Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contr...Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation.Moreover,due to the characteristics of stem cells,pericytes can differentiate into a variety of inflammatory cell phenotypes,which then affect the immune function.Additionally,pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders.Here we review the origin,biological phenotype and function of pericytes,and discuss the potential mechanisms of pericytes in vascular microcirculation disorders,especially in pulmonary hypertension,so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.展开更多
Background:Aberrant expression of microRNAs(miRNAs)has been associated with the pathogenesis of pulmonary hypertension(PH).It is,however,not clear whether miRNAs are involved in estrogen rescue of PH.Methods:Fresh pla...Background:Aberrant expression of microRNAs(miRNAs)has been associated with the pathogenesis of pulmonary hypertension(PH).It is,however,not clear whether miRNAs are involved in estrogen rescue of PH.Methods:Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension(IPAH)patients and 12 healthy controls undergoing right heart cath-eterization in Shanghai Pulmonary Hospital.From each sample,5μg of total RNA was tagged and hybridized on microRNA microarray chips.Monocrotaline-induced PH(MCT-PH)male rats were treated with 17β-estradiol(E_(2))or vehicle.Subgroups were cotreated with estrogen receptor(ER)antagonist or with antagonist of miRNA.Results:Many circulating miRNAs,including miR-21-5p and miR-574-5p,were mark-edly expressed in patients and of interest in predicting mean pulmonary arterial pres-sure elevation in patients.The expression of miR-21-5p in the lungs was significantly upregulated in MCT-PH rats compared with the controls.However,miR-574-5p showed no difference in the lungs of MCT-PH rats and controls.miR-21-5p was se-lected for further analysis in rats as E_(2) strongly regulated it.E_(2) decreased miR-21-5p expression in the lungs of MCT-PH rats by ERβ.E_(2) reversed miR-21-5p target gene FilGAP downregulation in the lungs of MCT-PH rats.The abnormal expression of RhoA,ROCK2,Rac1 and c-Jun in the lungs of MCT-PH rats was inhibited by E_(2) and miR-21-5p antagonist.Conclusions:miR-21-5p level was remarkably associated with PH severity in patients.Moreover,the miR-21-5p/FilGAP signaling pathway modulated the protective effect of E_(2) on MCT-PH through ERβ.展开更多
Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial...Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.展开更多
Circular RNAs(circRNAs)are endogenous RNAs with a covalently closed single-stranded transcript.They are a novel class of genomic regulators that are linked to many important development and disease processes and are b...Circular RNAs(circRNAs)are endogenous RNAs with a covalently closed single-stranded transcript.They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets.Using the most powerful RNA sequencing and bioinformatics techniques,a large number of circRNAs have been identified and further functional studies have been performed.It is known that circRNAs act as potential biomarkers,sponges for microRNAs(miRNAs)and RNA-binding proteins(RBPs),and regulators of mRNA transcription.They also participate in the translation of peptides or proteins.Many types of circRNAs are dysregulated in plasma or lung tissues,and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells(PAECs)and pulmonary artery smooth muscle cells(PASMCs),leading to pulmonary vascular remodeling in pulmonary hypertension(PH).One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge.However,other potential mechanisms of action of circRNAs are still being actively explored in PH.This paper presents a systematic review of the biogenesis,biological characterization,relevant underlying functions,and future perspectives for studies of circRNAs in the pathogenesis of PH.展开更多
Multifunctional bismuth sulfide(Bi_(2)S_(3))nanomate rials exhibit significant potential as na no medicines for the diagnosis and treatment of cancer.These nanomaterials act as excellent photothermal agents and radiat...Multifunctional bismuth sulfide(Bi_(2)S_(3))nanomate rials exhibit significant potential as na no medicines for the diagnosis and treatment of cancer.These nanomaterials act as excellent photothermal agents and radiation sensitizers for the treatment of tumors,and they can also act as contrast agents for computed tomography(CT)imaging,photoacoustic imaging(PA),and other forms of imaging to provide real-time tumor monitoring and testing guidance.Compared with other nanomaterials,Bi2S3 nanomaterials can readily adapt to different applications by virtue of the fact that they can be easily functionalized.However,these nanomaterials have some limitations that cannot be ignored and need to be addressed,such as poor biocompatibility,toxicity,and low chemical stability.It is widely believed that appropriate functionalization of Bi_(2)S_(3) nanomaterials could remedy such defects and significantly improve performance.This review summarizes the ways in which Bi_(2)S_(3) nanomaterials can be functionalized and discusses their applications in cancer theranostics over the last few years,focusing particularly on imaging and therapy.We also discuss issues relating to how Bi_(2)S_(3) nanomaterials can be analyzed,including how we might be able to use these systems to inhibit and treat tumors and how current limitations might be ove rcome to improve treatment efficacy.Finally,we hope to provide inspiration and guidance as to how we might create a mo re optimized multifunctio nal nano-system for the diagnosis and treatment of tumors.展开更多
