BACKGROUND:The signal of choline containing compounds（Cho）in proton magnetic resonance spectroscopy（1H-MRS）is elevated in brain tumors.[<sup>11</sup>C]choline uptake as assessed using positron emission...BACKGROUND:The signal of choline containing compounds（Cho）in proton magnetic resonance spectroscopy（1H-MRS）is elevated in brain tumors.[<sup>11</sup>C]choline uptake as assessed using positron emission tomography（PET）has also been suggested to be higher in brain tumors than in the normal brain.We examined whetherquantitative analysis of choline accumulation and content using these 1wo novel techniques would be helpful innon-invasive,preoperative evaluation of suspected brain tumors and tumor malignancy grade.METHODS:12patients with suspected brain tumor were studied using[<sup>11</sup>C]choline PET,gadolinium enhanced 3-D magneticresonance imaging and<sup>1</sup>H-MRS prior to diagnostic biopsy or resection.Eleven normal subjects served as展开更多
Maternal one-carbon metabolism plays an important role in early life programming.There is a well-established connection between the fetal environment and the health status of the offspring.Howeve r,there is a knowledg...Maternal one-carbon metabolism plays an important role in early life programming.There is a well-established connection between the fetal environment and the health status of the offspring.Howeve r,there is a knowledge gap on how maternal nutrition impacts stro ke outcomes in offspring.The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcomes in 3-month-old offspring.Adult female mice were fed a folic acid-deficient diet,choline-deficient diet,or control diet 4 weeks before pregnancy.They we re continued on diets during pregnancy and la ctation.Male and female offspring were weaned onto a control diet and at 2 months of age were subjected to ischemic stroke within the sensorimotor cortex via photothrombotic damage.Mothers maintained on either a folic acid-deficient diet or choline-deficient diet had reduced levels of S-adenosylm ethionine in the liver and S-adenosylhomocysteine in the plasma.After ischemic stro ke,motor function was impaired in 3-month-old offspring from mothers receiving either a folic acid-deficient diet or choline-deficient diet compared to the animals receiving a control diet.In brain tissue,there was no difference in ischemic damage volume.When protein levels were assessed in ischemic brain tissue,there were lower levels of active caspase-3 and hypoxia-inducible factor 1α in males compared to females and betaine levels were reduced in offspring from the mothers receiving a choline-deficient diet.Our results demonstrate that a deficient maternal diet at critical time points in neurodevelopment results in worse stro ke outcomes.This study emphasizes the importance of maternal diet and the impact it can have on offspring health.展开更多
BACKGROUND： Cholinergic neuron directly participants in human motion, learning and memory and is a target cell for multiple degenerative diseases of central nervous system. OBJECTIVE： To investigate whether the mito...BACKGROUND： Cholinergic neuron directly participants in human motion, learning and memory and is a target cell for multiple degenerative diseases of central nervous system. OBJECTIVE： To investigate whether the mitotic cell is the radial glial cell expressing choline acetyltransferase （CHAT） in ventricle zone （VZ） of telencephalon and whether cholinergic neuron is derived from radial glial cell in ventricle zone of telencephalon. DESIGN： Observational study. SETTING： Department of Histology and Embryology, Basic Medical College of Jilin University. MATERIALS： Nine healthy Wistar rats included 6 females and 3 male. Male and female rats were mated routinely, and the day when spermatozoa or vaginal plug were found was regarded as embryonic 0 （E0）. Primary monoclonal antibodies ChAT and vimentin were provided respectively by Wuhan Boster Company, and Biogenex Company, USA. METHODS： The experiment was carried out in the Laboratory of Cell Culture and Immunohistochemistry, Department of Histology and Embryology from march 2002 to January 2003. Firstly, fluorescence-activated cell sorting （FACS） was used to confirm the time of generation of cholinergic neuron; secondly, telencephalons of rats at embryonic 14 days （E14） were performed coronary sections, then immunohistochemistry double staining for vimentin （a protein marker of radial neuroglia cell） and ChAT （a protein marker of cholinergic neuron） were used to test whether ChAT was expressed in the radial neuroglia cells. MAIN OUTCOME MEASURES： （1） Fluorescence-activated cell numbers of ChAT in telencephalon; （2） results of immunohistochemistry double staining. RESULTS： It is confirmed using by flow cytometer that embryogenesis time of cholinergic neuron was at E12, and shown the population of cells in VZ of dorsal telencephalon of E14 rat co-expressed vimentin and ChAT through immunohistochemistry double staining. A lot of vimentin-positive cells and ChAT-positive cells respectively were observed in VZ of lateral ganglionic eminence. CONCLUSION： Cholinergic neuron in cerebral cortex is derived from radial glial cells in VZ of dorsal telencephalon; meanwhile, cholinergic neuron of striatum is derived from radial glial cells in VZ of lateral ganglionic eminence.展开更多
