Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron rege...Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron regeneration and the glial scar formation.Herein,we apply extracellular vesicles(EVs)secreted by M2 microglia to improve the differentiation of neural stem cells(NSCs)at the injured site,and simultaneously modify them with the injured vascular targeting peptide(DA7R)and the stem cell recruiting factor(SDF-1)on their surface via copper-free click chemistry to recruit NSCs,inducing their neuronal differentiation,and serving as the nanocarriers at the injured site(Dual-EV).Results prove that the Dual-EV could target human umbilical vascular endothelial cells(HUVECs),recruit NSCs,and promote the neuronal differentiation of NSCs in vitro.Furthermore,10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis,and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs,miR30b-3p,miR-222-3p,miR-129-5p,and miR-155-5p may exert effect of inducing NSC to differentiate into neurons.In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice,potentiate NSCs recruitment,and increase neurogenesis.This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells,and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.展开更多
In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.A...In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.Although a growing number of therapeutic targets have been identified in preclinical studies,the ones that can ultimately be used in the clinic are limited.Therefore,the research process and clinical application of drugs for treating CNS diseases are still large challenges.Physiological barriers such as the blood‒brain barrier(BBB)act as selective permeable membranes,allowing only certain molecules to enter the brain;this barrier is the major obstacle restricting the arrival of most drugs to brain lesions.Recently,nanoparticles,including lipid-based,cell-derived biomimetic,polymeric and inorganic nanoparticles,have gained increasing attention because of their ability to cross physiological barriers,and could play an important role as delivery carriers and immunomodulators.Additionally,clinical applications of nanoparticles in CNS diseases are underway.This review focuses on the progress of current research on the use of nanoparticles for the treatment of CNS diseases to provide additional insight into the treatment of CNS diseases.展开更多
Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism ...Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism spectrum disorder,and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes.The treatment of neurodegenerative and neurodevelopmental conditions,together affecting~120 million people worldwide,is challenged by the blood—brain barrier(BBB)and the blood—cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS.The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions.This pathway is more efficient for nanoparticles than for solutions,hence,the research on intranasal nano-drug delivery systems has grown exponentially over the last decade.Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility.This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions,the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them.Then,a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.展开更多
Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these...Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.展开更多
Gene deletion has been a valuable tool for unraveling the mysteries of molecular biology.Early approaches included gene trapping and gene targetting to disrupt or delete a gene randomly or at a specific location,respe...Gene deletion has been a valuable tool for unraveling the mysteries of molecular biology.Early approaches included gene trapping and gene targetting to disrupt or delete a gene randomly or at a specific location,respectively.Using these technologies in mouse embryos led to the generation of mouse knocko ut models and many scientific discoveries.The efficacy and specificity of these approaches have significantly increased with the advent of new technology such as cluste red regula rly inters paced short palindromic repeats for targetted gene deletion.However,several limitations including unwanted off-target gene deletion have hindered their widespread use in the field.Crerecombinase technology has provided additional capacity for cell-specific gene deletion.In this review,we provide a summary of currently available literature on the application of this system for targetted deletion of neuronal genes.This article has been constructed to provide some background info rmation for the new trainees on the mechanism and to provide necessary information for the design,and application of the Cre-recombinase system thro ugh reviewing the most f requent promoters that are currently available for genetic manipulation of neuro ns.We additionally will provide a summary of the latest technological developments that can be used for targeting neurons.This may also serve as a general guide for the selection of appropriate models for biomedical research.展开更多