Based on the difference in the density and content of kerogen and inorganic minerals, oil shale can be separatedinto different density fractions. The structural features of kerogens in Beipiao oil shale (a kind of typ...Based on the difference in the density and content of kerogen and inorganic minerals, oil shale can be separatedinto different density fractions. The structural features of kerogens in Beipiao oil shale (a kind of typical lowgrade oil shale resources) with densities of 1.8–1.9, 1.9–2.0 and 2.0–2.1 g/cm3 were studied. Combined withour previous study on the structural features of Longkou and Huadian oil shales (two kinds of high-grade oil shaleresources) with different densities, the relationship between the oil shale density and the structural features ofcorresponding kerogens was revealed from aromatic, aliphatic structures and heteroatom species. The resultsshow that with increasing the density, the content of minerals increases, whereas that of kerogen decreases. Withincreasing the density, the aliphaticity, average methylene chain length and average number of attachments oneach aromatic ring increase. Whereas, the aromaticity and average size of aromatic cluster are inversely proportional to the oil shale density. For Longkou, Huadian and Beipiao oil shales with different densities, thechange rules of aromatic and aliphatic structures with the density are similar, indicating that these change rulesare independent of the grade and origin of oil shale. The change rules of heteroatom species in Beipiao oil shaleare different from that of Longkou and Huadian oil shales.展开更多
To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging,novel Au@Bi2S3 core shell nanobones(NBs)(Au@Bi2S3 NBs)with Au nanorods as cores were synthesized.The combination of A...To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging,novel Au@Bi2S3 core shell nanobones(NBs)(Au@Bi2S3 NBs)with Au nanorods as cores were synthesized.The combination of Au nanorods with Bi2S3 film made the Au@Bi2S3 NBs exhibit ultrahigh photothermal(PT)conversion efficiency,remarkable photoacoustic(PA)imaging and high computed tomography(CT)performance;these Au@Bi2S3 NBs thus are a promising nanotheranostic agent for PT/PA/CT imaging.Subsequently,poly(N-vinylpyrrolidone)-modified Au@Bi2S3 NBs(Au@Bi2S3-PVP NBs)were successfully loaded with the anticancer drug doxorubicin(DOX),and a satisfactory pH sensitive release profile was achieved,thus revealing the great potential of Au@Bi2S3-PVP NBs in chemotherapy as a drug carrier to deliver DOX into cancer cells.Both in vitro and in vivo investigations demonstrated that the Au@Bi2S3-PVP NBs possessed multiple desired features for cancer therapy,including extremely low toxicity,good biocompatibility,high drug loading ability,precise tumor targeting and effective accumulation.Highly efficient ablation of the human liver cancer cell HepG2 was achieved through Au@Bi2S3-PVP NB-mediated photothermal therapy(PTT).As both a contrast enhancement probe and therapeutic agent,Au@Bi2S3-PVP NBs provided outstanding NIR-triggered multi-modal PT/PA/CT imaging-guided PTT and effectively inhibited the growth of HepG2 liver cancer cells via synergistic chemo/PT therapy.展开更多
基金Program of Fundamental Research Funds for the Central Universities,Grant/Award Number:22120220562Program of Natural Science Foundation of Shanghai,Grant/Award Number:201409004100 and 21ZR1453800+1 种基金Three Year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals,Grant/Award Number:SHDC2020CR6016-002 and SHDC2020CR4021Program of Shanghai Pulmonary Hospital,Grant/Award Number:fkzr2320 and FKLY20005。
文摘Pericytes are the main cellular components of tiny arteries and capillaries.Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines,thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation.Moreover,due to the characteristics of stem cells,pericytes can differentiate into a variety of inflammatory cell phenotypes,which then affect the immune function.Additionally,pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders.Here we review the origin,biological phenotype and function of pericytes,and discuss the potential mechanisms of pericytes in vascular microcirculation disorders,especially in pulmonary hypertension,so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.
