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 β-amyloid peptide （Aβ） is considered responsible for the pathogenesis of Alzheimer＇s disease （AD）. Possible mechanisms underlying Aβ-induced neuronal cytotoxicity include excessive production of rea...Background β-amyloid peptide （Aβ） is considered responsible for the pathogenesis of Alzheimer＇s disease （AD）. Possible mechanisms underlying Aβ-induced neuronal cytotoxicity include excessive production of reactive oxidative species （ROS） and apoptosis. Cyclophilin A （CypA）, exhibits antioxidant properties and protects neurons against oxidative stress induced injury. This study was conducted to demonstrate whether CyPA added to cultured PC12 cells could alleviate Aβ-induced oxidative stress and protect them from apoptosis.Methods PC12 cells were pre-incubated for 30 minutes with recombinant human cyclophilin A （rhCyPA） in 0.1 nmol/L, 1.0 nmol/L, 10 nmol/L and 100 nmol/L and then incubated with 10 μmol/L Aβ25-35. In every group, cell viability, apoptotic morphology, apoptotic rate, intracellular ROS accumulation, the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） of PC12 cells and mitochondrial transmembrane potential were detected. Subsequently, the expression of the active form of caspase-3 was determined by Western blotting.Results It was shown that cultures treated with 1.0 nmol/L, 1U nmol/L or 100 nmol/L rnL, rhCyPA＋Aβ25-35 had significantly higher cell viability and a lower rate of apoptosis compared with the cultures exposed only to Aβ25-35. In addition, rhCyPA attenuated Aβ25-35-induced overproduction of intracellular ROS and Aβ25.35-induced a decrease in activity of the key antioxidant enzymes SOD and GSH-Px. Furthermore, rhCyPA also attenuated Aβ25.35-induced mitochondrial dysfunction and the activation of caspase-3.Conclusion CyPA may act as an ROS scavenger, and prevent Aβ25-35-induced neurotoxicity through attenuating oxidative stress induced by Aβ25-35.展开更多
Alzheimer’s disease is a common progressive neurodegenerative disorder, pathologically characterized by the presence of β-amyloid plaques and neurofibrillary tangles. Current treatment approaches using drugs only al...Alzheimer’s disease is a common progressive neurodegenerative disorder, pathologically characterized by the presence of β-amyloid plaques and neurofibrillary tangles. Current treatment approaches using drugs only alleviate the symptoms without curing the disease, which is a serious issue and influences the quality of life of the patients and their caregivers. In recent years, stem cell technology has provided new insights into the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Currently, the main sources of stem cells include neural stem cells, embryonic stem cells, mesenchymal stem cells, and induced pluripotent stem cells. In this review, we discuss the pathophysiology and general treatment of Alzheimer’s disease, and the current state of stem cell transplantation in the treatment of Alzheimer’s disease. We also assess future challenges in the clinical application and drug development of stem cell transplantation as a treatment for Alzheimer’s disease.展开更多
目的:探讨清心开窍方有效成分对AD大鼠海马区IL-1β、GFAP及Aβ表达的影响。方法:动物实验采用对照观察法。雄性SD大鼠112只,称体质量后按随机数字表分为7组:正常组、假手术组,模型组、安理申组,皂苷组、挥发油组、多糖组,每组16只。采...目的:探讨清心开窍方有效成分对AD大鼠海马区IL-1β、GFAP及Aβ表达的影响。方法:动物实验采用对照观察法。雄性SD大鼠112只,称体质量后按随机数字表分为7组:正常组、假手术组,模型组、安理申组,皂苷组、挥发油组、多糖组,每组16只。采用双侧海马注射Aβ1-40制造AD大鼠模型,造模后第2天开始灌胃,连续灌胃2周(每天上午10点开始),清心开窍方皂苷组、清心开窍方挥发油组、清心开窍方多糖组剂量分别是9、3.33、8.33 m L/(kg·d),安理申组给药剂量为1.67 mg/(kg·d),予对照组和模型组等体积生理盐水。2周后,采用免疫组化、实时定量荧光PCR及WB法检测AD大鼠海马区IL-1β、GFAP及Aβ表达。结果:清心开窍方各有效成分组大鼠海马区IL-1β、GFAP及Aβ表达水平降低,与对照组比较差异非常显著(P<0.01,P<0.05)。结论:清心开窍方有效成分可能是通过降低海马区IL-1β、GFAP及Aβ的表达发挥抗AD的作用。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
