Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the c...Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.展开更多
BACKGROUND Post-stroke cognitive impairment(PSCI)is not only a common consequence of stroke but also an important factor for adverse prognosis of patients.Biochemical indicators such as blood lipids and blood pressure...BACKGROUND Post-stroke cognitive impairment(PSCI)is not only a common consequence of stroke but also an important factor for adverse prognosis of patients.Biochemical indicators such as blood lipids and blood pressure are affected by many factors,and the ability of evaluating the progress of patients with PSCI is insufficient.Therefore,it is necessary to find sensitive markers for predicting the progress of patients and avoiding PSCI.Recent studies have shown thatβ-amyloid protein 1-42(Aβ1-42)and thyroid hormone levels are closely related to PSCI,which may be the influencing factors of PSCI,but there are few related studies.AIM To investigate the relationship between serum levels of Aβand thyroid hormones in acute stage and PSCI and its predicted value.METHODS A total of 195 patients with acute cerebral infarction confirmed from June 2016 to January 2018 were enrolled in this study.Baseline data and serological indicators were recorded to assess cognitive function of patients.All patients were followed up for 1 year.Their cognitive functions were evaluated within 1 wk,3 mo,6 mo and 1 yr after stroke.At the end of follow-up,the patients were divided into PSCI and non-PSCI according to Montreal cognitive assessment score,and the relationship between biochemical indexes and the progression of PSCI was explored.RESULTS Compared with patients with non-PSCI,the levels of Aβ1-42,triiodothyronine(T3)and free thyroxin were lower in the patients with PSCI.Repeated measures analysis of variance showed that the overall content of Aβ1-42 and T3 in PSCI was also lower than that of the non-PSCI patients.Further analysis revealed that Aβ1-42(r=0.348),T3(r=0.273)and free thyroxin(r=0.214)were positively correlated with disease progression(P<0.05),suggesting that these indicators have the potential to predict disease progression and outcome.Cox regression analysis showed that Aβ1-42 and T3 were important factors of PSCI.Then stratified analysis showed that the lower the Aβ1-42 and T3,the higher risk of PSCI in patients who展开更多
Background Neuropathologically, Alzheimer disease （AD） is characterized by the presence of extracellular plaques enriched in β-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is un...Background Neuropathologically, Alzheimer disease （AD） is characterized by the presence of extracellular plaques enriched in β-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is uncertain. The purpose of this study was to investigate whether it would prompt the progress of Alzheimer disease via enhancement of aberrant phosphorylated tau that results from its increased kinase gene expression. Methods Twenty-four male rats were divided into three groups, and each group had 8 rats： control, sham-operated, and Aβ25-35 injected AD model groups. AD rat models were created by unilateral injections of Aβ25-35 into the amygdala. The hyperphosphorylated tau protein was estimated by immunohistochemistry with paired helical filament-1 （PHF-1） antibody and paired helical filament-tau （AT8） antibody. The expressions of glycogen synthase kinase-3β （GSK-3β） and p38 mitogen-activated protein kinase （P38MAPK） mRNA were observed by in situ hybridization. Results Compared with the control and sham-operated groups, the evaluation of paired AT8 and paired helical filament-1 （PHF-1） in the cortexes and hippocampus of the AD model group showed the numbers of AT8 and PHF-1 positive cells, as well as the optical density （OD） values of the proteins were significantly higher （AT8： in CA2： 0.318±0.037 vs. 0.135±0.028, 0.136±0.031; in frontal cortex： 0.278±0.040 vs. 0.130±0.028, 0.190±0.037. PHF-1 ： in CA2： 0.386±0.034 vs. 0.139±0.010, 0.193±0.041; in frontal cortex： 0.395±0.050 vs. 0.159±0.030, 0.190±0.044, respectively, P 〈0.01）; the number of GSK-3β mRNA and P38MAPK mRNA positive cells of the AD model group, as well as the OD values, also increased significantly in the cortexes, hippocampus （GSK-3β-mRNA： in CA2：0.384±0.012 vs. 0.190±0.015, 0.258±0.064; in frontal cortex： 0.398±0.018 vs. 0.184±0.031, 0.218±0.049. P38MAPK mRNA： in CA2：0.409±0.038 vs. 0.161±0.041, 0.189±0.035; in frontal cortex： 0.423±0.070 vs. 0.160±0展开更多
基金supported by National Basic Research Development Program(973 Program)of China(2011CBA00400)the National Natural Science Foundation of China(91332201)+1 种基金the Natural Science Foundation of Shanghai Municipality,China(13JC1401500)fund for Medical Emerging Cutting-edge Technology in Shanghai Municipality,China(SHDC12012114)
文摘Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.
