Mesenchymal stem cells(MSCs)delivered into the post-ischemic heart milieu have a low survival and retention rate,thus restricting the cardioreparative efficacy of MSC-based therapy.Chronic ischemia results in metaboli...Mesenchymal stem cells(MSCs)delivered into the post-ischemic heart milieu have a low survival and retention rate,thus restricting the cardioreparative efficacy of MSC-based therapy.Chronic ischemia results in metabolic reprogramming in the heart,but little is known about how these metabolic changes influence implanted MSCs.Here,we found that excessive branched-chain amino acid(BCAA)accumulation,a metabolic signature seen in the post-ischemic heart,was disadvantageous to the retention and cardioprotection of intramyocardially injected MSCs.Discovery-driven experiments revealed that BCAA at pathological levels sensitized MSCs to stress-induced cell death and premature senescence via accelerating the loss of histone 3 lysine 9 trimethylation(H3K9me3).A novel mTORC1/DUX4/KDM4E axis was identified as the cause of BCAA-induced H3K9me3 loss and adverse phenotype acquisition.Enhancing BCAA catabolic capability in MSCs via genetic/pharmacological approaches greatly improved their adaptation to the high BCAA milieu and strengthened their cardioprotective efficacy.We conclude that aberrant BCAA accumulation is detrimental to implanted MSCs via a previously unknown metabolite-signaling-epigenetic mechanism,emphasizing that the metabolic changes of the post-ischemic heart crucially influence the fate of implanted MSCs and their therapeutic benefits.展开更多
Scale not only affects the taste and color ofwater,but also increases the risks of osteoporosis and cardiovascular diseases associated with drinking it.As a popular beverage,tea is rich many substances that have consi...Scale not only affects the taste and color ofwater,but also increases the risks of osteoporosis and cardiovascular diseases associated with drinking it.As a popular beverage,tea is rich many substances that have considerable potential for scale inhibition,including protein,tea polyphenols and organic acids.In this study,the effect of tea brewing on scale formationwas explored.It was found that the proteins,catechins and organic acids in tea leaves could be released when the green tea was brewed in water with sufficient hardness and alkalinity.The tea-released protein was able to provide carboxyl groups to chelate with calcium ions(Ca^(2+)),preventing the Ca^(2+)from reacting with the carbonate ions(CO_(3)^(2-)).The B rings of catechins were another important structure in the complexation of Ca^(2+)and magnesium ions(Mg2+).The carboxyl and hydroxyl groups on the organic acids was able to form fivemembered chelating rings with Ca^(2+)and Mg^(2+),resulting in a significant decrease in Ca^(2+)from 100.0 to 60.0 mg/L.Additionally,the hydrogen ions(H^(+))provided by the organic acids consumed and decreased the alkalinity of the water from 250.0 to 131.4 mg/L,leading to a remarkable reduction in pH from 8.93 to 7.73.It further prevented the bicarbonate(HCO_(3)^(-))from producing CO_(3)^(2−)when the water was heated.The reaction of the tea constituents with the hardness and alkalinity inhibited the formation of scale,leading to a significant decrease in turbidity from 10.6 to 1.4 NTU.Overall,this study provides information to help build towards an understanding of the scale inhibition properties of tea and the prospects of tea for anti-scaling in industrial applications.展开更多
基金supported by the National Key R&D Program of China(Grant No.2018YFA0107400)Program for National Natural Science Foundation of China(Grants No.82170337,81730011,81970721,and 81927805)Program for Chang-Jiang Scholars and Innovative Research Team in University(Grant No.PCSIRT-14R08).
文摘Mesenchymal stem cells(MSCs)delivered into the post-ischemic heart milieu have a low survival and retention rate,thus restricting the cardioreparative efficacy of MSC-based therapy.Chronic ischemia results in metabolic reprogramming in the heart,but little is known about how these metabolic changes influence implanted MSCs.Here,we found that excessive branched-chain amino acid(BCAA)accumulation,a metabolic signature seen in the post-ischemic heart,was disadvantageous to the retention and cardioprotection of intramyocardially injected MSCs.Discovery-driven experiments revealed that BCAA at pathological levels sensitized MSCs to stress-induced cell death and premature senescence via accelerating the loss of histone 3 lysine 9 trimethylation(H3K9me3).A novel mTORC1/DUX4/KDM4E axis was identified as the cause of BCAA-induced H3K9me3 loss and adverse phenotype acquisition.Enhancing BCAA catabolic capability in MSCs via genetic/pharmacological approaches greatly improved their adaptation to the high BCAA milieu and strengthened their cardioprotective efficacy.We conclude that aberrant BCAA accumulation is detrimental to implanted MSCs via a previously unknown metabolite-signaling-epigenetic mechanism,emphasizing that the metabolic changes of the post-ischemic heart crucially influence the fate of implanted MSCs and their therapeutic benefits.
基金supported by the National Natural Science Foundation of China (No. 51978558)the National Key Research and Development Program of China (No. 2019YFD1100102-04)the Chemical Institute of Chemical Industry of Shaanxi Normal University,Open Project of State Key Laboratory of Urban Water Resource and Environment (No. ES202121)
文摘Scale not only affects the taste and color ofwater,but also increases the risks of osteoporosis and cardiovascular diseases associated with drinking it.As a popular beverage,tea is rich many substances that have considerable potential for scale inhibition,including protein,tea polyphenols and organic acids.In this study,the effect of tea brewing on scale formationwas explored.It was found that the proteins,catechins and organic acids in tea leaves could be released when the green tea was brewed in water with sufficient hardness and alkalinity.The tea-released protein was able to provide carboxyl groups to chelate with calcium ions(Ca^(2+)),preventing the Ca^(2+)from reacting with the carbonate ions(CO_(3)^(2-)).The B rings of catechins were another important structure in the complexation of Ca^(2+)and magnesium ions(Mg2+).The carboxyl and hydroxyl groups on the organic acids was able to form fivemembered chelating rings with Ca^(2+)and Mg^(2+),resulting in a significant decrease in Ca^(2+)from 100.0 to 60.0 mg/L.Additionally,the hydrogen ions(H^(+))provided by the organic acids consumed and decreased the alkalinity of the water from 250.0 to 131.4 mg/L,leading to a remarkable reduction in pH from 8.93 to 7.73.It further prevented the bicarbonate(HCO_(3)^(-))from producing CO_(3)^(2−)when the water was heated.The reaction of the tea constituents with the hardness and alkalinity inhibited the formation of scale,leading to a significant decrease in turbidity from 10.6 to 1.4 NTU.Overall,this study provides information to help build towards an understanding of the scale inhibition properties of tea and the prospects of tea for anti-scaling in industrial applications.
