Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer＇s dis- ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese her...Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer＇s dis- ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer＇s disease patients. An APPs,~JPSI^E9 double transgenic mouse model of Alzheimer＇s disease was used. The intragas- tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer＇s disease. These com- pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer＇s disease.展开更多
Non-alcoholic fatty liver disease （NAFLD） has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major in- dependent cardiovascular risk factor. Lacking a definit...Non-alcoholic fatty liver disease （NAFLD） has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major in- dependent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty ac- ids （n-3 PUFAs） as a potential treatment of NAFLD have been described, n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors （hy- pertension, hyperlipidemia, endothelial dysfunction and atherosclerosis） by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor （PPAR） cz, PPARy, sterol regulatory element-binding protein-i, carbohydrate responsive element-binding protein], im- pacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules （tumor necrosis factor-~ and interleukin-6） and of oxygen reac- tive species. Further strengthening the results of the in vitro studies, both animal models and human interven- tion trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory pa- rameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well- designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources （fish oil, flaxseeds, olive oil） which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.展开更多
Human life span has dramatically increased over several decades,and the quality of life has been considered to be equally important.However,diabetes mellitus(DM) characterized by problems related to insulin secretion ...Human life span has dramatically increased over several decades,and the quality of life has been considered to be equally important.However,diabetes mellitus(DM) characterized by problems related to insulin secretion and recognition has become a serious health problem in recent years that threatens human health by causing decline in brain functions and finally leading to neurodegenerative diseases.Exercise is recognized as an effective therapy for DM without medication administration.Exercise studiesusing experimental animals are a suitable option to overcome this drawback,and animal studies have improved continuously according to the needs of the experimenters.Since brain health is the most significant factor in human life,it is very important to assess brain functions according to the different exercise conditions using experimental animal models.Generally,there are two types of DM; insulin-dependent type 1 DM and an insulin-independent type 2 DM(T2DM); however,the author will mostly discuss brain functions in T2 DM animal models in this review.Additionally,many physiopathologic alterations are caused in the brain by DM such as increased adiposity,inflammation,hormonal dysregulation,uncontrolled hyperphagia,insulin and leptin resistance,and dysregulation of neurotransmitters and declined neurogenesis in the hippocampus and we describe how exercise corrects these alterations in animal models.The results of changes in the brain environment differ according to voluntary,involuntary running exercises and resistance exercise,and gender in the animal studies.These factors have been mentioned in this review,and this review will be a good reference for studying how exercise can be used with therapy for treating DM.展开更多
Degeneration of the locus coeruleus noradrenergic system is thought to play a key role in the pathogenesis of Parkinson＇s disease （PD）, whereas pharmacological approaches to increase noradrenaline bioavailability m...Degeneration of the locus coeruleus noradrenergic system is thought to play a key role in the pathogenesis of Parkinson＇s disease （PD）, whereas pharmacological approaches to increase noradrenaline bioavailability may provide neuroprotection. Noradrenaline inhibits microglial activation and suppresses pro-inflamma- tory mediator production （e.g., tumor necrosis factor-a, interleukin-1β ＆ inducible nitric oxide synthase activity）, thus limiting the cytotoxicity of midbrain dopaminergic neurons in response to an inflamma- tory stimulus. Neighbouring astrocyte populations promote a neurotrophic environment in response to β2-adrenoceptor （β2-AR） stimulation via the production of growth factors （e.g., brain derived neurotrophic factor, cerebral dopamine neurotrophic factor ＆ glial cell derived neurotrophic factor which have shown promising neuroprotective and neuro-restorative effects in the nigrostriatal dopaminergic system. More recent findings have demonstrated a role for the β2-AR in down-regulating expression levels of the human a-synuclein gene SNCA and relative a-synuclein protein abundance. Given that a-synuclein is a major protein constituent of Lewy body pathology, a hallmark neuropathological feature in Parkinson＇s disease, these findings could open up new avenues for pharmacological intervention strategies aimed at alleviating the burden of a-synucleinopathies in the Parkinsonian brain. In essence, the literature reviewed herein supports our hypothesis of a tripartite neuroprotective role for noradrenaline in combating PD-related neuropathology and motor dysfunction via （1） inhibiting nigral microglial activation ＆ pro-inflammatory mediator production, （2） promoting the synthesis of neurotrophic factors from midbrain astrocytes and （3） downregulating a-synuclein gene expression and protein abundance in a β2-AR-dependent manner. Thus, taken together, either pharmacologically enhancing extra-synaptic noradrenaline bioavailability or targeting glial β2-ARs directly makes itself as a promising treatment option aimed at slowing/halting PD progression.展开更多
基金supported by the National Natural Science Foundation of China,No.81273983the Natural Science Foundation of Hebei Province in China,No.C2010001471+1 种基金the Scientific and Technological Research Youth Foundation of Colleges and Universities in Hebei Province of China,No.Q2012036the Hebei Provincial Food and Drug Administration in China,No.PT2014053
文摘Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer＇s dis- ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer＇s disease patients. An APPs,~JPSI^E9 double transgenic mouse model of Alzheimer＇s disease was used. The intragas- tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer＇s disease. These com- pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer＇s disease.
