Neural stem cells,which are capable of multi-potential differentiation and self-renewal,have recently been shown to have clinical potential for repairing central nervous system tissue damage.However,the theme trends a...Neural stem cells,which are capable of multi-potential differentiation and self-renewal,have recently been shown to have clinical potential for repairing central nervous system tissue damage.However,the theme trends and knowledge structures for human neural stem cells have not yet been studied bibliometrically.In this study,we retrieved 2742 articles from the PubMed database from 2013 to 2018 using "Neural Stem Cells" as the retrieval word.Co-word analysis was conducted to statistically quantify the characteristics and popular themes of human neural stem cell-related studies.Bibliographic data matrices were generated with the Bibliographic Item Co-Occurrence Matrix Builder.We identified 78 high-frequency Medical Subject Heading(MeSH)terms.A visual matrix was built with the repeated bisection method in gCLUTO software.A social network analysis network was generated with Ucinet 6.0 software and GraphPad Prism 5 software.The analyses demonstrated that in the 6-year period,hot topics were clustered into five categories.As suggested by the constructed strategic diagram,studies related to cytology and physiology were well-developed,whereas those related to neural stem cell applications,tissue engineering,metabolism and cell signaling,and neural stem cell pathology and virology remained immature.Neural stem cell therapy for stroke and Parkinson’s disease,the genetics of microRNAs and brain neoplasms,as well as neuroprotective agents,Zika virus,Notch receptor,neural crest and embryonic stem cells were identified as emerging hot spots.These undeveloped themes and popular topics are potential points of focus for new studies on human neural stem cells.展开更多
Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs...Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.展开更多
Previous studies have shown that caveolin-1 is involved in regulating the differentiation of mesenchymal stem cells.However,its role in the differentiation of human adipose mesenchymal stem cells into dopaminergic neu...Previous studies have shown that caveolin-1 is involved in regulating the differentiation of mesenchymal stem cells.However,its role in the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons remains unclear.The aim of this study was to investigate whether caveolin-1 regulates the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons.We also examined whether the expression of caveolin-1 could be modulated by RNA interference technology to promote the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons.The differentiation of human adipose mesenchymal stem cells into dopaminergic neurons was evaluated morphologically and by examining expression of the markers tyrosine hydroxylase,Lmx1a and Nurr1.The analyses revealed that during the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons,the expression of caveolin-1 is decreased.Notably,the downregulation of caveolin-1 promoted the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons,and it increased the expression of tyrosine hydroxylase,Lmx1a and Nurr1.Together,our findings suggest that caveolin-1 plays a negative regulatory role in the differentiation of dopaminergic-like neurons from stem cells,and it may therefore be a potential molecular target for strategies for regulating the differentiation of these cells.This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Dalian Medical University of China(approval No.PJ-KS-KY-2020-54)on March 7,2017.展开更多
AIM：To investigate the effect of activating transcription factor-3（ATF3）-deletion on apoptosis of cultured retinal ganglion cells（RGCs）.METHODS：Three ATF3 siR NA（ATF3-rat-651, ATF3-rat-319, ATF3-rat-520） were ...AIM：To investigate the effect of activating transcription factor-3（ATF3）-deletion on apoptosis of cultured retinal ganglion cells（RGCs）.METHODS：Three ATF3 siR NA（ATF3-rat-651, ATF3-rat-319, ATF3-rat-520） were constructed, and were transiently transfected into RGC-5 cells. Quantitative real-time polymerase chain reaction（PCR） was used to examine ATF3 expression and the most effective ATF3 siR NA was selected for further studies. Flow cytometry was applied to investigate the effects of ATF3 deletion on RGC-5 apoptosis under elevated hydrostatic pressure. Quantitative realtime PCR and Western blot were performed to validate differentially expressed genes and proteins in ATF3-knockdown RGC-5 cells.RESULTS：ATF3 specific siR NA effectively down-regulated ATF3 expression and significantly inhibited cell apoptosis in RGC-5 cells. Quantitative real-time PCR and Western blot confirmed that ATF3 knockdown remarkably decreased Jun-B and increased c-Jun at both m RNA and protein levels in RGC-5 cells.CONCLUSION：ATF/cA MP-response element-binding family of transcription factors may be involved in the development of glaucoma and could be novel treatment targets for glaucoma.展开更多
Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external stimuli.Microfluidic te...Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external stimuli.Microfluidic technology has advantages of high-throughput screening,accurate control of the fluid velocity,low cell consumption,long-term culture,and high integration.By combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology,an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons,astrocytes,oligodendrocytes,and a functional microvascular barrier.The model comprises a multi-layer vertical neural module and vascular module,both of which were connected with a syringe pump.This provides controllable conditions for cell inoculation and nutrient supply,and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the brain.The in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research,drug screening,and new drug development.展开更多
