Objective: Our previous studies have revealed that ferulic acid (FA) and sodium ferulate (SF) show significant protective effect on excitotoxicity, the present study was conducted to compare its potential favorable ef...Objective: Our previous studies have revealed that ferulic acid (FA) and sodium ferulate (SF) show significant protective effect on excitotoxicity, the present study was conducted to compare its potential favorable effects of maternal,newborn,and both maternal and newborn intraperitoneal (ip) injection of SF on repair following excitotoxic neuronal damages induced by monosodium glutamate (MSG). Methods: The maternal mice were assigned randomly into seven groups (n = 10 animals in each group): control, 3SF, 20SF, 23SF, MSG, MSG + 3SF, MSG + 20SF, MSG + 23SF groups. The mice at 17 days of pregnancy were treated with or without MSG (2.0 g/kg body weight, ig, once) or/and SF (40 mg/kg body weight, ip), and their offerings treated with or without SF. And then their filial behaviors and hippocampal histopathology were studied. Results: The results showed that maternal, newborn, and both maternal and newborn administration of SF facilitated their filial brain repair, and attenuated the behavioral disorders and histopathological damages of their filial mice in MSG + 3SF, MSG + 20SF, and MSG + 23SF groups in varying degrees. However, the best effects were detected in the filial mice in MSG + 23SF group. Conclusion: Both maternal and newborn administration of SF is conducive to the filial neuronal repair following excitotoxic damages induced by glutamate.展开更多
In this study, we synthesized degradable PRGD/PDLLA/β-TCP/NGF composites to facilitate neuronal repair. To this end, we (1) examined the release of nerve growth factor (NGF) from the composites, (2) evaluated the dif...In this study, we synthesized degradable PRGD/PDLLA/β-TCP/NGF composites to facilitate neuronal repair. To this end, we (1) examined the release of nerve growth factor (NGF) from the composites, (2) evaluated the differentiation status of the cells and (3) address how transcriptional activity may regulate the differentiation mechanism of these cells. NGF content was determined using enzyme-linked immunosorbent assay, while the cellular mRNA expression was examined by real-time PCR analysis. Our results indicated that NGF release was robust during the first 10 days and then stabilized at a lower level thereafter. Treatment of PC12 cells with the extract of the NGF-embedded composites induced the formation of neurites and, in some cases, net-like neurites. Analysis of the expression level of differentiation-related genes, such as TrkA, VGF, Rab1, GAP43 and β-tubulin Ⅱ, were significantly up-regulated. These findings suggest that these composites might be a suitable delivery system for growth factors like NGF that can be used to facilitate neuronal repair after injury.展开更多
Among the macromolecular drug targets in neurodegenerative disorders, the neurotrophin brain-derived neurotrophic factor（BDNF） and its high-affinity tropomyosin-related kinase receptor（Trk B） present strong intere...Among the macromolecular drug targets in neurodegenerative disorders, the neurotrophin brain-derived neurotrophic factor（BDNF） and its high-affinity tropomyosin-related kinase receptor（Trk B） present strong interest for nanomedicine development aiming at neuronal and synaptic repair. Currently, BDNF is regarded as the neurotrophic factor of highest therapeutic significance. However, BDNF has delivery problems as a protein drug. The enhanced activation of the transcription factor CREB（c AMP response element-binding protein） has been evidenced to increase the BDNF gene expression and hence the production of endogenous BDNF. We assume that BDNF delivery by nanocarriers and mitochondrial protection may provide high potential for therapeutic amelioration of the neuroregenerative strategies. Beneficial therapeutic outcomes may be expected for synergistic dual or multi-drug action aiming at（i） neurotrophic protein regulation in the central and peripheral nervous systems, and（ii） diminishment of the production of reactive oxygen species（ROS） and the oxidative damage in mitochondria. Our research strategy is based on a nanoarchitectonics approach for the design of nanomedicine assemblies by hierarchical self-assembly. We explore nanoarchitectonics concepts in soft-matter nanotechnology towards preparation of biodegradable self-assembled lipid nanostructures for safe neuro-therapeutic applications of multi-target nanomedicines.展开更多
