Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation,differing from apoptosis,necroptosis,and autophagy in several aspects.Ferroptosis is regar...Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation,differing from apoptosis,necroptosis,and autophagy in several aspects.Ferroptosis is regarded as a critical mechanism of a series of pathophysiological reactions after stroke because of iron overload caused by hemoglobin degradation and iron metabolism imbalance.In this review,we discuss ferroptosis-related metabolisms,important molecules directly or indirectly targeting iron metabolism and lipid peroxidation,and transcriptional regulation of ferroptosis,revealing the role of ferroptosis in the progression of stroke.We present updated progress in the intervention of ferroptosis as therapeutic strategies for stroke in vivo and in vitro and summarize the effects of ferroptosis inhibitors on stroke.Our review facilitates further understanding of ferroptosis pathogenesis in stroke,proposes new targets for the treatment of stroke,and suggests that more efforts should be made to investigate the mechanism of ferroptosis in stroke.展开更多
Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we use...Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.展开更多
For improving the managed level and guiding the environmental management of reclamation engineering, a synthetic assessment method based on cloud theory is applied to evaluate the environment carrying capacity of part...For improving the managed level and guiding the environmental management of reclamation engineering, a synthetic assessment method based on cloud theory is applied to evaluate the environment carrying capacity of part of Tianjin Port in this paper. This retrospective assessment of carrying capacity aims to obtain the historical development situation of reclamation domain. The research is meaningful and efficient for judging the feasibility of marine reclamation.展开更多
Reactive oxygen species(RoS)are essential for biological processes like cell signaling and chemical processes like organic oxidation.Moreover,the sufficient generation of RoS plays a significant role in targeted tumor...Reactive oxygen species(RoS)are essential for biological processes like cell signaling and chemical processes like organic oxidation.Moreover,the sufficient generation of RoS plays a significant role in targeted tumor treatments or oxidation of organics.Herein,a hydrazone-linked porphyrin covalent organic framework(Por-DETH-COF)is developed for red light-induced generation of ROS like singlet oxygen(^(1)O_(2))or superoxide(O_(2)·^(-))to undertake different but targeted oxidations.First,^(1)O_(2)is adopted in photodynamic therapy(PDT)for the oxidation of glioma cells.The PDT efficiency of Por-DETH-COF on the apoptosis of glioma cells is explored through flow cytometry and western blot assay.The apoptosis rate of glioma cells significantly increases over Por-DETH-COF under 660nm red light illumination,suggestive of the potency of^(1)O_(2).Second,O_(2)^(·-)is employed for the targeted oxidation of thiols.A series of thiols could be efficiently oxidized to corresponding disulfides over Por-DETH-COF under 660 nm red light illumination,indicative of the significance of O_(2)^(·-).This work highlights the potential of covalent organic frameworks in generating Ros for precise medical applications of complex chemical environments.展开更多
Mesenchymal stem cells(MSCs)are promising seed cells for neural regeneration therapy owing to their plasticity and accessibility.They possess several inherent characteristics advantageous for the transplantation-based...Mesenchymal stem cells(MSCs)are promising seed cells for neural regeneration therapy owing to their plasticity and accessibility.They possess several inherent characteristics advantageous for the transplantation-based treatment of neurological disorders,including neural differentiation,immunosuppression,neurotrophy,and safety.However,the therapeutic efficacy of MSCs alone remains unsatisfactory in most cases.To improve some of their abilities,many studies have employed genetic engineering to transfer key genes into MSCs.Both viral and nonviral methods can be used to overexpress therapeutic proteins that complement the inherent properties.However,to date,different modes of gene transfer have specific drawbacks and advantages.In addition,MSCs can be functionalized through targeted gene modification to facilitate neural repair by promoting neural differentiation,enhancing neurotrophic and neuroprotective functions,and increasing survival and homing abilities.The methods of gene transfer and selection of delivered genes still need to be optimized for improved therapeutic and targeting efficacies while minimizing the loss of MSC function.In this review,we focus on gene transport technologies for engineering MSCs and the application of strategies for selecting optimal delivery genes.Further,we describe the prospects and challenges of their application in animal models of different neurological lesions to broaden treatment alternatives for neurological diseases.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81971870 and 82172173(to ML).
