Shenmai injection(SMI)is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer.Previously,we found that SMI synergistically enhanced the activity of chemotherapy on col...Shenmai injection(SMI)is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer.Previously,we found that SMI synergistically enhanced the activity of chemotherapy on colorectal cancer by promoting the distribution of drugs in xenograft tumors.However,the underlying mechanisms and bioactive constituents remained unknown.In the present work,the regulatory effects of SMI on tumor vasculature were determined,and the potential anti-angiogenic components targeting tumor endothelial cells(TECs)were identified.Multidimensional pharmacokinetic profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.The results showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD-type ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In vivo bioactivity results showed that Rd suppressed neovascularization in tumors,normalized the structure of tumor vessels,and improved the anti-tumor effect of 5-fluorouracil(5 FU)in xenograft mice.Furthermore,Rd inhibited the migration and tube formation capacity of endothelial cells in vitro.In conclusion,Rd may be an important active form to exert the anti-angiogenic effect on tumor after SMI treatment.展开更多
Microtubules grow not only from the centrosome but also from various noncentrosomal microtubule-organizing centers(MTOCs),including the nuclear envelope(NE)and pre-existing microtubules.The evolutionarily conserved pr...Microtubules grow not only from the centrosome but also from various noncentrosomal microtubule-organizing centers(MTOCs),including the nuclear envelope(NE)and pre-existing microtubules.The evolutionarily conserved proteins Mtol/CDK5RAP2 and Alpl4/TOG/XMAP215 have been shown to be involved in promoting microtubule nucleation.However,it has remained elusive as to how the microtubule nucleation promoting factors are specified to various noncentrosomal MTOCs,particularly the NE,and how these proteins coordinate to organize microtubule assembly.Here,we demonstrate that in the fission yeast Schizosaccharomyces pombe,efficient interphase microtubule growth from the NE requires Alp7/TACC,Alpl4/TOG/XMAP215,and Mtol/CDK5RAP2.The absence of Alp7,A lp l4 t or Mtol compromises microtubule regrowth on the NE in cells undergoing microtubule repolymerization.We further demonstrate that Alp7 and Mtol interdependently localize to the NE in cells without microtubules and that A lp l4 localizes to the NE in an Alp7 and Mtol-dependent manner.Tethering Mtol to the NE in cells lacking Alp7 partially restores microtubule number and the efficiency of microtubule generation from the NE.Hence,our study delineates that Alp7,A lpl4,and Mtol work in concert to regulate interphase microtubule regrowth on the NE.展开更多
The novel coronavirus(SARS-CoV-2)infection has become a heavy burden on global health.Although the coronavirus disease 2019(COVID-19)may adversely affect multiple organs and systems of infected patients,to the best of...The novel coronavirus(SARS-CoV-2)infection has become a heavy burden on global health.Although the coronavirus disease 2019(COVID-19)may adversely affect multiple organs and systems of infected patients,to the best of our knowledge,there is little investigation of the SARS-CoV-2’s impact on bone marrow.Our clinical and cytological findings in this case of severe COVID-19 infection provide novel insights into the pathogenesis of SARS-CoV-2 infection in the hematopoietic system.We recommend that physicians consider SARS-CoV-2 infection’s effect on bone marrow in patients who are slow to recover and suggest that a better understanding of the bone marrow morphology in COVID-19-infected patients is needed.展开更多
基金supported by the China National Nature Science Foundation(81573496,81773989,81530098 and 81573494)National Research Council of Science and Technology Major Project of China(2017ZX09201004-019 and 2019ZX09721001006-005)+6 种基金International Science and Technology Center Program of China(2017YFE0109600)Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421005)Jiangsu Province Nature Science Foundation(No.BK20160076,China)Jiangsu Province“333”project,ChinaSix talent peaks project in Jiangsu Province(YY-060),ChinaNational Basic Research Program of China(973 Program,No.2017YFA0205400)“Double First-Class”University project(CPU2018GF01,China)
文摘Shenmai injection(SMI)is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer.Previously,we found that SMI synergistically enhanced the activity of chemotherapy on colorectal cancer by promoting the distribution of drugs in xenograft tumors.However,the underlying mechanisms and bioactive constituents remained unknown.In the present work,the regulatory effects of SMI on tumor vasculature were determined,and the potential anti-angiogenic components targeting tumor endothelial cells(TECs)were identified.Multidimensional pharmacokinetic profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.The results showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD-type ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In vivo bioactivity results showed that Rd suppressed neovascularization in tumors,normalized the structure of tumor vessels,and improved the anti-tumor effect of 5-fluorouracil(5 FU)in xenograft mice.Furthermore,Rd inhibited the migration and tube formation capacity of endothelial cells in vitro.In conclusion,Rd may be an important active form to exert the anti-angiogenic effect on tumor after SMI treatment.
基金the National Key Research and Development Program of China(2017YFA0503600)the National Natural Science Foundation of China(91754106,31871350,31671406,31601095,and 31621002)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19040101)the Major/lnnovative Program of Development Foundation of Hefei Center for Physical Science and Technology(2017FXCX008)China’s 1000 Young Talents Recruitment Program.
文摘Microtubules grow not only from the centrosome but also from various noncentrosomal microtubule-organizing centers(MTOCs),including the nuclear envelope(NE)and pre-existing microtubules.The evolutionarily conserved proteins Mtol/CDK5RAP2 and Alpl4/TOG/XMAP215 have been shown to be involved in promoting microtubule nucleation.However,it has remained elusive as to how the microtubule nucleation promoting factors are specified to various noncentrosomal MTOCs,particularly the NE,and how these proteins coordinate to organize microtubule assembly.Here,we demonstrate that in the fission yeast Schizosaccharomyces pombe,efficient interphase microtubule growth from the NE requires Alp7/TACC,Alpl4/TOG/XMAP215,and Mtol/CDK5RAP2.The absence of Alp7,A lp l4 t or Mtol compromises microtubule regrowth on the NE in cells undergoing microtubule repolymerization.We further demonstrate that Alp7 and Mtol interdependently localize to the NE in cells without microtubules and that A lp l4 localizes to the NE in an Alp7 and Mtol-dependent manner.Tethering Mtol to the NE in cells lacking Alp7 partially restores microtubule number and the efficiency of microtubule generation from the NE.Hence,our study delineates that Alp7,A lpl4,and Mtol work in concert to regulate interphase microtubule regrowth on the NE.
文摘The novel coronavirus(SARS-CoV-2)infection has become a heavy burden on global health.Although the coronavirus disease 2019(COVID-19)may adversely affect multiple organs and systems of infected patients,to the best of our knowledge,there is little investigation of the SARS-CoV-2’s impact on bone marrow.Our clinical and cytological findings in this case of severe COVID-19 infection provide novel insights into the pathogenesis of SARS-CoV-2 infection in the hematopoietic system.We recommend that physicians consider SARS-CoV-2 infection’s effect on bone marrow in patients who are slow to recover and suggest that a better understanding of the bone marrow morphology in COVID-19-infected patients is needed.