基金This work was supported by the National Basic Research Priorities Programme of China(G1999054008)the National Natural Science Foundation of China(3027 1494).
基金Supported by Science and Technology Support Projects in Biomedicine Field of Shanghai Science and Technology Commission,No.19441907500Naval Medical University Military Medical Innovation,No.2017JS07Science and Technology Action Innovation Program by Science and Technology Commission of Shanghai,No.17411950104
文摘BACKGROUND Post-stroke cognitive impairment(PSCI)is not only a common consequence of stroke but also an important factor for adverse prognosis of patients.Biochemical indicators such as blood lipids and blood pressure are affected by many factors,and the ability of evaluating the progress of patients with PSCI is insufficient.Therefore,it is necessary to find sensitive markers for predicting the progress of patients and avoiding PSCI.Recent studies have shown thatβ-amyloid protein 1-42(Aβ1-42)and thyroid hormone levels are closely related to PSCI,which may be the influencing factors of PSCI,but there are few related studies.AIM To investigate the relationship between serum levels of Aβand thyroid hormones in acute stage and PSCI and its predicted value.METHODS A total of 195 patients with acute cerebral infarction confirmed from June 2016 to January 2018 were enrolled in this study.Baseline data and serological indicators were recorded to assess cognitive function of patients.All patients were followed up for 1 year.Their cognitive functions were evaluated within 1 wk,3 mo,6 mo and 1 yr after stroke.At the end of follow-up,the patients were divided into PSCI and non-PSCI according to Montreal cognitive assessment score,and the relationship between biochemical indexes and the progression of PSCI was explored.RESULTS Compared with patients with non-PSCI,the levels of Aβ1-42,triiodothyronine(T3)and free thyroxin were lower in the patients with PSCI.Repeated measures analysis of variance showed that the overall content of Aβ1-42 and T3 in PSCI was also lower than that of the non-PSCI patients.Further analysis revealed that Aβ1-42(r=0.348),T3(r=0.273)and free thyroxin(r=0.214)were positively correlated with disease progression(P<0.05),suggesting that these indicators have the potential to predict disease progression and outcome.Cox regression analysis showed that Aβ1-42 and T3 were important factors of PSCI.Then stratified analysis showed that the lower the Aβ1-42 and T3,the higher risk of PSCI in patients who
基金This study was supported by the grants from the National Natural Science Foundation of China （No. 30971029）, Fund of Shanghai Science and Technology Committee （No. 08411950900）, and Young Excellent Talents Award of Tongji University （No. 2006KJ067）.
文摘Background Neuropathologically, Alzheimer disease （AD） is characterized by the presence of extracellular plaques enriched in β-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is uncertain. The purpose of this study was to investigate whether it would prompt the progress of Alzheimer disease via enhancement of aberrant phosphorylated tau that results from its increased kinase gene expression. Methods Twenty-four male rats were divided into three groups, and each group had 8 rats： control, sham-operated, and Aβ25-35 injected AD model groups. AD rat models were created by unilateral injections of Aβ25-35 into the amygdala. The hyperphosphorylated tau protein was estimated by immunohistochemistry with paired helical filament-1 （PHF-1） antibody and paired helical filament-tau （AT8） antibody. The expressions of glycogen synthase kinase-3β （GSK-3β） and p38 mitogen-activated protein kinase （P38MAPK） mRNA were observed by in situ hybridization. Results Compared with the control and sham-operated groups, the evaluation of paired AT8 and paired helical filament-1 （PHF-1） in the cortexes and hippocampus of the AD model group showed the numbers of AT8 and PHF-1 positive cells, as well as the optical density （OD） values of the proteins were significantly higher （AT8： in CA2： 0.318±0.037 vs. 0.135±0.028, 0.136±0.031; in frontal cortex： 0.278±0.040 vs. 0.130±0.028, 0.190±0.037. PHF-1 ： in CA2： 0.386±0.034 vs. 0.139±0.010, 0.193±0.041; in frontal cortex： 0.395±0.050 vs. 0.159±0.030, 0.190±0.044, respectively, P 〈0.01）; the number of GSK-3β mRNA and P38MAPK mRNA positive cells of the AD model group, as well as the OD values, also increased significantly in the cortexes, hippocampus （GSK-3β-mRNA： in CA2：0.384±0.012 vs. 0.190±0.015, 0.258±0.064; in frontal cortex： 0.398±0.018 vs. 0.184±0.031, 0.218±0.049. P38MAPK mRNA： in CA2：0.409±0.038 vs. 0.161±0.041, 0.189±0.035; in frontal cortex： 0.423±0.070 vs. 0.160±0
