The influenza A virus(IAV)damages intestinal mucosal tissues beyond the respiratory tract.Probiotics play a crucial role in maintaining the balance and stability of the intestinal microecosystem.Extracellular vesicles...The influenza A virus(IAV)damages intestinal mucosal tissues beyond the respiratory tract.Probiotics play a crucial role in maintaining the balance and stability of the intestinal microecosystem.Extracellular vesicles(EVs)derived from probiotics have emerged as potential mediators of host immune response and anti-inflammatory effect.However,the specific anti-inflammatory effects and underlying mechanisms of probiotics-derived EVs on IAV remain unclear.In the present study,we investigated the therapeutic efficacy of Lactobacillus reuteri EHA2-derived EVs(LrEVs)in a mouse model of IAV infection.Oral LrEVs were distributed in the liver,lungs,and gastrointestinal tract.In mice infected with IAV,oral LrEVs administration alleviated IAV-induced damages in the lungs and intestines,modified the microbiota compositions,and increased the levels of short-chain fatty acids in those organs.Mechanistically,LrEVs exerted their protective effects against IAV infection by blunting the pro-inflammatory IL-17 signaling.Furthermore,FISH analysis detected miR-4239,one of the most abundant miRNAs in LrEVs,in both lung and intestinal tissues.We confirmed that miR-4239 directly targets IL-17a.Our findings paved the ground for future application of LrEVs in influenza treatment and offered new mechanistic insights regarding the anti-inflammatory role of miR-4239.展开更多
Aortic aneurysm and dissection(AAD)are leading causes of death in the elderly.Recent studies have demonstrated that silicate ions can manipulate multiple cells,especially vascular-related cells.We demonstrated in this...Aortic aneurysm and dissection(AAD)are leading causes of death in the elderly.Recent studies have demonstrated that silicate ions can manipulate multiple cells,especially vascular-related cells.We demonstrated in this study that silicate ions as soluble form of bioactive ceramics effectively alleviated aortic aneurysm and dissection in both Ang II andβ-BAPN induced AAD models.Different from the single targeting therapeutic drug approaches,the bioactive ceramic derived approach attributes to the effect of bioactive silicate ions on the inhibition of the AAD progression through regulating the local vascular microenvironment of aorta systematically in a multi-functional way.The in vitro experiments revealed that silicate ions did not only alleviate senescence and inflammation of the mouse aortic endothelial cells,enhance M2 polarization of mouse bone marrow-derived macrophages,and reduce apoptosis of mouse aortic smooth muscle cells,but also regulate their interactions.The in vivo studies further confirm that silicate ions could effectively alleviate senescence,inflammation,and cell apoptosis of aortas,accomplished with reduced aortic dilation,collagen deposition,and elastin laminae degradation.This bioactive ceramic derived therapy provides a potential new treatment strategy in attenuating AAD progression.展开更多
Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell viability.Although direct injection of exosomes can have a curative effect simila...Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell viability.Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation,high clearance hinders its application in clinical practice.Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia.In this study,to mimic the paracrine and biological activity of stem cells,we developed artificial stem cells that can continuously release Tβ4-exosomes(Tβ4-ASCs)by encapsulating specific exosomes within microspheres using microfluidics technology.The results show that Tβ4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area,and its therapeutic effect is superior to that of directly injecting the exosomes.In addition,to better understand how it works,we demonstrated that the Tβ4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells(CAECs)via the miR-17-5p/PHD3/Hif-1αpathway.In brief,as artificial stem cells,Tβ4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction,providing a feasible and alternative method for clinical revascularization.展开更多
基金supported by the National Natural Science Foundation of China(No.82172103 and No.32371428)GuangDong Basic and Applied Basic Research Foundation(No.2023B1515130005,No.2022B1515120065 and No.2020A1515110151)Dongguan Science and Technology of Social Development Program(No.G202306).
文摘The influenza A virus(IAV)damages intestinal mucosal tissues beyond the respiratory tract.Probiotics play a crucial role in maintaining the balance and stability of the intestinal microecosystem.Extracellular vesicles(EVs)derived from probiotics have emerged as potential mediators of host immune response and anti-inflammatory effect.However,the specific anti-inflammatory effects and underlying mechanisms of probiotics-derived EVs on IAV remain unclear.In the present study,we investigated the therapeutic efficacy of Lactobacillus reuteri EHA2-derived EVs(LrEVs)in a mouse model of IAV infection.Oral LrEVs were distributed in the liver,lungs,and gastrointestinal tract.In mice infected with IAV,oral LrEVs administration alleviated IAV-induced damages in the lungs and intestines,modified the microbiota compositions,and increased the levels of short-chain fatty acids in those organs.Mechanistically,LrEVs exerted their protective effects against IAV infection by blunting the pro-inflammatory IL-17 signaling.Furthermore,FISH analysis detected miR-4239,one of the most abundant miRNAs in LrEVs,in both lung and intestinal tissues.We confirmed that miR-4239 directly targets IL-17a.Our findings paved the ground for future application of LrEVs in influenza treatment and offered new mechanistic insights regarding the anti-inflammatory role of miR-4239.
基金This work was supported by National Natural Science Foundation of China(82100427)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010203)the seed grants from the Wenzhou Institute,University of Chinese Academy of Sciences(WIUCASQD2020013,WIUCASQD2021030),the founding from First Affiliated Hospital of Wenzhou Medical University.
文摘Aortic aneurysm and dissection(AAD)are leading causes of death in the elderly.Recent studies have demonstrated that silicate ions can manipulate multiple cells,especially vascular-related cells.We demonstrated in this study that silicate ions as soluble form of bioactive ceramics effectively alleviated aortic aneurysm and dissection in both Ang II andβ-BAPN induced AAD models.Different from the single targeting therapeutic drug approaches,the bioactive ceramic derived approach attributes to the effect of bioactive silicate ions on the inhibition of the AAD progression through regulating the local vascular microenvironment of aorta systematically in a multi-functional way.The in vitro experiments revealed that silicate ions did not only alleviate senescence and inflammation of the mouse aortic endothelial cells,enhance M2 polarization of mouse bone marrow-derived macrophages,and reduce apoptosis of mouse aortic smooth muscle cells,but also regulate their interactions.The in vivo studies further confirm that silicate ions could effectively alleviate senescence,inflammation,and cell apoptosis of aortas,accomplished with reduced aortic dilation,collagen deposition,and elastin laminae degradation.This bioactive ceramic derived therapy provides a potential new treatment strategy in attenuating AAD progression.
基金supported by grants from the National Natural Science Foundation of China(No.81971765,31771060,31671025,81871504,32171355 and 82172103).
文摘Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell viability.Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation,high clearance hinders its application in clinical practice.Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia.In this study,to mimic the paracrine and biological activity of stem cells,we developed artificial stem cells that can continuously release Tβ4-exosomes(Tβ4-ASCs)by encapsulating specific exosomes within microspheres using microfluidics technology.The results show that Tβ4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area,and its therapeutic effect is superior to that of directly injecting the exosomes.In addition,to better understand how it works,we demonstrated that the Tβ4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells(CAECs)via the miR-17-5p/PHD3/Hif-1αpathway.In brief,as artificial stem cells,Tβ4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction,providing a feasible and alternative method for clinical revascularization.
