery occlusion (MCAO) and primary cultured rat hippocampal neurons with oxygen glucose deprivation (OGD) were used as acute cerebral ischemia models in vivo and in vitro, respectively. Sirt3 overexpression was induced in rat hippocampal neurons by lentivirus transfection. Western blot was utilized to measure the changes in Sirt3 protein expression level. CCK8 assay was used to detect cell viability. Immunofluorescent staining was used to detect mitochondrial function. Transmission electron microscope was used to detect mitochondrial autophagy. The results showed that, compared with the normoxia group, hippocampal neurons from OGD1 h/reoxygenation 2 h (R2 h) and OGD1 h/R12 h groups exhibited down-regulated Sirt3 protein expression levels. Compared with contralateral normal brain tissue, the ipsilateral penumbra region from MCAO1 h/reperfusion 24 h (R24 h) and MCAO1 h/R72 h groups exhibited down-regulated Sirt3 protein expression levels, while there was no significant difference between the Sirt3 protein levels on both sides of sham group. OGD1 h/R12 h treatment damaged mitochondrial function, activated mitochondrial autophagy and reduced cell viability in hippocampal neurons, whereas Sirt3 over-expression attenuated the above damage effects of OGD1 h/R12 h treatment. These results suggest that acute cerebral ischemia results in a decrease in Sirt3 protein level. Sirt3 overexpression can alleviate acute cerebral ischemia-induced neural injuries by improving the mitochondrial function. The current study sheds light on a novel strategy against neural injuries caused by acute cerebral ischemia.

Protective Effects of Tetramethylpyrazine on Cerebrovascular Regulations in Rats with Chronic Alcoholic Encephalopathy / 生物医学与环境科学（英文）

Recent studies showed that pathology of alcoholic encephalopathy was associated with cerebral vascular damage. TMP (tetramethyl- pyrazine) is widely used in the treatment of cerebrovascular diseases, however, it has not been reported whether TMP can relieve alcohol-induced cerebral vascular damages. The study was performed to investigate the learning and memory, cerebrovascular pathological changes and the expressions of vascular endothelial growth factor (VEGF) and serum levelsofendothelin-1 (ET-1) in the rat model of chronic alcoholic encephalopathy, and explore the effects of TMP intervention on alcoholic encephalopathy. In the present study, the rat model of chronic alcoholic encephalopathy was established by the gavage administration of alcohol; the learning and memory ability was tested by Morris water maze; the expression of VEGF was measured by RT-PCR and Western blot; and the serum levels of ET-1 was measured by radioimmunoassay. We found that alcohol intoxication impaired learning and memory, induced VEGF overexpression and increased ET 1 concentrations. TMP intervention improved learning abilities, increased the VEGF expression and reduced ET-1 level. These results indicate that TMP exhibits therapeutic effects on chronic alcoholic encephalopathy.

C742T mutation of α1, 3 N-acetyl-D-galactosaminyltransferase gene is responsible for A2 subgroup / 中国实验血液学杂志

The objective of this study was to analyze the molecular genetic basis for 2 individuals with A2B phenotype of ABO subtype. The ABO group antigens on red blood cells were identified by monoclonal antibodies and the ABO antibodies in serum were detected by the standard A, B, O cells. The exon 5 to exon 7 coding region of ABO gene was amplified by polymerase chain reaction (PCR) and the PCR product was sequenced directly after the enzymes digested. The amplified product was also cloned by TOPO TA cloning sequencing kit to split the 2 alleles apart and chosen colonies were sequencing bidirectionally for exon 6 to 7 of ABO gene. The results showed that both A and B antigen were identified on red blood cells of the individuals and there was anti-A1 antibody in their serum. There was no 261G deletion and showed 297A/G, 467C/T, 526C/G, 657C/T, 703G/A, 742C/T, 796C/A, 803G/C, 930G/A heterozygotes by direct DNA sequencing. After cloning and sequencing, it was obtained the B101 and one novel A allele. The novel allele has one nucleotide change at 742 position C to T compared with A102, which results in an amino acid Arg to Cys at 248 position and was nominated as A213. It is concluded that C742T mutation of the α1, 3 N-acetyl-D-galactosaminyl-transferase gene can lead to A2 phenotype and with anti-A1 antibody in serum.