基金National Natural Science Foundation of China,Grant/Award Number:8 1870042Natural Science Foundation of Shanghai,Grant/Award Number:21ZR1453800。
文摘Background:Aberrant expression of microRNAs(miRNAs)has been associated with the pathogenesis of pulmonary hypertension(PH).It is,however,not clear whether miRNAs are involved in estrogen rescue of PH.Methods:Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension(IPAH)patients and 12 healthy controls undergoing right heart cath-eterization in Shanghai Pulmonary Hospital.From each sample,5μg of total RNA was tagged and hybridized on microRNA microarray chips.Monocrotaline-induced PH(MCT-PH)male rats were treated with 17β-estradiol(E_(2))or vehicle.Subgroups were cotreated with estrogen receptor(ER)antagonist or with antagonist of miRNA.Results:Many circulating miRNAs,including miR-21-5p and miR-574-5p,were mark-edly expressed in patients and of interest in predicting mean pulmonary arterial pres-sure elevation in patients.The expression of miR-21-5p in the lungs was significantly upregulated in MCT-PH rats compared with the controls.However,miR-574-5p showed no difference in the lungs of MCT-PH rats and controls.miR-21-5p was se-lected for further analysis in rats as E_(2) strongly regulated it.E_(2) decreased miR-21-5p expression in the lungs of MCT-PH rats by ERβ.E_(2) reversed miR-21-5p target gene FilGAP downregulation in the lungs of MCT-PH rats.The abnormal expression of RhoA,ROCK2,Rac1 and c-Jun in the lungs of MCT-PH rats was inhibited by E_(2) and miR-21-5p antagonist.Conclusions:miR-21-5p level was remarkably associated with PH severity in patients.Moreover,the miR-21-5p/FilGAP signaling pathway modulated the protective effect of E_(2) on MCT-PH through ERβ.
基金Program of Natural Science Foundation of Shanghai,Grant/Award Number:21ZR1453800 and 22ZR1452400Program of National Natural Science Foundation of China,Grant/Award Number:82370057+3 种基金Fundamental Research Funds for the Central Universities,Grant/Award Number:22120220562Program of Shanghai Municipal Health Commission,Grant/Award Number:20204Y0384Program of National Key Research and Development Project of China,Grant/Award Number:2023YFC2509500。
文摘Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.
基金supported by the Program of National Natural Science Foundation of China (81870042 and 81900050)Program of Natural Science Foundation of Shanghai (21ZR1453800)Program of Shanghai Pulmonary Hospital (FKLY20005)
文摘Circular RNAs(circRNAs)are endogenous RNAs with a covalently closed single-stranded transcript.They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets.Using the most powerful RNA sequencing and bioinformatics techniques,a large number of circRNAs have been identified and further functional studies have been performed.It is known that circRNAs act as potential biomarkers,sponges for microRNAs(miRNAs)and RNA-binding proteins(RBPs),and regulators of mRNA transcription.They also participate in the translation of peptides or proteins.Many types of circRNAs are dysregulated in plasma or lung tissues,and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells(PAECs)and pulmonary artery smooth muscle cells(PASMCs),leading to pulmonary vascular remodeling in pulmonary hypertension(PH).One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge.However,other potential mechanisms of action of circRNAs are still being actively explored in PH.This paper presents a systematic review of the biogenesis,biological characterization,relevant underlying functions,and future perspectives for studies of circRNAs in the pathogenesis of PH.
