Numerous therapeutic anti-tumor strategies have been developed in recent decades.However,their therapeutic efficacy is reduced by the intrinsic protective autophagy of tumors.Autophagy plays a key role in tumorigenesi...Numerous therapeutic anti-tumor strategies have been developed in recent decades.However,their therapeutic efficacy is reduced by the intrinsic protective autophagy of tumors.Autophagy plays a key role in tumorigenesis and tumor treatment,in which the overproduction of reactive oxygen species(ROS)is recognized as the direct cause of protective autophagy.Only a few molecules have been employed as autophagy inhibitors in tumor therapy to reduce protective autophagy.Among them,hydroxychloroquine is the most commonly used autophagy inhibitor in clinics,but it is severely limited by its high therapeutic dose,significant toxicity,poor reversal efficacy,and nonspecific action.Herein,we demonstrate a reductive-damage strategy to enable tumor therapy by the inhibition of protective autophagy via the catalytic scavenging of ROS using porous nanorods of ceria(PN-CeO_(2))nanozymes as autophagy inhibitor.The antineoplastic effects of PN-CeO_(2)were mediated by its high reductive activity for intratumoral ROS degradation,thereby inhibiting protective autophagy and activating apoptosis by suppressing the activities of phosphatidylinositide 3-kinase/protein kinase B and p38 mitogen-activated protein kinase pathways in human cutaneous squamous cell carcinoma.Further investigation highlighted PN-CeO_(2)as a safe and efficient anti-tumor autophagy inhibitor.Overall,this study presents a reductive-damage strategy as a promising anti-tumor approach that catalytically inhibits autophagy and activates the intrinsic antioxidant pathways of tumor cells and also shows its potential for the therapy of other autophagy-related diseases.展开更多
As an invisible“endocrine organ”,gut microbiota is widely involved in the regulation of nervous system,endocrine system,circulatory system,and digestive system.It is also closely related to host health and the occur...As an invisible“endocrine organ”,gut microbiota is widely involved in the regulation of nervous system,endocrine system,circulatory system,and digestive system.It is also closely related to host health and the occurrence of many chronic diseases.Relevant literature shows that high temperature,low temperature,and highaltitude hypoxia may have negative effects on commensal microorganisms.The stimulation of exercise may aggravate this reaction,which is related to the occurrence of exercise-induced fever and gastrointestinal and respiratory diseases.The intervention of probiotics can alleviate the above problems to a certain extent.Therefore,this paper takes exercise in a special environment as the starting point,deeply analyses the intervention effect and potential mechanism of probiotics,and provides the theoretical basis and reference for follow-up research and application of probiotics in sports science.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.81972938,52002314,and 21872109)partially supported by Funds of Shaanxi Province(Nos.2021ZDLSF03-01,2020TD-043,and TZ0124)+2 种基金General Project of Shaanxi Natural Science Basic Research Plan(No.2021JM-589)Xi’an People’s Hospital(Xi’an Fourth Hospital)Research Incubation Fund Project(LH-1)the support from the Fundamental Research Funds for the Central Universities(Nos.D5000210829 and G2021KY05102).
文摘Numerous therapeutic anti-tumor strategies have been developed in recent decades.However,their therapeutic efficacy is reduced by the intrinsic protective autophagy of tumors.Autophagy plays a key role in tumorigenesis and tumor treatment,in which the overproduction of reactive oxygen species(ROS)is recognized as the direct cause of protective autophagy.Only a few molecules have been employed as autophagy inhibitors in tumor therapy to reduce protective autophagy.Among them,hydroxychloroquine is the most commonly used autophagy inhibitor in clinics,but it is severely limited by its high therapeutic dose,significant toxicity,poor reversal efficacy,and nonspecific action.Herein,we demonstrate a reductive-damage strategy to enable tumor therapy by the inhibition of protective autophagy via the catalytic scavenging of ROS using porous nanorods of ceria(PN-CeO_(2))nanozymes as autophagy inhibitor.The antineoplastic effects of PN-CeO_(2)were mediated by its high reductive activity for intratumoral ROS degradation,thereby inhibiting protective autophagy and activating apoptosis by suppressing the activities of phosphatidylinositide 3-kinase/protein kinase B and p38 mitogen-activated protein kinase pathways in human cutaneous squamous cell carcinoma.Further investigation highlighted PN-CeO_(2)as a safe and efficient anti-tumor autophagy inhibitor.Overall,this study presents a reductive-damage strategy as a promising anti-tumor approach that catalytically inhibits autophagy and activates the intrinsic antioxidant pathways of tumor cells and also shows its potential for the therapy of other autophagy-related diseases.
基金National Natural Science Foundation of China(11775059)National Key Technology R&D Program of China(2019YFF0301600).
文摘As an invisible“endocrine organ”,gut microbiota is widely involved in the regulation of nervous system,endocrine system,circulatory system,and digestive system.It is also closely related to host health and the occurrence of many chronic diseases.Relevant literature shows that high temperature,low temperature,and highaltitude hypoxia may have negative effects on commensal microorganisms.The stimulation of exercise may aggravate this reaction,which is related to the occurrence of exercise-induced fever and gastrointestinal and respiratory diseases.The intervention of probiotics can alleviate the above problems to a certain extent.Therefore,this paper takes exercise in a special environment as the starting point,deeply analyses the intervention effect and potential mechanism of probiotics,and provides the theoretical basis and reference for follow-up research and application of probiotics in sports science.