Background：Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells （RGCs）.High intraocular pressure （HIOP）,the main risk factor,causes the optic n...Background：Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells （RGCs）.High intraocular pressure （HIOP）,the main risk factor,causes the optic nerve damage.However,the precise mechanism of HIOP-induced RGC death is not yet completely understood.This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures,explore whether laminin is associated with apoptosis under pressure,whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival.Methods：RGC-5 cells were exposed to 0,20,40,and 60 mmHg in a pressurized incubator for 6,12,and 24 h,respectively.The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining,3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay,and Western blotting of cleaved caspase-3 protein.Location and expression oflaminin were detected by immunofluorescence.The expression of β 1-integrin,phosphorylation of focal adhesion kinase （FAK） and protein kinase B （PKB,or AKT） were investigated with real-time polymerase chain reaction and Western blotting analysis.Results：Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells.Pressure with 40 mmHg for 24 h induced a maximum apoptosis.Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h.After pretreating with laminin,RGC-5 cells survived from elevated pressure.Furthermore,β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group.Conclusions：The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure.Laminin can protect RGC-5 cells against high pressure via β 1-integrin/FAK/AKT signaling pathway.These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure,and laminin or activating β1-integrin/FAK/AKT pathway might be potential treatments to prevent RGC loss in glaucomatous optic neuropathy.展开更多
Background： The relationship between monosymptomatic resting tremor （mRT） and Parkinson＇s disease （PD） Iemains controversial. In this study, we aimed to assess tile function ofpresynaptic dopaminergic neurons in...Background： The relationship between monosymptomatic resting tremor （mRT） and Parkinson＇s disease （PD） Iemains controversial. In this study, we aimed to assess tile function ofpresynaptic dopaminergic neurons in patients with mRT by dopamine transporter positron emission tomography （DAT-PET） and to evaluate the utility of clinical features or electrophysioIogical studies in differential diagnosis. Methods： Thirty-three consecutive patients with toRT were enrolled prospectively. The Unified Parkinson＇s Disease Rating Scale and electromyography were tested before DAT-PET. Striatal asymmetry index （SAI） was calculated, and a normal DATPET was defined as a SAI of 〈15%. Scans without evidence of dopaminergic deficits （SWEDDs） were diagnosed in patients with a subsequent normal DAT-PET and structural magnetic resonance imaging. Results： Twenty-eight toRT patients with a significant reduction in uptake of DAT binding in the striatum were diagnosed with PD, while the remained 5 with a normal DAT-PET scan were SWEDDs. As for UPRDS, the dressing and hygiene score, walking m motor experiences of daily living （Part I1） and motor examination （Part Ill ） were significant different between two groups （P 〈 0.05 and P 〈 0.01, respectively）. Bilateral tremor was more frequent in the SWEDDs group （P 〈 0.05）. The frequency of resting tremor and the amplitude ofpostural tremor tend to be higher in the SWEDDs group （P = 0.08 and P= 0.05, respectively）. Conclusions： mRT is heterogeneous in presynaptic nigrostriatal dopaminergic degeneration, which can be determined by DAT-PET brain imaging. Clinical and electrophysiological features may provide clues to distinguish PD from SWEDDs.展开更多
基金supported by the National Natural Science Foundation of China,No.81471308(to JL)the Stem Cell Clinical Research Project in China,No.CMR-20161129-1003(to JL)the Innovation Technology Funding of Dalian in China,No.2018J11CY025(to JL)
文摘Neural stem cells,which are capable of multi-potential differentiation and self-renewal,have recently been shown to have clinical potential for repairing central nervous system tissue damage.However,the theme trends and knowledge structures for human neural stem cells have not yet been studied bibliometrically.In this study,we retrieved 2742 articles from the PubMed database from 2013 to 2018 using "Neural Stem Cells" as the retrieval word.Co-word analysis was conducted to statistically quantify the characteristics and popular themes of human neural stem cell-related studies.Bibliographic data matrices were generated with the Bibliographic Item Co-Occurrence Matrix Builder.We identified 78 high-frequency Medical Subject Heading(MeSH)terms.A visual matrix was built with the repeated bisection method in gCLUTO software.A social network analysis network was generated with Ucinet 6.0 software and GraphPad Prism 5 software.The analyses demonstrated that in the 6-year period,hot topics were clustered into five categories.As suggested by the constructed strategic diagram,studies related to cytology and physiology were well-developed,whereas those related to neural stem cell applications,tissue engineering,metabolism and cell signaling,and neural stem cell pathology and virology remained immature.Neural stem cell therapy for stroke and Parkinson’s disease,the genetics of microRNAs and brain neoplasms,as well as neuroprotective agents,Zika virus,Notch receptor,neural crest and embryonic stem cells were identified as emerging hot spots.These undeveloped themes and popular topics are potential points of focus for new studies on human neural stem cells.
