Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzhe...Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.展开更多
Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress ev...Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress even at reduced intraocular pressure. This indicates additional key factors that contribute to the etiopathogenesis. There has been a growing amount of literature suggesting glaucoma as a neurodegenerative disease of the visual system. However, it remains debatable whether the observed pathophysiological conditions are causes or consequences. This review summarizes recent in vivo imaging studies that helped advance the understanding of early glaucoma involvements and disease progression in the brains of humans and experimental animal models. In particular, we focused on the non-invasive detection of early structural and functional brain changes before substantial clinical visual field loss in glaucoma patients; the eye-brain interactions across disease severity; the metabolic changes occurring in the brain's visual system in glaucoma; and, the widespread brain involvements beyond the visual pathway as well as the potential behavioral relevance. If the mechanisms of glaucomatous brain changes are reliably identified, novel neurotherapeutics that target parameters beyond intraocular pressure lowering can be the promise of the near future, which would lead to reduced prevalence of this irreversible but preventable disease.展开更多
In this review, the characteristics of gut microbiota changes in 11 metabolic diseases, as well as the research progress on their interventions, are summarized. The gut microbiota contributes to metabolic diseases thr...In this review, the characteristics of gut microbiota changes in 11 metabolic diseases, as well as the research progress on their interventions, are summarized. The gut microbiota contributes to metabolic diseases through intestinal mucosal dysfunction, chronic metabolic inflammatory response, gut brain axis imbalance, gene regulation, insulin resistance, and the action of its metabolites. The researches of cause effect relationship and mechanism are relatively few, need further study, expecting a breakthrough in the future to be a new path in the treatment of some metabolic diseases.展开更多
Data indicate that perinatal nutritional insults not onlyhave short-term consequences on the growth velocity of the fetus/neonate but also sensitize to the development of metabolic adult diseases.The pathophysiologica...Data indicate that perinatal nutritional insults not onlyhave short-term consequences on the growth velocity of the fetus/neonate but also sensitize to the development of metabolic adult diseases.The pathophysiological mechanisms involved in the so-called "Developmental Origin of Health and Adult Diseases" are still largely unknown and depend on the type of alteration (nutritional,psychological,endocrine disruptors,etc.),its intensity and duration,species,sex and the time during which it is applied.Perinatal stress,via disturbances of both hy-pothalamo-pituitary-adrenal (HPA) axis and sympathoadrenal-system (SAS),as well as brain-adipose axis and pancreas alterations could play a crucial role.Interestingly,it has been demonstrated that perinatal insults may be transmitted transgenerationally,suggesting that these long-term consequences may be inherited via epigenetic mechanisms.Finally,since the placenta has been demonstrated to be sensitive to perinatal nutritional manipulations,the identification of placental markers may thus represent an important new avenue to identify the more susceptible babies prone to developing meta-bolic diseases.展开更多
Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited dis...Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signalin...Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.展开更多
Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. T...Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier function.However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions.展开更多
Circular RNAs(circRNAs)with a covalently closed loop structure which was different with linear RNAs,recently re-merged as novel regulator and exerted function in multiple biological processes.Through deep RNA sequenci...Circular RNAs(circRNAs)with a covalently closed loop structure which was different with linear RNAs,recently re-merged as novel regulator and exerted function in multiple biological processes.Through deep RNA sequencing(RNA-seq)technology coupled with bioinformatic analyses,a number of circRNAs has been identified.Moreover,circRNAs exhibit tissue-and development-specific expression indicating their potential biological significance.Actually,function of circRNAs as miRNA sponge has been well demonstrated in some diseases,besides,circRNAs also could function as RNA binding protein sponge and regulate alternative splicing and gene transcription.Notably,Emerging evidences showed that circRNAs played a pivotal role on the development of diseases including atherosclerotic vascular disease,neurological disorders and liver diseases,and served as diagnostic or predictive biomarkers of some diseases.This review mainly discusses the current advance of circRNAs as regulator involved in many diseases,and highlights circRNAs which have been well elucidated biological and pathogenic mechanism.展开更多
