Alzheimer's disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain.The ketogenic diet,a widely recognized therapeutic intervention for refractor...Alzheimer's disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain.The ketogenic diet,a widely recognized therapeutic intervention for refractory epilepsy,has recently been proposed as a potential treatment for a variety of neurological diseases,including Alzheimer's disease.However,the efficacy of ketogenic diet in treating Alzheimer's disease and the underlying mechanism remains unclear.The current investigation aimed to explore the effect of ketogenic diet on cognitive function and the underlying biological mechanisms in a mouse model of Alzheimer's disease.Male amyloid precursor protein/presenilin 1(APP/PS1)mice were randomly assigned to either a ketogenic diet or control diet group,and received their respective diets for a duration of 3 months.The findings show that ketogenic diet administration enhanced cognitive function,attenuated amyloid plaque formation and proinflammatory cytokine levels in APP/PS1 mice,and augmented the nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 signaling pathway while suppressing the nuclear factor-kappa B pathway.Collectively,these data suggest that ketogenic diet may have a therapeutic potential in treating Alzheimer's disease by ameliorating the neurotoxicity associated with Aβ-induced inflammation.This study highlights the urgent need for further research into the use of ketogenic diet as a potential therapy for Alzheimer's disease.展开更多
Stroke is the second leading cause of mortality and morbidity worldwide.Early intervention is of great importance in reducing disease burden.Since the conventional risk factors cannot fully account for the pathogenesi...Stroke is the second leading cause of mortality and morbidity worldwide.Early intervention is of great importance in reducing disease burden.Since the conventional risk factors cannot fully account for the pathogenesis of stroke,it is extremely important to detect useful biomarkers of the vascular disorder for appropriate intervention.Arterial stiffness,a newly recognised reliable feature of arterial structure and function,is demonstrated to be associated with stroke onset and serve as an independent predictor of stroke incidence and poststroke functional outcomes.In this review article,different measurements of arterial stiffness,especially pressure wave velocity,were discussed.We explained the association between arterial stiffness and stroke occurrence by discussing the secondary haemodynamic changes.We reviewed clinical data that support the prediction role of arterial stiffness on stroke.Despite the lack of long-term randomised double-blind controlled therapeutic trials,it is high potential to reduce stroke prevalence through a significant reduction of arterial stiffness(which is called de-stiffening therapy).Pharmacological interventions or lifestyle modification that can influence blood pressure,arterial function or structure in either the short or long term are promising de-stiffening therapies.Here,we summarised different de-stiffening strategies including antihypertension drugs,antihyperlipidaemic agents,chemicals that target arterial remodelling and exercise training.Large and well-designed clinical trials on de-stiffening strategy are needed to testify the prevention effect for stroke.Novel techniques such as modern microscopic imaging and reliable animal models would facilitate the mechanistic analyses in pathophysiology,pharmacology and therapeutics.展开更多
基金the National Natural Science Foundation of China,Nos.82171401,81971187(to SC)and 81971183(to YT)grants from Shanghai Municipal Science and Technology Major Project,No.2018SHZDZX05(to SC)Shanghai Municipal Education Commission,No.2017-01-07-00-01-E00046(to SC)。
文摘Alzheimer's disease is a progressive neurological disorder characterized by cognitive decline and chronic inflammation within the brain.The ketogenic diet,a widely recognized therapeutic intervention for refractory epilepsy,has recently been proposed as a potential treatment for a variety of neurological diseases,including Alzheimer's disease.However,the efficacy of ketogenic diet in treating Alzheimer's disease and the underlying mechanism remains unclear.The current investigation aimed to explore the effect of ketogenic diet on cognitive function and the underlying biological mechanisms in a mouse model of Alzheimer's disease.Male amyloid precursor protein/presenilin 1(APP/PS1)mice were randomly assigned to either a ketogenic diet or control diet group,and received their respective diets for a duration of 3 months.The findings show that ketogenic diet administration enhanced cognitive function,attenuated amyloid plaque formation and proinflammatory cytokine levels in APP/PS1 mice,and augmented the nuclear factor-erythroid 2-p45 derived factor 2/heme oxygenase-1 signaling pathway while suppressing the nuclear factor-kappa B pathway.Collectively,these data suggest that ketogenic diet may have a therapeutic potential in treating Alzheimer's disease by ameliorating the neurotoxicity associated with Aβ-induced inflammation.This study highlights the urgent need for further research into the use of ketogenic diet as a potential therapy for Alzheimer's disease.
基金This work was supported by NSFC project 81070939(G-YY)and U1232205(G-YY).
文摘Stroke is the second leading cause of mortality and morbidity worldwide.Early intervention is of great importance in reducing disease burden.Since the conventional risk factors cannot fully account for the pathogenesis of stroke,it is extremely important to detect useful biomarkers of the vascular disorder for appropriate intervention.Arterial stiffness,a newly recognised reliable feature of arterial structure and function,is demonstrated to be associated with stroke onset and serve as an independent predictor of stroke incidence and poststroke functional outcomes.In this review article,different measurements of arterial stiffness,especially pressure wave velocity,were discussed.We explained the association between arterial stiffness and stroke occurrence by discussing the secondary haemodynamic changes.We reviewed clinical data that support the prediction role of arterial stiffness on stroke.Despite the lack of long-term randomised double-blind controlled therapeutic trials,it is high potential to reduce stroke prevalence through a significant reduction of arterial stiffness(which is called de-stiffening therapy).Pharmacological interventions or lifestyle modification that can influence blood pressure,arterial function or structure in either the short or long term are promising de-stiffening therapies.Here,we summarised different de-stiffening strategies including antihypertension drugs,antihyperlipidaemic agents,chemicals that target arterial remodelling and exercise training.Large and well-designed clinical trials on de-stiffening strategy are needed to testify the prevention effect for stroke.Novel techniques such as modern microscopic imaging and reliable animal models would facilitate the mechanistic analyses in pathophysiology,pharmacology and therapeutics.
