BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate th...BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD.AIM To explore whether exosomal miR-320e could suppress the Wnt/β-catenin pathway and play a protective role in CVSD progression,as well as examine its potential correlation with cognitive impairment and depression in patients with CVSD.METHODS Differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from patients with CVSD and healthy controls.Bioinformatics and dual luciferase analyses were used to confirm the binding of miR-320e to Wnt2,and the mRNA and protein levels of downstream components in the Wnt/β-catenin pathway were evaluated when overexpressed or with knockdown of miR-320e under H2O2-induced oxidative stress.In addition,Wnt2-targeting siRNA was used to confirm the role of miR-320e in the Wnt2-mediated inhibition of the Wnt/β-catenin pathway.A retrospective analysis was conducted among patients with CVSD to confirm the correlation between miR-320e expression and the severity of cognitive impairment and depression,which were quantified using the Montreal Cognitive Assessment(MoCA)/Executive Function Assessment(EFA),and the Hamilton Depression Scale(HAMD)/Beck Depression Inventory(BDI),respectively.RESULTS High-throughput sequencing revealed that exosomal miR-320e was downregulated in patients with CVSD.Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e inhibited the Wnt/β-catenin pathway in response to oxidative stress by targeting the 3'noncoding region of Wnt2.Uptake of exosomes carrying miR-320e into endothelial cells could also target Wnt2 and inhibit the Wnt2/β-catenin pathway.Elevated miR-320e expression may protect patients with CVSD from relatively severe cognitive impairment and depression,as it was found to have a positive correlation with the MoCA/EFA and HAMD/BDI scores.CONCLUSION Our results suggest that exosomal miR-320e suppresses the Wnt/β-catenin pathway and may play a protective role in CVSD progression.展开更多
The contributions for the kaon pair from the intermediate statesρ(1450)^(+) andρ(1700)^(+) in the decays B+→D¯^(0)K+K¯^(0),B^(0)→D−K+K¯^(0),and B^(0)_(s)→D−_(s)K+K¯^(0)are analyzed within the ...The contributions for the kaon pair from the intermediate statesρ(1450)^(+) andρ(1700)^(+) in the decays B+→D¯^(0)K+K¯^(0),B^(0)→D−K+K¯^(0),and B^(0)_(s)→D−_(s)K+K¯^(0)are analyzed within the perturbative QCD factorization approach.The decay amplitudes for all concerned decays in this work are dominated by the factorizable Feynman diagrams with the emission of the kaon pair,and the chargedρmesons should be of great importance in the KK channel of the related three-body B decays.Moreover,these quasi-two-body decays are CKM-favored,and the relevant branching ratios are predicted to be in the order of 10^(−5),which have the potential to be measured by experiments.It is also shown that the contributions of the subprocessesρ(1450,1700)^(+)→KK for the three-body B meson decays are considerable according to the total three-body branching fractions presented by Belle.Therefore,the decays B+→D¯^(0)K+K¯^(0),B^(0)→D−K+K¯^(0),and B^(0)_(s)→D−_(s)K^(+)K¯^(0)can be employed to study the properties ofρ(1450)andρ(1700)in the LHCb and Belle-II experiments.展开更多
文摘BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD.AIM To explore whether exosomal miR-320e could suppress the Wnt/β-catenin pathway and play a protective role in CVSD progression,as well as examine its potential correlation with cognitive impairment and depression in patients with CVSD.METHODS Differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from patients with CVSD and healthy controls.Bioinformatics and dual luciferase analyses were used to confirm the binding of miR-320e to Wnt2,and the mRNA and protein levels of downstream components in the Wnt/β-catenin pathway were evaluated when overexpressed or with knockdown of miR-320e under H2O2-induced oxidative stress.In addition,Wnt2-targeting siRNA was used to confirm the role of miR-320e in the Wnt2-mediated inhibition of the Wnt/β-catenin pathway.A retrospective analysis was conducted among patients with CVSD to confirm the correlation between miR-320e expression and the severity of cognitive impairment and depression,which were quantified using the Montreal Cognitive Assessment(MoCA)/Executive Function Assessment(EFA),and the Hamilton Depression Scale(HAMD)/Beck Depression Inventory(BDI),respectively.RESULTS High-throughput sequencing revealed that exosomal miR-320e was downregulated in patients with CVSD.Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e inhibited the Wnt/β-catenin pathway in response to oxidative stress by targeting the 3'noncoding region of Wnt2.Uptake of exosomes carrying miR-320e into endothelial cells could also target Wnt2 and inhibit the Wnt2/β-catenin pathway.Elevated miR-320e expression may protect patients with CVSD from relatively severe cognitive impairment and depression,as it was found to have a positive correlation with the MoCA/EFA and HAMD/BDI scores.CONCLUSION Our results suggest that exosomal miR-320e suppresses the Wnt/β-catenin pathway and may play a protective role in CVSD progression.
基金Supported by the National Natural Science Foundation of China(11947011)the Natural Science Foundation of Jiangsu Province(BK20191010)the Scientific Research Foundation of Nanjing Institute of Technology(YKJ201854)。
文摘The contributions for the kaon pair from the intermediate statesρ(1450)^(+) andρ(1700)^(+) in the decays B+→D¯^(0)K+K¯^(0),B^(0)→D−K+K¯^(0),and B^(0)_(s)→D−_(s)K+K¯^(0)are analyzed within the perturbative QCD factorization approach.The decay amplitudes for all concerned decays in this work are dominated by the factorizable Feynman diagrams with the emission of the kaon pair,and the chargedρmesons should be of great importance in the KK channel of the related three-body B decays.Moreover,these quasi-two-body decays are CKM-favored,and the relevant branching ratios are predicted to be in the order of 10^(−5),which have the potential to be measured by experiments.It is also shown that the contributions of the subprocessesρ(1450,1700)^(+)→KK for the three-body B meson decays are considerable according to the total three-body branching fractions presented by Belle.Therefore,the decays B+→D¯^(0)K+K¯^(0),B^(0)→D−K+K¯^(0),and B^(0)_(s)→D−_(s)K^(+)K¯^(0)can be employed to study the properties ofρ(1450)andρ(1700)in the LHCb and Belle-II experiments.