Increased physical activity and higher adherence to a Mediterranean-type diet (MeDi) have been independently associated with reduced risk of Alzheimer’s disease (AD). Their association has not been investigated with ...Increased physical activity and higher adherence to a Mediterranean-type diet (MeDi) have been independently associated with reduced risk of Alzheimer’s disease (AD). Their association has not been investigated with the use of biomarkers. This study examines whether, among cognitively normal (NL) individuals, those who are less physically active and show lower MeDi adherence have brain biomarker abnormalities consistent with AD. Methods: Forty-five NL individuals (age 54 ± 11, 71% women) with complete leisure time physical activity (LTA), dietary information, and cross-sectional 3D T1-weigthed MRI, 11C-Pittsburgh Compound B (PiB) and 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scans were examined. Voxel-wise multivariate partial least square (PLS) regression was used to examine the effects of LTA, MeDi and their interaction on brain biomarkers. Age, gender, ethnicity, education, caloric intake, BMI, family history of AD, Apolipoprotein E (APOE) genotype, presence of hypertension and insulin resistance were examined as confounds. Subjects were dichotomized into more and less physically active (LTA+ vs. LTA-;n = 21 vs. 24), and into higher vs. lower MeDi adherence groups (n = 18 vs. 27) using published scoring methods. Spatial patterns of brain biomarkers that represented the optimal association between the images and the groups were generated for all modalities using voxel-wise multivariate Partial Least Squares (PLS) regression. Results: Groups were comparable for clinical and neuropsychological measures. Independent effects of LTA and MeDi factors were observed in AD-vulnerable brain regions for all modalities (p β load and lower glucose metabolism) were observed in LTA- compared to LTA+ subjects, and in MeDi- as compared to MeDi+ subjects. A gradient effect was observed for all modalities so that LTA+/MeDi+ subjects had the highest and LTA+/MeDi+ subjects had the lowest AD-burden (p < 0.001), although the LTA × MeDi interaction was significant only for FDG measures (p < 0.03). Adjusting for covariates did not attenuate these relationships. Conclusion: Lower physical activity and MeDi adherence were associated with increased brain AD-burden among NL individuals, in-dicating that lifestyle factors may modulate AD risk. Studies with larger samples and longitudinal evaluations are needed to determine the predictive power of the observed associations.展开更多
Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells a...Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson＇s disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups （PBS injection） demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase （dopaminergic neuronal marker） staining and G protein-activated inward rectifier potassium channel 2 （A9 dopaminergic neuronal marker） were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stern cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.展开更多
目的探讨不同剂量奥氮平治疗脑器质性和躯体疾病所致精神障碍患者的效果。方法以收治的108例脑器质性和躯体疾病致精神障碍患者为研究对象,用随机数字表法分为对照组和观察组,每组54例。对照组予以大剂量奥氮平片治疗,观察组予以小剂量...目的探讨不同剂量奥氮平治疗脑器质性和躯体疾病所致精神障碍患者的效果。方法以收治的108例脑器质性和躯体疾病致精神障碍患者为研究对象,用随机数字表法分为对照组和观察组,每组54例。对照组予以大剂量奥氮平片治疗,观察组予以小剂量奥氮平片治疗。2组均治疗8周。比较2组治疗后的效果,治疗前后阳性与阴性症状量表(positive and negative symptom scale,PANSS)评分、神经功能缺损评分量表(national institute of health strokescale,NIHSS)评分、日常生活能力量表(activity of daily living,ADL)评分、简明精神病评定量表(brief psychiatric rating scale,BPRS)评分和糖脂代谢指标。结果治疗后,观察组的临床总有效率高于对照组;2组阳性症状评分、阴性症状评分、一般精神病理评分、总评分、NIHSS评分及BPRS评分均降低,且观察组低于对照组(P<0.05),ADL评分升高,且观察组高于对照组(P<0.05);2组血清总胆固醇(total cholesterol,TC)、低密度脂蛋白-胆固醇(low-density lipoprotein cholesterol,LDL-C)、三酰甘油(triglycerides,TG)、空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS)、稳态胰岛素评价指数(homeostasis model assessment of insulin resistance,HOMA-IR)及餐后2 h血糖(2 hours postprandial blood glucose,2 h PBG)水平均升高,且观察组低于对照组,血清高密度脂蛋白-胆固醇(high-density lipoprotein cholesterol,HDL-C)水平均降低,且观察组高于对照组(P<0.05)。结论脑器质性和躯体疾病所致精神障碍患者应用小剂量奥氮平能够有效提高其临床治疗效果及日常生活能力,改善其精神状况、临床症状及神经功能,同时对患者糖脂代谢的影响较小。展开更多
文摘Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.