This study assessed six commercially available in-duct air cleaning devices which are designed to be mounted in the central ventilation system of offices or commercial buildings.The selected devices use different air ...This study assessed six commercially available in-duct air cleaning devices which are designed to be mounted in the central ventilation system of offices or commercial buildings.The selected devices use different air cleaning technologies:mechanical filtration,electrostatic precipitation,gas filtration,ionization/cold plasma,photocatalytic oxidation(PCO)and catalysis under UV light.They were tested against particles,a mixture of volatile organic compounds containing acetone,acetaldehyde,toluene,heptane and formaldehyde,and two bio-contaminants:Aspergillus brasiliensis(fungus)and Staphylococcus epidermidis(bacteria).Two different test rigs were used.The single pass efficiency of each device was determined for three airflow rates,corresponding to face velocities ranging from 0.9 to 2.7 m/s,and two sets of temperature and humidity that are representative of indoor air conditions in wintertime and summertime.The concentration of the chal-lenge volatile organic compounds was also varied in the 30 to 100μg/m^(3)range as a way to characterize their influence on efficiency at realistic concentration levels for non-industrial buildings.Measurements of ozone and formaldehyde concentration downstream of the air cleaners were carried out to determine the emission rate of by-products into the air stream.Finally,the energy issue was addressed by measuring the electric power drawn and pressure loss of the devices.The results showed that two devices,namely a radiant catalytic ionizer and a plasma ionizer,had a very low single pass efficiency against all the challenge pollutants.The association of the plasma ionizer and the electrostatic precipitator did not produce a synergetic effect between the two technologies either,contrary to what their manufacturer claims.Finally,three of the six devices tested were effective in terms of pollutant removal,but only two had an acceptable energy effectiveness in view of their use in low or zero energy buildings.Their energy effectiveness ranged from a few thousand m^(3)/kWh for VOCs at the 展开更多
目的探索改良送管方法预防经外周静脉置入中心静脉导管(peripherally inserted central catheter,PICC)异位至颈内静脉的应用效果。方法 2015年6-12月便利抽样法选取嘉兴学院附属第一医院需留置PICC导管的住院患者400例,按随机数字表法...目的探索改良送管方法预防经外周静脉置入中心静脉导管(peripherally inserted central catheter,PICC)异位至颈内静脉的应用效果。方法 2015年6-12月便利抽样法选取嘉兴学院附属第一医院需留置PICC导管的住院患者400例,按随机数字表法分为对照组和观察组各200例,对照组采用常规送管方法,观察组采用改良送管方法。比较两组患者一次送管成功率、导管异位至颈内静脉发生率。结果对照组一次送管成功179例(成功率为89.5%),导管异位至颈内静脉21例(异位率为10.5%),观察组一次送管成功198例(成功率为99.0%),导管异位至颈内静脉2例(异位率为1.0%),两组比较差异均有统计学意义(均P<0.05)。结论采用改良送管方法,能提高一次送管成功率,降低颈内静脉异位发生率,确保导管安全留置,为预防导管异位提供临床实践与理论依据。展开更多
基金support from Harvard/MITsupport by grants from the National Key R&D Program of China(2019YFA0112000)+5 种基金National Natural Science Foundation of China(Nos.81930051,82003658,81801170)the Interdisciplinary Program of Shanghai Jiao Tong University(ZH2018ZDA04,China)Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20171906,China)China Postdoctoral Science Foundation(2019M661546)National Postdoctoral Program for Innovative Talents(BX20200212,China)Zhejiang Provincial Natural Science Foundation of China(No.LQ21H300009,China)。
文摘Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron regeneration and the glial scar formation.Herein,we apply extracellular vesicles(EVs)secreted by M2 microglia to improve the differentiation of neural stem cells(NSCs)at the injured site,and simultaneously modify them with the injured vascular targeting peptide(DA7R)and the stem cell recruiting factor(SDF-1)on their surface via copper-free click chemistry to recruit NSCs,inducing their neuronal differentiation,and serving as the nanocarriers at the injured site(Dual-EV).Results prove that the Dual-EV could target human umbilical vascular endothelial cells(HUVECs),recruit NSCs,and promote the neuronal differentiation of NSCs in vitro.Furthermore,10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis,and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs,miR30b-3p,miR-222-3p,miR-129-5p,and miR-155-5p may exert effect of inducing NSC to differentiate into neurons.In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice,potentiate NSCs recruitment,and increase neurogenesis.This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells,and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.
基金supported by the National Natural Science Foundation of China(Nos.82073366 and 32100748)the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD18007)the National Natural Science Foundation of Sichuan Province(No.2022NSFSC1642).
文摘In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.Although a growing number of therapeutic targets have been identified in preclinical studies,the ones that can ultimately be used in the clinic are limited.Therefore,the research process and clinical application of drugs for treating CNS diseases are still large challenges.Physiological barriers such as the blood‒brain barrier(BBB)act as selective permeable membranes,allowing only certain molecules to enter the brain;this barrier is the major obstacle restricting the arrival of most drugs to brain lesions.Recently,nanoparticles,including lipid-based,cell-derived biomimetic,polymeric and inorganic nanoparticles,have gained increasing attention because of their ability to cross physiological barriers,and could play an important role as delivery carriers and immunomodulators.Additionally,clinical applications of nanoparticles in CNS diseases are underway.This review focuses on the progress of current research on the use of nanoparticles for the treatment of CNS diseases to provide additional insight into the treatment of CNS diseases.
