Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection.Effective treatment of bacterial sepsis remains a paramount clinical challenge,due to its astonishingl...Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection.Effective treatment of bacterial sepsis remains a paramount clinical challenge,due to its astonishingly rapid progression and the prevalence of bacterial drug resistance.展开更多
Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site,exacerbating spinal cord damage.Simultaneously,bone marrow hematopoietic stem cells(HSCs)and splenic leukocytes rap...Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site,exacerbating spinal cord damage.Simultaneously,bone marrow hematopoietic stem cells(HSCs)and splenic leukocytes rapidly mobilize to replenish the depleted peripheral blood leukocyte pool.However,current treatments for spinal cord injuries overlook interventions targeting peripheral immune organs and tissues,highlighting the need to develop novel drugs capable of effectively regulating peripheral immunity and treating spinal cord injuries.In this study,we designed,synthesized,and characterized novel Ejiao carbon dots(EJCDs)that inhibit myeloid cell proliferation and peripheral migration by promoting HSC self-renewal,and distinct differentiation into erythroid progenitors in vitro and in vivo.Additionally,EJCDs attenuate the immune response in the spleen,leukocytes’reservoir,following spinal cord injury by diminishing the local infiltration of monocytes and macrophages while promoting motor function recovery.These effects are mediated through the downregulation of CCAAT enhancer binding protein-βexpression in the spleen and the upregulation of FZD4 protein expression in LinSca-1+c-kit+cells(LSKs)within the bone marrow.Our findings demonstrate that EJCDs effectively reduce myeloid cell infiltration post-spinal cord injury and promote neurological recovery,making them promising therapeutic candidates for treating spinal cord injuries.展开更多
基金This work was supported by the National Natural Science Foundation of China(31500802,82172132,and 82000523)the Natural Science Foundation of Jiangsu Province(BK20190097 and BK20190053)+2 种基金the Program of Qilu Young Scholars of Shandong UniversityThis work was also supported by the Cyrus Tang Foundation,the Taishan Scholars Program for Young Expert of Shandong Province(tsqn201909021)the Youth Cross-Scientific Innovation Group of Shandong University.
文摘Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection.Effective treatment of bacterial sepsis remains a paramount clinical challenge,due to its astonishingly rapid progression and the prevalence of bacterial drug resistance.
基金supported by grants from the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100)the National Natural Science of China(81930070,82102671)+3 种基金Tianjin Key Medical Discipline(Specialty)Construct Project(TJYXZDXK-027A)Tianjin Science and Technology Project(21JCZDJC01100)the Beijing-Tianjin-Hebei Basic Research Cooperation Project(J230012)Taishan Scholar Young Expert(tsqnz20221168).
文摘Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site,exacerbating spinal cord damage.Simultaneously,bone marrow hematopoietic stem cells(HSCs)and splenic leukocytes rapidly mobilize to replenish the depleted peripheral blood leukocyte pool.However,current treatments for spinal cord injuries overlook interventions targeting peripheral immune organs and tissues,highlighting the need to develop novel drugs capable of effectively regulating peripheral immunity and treating spinal cord injuries.In this study,we designed,synthesized,and characterized novel Ejiao carbon dots(EJCDs)that inhibit myeloid cell proliferation and peripheral migration by promoting HSC self-renewal,and distinct differentiation into erythroid progenitors in vitro and in vivo.Additionally,EJCDs attenuate the immune response in the spleen,leukocytes’reservoir,following spinal cord injury by diminishing the local infiltration of monocytes and macrophages while promoting motor function recovery.These effects are mediated through the downregulation of CCAAT enhancer binding protein-βexpression in the spleen and the upregulation of FZD4 protein expression in LinSca-1+c-kit+cells(LSKs)within the bone marrow.Our findings demonstrate that EJCDs effectively reduce myeloid cell infiltration post-spinal cord injury and promote neurological recovery,making them promising therapeutic candidates for treating spinal cord injuries.