The limitations of fluorine-18 fluorodeoxy-D-glucose (FDG) in detecting some cancers has prompted a longstanding search for other positron emission tomography (PET) tracers to complement the imaging of glycolysis in o...The limitations of fluorine-18 fluorodeoxy-D-glucose (FDG) in detecting some cancers has prompted a longstanding search for other positron emission tomography (PET) tracers to complement the imaging of glycolysis in oncology, with much attention paid to lipogenesis based on observations that the production of various lipid and lipid-containing compounds is increased in most cancers. Radiolabeled analogs of choline and acetate have now been used as oncologic PET probes for over a decade, showing convincingly improved detection sensitivity over FDG for certain cancers. However, neither choline nor acetate have been thoroughly validated as lipogenic biomarkers, and while acetyl-CoA produced from acetate is used in de-novo lipogenesis to synthesize fatty acids, acetate is also consumed by various other synthetic and metabolic pathways, with recent experimental observations challenging the assumption that lipogenesis is its predominant role in all cancers. Since tumors detected by acetate PET are also frequently detected by choline PET, imaging of choline metabolism might serve as an alternative albeit indirect marker of lipogenesis, particularly if the fatty acids produced in cancer cells are mainly destined for membrane synthesis through incorporation into phosphatidylcholines. Aerobic glycolysis may or may not coincide with changes in lipid metabolism, resulting in combinatorial metabolic phenotypes that may have different prognostic or therapeutic implications. Consequently, PET imaging using dual metabolic tracers, in addition to being diagnostically superior to imaging with individual tracers, could eventually play a greater role in supporting precision medicine, as efforts to develop small-molecule metabolic pathway inhibitors are coming to fruition. To prepare for this advent, clinical and translational studies of metabolic PET tracers must go beyond simply estimating tracer diagnostic utility, and aim to uncover potential therapeutic avenues associated with these metabolic alterations.展开更多
文摘BACKGROUND:The signal of choline containing compounds（Cho）in proton magnetic resonance spectroscopy（1H-MRS）is elevated in brain tumors.[<sup>11</sup>C]choline uptake as assessed using positron emission tomography（PET）has also been suggested to be higher in brain tumors than in the normal brain.We examined whetherquantitative analysis of choline accumulation and content using these 1wo novel techniques would be helpful innon-invasive,preoperative evaluation of suspected brain tumors and tumor malignancy grade.METHODS:12patients with suspected brain tumor were studied using[<sup>11</sup>C]choline PET,gadolinium enhanced 3-D magneticresonance imaging and<sup>1</sup>H-MRS prior to diagnostic biopsy or resection.Eleven normal subjects served as
文摘Maternal one-carbon metabolism plays an important role in early life programming.There is a well-established connection between the fetal environment and the health status of the offspring.Howeve r,there is a knowledge gap on how maternal nutrition impacts stro ke outcomes in offspring.The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcomes in 3-month-old offspring.Adult female mice were fed a folic acid-deficient diet,choline-deficient diet,or control diet 4 weeks before pregnancy.They we re continued on diets during pregnancy and la ctation.Male and female offspring were weaned onto a control diet and at 2 months of age were subjected to ischemic stroke within the sensorimotor cortex via photothrombotic damage.Mothers maintained on either a folic acid-deficient diet or choline-deficient diet had reduced levels of S-adenosylm ethionine in the liver and S-adenosylhomocysteine in the plasma.After ischemic stro ke,motor function was impaired in 3-month-old offspring from mothers receiving either a folic acid-deficient diet or choline-deficient diet compared to the animals receiving a control diet.In brain tissue,there was no difference in ischemic damage volume.When protein levels were assessed in ischemic brain tissue,there were lower levels of active caspase-3 and hypoxia-inducible factor 1α in males compared to females and betaine levels were reduced in offspring from the mothers receiving a choline-deficient diet.Our results demonstrate that a deficient maternal diet at critical time points in neurodevelopment results in worse stro ke outcomes.This study emphasizes the importance of maternal diet and the impact it can have on offspring health.
