Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer(TNBC)due to its relatively low response to traditional therapeutics.The existing metabolic intervention...Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer(TNBC)due to its relatively low response to traditional therapeutics.The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity,resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment.To address these limitations,here we developed a robust pyroelectric BaTiO_(3)@Au core–shell nanostructure(BTO@Au)to selectively and persistently block energy generation of tumor cells.Stimulated by near-infrared(NIR)laser,the Au shell could generate heat to activate the BaTiO_(3)core to produce reactive oxygen species(ROS)regardless of the constrained microenvironment,thus prominently inhibits mitochondrial oxidative phosphorylation(OXPHOS)and reduces ATP production to induce TNBC cell apoptosis.The therapeutic effects have been well demonstrated in vitro and in vivo,paving a new way for the development of metabolic interventions.展开更多
Multi-walled carbon nanotubes(MWCNTs) have wide application prospects but also exhibit notable biotoxicity that is tightly associated with macrophages. Macrophages simultaneously act as initiators and defenders in MWC...Multi-walled carbon nanotubes(MWCNTs) have wide application prospects but also exhibit notable biotoxicity that is tightly associated with macrophages. Macrophages simultaneously act as initiators and defenders in MWCNT-induced organ lesions,and targeting macrophages with MWCNTs may be a potential immunotherapy and oncotherapy approach. This review focuses on the impacts of MWCNTs on macrophages and further discusses the influence of MWCNT characteristics on their bioactivity.Based on existing studies, MWCNTs stimulate macrophage migration, induce secretion of various cytokines and activate inflammatory pathways in macrophages, especially NLRP3-mediated IL-1β production. This inflammatory state, together with the oxidative stress and cell membrane lesions induced by MWCNTs, contributes to decreased phagocytic ability and cell viability, which finally results in cell apoptosis and necrosis. A series of intracellular and systemic components, such as toll-like receptor, high-mobility group box 1, Rho-associated kinases, scavenger receptor and complement components, may be involved in the above-mentioned cell-MWCNT interactions. The characteristics of MWCNTs can influence their bioactivity in macrophages both mechanically and chemically. The size(length and/or diameter), functionalization, purification and even the experimental method can affect the influence of MWCNTs on macrophages, and a better understanding of these MWCNT characteristics may benefit utilization of this nanomaterial in associated nanomedical applications.展开更多
Dear Editor,Small conductance Ca2+-activated potassium (SK) channels are widely expressed in various tissues and play a unique role in regulating cell function by integrating cytosolic Ca2+ levels and membrane potenti...Dear Editor,Small conductance Ca2+-activated potassium (SK) channels are widely expressed in various tissues and play a unique role in regulating cell function by integrating cytosolic Ca2+ levels and membrane potential (Adelman et al., 2012). Xu et al. first identified SK channels in the heart and found that SK channels, particularly the SK2 channel, are preferentially expressed in human and mouse atrial myocytes but not in ventricular myocytes (Xu et al., 2003). This suggests that the展开更多
Asthma is a chronic inflammatory disease,characterized by reversible airflow obstruction and airway hyperresponsiveness.There has been a sharp increase in the prevalence,morbidity,mortality and economic burden associa...Asthma is a chronic inflammatory disease,characterized by reversible airflow obstruction and airway hyperresponsiveness.There has been a sharp increase in the prevalence,morbidity,mortality and economic burden associated with this disorder over the last several decades,which triggers the development of various antiasthmatic agents[1].Maintenance of airway tone is the key in asthma therapy.展开更多
Large conductance calcium-activated potassium(BKCa)channels are broadly expressed in vascular smooth muscle cells(VSMCs)and play a crucial role in the regulation of vascular tone[1].Activation of BKCachannel by elevat...Large conductance calcium-activated potassium(BKCa)channels are broadly expressed in vascular smooth muscle cells(VSMCs)and play a crucial role in the regulation of vascular tone[1].Activation of BKCachannel by elevation of the[Ca^(2+)]idue to membrane depolarization increases the K^+ conductance of the membrane,and drives the VSMC membrane potential to hyperpolarization,which展开更多
基金supported by the National Natural Science Foundation of China(Nos.22007063 and 82002063)Shanxi Medical Key Science and Technology Project Plan of China(No.2020XM01)+4 种基金the National University of Singapore Start-up Grant(No.NUHSRO/2020/133/Startup/08)NUS School of Medicine Nanomedicine Translational Research Program(No.NUHSRO/2021/034/TRP/09/Nanomedicine)the Science Research Start-up Fund for Doctor of Shanxi Province(No.XD1809 and XD2011)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0414)Shanxi Province Science Foundation for Youths(No.201901D211316).
