The prevention of air pollution-related cardiopulmonary disorders has been largely overlooked despite its important burden.Extracellular vesicles(EVs)have shown great potential as carriers for drug delivery.However,th...The prevention of air pollution-related cardiopulmonary disorders has been largely overlooked despite its important burden.Extracellular vesicles(EVs)have shown great potential as carriers for drug delivery.However,the efficiency and effect of EVs derived from different sources on ambient fine particulate matter(PM2.5)-induced cardiopulmonary injury remain unknown.Using PM2.5-exposed cellular and mouse models,we investigated the prevention of air pollution-related cardiopulmonary injury via an innovative strategy based on EV delivery.By using a“2-step”method that combines bibliometric and bioinformatic analysis,we identified superoxide dismutase 2(Sod2)as a potential target for PM2.5-induced injury.Sod2-overexpressing plasmid was constructed and loaded into human plasma-,bovine milk-,and fresh grape-derived EVs,ultimately obtaining modified nanoparticles including PEV^(Sod2),MEV^(Sod2),and GEV^(Sod2),respectively.GEV^(Sod2),especially its lyophilized GEV^(Sod2) powder,exhibited superior protection against PM2.5-induced cardiopulmonary injury as compared to PEV^(Sod2) and MEV^(Sod2).High-sensitivity structured illumination microscopy imaging and immunoblotting showed that GEV^(Sod2) powder treatment altered lysosome positioning by reducing Rab-7 expression.Our findings support the use of fruit-derived EVs as a preferred candidate for nucleic acid delivery and disease treatment,which may facilitate the translation of treatments for cardiopulmonary injuries.展开更多
Cardiovascular disease is one of the leading causes of mortality worldwide.Recent studies have shown that circular RNAs(circRNAs)have emerged as important players in the prevention and treatment of cardiovascular dise...Cardiovascular disease is one of the leading causes of mortality worldwide.Recent studies have shown that circular RNAs(circRNAs)have emerged as important players in the prevention and treatment of cardiovascular diseases.circRNAs are a class of endogenous noncoding RNAs that are generated by back-splicing and are involved in many pathophysiological processes.In this review,we outline the current research progress on the regulatory roles of circRNAs in cardiovascular diseases.Further,new technologies and methods available for identifying,validating,synthesizing,and analyzing circRNAs,as well as their applications in therapeutics,are highlighted here.Moreover,we summarize the increasing insights into the potential use of circRNAs as circulating diagnostic and prognostic biomarkers.Finally,we discuss the prospects and challenges of circRNA therapeutic applications for cardiovascular disease therapy,with a particular focus on developing circRNA synthesis and engineering delivery systems.展开更多
Polyploid cells,which contain more than one set of chromosome pairs,are very common in nature.Polyploidy can provide cells with several potential benefits over their diploid counterparts,including an increase in cell ...Polyploid cells,which contain more than one set of chromosome pairs,are very common in nature.Polyploidy can provide cells with several potential benefits over their diploid counterparts,including an increase in cell size,contributing to organ growth and tissue homeostasis,and improving cellular robustness via increased tolerance to genomic stress and apoptotic signals.Here,we focus on why polyploidy in the cell occurs and which stress responses and molecular signals trigger cells to become polyploid.Moreover,we discuss its crucial roles in cell growth and tissue regeneration in the heart,liver,and other tissues.展开更多
基金supported by the National Key Research and Development Project(2022YFA1104500 to J.X.)the National Natural Science Foundation of China(82020108002 and 82225005 to J.X.and 82370277 to H.W.)the Science and Technology Commission of Shanghai Municipality(23ZR1422900 to H.W.and 23410750100 to J.X.).
文摘The prevention of air pollution-related cardiopulmonary disorders has been largely overlooked despite its important burden.Extracellular vesicles(EVs)have shown great potential as carriers for drug delivery.However,the efficiency and effect of EVs derived from different sources on ambient fine particulate matter(PM2.5)-induced cardiopulmonary injury remain unknown.Using PM2.5-exposed cellular and mouse models,we investigated the prevention of air pollution-related cardiopulmonary injury via an innovative strategy based on EV delivery.By using a“2-step”method that combines bibliometric and bioinformatic analysis,we identified superoxide dismutase 2(Sod2)as a potential target for PM2.5-induced injury.Sod2-overexpressing plasmid was constructed and loaded into human plasma-,bovine milk-,and fresh grape-derived EVs,ultimately obtaining modified nanoparticles including PEV^(Sod2),MEV^(Sod2),and GEV^(Sod2),respectively.GEV^(Sod2),especially its lyophilized GEV^(Sod2) powder,exhibited superior protection against PM2.5-induced cardiopulmonary injury as compared to PEV^(Sod2) and MEV^(Sod2).High-sensitivity structured illumination microscopy imaging and immunoblotting showed that GEV^(Sod2) powder treatment altered lysosome positioning by reducing Rab-7 expression.Our findings support the use of fruit-derived EVs as a preferred candidate for nucleic acid delivery and disease treatment,which may facilitate the translation of treatments for cardiopulmonary injuries.
基金the grants from National Key Research and Development Project(2018YFE0113500 to J.X.)National Natural Science Foundation of China(82020108002 and 82225005 to J.X.and 82270291 to L.W.)+3 种基金Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-09-E00042 to J.X.)the grant from Science and Technology Commission of Shanghai Municipality(21XD1421300 and 20DZ2255400 to J.X.)the“Dawn”Program of Shanghai Education Commission(19SG34 to J.X.)ZonMw PSIDER grant(no.10250022110004)to J.P.G.S.
文摘Cardiovascular disease is one of the leading causes of mortality worldwide.Recent studies have shown that circular RNAs(circRNAs)have emerged as important players in the prevention and treatment of cardiovascular diseases.circRNAs are a class of endogenous noncoding RNAs that are generated by back-splicing and are involved in many pathophysiological processes.In this review,we outline the current research progress on the regulatory roles of circRNAs in cardiovascular diseases.Further,new technologies and methods available for identifying,validating,synthesizing,and analyzing circRNAs,as well as their applications in therapeutics,are highlighted here.Moreover,we summarize the increasing insights into the potential use of circRNAs as circulating diagnostic and prognostic biomarkers.Finally,we discuss the prospects and challenges of circRNA therapeutic applications for cardiovascular disease therapy,with a particular focus on developing circRNA synthesis and engineering delivery systems.
基金supported by the Project EVICARE (No.725229)of the European Research Council (ERC)to J.P.G.S.the ZonMw-TAS program (No.116002016)to J.P.G.S./Z.L.+2 种基金the Dutch Ministry of Economic Affairs,Agriculture and Innovation and the Netherlands CardioVascular Research Initiative (CVON)the Dutch Heart Foundation to J.P.G.S.Juntao Fang is supported by a Chinese Scholarship Council (CSC)fellowship program (No.201906210082).AV acknowledges support by the ERCAdG 787171,POLICE.
文摘Polyploid cells,which contain more than one set of chromosome pairs,are very common in nature.Polyploidy can provide cells with several potential benefits over their diploid counterparts,including an increase in cell size,contributing to organ growth and tissue homeostasis,and improving cellular robustness via increased tolerance to genomic stress and apoptotic signals.Here,we focus on why polyploidy in the cell occurs and which stress responses and molecular signals trigger cells to become polyploid.Moreover,we discuss its crucial roles in cell growth and tissue regeneration in the heart,liver,and other tissues.