基金supported by the National Institutes of Health R01-EY028125(Bethesda,MD,USA)(to KCC)BrightFocus Foundation G2013077 and G2016030(Clarksburg,MD,USA)(to KCC)Research to Prevent Blindness/Stavros Niarchos Foundation International Research Collaborators Award(New York,NY,USA)(to KCC)
文摘Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress even at reduced intraocular pressure. This indicates additional key factors that contribute to the etiopathogenesis. There has been a growing amount of literature suggesting glaucoma as a neurodegenerative disease of the visual system. However, it remains debatable whether the observed pathophysiological conditions are causes or consequences. This review summarizes recent in vivo imaging studies that helped advance the understanding of early glaucoma involvements and disease progression in the brains of humans and experimental animal models. In particular, we focused on the non-invasive detection of early structural and functional brain changes before substantial clinical visual field loss in glaucoma patients; the eye-brain interactions across disease severity; the metabolic changes occurring in the brain's visual system in glaucoma; and, the widespread brain involvements beyond the visual pathway as well as the potential behavioral relevance. If the mechanisms of glaucomatous brain changes are reliably identified, novel neurotherapeutics that target parameters beyond intraocular pressure lowering can be the promise of the near future, which would lead to reduced prevalence of this irreversible but preventable disease.
文摘In this review, the characteristics of gut microbiota changes in 11 metabolic diseases, as well as the research progress on their interventions, are summarized. The gut microbiota contributes to metabolic diseases through intestinal mucosal dysfunction, chronic metabolic inflammatory response, gut brain axis imbalance, gene regulation, insulin resistance, and the action of its metabolites. The researches of cause effect relationship and mechanism are relatively few, need further study, expecting a breakthrough in the future to be a new path in the treatment of some metabolic diseases.
文摘Data indicate that perinatal nutritional insults not onlyhave short-term consequences on the growth velocity of the fetus/neonate but also sensitize to the development of metabolic adult diseases.The pathophysiological mechanisms involved in the so-called "Developmental Origin of Health and Adult Diseases" are still largely unknown and depend on the type of alteration (nutritional,psychological,endocrine disruptors,etc.),its intensity and duration,species,sex and the time during which it is applied.Perinatal stress,via disturbances of both hy-pothalamo-pituitary-adrenal (HPA) axis and sympathoadrenal-system (SAS),as well as brain-adipose axis and pancreas alterations could play a crucial role.Interestingly,it has been demonstrated that perinatal insults may be transmitted transgenerationally,suggesting that these long-term consequences may be inherited via epigenetic mechanisms.Finally,since the placenta has been demonstrated to be sensitive to perinatal nutritional manipulations,the identification of placental markers may thus represent an important new avenue to identify the more susceptible babies prone to developing meta-bolic diseases.
文摘Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by the National Natural Science Foundation of China,Nos.82230042 and 81930029(to ZY),U2004201(to FG and RYP)the China Postdoctoral Science Foundation,No.2020M683748(to RYP)。
文摘Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.
基金supported by the National Natural Science Foundation of China,Nos.31871477,32170971 (both to SQ)the Qing-Feng Scholar Research Foundation of Shanghai Medical College,Fudan University,No.QF2212 (to HT)。
文摘Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier function.However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions.
基金This work was supported by National Natural Science Foundation of China(31571401 and 81770861 to X.Li)ChongQing Science and Technology Foundation(cstc2017jcyjAX0027 to ZC.Zhang).
文摘Circular RNAs(circRNAs)with a covalently closed loop structure which was different with linear RNAs,recently re-merged as novel regulator and exerted function in multiple biological processes.Through deep RNA sequencing(RNA-seq)technology coupled with bioinformatic analyses,a number of circRNAs has been identified.Moreover,circRNAs exhibit tissue-and development-specific expression indicating their potential biological significance.Actually,function of circRNAs as miRNA sponge has been well demonstrated in some diseases,besides,circRNAs also could function as RNA binding protein sponge and regulate alternative splicing and gene transcription.Notably,Emerging evidences showed that circRNAs played a pivotal role on the development of diseases including atherosclerotic vascular disease,neurological disorders and liver diseases,and served as diagnostic or predictive biomarkers of some diseases.This review mainly discusses the current advance of circRNAs as regulator involved in many diseases,and highlights circRNAs which have been well elucidated biological and pathogenic mechanism.
