Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specifically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The ...Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specifically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.展开更多
Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previou...Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previous studies primarily used fixed tissue or delayed injury models. Therefore, in the present study, we used in vivo imaging to observe the dynamic changes in cerebral microcirculation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by perforation of the bifurcation of the middle cerebral and anterior cerebral arteries in male C57/BL6 mice. The diameter of pial arterioles and venules was measured by in vivo fluorescence microscopy at different time points within 180 minutes after subarachnoid hemorrhage. Cerebral blood flow was examined and leukocyte adhesion/albumin extravasation was determined at different time points before and after subarachnoid hemorrhage. Cerebral pial microcirculation was abnormal and cerebral blood flow was reduced after subarachnoid hemorrhage. Acute vasoconstriction occurred predominantly in the arterioles instead of the venules. A progressive increase in the number of adherent leukocytes in venules and substantial albumin extravasation were observed between 10 and 180 minutes after subarachnoid hemorrhage. These results show that major changes in microcirculation occur in the early stage of subarachnoid hemorrhage. Our findings may promote the development of novel therapeutic strategies for the early treatment of subarachnoid hemorrhage.展开更多
Chronic pollution in aquatic ecosystems can lead to many adverse effects,including a greater susceptibility to pathogens among resident biota.Trifloxystrobin(TFS)is a strobilurin fungicide widely used in Asia to contr...Chronic pollution in aquatic ecosystems can lead to many adverse effects,including a greater susceptibility to pathogens among resident biota.Trifloxystrobin(TFS)is a strobilurin fungicide widely used in Asia to control soybean rust.However,it has the potential to enter aquatic ecosystems,where it may impair fish resistance to viral infections.To explore the potential environmental risks of TFS,we characterized the antiviral capacities of fish chronically exposed to TFS and subsequently infected with spring viraemia of carp virus(SVCV).Although TFS exhibited no significant cytotoxicity at the tested environmental concentrations during viral challenge,SVCV replication increased significantly in a time-dependent manner within epithelioma papulosum cyprini(EPC)cells and zebrafish exposed to 25μg/L TFS.Results showed that the highest viral load was more than 100-fold that of the controls.Intracellular biochemical assays indicated that autophagy was induced by TFS,and associated changes included an increase in autophagosomes,conversion of LC3-II,accumulation of Beclin-1,and degradation of P62 in EPC cells and zebrafish.In addition,TFS markedly decreased the expression and phosphorylation of mTOR,indicating that activation of TFS may be associated with the mTORmediated autophagy pathway.This study provides new insights into the mechanism of the immunosuppressive effects of TFS on non-target aquatic hosts and suggests that the existence of TFS in aquatic environments may contribute to outbreaks of viral diseases.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province,China(Grant No.:LY24C190001)the General Scientific Research Project of Education of Zhejiang Province,China(Grant Nos.:Y202352559 and Y202147351)+1 种基金the Starting Research Fund of Ningbo University,China(Grant Nos.:421912073 and 422204123)the Student Research and Innovation Program of Ningbo University,China(Grant Nos.:2023SRIP1810 and 2023SRIP1804).
文摘Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specifically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.
基金supported by the National Natural Science Foundation of China,No.81100856
文摘Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previous studies primarily used fixed tissue or delayed injury models. Therefore, in the present study, we used in vivo imaging to observe the dynamic changes in cerebral microcirculation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by perforation of the bifurcation of the middle cerebral and anterior cerebral arteries in male C57/BL6 mice. The diameter of pial arterioles and venules was measured by in vivo fluorescence microscopy at different time points within 180 minutes after subarachnoid hemorrhage. Cerebral blood flow was examined and leukocyte adhesion/albumin extravasation was determined at different time points before and after subarachnoid hemorrhage. Cerebral pial microcirculation was abnormal and cerebral blood flow was reduced after subarachnoid hemorrhage. Acute vasoconstriction occurred predominantly in the arterioles instead of the venules. A progressive increase in the number of adherent leukocytes in venules and substantial albumin extravasation were observed between 10 and 180 minutes after subarachnoid hemorrhage. These results show that major changes in microcirculation occur in the early stage of subarachnoid hemorrhage. Our findings may promote the development of novel therapeutic strategies for the early treatment of subarachnoid hemorrhage.
基金This work was supported by the National Natural Science Foundation of China(31902410)Program of State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products(KF20200106)+1 种基金Natural Science Foundation of Zhejiang Province(LY21C190002)Foundation of Ningbo City of China(202003N4120)。
文摘Chronic pollution in aquatic ecosystems can lead to many adverse effects,including a greater susceptibility to pathogens among resident biota.Trifloxystrobin(TFS)is a strobilurin fungicide widely used in Asia to control soybean rust.However,it has the potential to enter aquatic ecosystems,where it may impair fish resistance to viral infections.To explore the potential environmental risks of TFS,we characterized the antiviral capacities of fish chronically exposed to TFS and subsequently infected with spring viraemia of carp virus(SVCV).Although TFS exhibited no significant cytotoxicity at the tested environmental concentrations during viral challenge,SVCV replication increased significantly in a time-dependent manner within epithelioma papulosum cyprini(EPC)cells and zebrafish exposed to 25μg/L TFS.Results showed that the highest viral load was more than 100-fold that of the controls.Intracellular biochemical assays indicated that autophagy was induced by TFS,and associated changes included an increase in autophagosomes,conversion of LC3-II,accumulation of Beclin-1,and degradation of P62 in EPC cells and zebrafish.In addition,TFS markedly decreased the expression and phosphorylation of mTOR,indicating that activation of TFS may be associated with the mTORmediated autophagy pathway.This study provides new insights into the mechanism of the immunosuppressive effects of TFS on non-target aquatic hosts and suggests that the existence of TFS in aquatic environments may contribute to outbreaks of viral diseases.
