1.Effect of dopamine on glutamate-uptake ability of astrocytes by regulating mTOR-EAAT2 pathway
fang Fang WEN ; Zhu XU ; ping Le LIU ; jing Jan YANG ; dan Sai DING
Chinese Journal of Pathophysiology 2017;33(10):1746-1750
AIM:To investigate the effect of dopamine ( DA) on the glutamate ( Glu)-uptake ability of astro-cytes, and the role of mammalian target of rapamycin (mTOR)-excitatory amino acid transporter 2(EAAT2) pathway in this process .METHODS:Extracellular Glu levels in DA-treated primary cortical astrocytes ( PCAs) were measured by a fluorimetric method .The relative expression of EAAT 2 and mTOR at mRNA and protein levels was measured by RT-qPCR and Western blot .PCAs stimulated with or without DA in the presence or absence of mTOR antagonist rapamycin or mTOR agonist MHY1485 were used to determine the expression of mTOR and EAAT 2, and Glu content in the culture supernatant was also measured.RESULTS: The expression of mTOR in DA-treated PCAs was decreased, the expression of EAAT2 was also decreased .Extracellular Glu levels of DA-treated PCAs were elevated significantly .When the PCAs were stimula-ted with DA in the presence of rapamycin , the expression of EAAT2 was decreased , and the levels of extracellular Glu was significantly increased.In the presence of MHY1485, the expression of EAAT2 was elevated, and significant decrease in the levels of extracellular Glu was also observed .CONCLUSION:DA interacts with mTOR-EAAT2 pathway to reduce the Glu-uptake ability of the astrocytes , and causes extracellular Glu accumulation , ultimately destroys the function of astro-cytes.
2.An 18-year follow-up study on the risk factors of deaths regarding chronic obstructive pulmonary disease in Xi'an, China.
Xiao-Yong SAI ; Yao HE ; Bo WANG ; Ding-Ru MENG ; Qin-Ju XING ; Dan XIAO ; Yan WANG ; Yong-Ping YAN
Chinese Journal of Epidemiology 2006;27(9):765-768
OBJECTIVETo examine risk factors of chronic obstructive pulmonary disease (COPD) deaths in Chinese military elderly men.
METHODSA cohort analytic study was carried out in Xi'an, China. A total of 1268 retired military males aged 55 or older were examined in 1987 and followed for 18 years. Main outcome measures were all causes and COPD deaths.
RESULTSThe total person-years of follow-up from 1987 until June 2005 was 18 766.28. The mean follow-up time was 14.35 years; A total of 491 had died, with 748 alive and 29 lost of follow-up. COPD was the second cause of death in all deaths (16.90%). Results Univariate analysis of Cox model showed that age, number of smoking cigarettes per day, duration of smoking, negative affairs and existing COPD were risk factors of COPD deaths and the relative risks [95% confidence intervals (CI)] were 1.13 (1.09-1.17), 1.04 (1.02-1.06), 1.03 (1.01-1.04), 1.81 (2.85-6.77) and 4.39 (2.85-6.77) respectively. Data from Multivariate analysis of Cox model showed that age, number of smoking cigarettes per day and existing COPD were risk factors of COPD death with relative risks [95% confidence intervals (CI)] as 1.10 (1.06-1.15), 1.03 (1.01-1.06) and 3.07 (1.90-4.98) respectively. The risks for deaths increased significantly with increasing amount and duration of smoking resulting from all causes and COPD. Compared with current smokers, former smokers had lower risks of total mortality(excess risk reduction of 66.67%).
CONCLUSIONCOPD was the second cause among all deaths in this cohort. Age, number of smoking cigarettes per day and existing COPD were the risk factors of COPD deaths which called for further survey to examine the relationship between quitting smoking and COPD deaths in this cohort.
Age Factors ; Aged ; China ; epidemiology ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Military Personnel ; Pulmonary Disease, Chronic Obstructive ; mortality ; Risk Factors ; Smoking ; adverse effects
3.Association between cognitive impairment and main metals among oldest old aged 80 years and over in China.
Yi Dan QIU ; Yan Bo GUO ; Zhen Wei ZHANG ; Sai Sai JI ; Jin Hui ZHOU ; Bing WU ; Chen CHEN ; Yuan WEI ; Cong DING ; Jun WANG ; Xu Lin ZHENG ; Zhu Chun ZHONG ; Li hong YE ; Guang Di CHEN ; Yue Bin LYU ; Xiao Ming SHI
Chinese Journal of Preventive Medicine 2023;57(6):849-856
Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q1) of blood selenium, the ORs (95%CI) of Q3 and Q4 blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (Pnonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over
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Female
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Humans
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Selenium
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Cohort Studies
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Cross-Sectional Studies
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Metals/analysis*
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Cognitive Dysfunction/epidemiology*
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China/epidemiology*