基金the National Natural Science Foundation of China,No.81471308(to JL)Stem cell Clinical Research Registry Program,No.CMR-20161129-1003(to JL)+2 种基金Liaoning Province Excellent Talent Program Project of China,No.XLYC1902031(to JL)Dalian Innovation Fund of China,No.2018J11CY025(to JL)National Defense Science and Technology New Special Zone Contract,No.19-163-00-kx-003-001-01(to JL)。
文摘Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.
基金This work was supported by National Stem Cell Clinical Research Registered Project,No.CMR-20161129-1003(to JL)Dalian Science and Technology Innovation Fund,No.2018J11CY025(to JL).
文摘Previous studies have shown that caveolin-1 is involved in regulating the differentiation of mesenchymal stem cells.However,its role in the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons remains unclear.The aim of this study was to investigate whether caveolin-1 regulates the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons.We also examined whether the expression of caveolin-1 could be modulated by RNA interference technology to promote the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons.The differentiation of human adipose mesenchymal stem cells into dopaminergic neurons was evaluated morphologically and by examining expression of the markers tyrosine hydroxylase,Lmx1a and Nurr1.The analyses revealed that during the differentiation of human adipose mesenchymal stem cells into dopaminergic neurons,the expression of caveolin-1 is decreased.Notably,the downregulation of caveolin-1 promoted the differentiation of human adipose mesenchymal stem cells into dopaminergic-like neurons,and it increased the expression of tyrosine hydroxylase,Lmx1a and Nurr1.Together,our findings suggest that caveolin-1 plays a negative regulatory role in the differentiation of dopaminergic-like neurons from stem cells,and it may therefore be a potential molecular target for strategies for regulating the differentiation of these cells.This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Dalian Medical University of China(approval No.PJ-KS-KY-2020-54)on March 7,2017.
文摘AIM：To investigate the effect of activating transcription factor-3（ATF3）-deletion on apoptosis of cultured retinal ganglion cells（RGCs）.METHODS：Three ATF3 siR NA（ATF3-rat-651, ATF3-rat-319, ATF3-rat-520） were constructed, and were transiently transfected into RGC-5 cells. Quantitative real-time polymerase chain reaction（PCR） was used to examine ATF3 expression and the most effective ATF3 siR NA was selected for further studies. Flow cytometry was applied to investigate the effects of ATF3 deletion on RGC-5 apoptosis under elevated hydrostatic pressure. Quantitative realtime PCR and Western blot were performed to validate differentially expressed genes and proteins in ATF3-knockdown RGC-5 cells.RESULTS：ATF3 specific siR NA effectively down-regulated ATF3 expression and significantly inhibited cell apoptosis in RGC-5 cells. Quantitative real-time PCR and Western blot confirmed that ATF3 knockdown remarkably decreased Jun-B and increased c-Jun at both m RNA and protein levels in RGC-5 cells.CONCLUSION：ATF/cA MP-response element-binding family of transcription factors may be involved in the development of glaucoma and could be novel treatment targets for glaucoma.
