Cell therapy offers great promises in replacing the neurons lost due to neurodegenerative diseases or injuries.However,a key challenge is the cellular source for transplantation which is often limited by donor availab...Cell therapy offers great promises in replacing the neurons lost due to neurodegenerative diseases or injuries.However,a key challenge is the cellular source for transplantation which is often limited by donor availability.Direct reprogramming provides an exciting avenue to generate specialized neuron subtypes in vitro,which have the potential to be used for autologous transplantation,as well as generation of patient-specific disease models in the lab for drug discovery and testing gene therapy.Here we present a detailed review on transcription factors that promote direct reprogramming of specific neuronal subtypes with particular focus on glutamatergic,GABAergic,dopaminergic,sensory and retinal neurons.We will discuss the developmental role of master transcriptional regulators and specification factors for neuronal subtypes,and summarize their use in promoting direct reprogramming into different neuronal subtypes.Furthermore,we will discuss up-and-coming technologies that advance the cell reprogramming field,including the use of computational prediction of reprogramming factors,opportunity of cellular reprogramming using small chemicals and microRNA,as well as the exciting potential for applying direct reprogramming in vivo as a novel approach to promote neuro-regeneration within the body.Finally,we will highlight the clinical potential of direct reprogramming and discuss the hurdles that need to be overcome for clinical translation.展开更多
liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especial...liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.展开更多
Since the generation of induced pluripotent stem cells in 2006, cellular reprogramming has attracted increasing attention as a revolutionary strategy for cell replacement therapy. Recent advances have revealed that so...Since the generation of induced pluripotent stem cells in 2006, cellular reprogramming has attracted increasing attention as a revolutionary strategy for cell replacement therapy. Recent advances have revealed that somatic cells can be directly converted into other mature cell types, which eliminates the risk of neoplasia and the generation of undesired cell types. Astrocytes become reactive and undergo proliferation, which hampers axon regeneration following injury, stroke, and neurodegenerative diseases. An emerging technique to directly reprogram astrocytes into induced neural stem cells （iNSCs） and induced neurons （iNs） by neural fate determinants brings potential hope to cell replacement therapy for the above neurological problems. Here, we discuss the development of direct reprogramming of various cell types into iNs and iNSCs, then detail astrocyte-derived iNSCs and iNs in vivo and in vitro. Finally, we highlight the unsolved challenges and opportunities for improvement.展开更多
目的运用实时荧光定量PCR检测24株副溶血性弧菌热稳定直接溶血素(TDH)基因转录水平差异。方法普通PCR法检测分离自患者、海产品和环境中的副溶血性弧菌tdh基因,tdh阳性菌株提取细菌总RNA后逆转录合成cDNA,检测无DNA污染后定量至同一浓度...目的运用实时荧光定量PCR检测24株副溶血性弧菌热稳定直接溶血素(TDH)基因转录水平差异。方法普通PCR法检测分离自患者、海产品和环境中的副溶血性弧菌tdh基因,tdh阳性菌株提取细菌总RNA后逆转录合成cDNA,检测无DNA污染后定量至同一浓度,采用实时荧光定量PCR同时检测cDNA产物中tdh基因和内标基因16 S rRNA的Ct值,ΔCt等于tdh的Ct值减去16 S rRNA的Ct值,以ΔCt值反应tdh相对于内标基因16 S rRNA的转录水平。结果 24株副溶血性弧菌的tdh Ct值、内标基因16 S rRNA Ct值和各样本两者之差的ΔCt值结果范围分别为18.04～25.95、8.30～10.93和8.28～15.34,ΔCt最大值与最小值差为7.06,最高转录水平菌株为最低菌株的133倍(ΔΔCt=27.06)。结论副溶血性弧菌tdh基因转录水平存在较大差异,该差异性形成的分子机制以及与该菌的致病性的关系有待进一步研究。展开更多
基金Supported by funding from the Ophthalmic Research Institute of Australia,the University of Melbourne De Brettville Trustthe Kel and Rosie Day Foundationthe Centre for Eye Research Australia
文摘Cell therapy offers great promises in replacing the neurons lost due to neurodegenerative diseases or injuries.However,a key challenge is the cellular source for transplantation which is often limited by donor availability.Direct reprogramming provides an exciting avenue to generate specialized neuron subtypes in vitro,which have the potential to be used for autologous transplantation,as well as generation of patient-specific disease models in the lab for drug discovery and testing gene therapy.Here we present a detailed review on transcription factors that promote direct reprogramming of specific neuronal subtypes with particular focus on glutamatergic,GABAergic,dopaminergic,sensory and retinal neurons.We will discuss the developmental role of master transcriptional regulators and specification factors for neuronal subtypes,and summarize their use in promoting direct reprogramming into different neuronal subtypes.Furthermore,we will discuss up-and-coming technologies that advance the cell reprogramming field,including the use of computational prediction of reprogramming factors,opportunity of cellular reprogramming using small chemicals and microRNA,as well as the exciting potential for applying direct reprogramming in vivo as a novel approach to promote neuro-regeneration within the body.Finally,we will highlight the clinical potential of direct reprogramming and discuss the hurdles that need to be overcome for clinical translation.
文摘liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.
基金supported by a grant from Department of Neurology, Zhujiang Hospital, Southern Medical Universityl, China (2014257)
文摘Since the generation of induced pluripotent stem cells in 2006, cellular reprogramming has attracted increasing attention as a revolutionary strategy for cell replacement therapy. Recent advances have revealed that somatic cells can be directly converted into other mature cell types, which eliminates the risk of neoplasia and the generation of undesired cell types. Astrocytes become reactive and undergo proliferation, which hampers axon regeneration following injury, stroke, and neurodegenerative diseases. An emerging technique to directly reprogram astrocytes into induced neural stem cells （iNSCs） and induced neurons （iNs） by neural fate determinants brings potential hope to cell replacement therapy for the above neurological problems. Here, we discuss the development of direct reprogramming of various cell types into iNs and iNSCs, then detail astrocyte-derived iNSCs and iNs in vivo and in vitro. Finally, we highlight the unsolved challenges and opportunities for improvement.
文摘目的运用实时荧光定量PCR检测24株副溶血性弧菌热稳定直接溶血素(TDH)基因转录水平差异。方法普通PCR法检测分离自患者、海产品和环境中的副溶血性弧菌tdh基因,tdh阳性菌株提取细菌总RNA后逆转录合成cDNA,检测无DNA污染后定量至同一浓度,采用实时荧光定量PCR同时检测cDNA产物中tdh基因和内标基因16 S rRNA的Ct值,ΔCt等于tdh的Ct值减去16 S rRNA的Ct值,以ΔCt值反应tdh相对于内标基因16 S rRNA的转录水平。结果 24株副溶血性弧菌的tdh Ct值、内标基因16 S rRNA Ct值和各样本两者之差的ΔCt值结果范围分别为18.04～25.95、8.30～10.93和8.28～15.34,ΔCt最大值与最小值差为7.06,最高转录水平菌株为最低菌株的133倍(ΔΔCt=27.06)。结论副溶血性弧菌tdh基因转录水平存在较大差异,该差异性形成的分子机制以及与该菌的致病性的关系有待进一步研究。