文摘Non-alcoholic fatty liver disease （NAFLD） has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major in- dependent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty ac- ids （n-3 PUFAs） as a potential treatment of NAFLD have been described, n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors （hy- pertension, hyperlipidemia, endothelial dysfunction and atherosclerosis） by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor （PPAR） cz, PPARy, sterol regulatory element-binding protein-i, carbohydrate responsive element-binding protein], im- pacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules （tumor necrosis factor-~ and interleukin-6） and of oxygen reac- tive species. Further strengthening the results of the in vitro studies, both animal models and human interven- tion trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory pa- rameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well- designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources （fish oil, flaxseeds, olive oil） which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.
基金Supported by Fund of Soonchunhyang University,South Korea
文摘Human life span has dramatically increased over several decades,and the quality of life has been considered to be equally important.However,diabetes mellitus(DM) characterized by problems related to insulin secretion and recognition has become a serious health problem in recent years that threatens human health by causing decline in brain functions and finally leading to neurodegenerative diseases.Exercise is recognized as an effective therapy for DM without medication administration.Exercise studiesusing experimental animals are a suitable option to overcome this drawback,and animal studies have improved continuously according to the needs of the experimenters.Since brain health is the most significant factor in human life,it is very important to assess brain functions according to the different exercise conditions using experimental animal models.Generally,there are two types of DM; insulin-dependent type 1 DM and an insulin-independent type 2 DM(T2DM); however,the author will mostly discuss brain functions in T2 DM animal models in this review.Additionally,many physiopathologic alterations are caused in the brain by DM such as increased adiposity,inflammation,hormonal dysregulation,uncontrolled hyperphagia,insulin and leptin resistance,and dysregulation of neurotransmitters and declined neurogenesis in the hippocampus and we describe how exercise corrects these alterations in animal models.The results of changes in the brain environment differ according to voluntary,involuntary running exercises and resistance exercise,and gender in the animal studies.These factors have been mentioned in this review,and this review will be a good reference for studying how exercise can be used with therapy for treating DM.
基金Eoin O’Neill was supported by a Trinity College postgraduate award
文摘Degeneration of the locus coeruleus noradrenergic system is thought to play a key role in the pathogenesis of Parkinson＇s disease （PD）, whereas pharmacological approaches to increase noradrenaline bioavailability may provide neuroprotection. Noradrenaline inhibits microglial activation and suppresses pro-inflamma- tory mediator production （e.g., tumor necrosis factor-a, interleukin-1β ＆ inducible nitric oxide synthase activity）, thus limiting the cytotoxicity of midbrain dopaminergic neurons in response to an inflamma- tory stimulus. Neighbouring astrocyte populations promote a neurotrophic environment in response to β2-adrenoceptor （β2-AR） stimulation via the production of growth factors （e.g., brain derived neurotrophic factor, cerebral dopamine neurotrophic factor ＆ glial cell derived neurotrophic factor which have shown promising neuroprotective and neuro-restorative effects in the nigrostriatal dopaminergic system. More recent findings have demonstrated a role for the β2-AR in down-regulating expression levels of the human a-synuclein gene SNCA and relative a-synuclein protein abundance. Given that a-synuclein is a major protein constituent of Lewy body pathology, a hallmark neuropathological feature in Parkinson＇s disease, these findings could open up new avenues for pharmacological intervention strategies aimed at alleviating the burden of a-synucleinopathies in the Parkinsonian brain. In essence, the literature reviewed herein supports our hypothesis of a tripartite neuroprotective role for noradrenaline in combating PD-related neuropathology and motor dysfunction via （1） inhibiting nigral microglial activation ＆ pro-inflammatory mediator production, （2） promoting the synthesis of neurotrophic factors from midbrain astrocytes and （3） downregulating a-synuclein gene expression and protein abundance in a β2-AR-dependent manner. Thus, taken together, either pharmacologically enhancing extra-synaptic noradrenaline bioavailability or targeting glial β2-ARs directly makes itself as a promising treatment option aimed at slowing/halting PD progression.