文摘Objective: Our previous studies have revealed that ferulic acid (FA) and sodium ferulate (SF) show significant protective effect on excitotoxicity, the present study was conducted to compare its potential favorable effects of maternal,newborn,and both maternal and newborn intraperitoneal (ip) injection of SF on repair following excitotoxic neuronal damages induced by monosodium glutamate (MSG). Methods: The maternal mice were assigned randomly into seven groups (n = 10 animals in each group): control, 3SF, 20SF, 23SF, MSG, MSG + 3SF, MSG + 20SF, MSG + 23SF groups. The mice at 17 days of pregnancy were treated with or without MSG (2.0 g/kg body weight, ig, once) or/and SF (40 mg/kg body weight, ip), and their offerings treated with or without SF. And then their filial behaviors and hippocampal histopathology were studied. Results: The results showed that maternal, newborn, and both maternal and newborn administration of SF facilitated their filial brain repair, and attenuated the behavioral disorders and histopathological damages of their filial mice in MSG + 3SF, MSG + 20SF, and MSG + 23SF groups in varying degrees. However, the best effects were detected in the filial mice in MSG + 23SF group. Conclusion: Both maternal and newborn administration of SF is conducive to the filial neuronal repair following excitotoxic damages induced by glutamate.
基金supported by the National Basic Research Program of China (2011CB606205)
文摘In this study, we synthesized degradable PRGD/PDLLA/β-TCP/NGF composites to facilitate neuronal repair. To this end, we (1) examined the release of nerve growth factor (NGF) from the composites, (2) evaluated the differentiation status of the cells and (3) address how transcriptional activity may regulate the differentiation mechanism of these cells. NGF content was determined using enzyme-linked immunosorbent assay, while the cellular mRNA expression was examined by real-time PCR analysis. Our results indicated that NGF release was robust during the first 10 days and then stabilized at a lower level thereafter. Treatment of PC12 cells with the extract of the NGF-embedded composites induced the formation of neurites and, in some cases, net-like neurites. Analysis of the expression level of differentiation-related genes, such as TrkA, VGF, Rab1, GAP43 and β-tubulin Ⅱ, were significantly up-regulated. These findings suggest that these composites might be a suitable delivery system for growth factors like NGF that can be used to facilitate neuronal repair after injury.
基金supported by CNRSsupported by the Czech Science Foundation Grant GACR 17-00973S+1 种基金the projects ELI-Extreme Light Infrastructure–phase 2(CZ.02.1.01/0.0/0.0/15_008/0000162)ELIBIO(CZ.02.1.01/0.0/0.0/15_003/0000447)from the European Regional Development Fund
文摘Among the macromolecular drug targets in neurodegenerative disorders, the neurotrophin brain-derived neurotrophic factor（BDNF） and its high-affinity tropomyosin-related kinase receptor（Trk B） present strong interest for nanomedicine development aiming at neuronal and synaptic repair. Currently, BDNF is regarded as the neurotrophic factor of highest therapeutic significance. However, BDNF has delivery problems as a protein drug. The enhanced activation of the transcription factor CREB（c AMP response element-binding protein） has been evidenced to increase the BDNF gene expression and hence the production of endogenous BDNF. We assume that BDNF delivery by nanocarriers and mitochondrial protection may provide high potential for therapeutic amelioration of the neuroregenerative strategies. Beneficial therapeutic outcomes may be expected for synergistic dual or multi-drug action aiming at（i） neurotrophic protein regulation in the central and peripheral nervous systems, and（ii） diminishment of the production of reactive oxygen species（ROS） and the oxidative damage in mitochondria. Our research strategy is based on a nanoarchitectonics approach for the design of nanomedicine assemblies by hierarchical self-assembly. We explore nanoarchitectonics concepts in soft-matter nanotechnology towards preparation of biodegradable self-assembled lipid nanostructures for safe neuro-therapeutic applications of multi-target nanomedicines.
