1.Therapeutic effect of celecoxib on nerve protection in transgenic mice with five familial Alzheimer's disease
Xiaowen LIAN ; Bin LUO ; Jianliang CHEN ; Hengxing YOU ; Zhihao ZHAI
Chinese Journal of Neuromedicine 2018;17(8):778-783
Objective To investigate the effect of cyclooxygenase (COX)-2 inhibitor celecoxib on learning and memory capabilities of transgenic mice with five familial Alzheimer's disease (5×FAD) and its potential mechanism.Methods Totally 32 6-month male 5 ×FAD transgenic positive mice were selected and randomly divided into two equal groups (n=16):a model group (group AD) and a celecoxib treatment group (group S).The mice in group AD were fed with normal diet while those in group S took celecoxib in their diet.Another 16 wide-type (WT) gene mice,served as a normal control group (group WT),received normal diet.After treatment for 14 d,water maze test was arranged for the 3 groups to detect their learning capability.Thioflavin-S staining was conducted to detect the number and area of plaques in the cerebral cortex,hippocampus and thalamus of the mice,immunofluorescence staining was used to detect expressions of 4G8 and ion calcium junction protein molecule 1 (Iba-1) in the brain tissues,and quantitative real time-PCR (q-PCR) was used to detect expressions of markers of M1 and M2 microglia cells in the brain tissues.Results The latency periods in finding the platform in mice of group WT,group S and group AD successively increased on 24nd 3rd and 4th d of treatment,with significant differences among the 3 groups (P<0.05).The ratio of time of staying in target quadrant to total time in mice from group AD was significantly lower than that in group WT and group S (P<0.05).The average plaque number and volume per slice in group S were significantly reduced than those in group AD (P<0.05).Immunofluorescence staining showed no plaque formation and a small number of activated microglia cells in group WT,but plaque formation and a large number of activated microglia cells in group AD and group S.The expression of M1 marker in brain tissues was significantly decreased and the expression of M2 marker was significantly increased in group S than those in group AD (P<0.05).Conclusion COX-2 inhibitor celecoxib improves the learning and memory capabilities of 5×FAD mice,which is closely related to polarization of microglia cells.
2.Relationship between abnormal monitoring of VEEG and prognosis in patients with refractory epilepsy
Xiaowen LIAN ; Chunyan HOU ; Hengxing YOU ; Zhihao ZHAI ; Jianliang CHEN
The Journal of Practical Medicine 2018;34(9):1420-1423
Objective To investigate and study the relationship between abnormal monitoring and prognosis of long range video electroencephalogram(VEEG)in patients with intractable epilepsy. Methods 100 patients from March 2012 to May 2017 in our hospital whose diagnosis and treatment of refractory epilepsy were the research object,all patients were given VEEG monitoring records,epilepsy typing characteristics and antiepileptic drug(AEDs)use survey,prognosis of all patients and the correlation analysis. In 100 cases,GTCS 60 cases,CPS 30 cases,CPS-GTCS 10 cases;56 cases treated with sodium valproate,lamotrigine treatment in 44 cases. Results VEEG monitored 80 cases of epileptiform discharge in 100 patients and 20 cases without epileptiform discharge. There was no significant difference in the incidence of epileptiform discharges between different epileptic patients in VEEG monitoring(P > 0.05),and there was no significant difference in the incidence of epileptiform discharges between VEEG patients in different medication groups(P > 0.05). The total effective rate of treatment in the VEEG epileptiform discharge group was 91.3%,which was significantly lower than that of the VEEG non epileptic discharge group (100%,P < 0.05). The main adverse reactions during treatment were drowsiness , abnormal behavior, abnormal sensation and gastrointestinal reaction. There was no significant difference in monitoring epileptiform discharges between VEEG patients (P > 0.05). All adverse reactions were improved after symptomatic treatment. Conclusion The VEEG plays an important role in guiding the patients with refractory epilepsy for epilepsy typing characteristics and AEDs treatment ,so it has significant correlation to the prognosis , and it also has an important significance in assessing the prognosis.