文摘Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer(TNBC)due to its relatively low response to traditional therapeutics.The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity,resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment.To address these limitations,here we developed a robust pyroelectric BaTiO_(3)@Au core–shell nanostructure(BTO@Au)to selectively and persistently block energy generation of tumor cells.Stimulated by near-infrared(NIR)laser,the Au shell could generate heat to activate the BaTiO_(3)core to produce reactive oxygen species(ROS)regardless of the constrained microenvironment,thus prominently inhibits mitochondrial oxidative phosphorylation(OXPHOS)and reduces ATP production to induce TNBC cell apoptosis.The therapeutic effects have been well demonstrated in vitro and in vivo,paving a new way for the development of metabolic interventions.
基金supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-3-004)the National Key Research and Development Project from the Ministry of Science and Technology, China (2017YFA0205500)
文摘Multi-walled carbon nanotubes(MWCNTs) have wide application prospects but also exhibit notable biotoxicity that is tightly associated with macrophages. Macrophages simultaneously act as initiators and defenders in MWCNT-induced organ lesions,and targeting macrophages with MWCNTs may be a potential immunotherapy and oncotherapy approach. This review focuses on the impacts of MWCNTs on macrophages and further discusses the influence of MWCNT characteristics on their bioactivity.Based on existing studies, MWCNTs stimulate macrophage migration, induce secretion of various cytokines and activate inflammatory pathways in macrophages, especially NLRP3-mediated IL-1β production. This inflammatory state, together with the oxidative stress and cell membrane lesions induced by MWCNTs, contributes to decreased phagocytic ability and cell viability, which finally results in cell apoptosis and necrosis. A series of intracellular and systemic components, such as toll-like receptor, high-mobility group box 1, Rho-associated kinases, scavenger receptor and complement components, may be involved in the above-mentioned cell-MWCNT interactions. The characteristics of MWCNTs can influence their bioactivity in macrophages both mechanically and chemically. The size(length and/or diameter), functionalization, purification and even the experimental method can affect the influence of MWCNTs on macrophages, and a better understanding of these MWCNT characteristics may benefit utilization of this nanomaterial in associated nanomedical applications.
基金supported by the National Natural Science Foundation of China (30870903 to Xiaorong Zeng, 31300948,81670130 to Xiaoqiu Tan, 81670313 to Jimin Cao)Science and Technology Support Program of Sichuan Province (2011FZ0106 to Xiaorong Zeng)
文摘Dear Editor,Small conductance Ca2+-activated potassium (SK) channels are widely expressed in various tissues and play a unique role in regulating cell function by integrating cytosolic Ca2+ levels and membrane potential (Adelman et al., 2012). Xu et al. first identified SK channels in the heart and found that SK channels, particularly the SK2 channel, are preferentially expressed in human and mouse atrial myocytes but not in ventricular myocytes (Xu et al., 2003). This suggests that the
基金supported by the Innovative Experimental Program for College Students in China (20120023060)the National Natural Science Foundation of China (81670313) to J.C
文摘Asthma is a chronic inflammatory disease,characterized by reversible airflow obstruction and airway hyperresponsiveness.There has been a sharp increase in the prevalence,morbidity,mortality and economic burden associated with this disorder over the last several decades,which triggers the development of various antiasthmatic agents[1].Maintenance of airway tone is the key in asthma therapy.
基金supported by the National Natural Science Foundation of China (31171088 and 31471126 to JMC., and 31300948 and 81670310 to XQT)
文摘Large conductance calcium-activated potassium(BKCa)channels are broadly expressed in vascular smooth muscle cells(VSMCs)and play a crucial role in the regulation of vascular tone[1].Activation of BKCachannel by elevation of the[Ca^(2+)]idue to membrane depolarization increases the K^+ conductance of the membrane,and drives the VSMC membrane potential to hyperpolarization,which