Tumor-initiating cells(TICs)or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation,progression,metastasis,and drug resistance.It is hypothesized that gastrointestinal TICs(giTICs)mig...Tumor-initiating cells(TICs)or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation,progression,metastasis,and drug resistance.It is hypothesized that gastrointestinal TICs(giTICs)might originate from cell-cell fusion.Here,we systemically evaluate the evidence that supports or opposes the hypothesis of giTIC generation from cell-cell fusion both in vitro and in vivo.We review giTICs that are capable of initiating tumors in vivo with 5000 or fewer in vivo fused cells.Under this restriction,there is currently little evidence demonstrating that giTICs originate from cell-cell fusion in vivo.However,there are many reports showing that tumor generation in vitro occurs with more than 5000 fused cells.In addition,the mechanisms of giTIC generation via cell-cell fusion are poorly understood,and thus,we propose its potential mechanisms of action.We suggest that future research should focus on giTIC origination from cell-cell fusion in vivo,isolation or enrichment of giTICs that have tumor-initiating capabilities with 5000 or less in vivo fused cells,and further clarification of the underlying mechanisms.Our review of the current advances in our understanding of giTIC origination from cell-cell fusion may have significant implications for the understanding of carcinogenesis and future cancer therapeutic strategies targeting giTICs.展开更多
Metformin(MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension.This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rat...Metformin(MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension.This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus(PVN). Salt-sensitive rats received a highsalt(HS) diet to induce hypertension, or a normal-salt(NS)diet as control. At the same time, they received intracerebroventricular(ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure(MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity,reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in saltsensitive hypertension via attenuating oxidative stress,inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.展开更多
基金National Natural Science Foundation of China,No.81872412,No.81602303,and No.31700736Hubei Province Natural Science Foundation of China,No.2016CFB180 and No.2017CFB786+3 种基金Health and Family Planning Commission of Hubei Province,No.WJ2016Y07 and No.WJ2016Y10Hubei Province Scientific and Technological Research Project,No.Q20171306Jingzhou Science and Technology Development Planning Project,No.JZKJ15063Guangzhou Key Medical Discipline Construction Project(CSZ),National Innovation and Entrepreneurship Training Program for College Students,No.202010489017。
文摘Tumor-initiating cells(TICs)or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation,progression,metastasis,and drug resistance.It is hypothesized that gastrointestinal TICs(giTICs)might originate from cell-cell fusion.Here,we systemically evaluate the evidence that supports or opposes the hypothesis of giTIC generation from cell-cell fusion both in vitro and in vivo.We review giTICs that are capable of initiating tumors in vivo with 5000 or fewer in vivo fused cells.Under this restriction,there is currently little evidence demonstrating that giTICs originate from cell-cell fusion in vivo.However,there are many reports showing that tumor generation in vitro occurs with more than 5000 fused cells.In addition,the mechanisms of giTIC generation via cell-cell fusion are poorly understood,and thus,we propose its potential mechanisms of action.We suggest that future research should focus on giTIC origination from cell-cell fusion in vivo,isolation or enrichment of giTICs that have tumor-initiating capabilities with 5000 or less in vivo fused cells,and further clarification of the underlying mechanisms.Our review of the current advances in our understanding of giTIC origination from cell-cell fusion may have significant implications for the understanding of carcinogenesis and future cancer therapeutic strategies targeting giTICs.
基金supported by the National Natural Science Foundation of China(81600333,81770426,81800372,91439120,and 91639105)the Postdoctoral Science Foundation of China(2016M602835,2017M620457)the Postdoctoral Science Foundation of Shaanxi Province,China(2016BSHEDZZ91)
文摘Metformin(MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension.This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus(PVN). Salt-sensitive rats received a highsalt(HS) diet to induce hypertension, or a normal-salt(NS)diet as control. At the same time, they received intracerebroventricular(ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure(MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity,reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in saltsensitive hypertension via attenuating oxidative stress,inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.