Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
多囊卵巢综合征(PCOS)因其病因复杂,症状繁多,严重影响女性的身心健康,然而其发病机制尚未阐明。近年来越来越多的研究证实,细胞自噬和凋亡在PCOS的发生发展中起关键作用,且自噬与PCOS相关的代谢异常,如胰岛素抵抗(IR)密切相关。PI3K/Ak...多囊卵巢综合征(PCOS)因其病因复杂,症状繁多,严重影响女性的身心健康,然而其发病机制尚未阐明。近年来越来越多的研究证实,细胞自噬和凋亡在PCOS的发生发展中起关键作用,且自噬与PCOS相关的代谢异常,如胰岛素抵抗(IR)密切相关。PI3K/Akt/mTOR信号通路是经典的自噬信号通路。基于目前中医药治疗PCOS的研究现状,本文就PI3K/Akt/mTOR信号通路在PCOS中的作用机制及中医药通过调控该通路治疗PCOS的研究进展进行综述,为PCOS的防治提供新思路。Polycystic ovary syndrome (PCOS), due to its complex etiology and numerous symptoms, seriously affects the physical and mental health of women. However, its pathogenesis has not yet been elucidated. In recent years, more and more studies have confirmed that autophagy and apoptosis play a crucial role in the occurrence and development of PCOS, and autophagy is closely related to metabolic abnormalities related to PCOS, such as insulin resistance (IR). The PI3K/Akt/mTOR signaling pathway is a classic autophagy signaling pathway. Based on the current research status of traditional Chinese medicine in the treatment of PCOS, this article reviews the mechanism of PI3K/Akt/mTOR signaling pathway in PCOS and the research progress of traditional Chinese medicine in regulating this pathway to treat PCOS, providing new ideas for the prevention and treatment of PCOS.展开更多
Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem ce...Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.展开更多
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
文摘多囊卵巢综合征(PCOS)因其病因复杂,症状繁多,严重影响女性的身心健康,然而其发病机制尚未阐明。近年来越来越多的研究证实,细胞自噬和凋亡在PCOS的发生发展中起关键作用,且自噬与PCOS相关的代谢异常,如胰岛素抵抗(IR)密切相关。PI3K/Akt/mTOR信号通路是经典的自噬信号通路。基于目前中医药治疗PCOS的研究现状,本文就PI3K/Akt/mTOR信号通路在PCOS中的作用机制及中医药通过调控该通路治疗PCOS的研究进展进行综述,为PCOS的防治提供新思路。Polycystic ovary syndrome (PCOS), due to its complex etiology and numerous symptoms, seriously affects the physical and mental health of women. However, its pathogenesis has not yet been elucidated. In recent years, more and more studies have confirmed that autophagy and apoptosis play a crucial role in the occurrence and development of PCOS, and autophagy is closely related to metabolic abnormalities related to PCOS, such as insulin resistance (IR). The PI3K/Akt/mTOR signaling pathway is a classic autophagy signaling pathway. Based on the current research status of traditional Chinese medicine in the treatment of PCOS, this article reviews the mechanism of PI3K/Akt/mTOR signaling pathway in PCOS and the research progress of traditional Chinese medicine in regulating this pathway to treat PCOS, providing new ideas for the prevention and treatment of PCOS.
基金supported by the National Nature Science Foundation of China,No.81471308(to JL)the Innovative Leading Talents of Liaoning Province,No.XLYC1902031(to JL)+2 种基金Science and Technology Projects in Liaoning Province,No.2022-BS-238(to CH)Young Top Talents of Liaoning Province,No.XLYC1907009(to LW)Dalian Science and Technology Innovation Fund,No.2018J11CY025(to JL)。
文摘Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.