文摘Increased physical activity and higher adherence to a Mediterranean-type diet (MeDi) have been independently associated with reduced risk of Alzheimer’s disease (AD). Their association has not been investigated with the use of biomarkers. This study examines whether, among cognitively normal (NL) individuals, those who are less physically active and show lower MeDi adherence have brain biomarker abnormalities consistent with AD. Methods: Forty-five NL individuals (age 54 ± 11, 71% women) with complete leisure time physical activity (LTA), dietary information, and cross-sectional 3D T1-weigthed MRI, 11C-Pittsburgh Compound B (PiB) and 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scans were examined. Voxel-wise multivariate partial least square (PLS) regression was used to examine the effects of LTA, MeDi and their interaction on brain biomarkers. Age, gender, ethnicity, education, caloric intake, BMI, family history of AD, Apolipoprotein E (APOE) genotype, presence of hypertension and insulin resistance were examined as confounds. Subjects were dichotomized into more and less physically active (LTA+ vs. LTA-;n = 21 vs. 24), and into higher vs. lower MeDi adherence groups (n = 18 vs. 27) using published scoring methods. Spatial patterns of brain biomarkers that represented the optimal association between the images and the groups were generated for all modalities using voxel-wise multivariate Partial Least Squares (PLS) regression. Results: Groups were comparable for clinical and neuropsychological measures. Independent effects of LTA and MeDi factors were observed in AD-vulnerable brain regions for all modalities (p β load and lower glucose metabolism) were observed in LTA- compared to LTA+ subjects, and in MeDi- as compared to MeDi+ subjects. A gradient effect was observed for all modalities so that LTA+/MeDi+ subjects had the highest and LTA+/MeDi+ subjects had the lowest AD-burden (p < 0.001), although the LTA × MeDi interaction was significant only for FDG measures (p < 0.03). Adjusting for covariates did not attenuate these relationships. Conclusion: Lower physical activity and MeDi adherence were associated with increased brain AD-burden among NL individuals, in-dicating that lifestyle factors may modulate AD risk. Studies with larger samples and longitudinal evaluations are needed to determine the predictive power of the observed associations.
基金supported by a"KRCF National Agenda Project",by an Asan Life Science Institute Grant(12-241)from the Asan Medical Center,Seoul,Korea
文摘Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson＇s disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups （PBS injection） demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase （dopaminergic neuronal marker） staining and G protein-activated inward rectifier potassium channel 2 （A9 dopaminergic neuronal marker） were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stern cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.
文摘目的探讨不同剂量奥氮平治疗脑器质性和躯体疾病所致精神障碍患者的效果。方法以收治的108例脑器质性和躯体疾病致精神障碍患者为研究对象,用随机数字表法分为对照组和观察组,每组54例。对照组予以大剂量奥氮平片治疗,观察组予以小剂量奥氮平片治疗。2组均治疗8周。比较2组治疗后的效果,治疗前后阳性与阴性症状量表(positive and negative symptom scale,PANSS)评分、神经功能缺损评分量表(national institute of health strokescale,NIHSS)评分、日常生活能力量表(activity of daily living,ADL)评分、简明精神病评定量表(brief psychiatric rating scale,BPRS)评分和糖脂代谢指标。结果治疗后,观察组的临床总有效率高于对照组;2组阳性症状评分、阴性症状评分、一般精神病理评分、总评分、NIHSS评分及BPRS评分均降低,且观察组低于对照组(P<0.05),ADL评分升高,且观察组高于对照组(P<0.05);2组血清总胆固醇(total cholesterol,TC)、低密度脂蛋白-胆固醇(low-density lipoprotein cholesterol,LDL-C)、三酰甘油(triglycerides,TG)、空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS)、稳态胰岛素评价指数(homeostasis model assessment of insulin resistance,HOMA-IR)及餐后2 h血糖(2 hours postprandial blood glucose,2 h PBG)水平均升高,且观察组低于对照组,血清高密度脂蛋白-胆固醇(high-density lipoprotein cholesterol,HDL-C)水平均降低,且观察组高于对照组(P<0.05)。结论脑器质性和躯体疾病所致精神障碍患者应用小剂量奥氮平能够有效提高其临床治疗效果及日常生活能力,改善其精神状况、临床症状及神经功能,同时对患者糖脂代谢的影响较小。