3.Expressions of DEAD-box 5 and hepatoma-derived growth factor in glioma samples and their relations with prognoses
Xiaowen LIAN ; Hengxing YOU ; Zhihao ZHAI ; Jianliang CHEN ; Ye SONG ; Bin LUO
Chinese Journal of Neuromedicine 2019;18(6):583-588
Objective To investigate the expressions of DEAD-box (DDX) 5 and hepatoma-derived growth factor (HDGF) in glioma samples and their relations with prognoses of the patients.Methods Seventy-eight samples from the lesions and 78 samples from the adjacent tissues of glioma patients,admitted to hospital from February 2013 to June 2017,were selected.The protein expressions of DDX5 and HDGF were detected by immunohistochemistry.The positive expression rates of DDX5 and HDGF in the glioma tissues of patients with different clinical characteristics were compared.Kaplan-Meier method was used to plot the survival curves of patients with DDX5 positive expression and DDX5 negative expression;Log-rank test was used to compare the survival rates of these patients.Results Among 78 patients,the positive expression rates of DDX5 and HDGF in the lesion group were 85.9% and 80.8%,which were significantly higher than those in the paracancerous group (24.4% and 28.2%,P<0.05).There were no significant differences in the positive expression rates of DDX5 and HDGF in patients of different genders,ages,or body mass indexes (P>0.05);patients with tumor size > 3 cm had significantly higher positive expression rates of DDX5 and HDGF as compared with those with tumor size<3 cm (P<0.05);patients with WHO grading Ⅲ-Ⅳ had significantly higher positive expression rates of DDX5 and HDGF as compared with those with WHO grading Ⅰ-Ⅱ (P<0.05);patients with intracranial cerebrospinal fluid metastasis had significantly higher positive expression rates of DDX5 and HDGF as compared with those without intracranial cerebrospinal fluid metastasis (P<0.05).Log-rank analysis showed that the overall survival of patients from the DDX5 positive expression group was significantly lower than that of patients from the DDX5 negative expression group (P<0.05).Conclusion DDX5 and HDGF are highly expressed in glioma tissues,and their expressions are related to tumor sizes,WHO grading and intracranial metastasis;patients with positive DDX5 expression have poor prognosis.
4.Mechanism of micro RNA-1182 overexpression in inhibiting malignant phenotype of glioma cells
Zhihao ZHAI ; Bin LUO ; Xiaowen LIAN ; Jianliang CHEN ; Yuanqiang ZHONG ; Hengxing YOU
Chinese Journal of Neuromedicine 2021;20(10):973-980
Objective:To investigate the micro RNA (miR)-1182 expression in glioma, and explore the regulation role and mechanism of miR-1182 overexpression in malignant phenotype of glioma cells.Methods:(1) The data of miR-1182 expressions of 198 glioma samples and survival of these glioma patients were downloaded from the official website of Chinese Glioma Genome Atlas(CGGA), and the differences of miR-1182 expression levels among glioma tissues of different pathologic types and different WHO grades were compared. Kaplan-Meier survival curve was used to analyze the relation between miR-1182 expression level and patient survival. (2) Human glioma cell lines A172, LN229, T98G, U87, and U251, and human normal astrocyte cell line NHA were routinely cultured in vitro, and the miR-1182 expression levels in each group were detected by real-time quantitative PCR (qPCR). (3) U87 and U251 cells were divided into miR-1182 transfection group and negative control group; the miR-1182 mimics and miR-1182 negative control sequence were transfected, respectively. After 48 h of transfection, 5-ethynyl-2'-deoxyuridine (EdU) staining was used to detect the cell proliferation ability, flow cytometry was used to detect the cell apoptosis, Transwell assay was used to detect the cell migration ability, and Western blotting was used to detect the expression levels of cyclin (C-myC, C-Jun, CCND1, and P21), phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt), and epithelial-mesenchymal transformation (EMT) pathway related proteins (N-cadherin, β-catenin, and vimentin). Results:(1) The miR-1182 expressions in glioma tissues of WHO grading III and IV were significantly lower as compared with those in glioma tissues of WHO grading II ( P<0.05). The median survival time in patients from the low miR-1182 expression group ([701.00±11.14] d) was significantly shorter than that in the high miR-1182 expression group ([1812.00±23.21] d, P<0.05). (2) As compared with that in NHA cell group, the miR-1182 expression levels in A172, LN229, T98G, U87 and U251 cell groups were significantly decreased ( P<0.05), and the decrease was most significant in U87 and U251 cell groups. (3) As compared with the negative control group, the U87 and U251 cells in miR-1182 transfection group had significantly weaker proliferation ability, significantly higher apoptosis rate, significantly decreased number of transmembrane cells, significantly decreased protein expression levels of C-MyC, C-Jun and CCND1, significantly increased P21 protein expression level, significantly decreased expression levels of PI3K, phosphorylated (p)-PI3K, Akt and p-Akt, and significantly decreased expression levels of N-cadherin, β-catenin and vimentin ( P<0.05). Conclusions:Glioma patients with low miR-1182 expression have poor prognosis. Low miR-1182 expression is noted in glioma cells. Overexpression of miR-1182 can inhibit the malignant phenotype of glioma cells, which may be related to cell cycle-related proteins, PI3K/Akt, and EMT pathway ralated proteins.