基金supported by the Stem Cell Clinical Research Project of China,No.CMR-20161129-1003Liaoning Province Excellent Talent Program Project of China,No.XLYC1902031the Dalian Innovation Technology Foundation of China,No.2018J11CY025(all to JL).
文摘Biological studies typically rely on a simple monolayer cell culture,which does not reflect the complex functional characteristics of human tissues and organs,or their real response to external stimuli.Microfluidic technology has advantages of high-throughput screening,accurate control of the fluid velocity,low cell consumption,long-term culture,and high integration.By combining the multipotential differentiation of neural stem cells with high throughput and the integrated characteristics of microfluidic technology,an in vitro model of a functionalized neurovascular unit was established using human neural stem cell-derived neurons,astrocytes,oligodendrocytes,and a functional microvascular barrier.The model comprises a multi-layer vertical neural module and vascular module,both of which were connected with a syringe pump.This provides controllable conditions for cell inoculation and nutrient supply,and simultaneously simulates the process of ischemic/hypoxic injury and the process of inflammatory factors in the circulatory system passing through the blood-brain barrier and then acting on the nerve tissue in the brain.The in vitro functionalized neurovascular unit model will be conducive to central nervous system disease research,drug screening,and new drug development.
基金a grant from the National Natural Science Foundation of China
文摘Background：Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells （RGCs）.High intraocular pressure （HIOP）,the main risk factor,causes the optic nerve damage.However,the precise mechanism of HIOP-induced RGC death is not yet completely understood.This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures,explore whether laminin is associated with apoptosis under pressure,whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival.Methods：RGC-5 cells were exposed to 0,20,40,and 60 mmHg in a pressurized incubator for 6,12,and 24 h,respectively.The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining,3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay,and Western blotting of cleaved caspase-3 protein.Location and expression oflaminin were detected by immunofluorescence.The expression of β 1-integrin,phosphorylation of focal adhesion kinase （FAK） and protein kinase B （PKB,or AKT） were investigated with real-time polymerase chain reaction and Western blotting analysis.Results：Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells.Pressure with 40 mmHg for 24 h induced a maximum apoptosis.Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h.After pretreating with laminin,RGC-5 cells survived from elevated pressure.Furthermore,β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group.Conclusions：The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure.Laminin can protect RGC-5 cells against high pressure via β 1-integrin/FAK/AKT signaling pathway.These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure,and laminin or activating β1-integrin/FAK/AKT pathway might be potential treatments to prevent RGC loss in glaucomatous optic neuropathy.
文摘Background： The relationship between monosymptomatic resting tremor （mRT） and Parkinson＇s disease （PD） Iemains controversial. In this study, we aimed to assess tile function ofpresynaptic dopaminergic neurons in patients with mRT by dopamine transporter positron emission tomography （DAT-PET） and to evaluate the utility of clinical features or electrophysioIogical studies in differential diagnosis. Methods： Thirty-three consecutive patients with toRT were enrolled prospectively. The Unified Parkinson＇s Disease Rating Scale and electromyography were tested before DAT-PET. Striatal asymmetry index （SAI） was calculated, and a normal DATPET was defined as a SAI of 〈15%. Scans without evidence of dopaminergic deficits （SWEDDs） were diagnosed in patients with a subsequent normal DAT-PET and structural magnetic resonance imaging. Results： Twenty-eight toRT patients with a significant reduction in uptake of DAT binding in the striatum were diagnosed with PD, while the remained 5 with a normal DAT-PET scan were SWEDDs. As for UPRDS, the dressing and hygiene score, walking m motor experiences of daily living （Part I1） and motor examination （Part Ill ） were significant different between two groups （P 〈 0.05 and P 〈 0.01, respectively）. Bilateral tremor was more frequent in the SWEDDs group （P 〈 0.05）. The frequency of resting tremor and the amplitude ofpostural tremor tend to be higher in the SWEDDs group （P = 0.08 and P= 0.05, respectively）. Conclusions： mRT is heterogeneous in presynaptic nigrostriatal dopaminergic degeneration, which can be determined by DAT-PET brain imaging. Clinical and electrophysiological features may provide clues to distinguish PD from SWEDDs.