文摘Multifunctional bismuth sulfide(Bi_(2)S_(3))nanomate rials exhibit significant potential as na no medicines for the diagnosis and treatment of cancer.These nanomaterials act as excellent photothermal agents and radiation sensitizers for the treatment of tumors,and they can also act as contrast agents for computed tomography(CT)imaging,photoacoustic imaging(PA),and other forms of imaging to provide real-time tumor monitoring and testing guidance.Compared with other nanomaterials,Bi2S3 nanomaterials can readily adapt to different applications by virtue of the fact that they can be easily functionalized.However,these nanomaterials have some limitations that cannot be ignored and need to be addressed,such as poor biocompatibility,toxicity,and low chemical stability.It is widely believed that appropriate functionalization of Bi_(2)S_(3) nanomaterials could remedy such defects and significantly improve performance.This review summarizes the ways in which Bi_(2)S_(3) nanomaterials can be functionalized and discusses their applications in cancer theranostics over the last few years,focusing particularly on imaging and therapy.We also discuss issues relating to how Bi_(2)S_(3) nanomaterials can be analyzed,including how we might be able to use these systems to inhibit and treat tumors and how current limitations might be ove rcome to improve treatment efficacy.Finally,we hope to provide inspiration and guidance as to how we might create a mo re optimized multifunctio nal nano-system for the diagnosis and treatment of tumors.
基金The authors thank Dr.Chang Zhibing from China University of Mining&Technology(Beijing)for his kindly providing the oil shale samples.This work was supported by the National Natural Science Foundation of China(22008187)Ph.D.Research Initiation Fund of Xi’an Polytechnic University(107020401)the Natural Science Basic Research Program of Shaanxi(2021JQ-668).
文摘Based on the difference in the density and content of kerogen and inorganic minerals, oil shale can be separatedinto different density fractions. The structural features of kerogens in Beipiao oil shale (a kind of typical lowgrade oil shale resources) with densities of 1.8–1.9, 1.9–2.0 and 2.0–2.1 g/cm3 were studied. Combined withour previous study on the structural features of Longkou and Huadian oil shales (two kinds of high-grade oil shaleresources) with different densities, the relationship between the oil shale density and the structural features ofcorresponding kerogens was revealed from aromatic, aliphatic structures and heteroatom species. The resultsshow that with increasing the density, the content of minerals increases, whereas that of kerogen decreases. Withincreasing the density, the aliphaticity, average methylene chain length and average number of attachments oneach aromatic ring increase. Whereas, the aromaticity and average size of aromatic cluster are inversely proportional to the oil shale density. For Longkou, Huadian and Beipiao oil shales with different densities, thechange rules of aromatic and aliphatic structures with the density are similar, indicating that these change rulesare independent of the grade and origin of oil shale. The change rules of heteroatom species in Beipiao oil shaleare different from that of Longkou and Huadian oil shales.
基金This work was financially supported by the Natural Science Foundation of Shanghai(19ZR1434800,19ZR1461900)the National Natural Science Foundation of China(21305090)+1 种基金the Fundamental Research Funds for the Central Universities(to Shuang Zhou)The authors greatly appreciated these supports.
文摘To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging,novel Au@Bi2S3 core shell nanobones(NBs)(Au@Bi2S3 NBs)with Au nanorods as cores were synthesized.The combination of Au nanorods with Bi2S3 film made the Au@Bi2S3 NBs exhibit ultrahigh photothermal(PT)conversion efficiency,remarkable photoacoustic(PA)imaging and high computed tomography(CT)performance;these Au@Bi2S3 NBs thus are a promising nanotheranostic agent for PT/PA/CT imaging.Subsequently,poly(N-vinylpyrrolidone)-modified Au@Bi2S3 NBs(Au@Bi2S3-PVP NBs)were successfully loaded with the anticancer drug doxorubicin(DOX),and a satisfactory pH sensitive release profile was achieved,thus revealing the great potential of Au@Bi2S3-PVP NBs in chemotherapy as a drug carrier to deliver DOX into cancer cells.Both in vitro and in vivo investigations demonstrated that the Au@Bi2S3-PVP NBs possessed multiple desired features for cancer therapy,including extremely low toxicity,good biocompatibility,high drug loading ability,precise tumor targeting and effective accumulation.Highly efficient ablation of the human liver cancer cell HepG2 was achieved through Au@Bi2S3-PVP NB-mediated photothermal therapy(PTT).As both a contrast enhancement probe and therapeutic agent,Au@Bi2S3-PVP NBs provided outstanding NIR-triggered multi-modal PT/PA/CT imaging-guided PTT and effectively inhibited the growth of HepG2 liver cancer cells via synergistic chemo/PT therapy.