基金the NEVET Nanotechnology Grant of the Russell Berrie Nanotechnology Institute(RBNI)at Technion—Israel Institute of Technology(Israel)the Tamara and Harry Handelsman Academic Chair(Israel)for financial support。
文摘Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism spectrum disorder,and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes.The treatment of neurodegenerative and neurodevelopmental conditions,together affecting~120 million people worldwide,is challenged by the blood—brain barrier(BBB)and the blood—cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS.The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions.This pathway is more efficient for nanoparticles than for solutions,hence,the research on intranasal nano-drug delivery systems has grown exponentially over the last decade.Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility.This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions,the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them.Then,a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.
基金supported by the National Natural Science Foundation of China, Nos. 82271411 (to RG), 51803072 (to WLiu)grants from the Department of Finance of Jilin Province, Nos. 2022SCZ25 (to RG), 2022SCZ10 (to WLiu), 2021SCZ07 (to RG)+2 种基金Jilin Provincial Science and Technology Program, No. YDZJ202201ZYTS038 (to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University, No. 2022qnpy11 (to WLuo)The Project of China-Japan Union Hospital of Jilin University, No. XHQMX20233 (to RG)
文摘Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.
文摘Gene deletion has been a valuable tool for unraveling the mysteries of molecular biology.Early approaches included gene trapping and gene targetting to disrupt or delete a gene randomly or at a specific location,respectively.Using these technologies in mouse embryos led to the generation of mouse knocko ut models and many scientific discoveries.The efficacy and specificity of these approaches have significantly increased with the advent of new technology such as cluste red regula rly inters paced short palindromic repeats for targetted gene deletion.However,several limitations including unwanted off-target gene deletion have hindered their widespread use in the field.Crerecombinase technology has provided additional capacity for cell-specific gene deletion.In this review,we provide a summary of currently available literature on the application of this system for targetted deletion of neuronal genes.This article has been constructed to provide some background info rmation for the new trainees on the mechanism and to provide necessary information for the design,and application of the Cre-recombinase system thro ugh reviewing the most f requent promoters that are currently available for genetic manipulation of neuro ns.We additionally will provide a summary of the latest technological developments that can be used for targeting neurons.This may also serve as a general guide for the selection of appropriate models for biomedical research.
文摘This study assessed six commercially available in-duct air cleaning devices which are designed to be mounted in the central ventilation system of offices or commercial buildings.The selected devices use different air cleaning technologies:mechanical filtration,electrostatic precipitation,gas filtration,ionization/cold plasma,photocatalytic oxidation(PCO)and catalysis under UV light.They were tested against particles,a mixture of volatile organic compounds containing acetone,acetaldehyde,toluene,heptane and formaldehyde,and two bio-contaminants:Aspergillus brasiliensis(fungus)and Staphylococcus epidermidis(bacteria).Two different test rigs were used.The single pass efficiency of each device was determined for three airflow rates,corresponding to face velocities ranging from 0.9 to 2.7 m/s,and two sets of temperature and humidity that are representative of indoor air conditions in wintertime and summertime.The concentration of the chal-lenge volatile organic compounds was also varied in the 30 to 100μg/m^(3)range as a way to characterize their influence on efficiency at realistic concentration levels for non-industrial buildings.Measurements of ozone and formaldehyde concentration downstream of the air cleaners were carried out to determine the emission rate of by-products into the air stream.Finally,the energy issue was addressed by measuring the electric power drawn and pressure loss of the devices.The results showed that two devices,namely a radiant catalytic ionizer and a plasma ionizer,had a very low single pass efficiency against all the challenge pollutants.The association of the plasma ionizer and the electrostatic precipitator did not produce a synergetic effect between the two technologies either,contrary to what their manufacturer claims.Finally,three of the six devices tested were effective in terms of pollutant removal,but only two had an acceptable energy effectiveness in view of their use in low or zero energy buildings.Their energy effectiveness ranged from a few thousand m^(3)/kWh for VOCs at the
文摘目的探索改良送管方法预防经外周静脉置入中心静脉导管(peripherally inserted central catheter,PICC)异位至颈内静脉的应用效果。方法 2015年6-12月便利抽样法选取嘉兴学院附属第一医院需留置PICC导管的住院患者400例,按随机数字表法分为对照组和观察组各200例,对照组采用常规送管方法,观察组采用改良送管方法。比较两组患者一次送管成功率、导管异位至颈内静脉发生率。结果对照组一次送管成功179例(成功率为89.5%),导管异位至颈内静脉21例(异位率为10.5%),观察组一次送管成功198例(成功率为99.0%),导管异位至颈内静脉2例(异位率为1.0%),两组比较差异均有统计学意义(均P<0.05)。结论采用改良送管方法,能提高一次送管成功率,降低颈内静脉异位发生率,确保导管安全留置,为预防导管异位提供临床实践与理论依据。
