The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neuro...The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neurogenesis.Using 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ischemia.Nestin-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem cells.Using a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new neurons.Furthermore,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult cortex.In addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca mulatta.Our findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.展开更多
We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(...We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(G5) were functionalized stepby-step with Chol, fluorescein isothiocyanate(FI), and FA via a poly(ethylene glycol)(PEG) spacer(PEG-FA), and then acetamide to shield their remaining surface amines. The synthesized G5.NHAc-Chol-FI-PEG-FA(for short, G5-CFPF) dendrimers were utilized to encapsulate 10-hydroxycamptothecin(HCP), a hydrophobic anticancer drug. We find that each G5-CFPF dendrimer can encapsulate 13.8 HCP molecules. The complexes show a slower release profiles of HCP in a pH-dependent manner than the control complexes formed using the same dendrimers without Chol under the same conditions. Thanks to the targeting role played by FA, the complexes display a specific inhibition efficacy to FA receptor-expressing cervical cancer cells. The designed Chol-modified dendrimers may be adopted as a promising carrier for application in targeted cancer therapy.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171346(to YZW)82171269(to JLY)+1 种基金82171471(to HF)Beijing Nova Program,No.Z201100006820076(to JLY).
文摘The adult cortex has long been regarded as non-neurogenic.Whether injury can induce neurogenesis in the adult cortex is still controversial.Here,we report that focal ischemia stimulates a transient wave of local neurogenesis.Using 5′-bromo-2′-deoxyuridine labeling,we demonstrated a rapid generation of doublecortin-positive neuroblasts that died quickly in mouse cerebral cortex following ischemia.Nestin-Cre^(ER)-based cell ablation and fate mapping showed a small contribution of neuroblasts by subventricular zone neural stem cells.Using a mini-photothrombotic ischemia mouse model and retrovirus expressing green fluorescent protein labeling,we observed maturation of locally generated new neurons.Furthermore,fate tracing analyses using PDGFRα-,GFAP-,and Sox2-Cre^(ER) mice showed a transient wave of neuroblast generation in mild ischemic cortex and identified that Sox2-positive astrocytes were the major neurogenic cells in adult cortex.In addition,a similar upregulation of Sox2 and appearance of neuroblasts were observed in the focal ischemic cortex of Macaca mulatta.Our findings demonstrated a transient neurogenic response of Sox2-positive astrocytes in ischemic cortex,which suggests the possibility of inducing neuronal regeneration by amplifying this intrinsic response in the future.
基金financially supported by the Fundamental Research Funds for the Central Universities(for M.Shen and X.Shi)the National Natural Science Foundation of China(Nos.81761148028and 21773026)the Science and Technology Commission of Shanghai Municipality(Nos.15520711400 and 17540712000)
文摘We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(G5) were functionalized stepby-step with Chol, fluorescein isothiocyanate(FI), and FA via a poly(ethylene glycol)(PEG) spacer(PEG-FA), and then acetamide to shield their remaining surface amines. The synthesized G5.NHAc-Chol-FI-PEG-FA(for short, G5-CFPF) dendrimers were utilized to encapsulate 10-hydroxycamptothecin(HCP), a hydrophobic anticancer drug. We find that each G5-CFPF dendrimer can encapsulate 13.8 HCP molecules. The complexes show a slower release profiles of HCP in a pH-dependent manner than the control complexes formed using the same dendrimers without Chol under the same conditions. Thanks to the targeting role played by FA, the complexes display a specific inhibition efficacy to FA receptor-expressing cervical cancer cells. The designed Chol-modified dendrimers may be adopted as a promising carrier for application in targeted cancer therapy.