文摘Background β-amyloid peptide （Aβ） is considered responsible for the pathogenesis of Alzheimer＇s disease （AD）. Possible mechanisms underlying Aβ-induced neuronal cytotoxicity include excessive production of reactive oxidative species （ROS） and apoptosis. Cyclophilin A （CypA）, exhibits antioxidant properties and protects neurons against oxidative stress induced injury. This study was conducted to demonstrate whether CyPA added to cultured PC12 cells could alleviate Aβ-induced oxidative stress and protect them from apoptosis.Methods PC12 cells were pre-incubated for 30 minutes with recombinant human cyclophilin A （rhCyPA） in 0.1 nmol/L, 1.0 nmol/L, 10 nmol/L and 100 nmol/L and then incubated with 10 μmol/L Aβ25-35. In every group, cell viability, apoptotic morphology, apoptotic rate, intracellular ROS accumulation, the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） of PC12 cells and mitochondrial transmembrane potential were detected. Subsequently, the expression of the active form of caspase-3 was determined by Western blotting.Results It was shown that cultures treated with 1.0 nmol/L, 1U nmol/L or 100 nmol/L rnL, rhCyPA＋Aβ25-35 had significantly higher cell viability and a lower rate of apoptosis compared with the cultures exposed only to Aβ25-35. In addition, rhCyPA attenuated Aβ25-35-induced overproduction of intracellular ROS and Aβ25.35-induced a decrease in activity of the key antioxidant enzymes SOD and GSH-Px. Furthermore, rhCyPA also attenuated Aβ25.35-induced mitochondrial dysfunction and the activation of caspase-3.Conclusion CyPA may act as an ROS scavenger, and prevent Aβ25-35-induced neurotoxicity through attenuating oxidative stress induced by Aβ25-35.
基金supported by the National Natural Science Foundation of China,No.81701076(to LLZ)and No.31670795(to XQF)2017 Changbai Mountain Research Support Foundation,No.440050117010(to XQF)+1 种基金Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences,No.YKFJ2-007(to LLZ)grants from the Science and Technology Department of Jilin Province,China,No.20190701037GH(to FQZ),20180520138JH(to FQZ),20190701036GH(to LLZ)
文摘Alzheimer’s disease is a common progressive neurodegenerative disorder, pathologically characterized by the presence of β-amyloid plaques and neurofibrillary tangles. Current treatment approaches using drugs only alleviate the symptoms without curing the disease, which is a serious issue and influences the quality of life of the patients and their caregivers. In recent years, stem cell technology has provided new insights into the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Currently, the main sources of stem cells include neural stem cells, embryonic stem cells, mesenchymal stem cells, and induced pluripotent stem cells. In this review, we discuss the pathophysiology and general treatment of Alzheimer’s disease, and the current state of stem cell transplantation in the treatment of Alzheimer’s disease. We also assess future challenges in the clinical application and drug development of stem cell transplantation as a treatment for Alzheimer’s disease.
文摘目的:探讨清心开窍方有效成分对AD大鼠海马区IL-1β、GFAP及Aβ表达的影响。方法:动物实验采用对照观察法。雄性SD大鼠112只,称体质量后按随机数字表分为7组:正常组、假手术组,模型组、安理申组,皂苷组、挥发油组、多糖组,每组16只。采用双侧海马注射Aβ1-40制造AD大鼠模型,造模后第2天开始灌胃,连续灌胃2周(每天上午10点开始),清心开窍方皂苷组、清心开窍方挥发油组、清心开窍方多糖组剂量分别是9、3.33、8.33 m L/(kg·d),安理申组给药剂量为1.67 mg/(kg·d),予对照组和模型组等体积生理盐水。2周后,采用免疫组化、实时定量荧光PCR及WB法检测AD大鼠海马区IL-1β、GFAP及Aβ表达。结果:清心开窍方各有效成分组大鼠海马区IL-1β、GFAP及Aβ表达水平降低,与对照组比较差异非常显著(P<0.01,P<0.05)。结论:清心开窍方有效成分可能是通过降低海马区IL-1β、GFAP及Aβ的表达发挥抗AD的作用。