文摘Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation,differing from apoptosis,necroptosis,and autophagy in several aspects.Ferroptosis is regarded as a critical mechanism of a series of pathophysiological reactions after stroke because of iron overload caused by hemoglobin degradation and iron metabolism imbalance.In this review,we discuss ferroptosis-related metabolisms,important molecules directly or indirectly targeting iron metabolism and lipid peroxidation,and transcriptional regulation of ferroptosis,revealing the role of ferroptosis in the progression of stroke.We present updated progress in the intervention of ferroptosis as therapeutic strategies for stroke in vivo and in vitro and summarize the effects of ferroptosis inhibitors on stroke.Our review facilitates further understanding of ferroptosis pathogenesis in stroke,proposes new targets for the treatment of stroke,and suggests that more efforts should be made to investigate the mechanism of ferroptosis in stroke.
基金supported by the National Natural Science Foundation of China,Nos.81971870 and 82172173 (both to ML)。
文摘Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.
文摘For improving the managed level and guiding the environmental management of reclamation engineering, a synthetic assessment method based on cloud theory is applied to evaluate the environment carrying capacity of part of Tianjin Port in this paper. This retrospective assessment of carrying capacity aims to obtain the historical development situation of reclamation domain. The research is meaningful and efficient for judging the feasibility of marine reclamation.
基金supported by the National Natural Science Foundation of China(No.22072108).
文摘Reactive oxygen species(RoS)are essential for biological processes like cell signaling and chemical processes like organic oxidation.Moreover,the sufficient generation of RoS plays a significant role in targeted tumor treatments or oxidation of organics.Herein,a hydrazone-linked porphyrin covalent organic framework(Por-DETH-COF)is developed for red light-induced generation of ROS like singlet oxygen(^(1)O_(2))or superoxide(O_(2)·^(-))to undertake different but targeted oxidations.First,^(1)O_(2)is adopted in photodynamic therapy(PDT)for the oxidation of glioma cells.The PDT efficiency of Por-DETH-COF on the apoptosis of glioma cells is explored through flow cytometry and western blot assay.The apoptosis rate of glioma cells significantly increases over Por-DETH-COF under 660nm red light illumination,suggestive of the potency of^(1)O_(2).Second,O_(2)^(·-)is employed for the targeted oxidation of thiols.A series of thiols could be efficiently oxidized to corresponding disulfides over Por-DETH-COF under 660 nm red light illumination,indicative of the significance of O_(2)^(·-).This work highlights the potential of covalent organic frameworks in generating Ros for precise medical applications of complex chemical environments.
基金This work was supported by the National Natural Science Foundation of China(81871503 from Qingsong Ye)National Key R&D Program of China(2022YFC2504200 from Qingsong Ye)Key research and development project of Hubei Province and Chutian Researcher Project(X22020024 from Yan He).
文摘Mesenchymal stem cells(MSCs)are promising seed cells for neural regeneration therapy owing to their plasticity and accessibility.They possess several inherent characteristics advantageous for the transplantation-based treatment of neurological disorders,including neural differentiation,immunosuppression,neurotrophy,and safety.However,the therapeutic efficacy of MSCs alone remains unsatisfactory in most cases.To improve some of their abilities,many studies have employed genetic engineering to transfer key genes into MSCs.Both viral and nonviral methods can be used to overexpress therapeutic proteins that complement the inherent properties.However,to date,different modes of gene transfer have specific drawbacks and advantages.In addition,MSCs can be functionalized through targeted gene modification to facilitate neural repair by promoting neural differentiation,enhancing neurotrophic and neuroprotective functions,and increasing survival and homing abilities.The methods of gene transfer and selection of delivered genes still need to be optimized for improved therapeutic and targeting efficacies while minimizing the loss of MSC function.In this review,we focus on gene transport technologies for engineering MSCs and the application of strategies for selecting optimal delivery genes.Further,we describe the prospects and challenges of their application in animal models of different neurological lesions to broaden treatment alternatives for neurological diseases.