基金the Scientific Research Foundation of the Higher Education Institutions, No. 20030183048
文摘BACKGROUND： Cholinergic neuron directly participants in human motion, learning and memory and is a target cell for multiple degenerative diseases of central nervous system. OBJECTIVE： To investigate whether the mitotic cell is the radial glial cell expressing choline acetyltransferase （CHAT） in ventricle zone （VZ） of telencephalon and whether cholinergic neuron is derived from radial glial cell in ventricle zone of telencephalon. DESIGN： Observational study. SETTING： Department of Histology and Embryology, Basic Medical College of Jilin University. MATERIALS： Nine healthy Wistar rats included 6 females and 3 male. Male and female rats were mated routinely, and the day when spermatozoa or vaginal plug were found was regarded as embryonic 0 （E0）. Primary monoclonal antibodies ChAT and vimentin were provided respectively by Wuhan Boster Company, and Biogenex Company, USA. METHODS： The experiment was carried out in the Laboratory of Cell Culture and Immunohistochemistry, Department of Histology and Embryology from march 2002 to January 2003. Firstly, fluorescence-activated cell sorting （FACS） was used to confirm the time of generation of cholinergic neuron; secondly, telencephalons of rats at embryonic 14 days （E14） were performed coronary sections, then immunohistochemistry double staining for vimentin （a protein marker of radial neuroglia cell） and ChAT （a protein marker of cholinergic neuron） were used to test whether ChAT was expressed in the radial neuroglia cells. MAIN OUTCOME MEASURES： （1） Fluorescence-activated cell numbers of ChAT in telencephalon; （2） results of immunohistochemistry double staining. RESULTS： It is confirmed using by flow cytometer that embryogenesis time of cholinergic neuron was at E12, and shown the population of cells in VZ of dorsal telencephalon of E14 rat co-expressed vimentin and ChAT through immunohistochemistry double staining. A lot of vimentin-positive cells and ChAT-positive cells respectively were observed in VZ of lateral ganglionic eminence. CONCLUSION： Cholinergic neuron in cerebral cortex is derived from radial glial cells in VZ of dorsal telencephalon; meanwhile, cholinergic neuron of striatum is derived from radial glial cells in VZ of lateral ganglionic eminence.
文摘The limitations of fluorine-18 fluorodeoxy-D-glucose (FDG) in detecting some cancers has prompted a longstanding search for other positron emission tomography (PET) tracers to complement the imaging of glycolysis in oncology, with much attention paid to lipogenesis based on observations that the production of various lipid and lipid-containing compounds is increased in most cancers. Radiolabeled analogs of choline and acetate have now been used as oncologic PET probes for over a decade, showing convincingly improved detection sensitivity over FDG for certain cancers. However, neither choline nor acetate have been thoroughly validated as lipogenic biomarkers, and while acetyl-CoA produced from acetate is used in de-novo lipogenesis to synthesize fatty acids, acetate is also consumed by various other synthetic and metabolic pathways, with recent experimental observations challenging the assumption that lipogenesis is its predominant role in all cancers. Since tumors detected by acetate PET are also frequently detected by choline PET, imaging of choline metabolism might serve as an alternative albeit indirect marker of lipogenesis, particularly if the fatty acids produced in cancer cells are mainly destined for membrane synthesis through incorporation into phosphatidylcholines. Aerobic glycolysis may or may not coincide with changes in lipid metabolism, resulting in combinatorial metabolic phenotypes that may have different prognostic or therapeutic implications. Consequently, PET imaging using dual metabolic tracers, in addition to being diagnostically superior to imaging with individual tracers, could eventually play a greater role in supporting precision medicine, as efforts to develop small-molecule metabolic pathway inhibitors are coming to fruition. To prepare for this advent, clinical and translational studies of metabolic PET tracers must go beyond simply estimating tracer diagnostic utility, and aim to uncover potential therapeutic avenues associated with these metabolic alterations.
