Background and objective:Noninvasive non-alcoholic steatohepatitis(NASH)assessment is a clinical challenge to the management of non-alcoholic fatty liver disease.We aim to develop diagnostic models based on sequential...Background and objective:Noninvasive non-alcoholic steatohepatitis(NASH)assessment is a clinical challenge to the management of non-alcoholic fatty liver disease.We aim to develop diagnostic models based on sequential ultrasound molecular imaging(USMI)for the noninvasive identification of NASH in mouse models.Methods:Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University.Forty-nine C57BL/6 mice were divided into normal control,non-alcoholic fatty liver,NASH,and hepatitis groups.Sequential USMI was implemented using CD36-targeted microbubbles(MBs-CD36)and intercellular adhesion molecule-1(ICAM-1)-targeted microbubbles(MBs-ICAM-1)to visualize hepatic steatosis and inflammation.The targeting signal of USMI was quantified as the normalized intensity difference(NID)with the destruction-replenishment method.Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBsICAM-1 and pathological inflammation score.Finally,diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.Results:MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice.NID-MBs-CD36 values increased with the progression of steatosis,while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation.A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade(r_(s)=0.9078,P<0.0001)and between NIDMBs-ICAM-1 and pathological inflammation grade(r_(s)=0.9071,P<0.0001).Among various sequential USMI-based diagnostic models,the serial testing model showed high diagnostic performance in detecting NASH,with 95%sensitivity,97%specificity,95%positive predictive values,97%negative predictive values,and 96%accuracy.Conclusions:Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation.Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.展开更多
The purpose of this study was to examine the direct toxicity of PM2.5 collected from Beijing on human umbilical vein endothelial cells(HUVEC). A Cell Counting Kit 8(CCK8) assay demonstrated that PM2.5 exposure decreas...The purpose of this study was to examine the direct toxicity of PM2.5 collected from Beijing on human umbilical vein endothelial cells(HUVEC). A Cell Counting Kit 8(CCK8) assay demonstrated that PM2.5 exposure decreased the proliferation of HUVECs in a dosedependent manner. We also found that PM2.5 exposure induced autophagy in HUVECs, as evidenced by:(1) an increased number of double-membrane vesicles;(2) enhanced conversion and punctuation of the microtubule-associated protein light chain 3(LC3); and(3) decreased levels of the selective autophagy substrate p62 in a time-dependent manner.Furthermore, promoting autophagy in PM2.5-exposed HUVECs with rapamycin increased the cell survival rate, whereas inhibiting autophagy via 3-methyladenine significantly decreased cell survival. These results demonstrate that PM2.5 exposure can induce cytotoxicity and autophagy in HUVECs and that autophagy play a protective role against PM2.5-induced cytotoxicity. The findings of the present study imply a direct toxic effect of PM2.5 on HUVECs and provide novel insight into the mechanism of cardiovascular diseases caused by PM2.5 exposure.展开更多
基金the Science and Technology Planning Project of Guangzhou,China(No.2023A03J0216)the National Natural Science Foundation of China(No.82272021)the Natural Science Foundation of Guangdong Province,China(No.2021A1515010635)and the Major Talents Programme of the Third Affiliated Hospital of Sun Yat-sen University(No.P02445).
文摘Background and objective:Noninvasive non-alcoholic steatohepatitis(NASH)assessment is a clinical challenge to the management of non-alcoholic fatty liver disease.We aim to develop diagnostic models based on sequential ultrasound molecular imaging(USMI)for the noninvasive identification of NASH in mouse models.Methods:Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University.Forty-nine C57BL/6 mice were divided into normal control,non-alcoholic fatty liver,NASH,and hepatitis groups.Sequential USMI was implemented using CD36-targeted microbubbles(MBs-CD36)and intercellular adhesion molecule-1(ICAM-1)-targeted microbubbles(MBs-ICAM-1)to visualize hepatic steatosis and inflammation.The targeting signal of USMI was quantified as the normalized intensity difference(NID)with the destruction-replenishment method.Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBsICAM-1 and pathological inflammation score.Finally,diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.Results:MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice.NID-MBs-CD36 values increased with the progression of steatosis,while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation.A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade(r_(s)=0.9078,P<0.0001)and between NIDMBs-ICAM-1 and pathological inflammation grade(r_(s)=0.9071,P<0.0001).Among various sequential USMI-based diagnostic models,the serial testing model showed high diagnostic performance in detecting NASH,with 95%sensitivity,97%specificity,95%positive predictive values,97%negative predictive values,and 96%accuracy.Conclusions:Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation.Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.
基金supported by the National Natural Science Foundation of China (Nos. 21677006, 21177119)the State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences (No. SKLECRA2016OFP)the State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (No. KF2015-19)
文摘The purpose of this study was to examine the direct toxicity of PM2.5 collected from Beijing on human umbilical vein endothelial cells(HUVEC). A Cell Counting Kit 8(CCK8) assay demonstrated that PM2.5 exposure decreased the proliferation of HUVECs in a dosedependent manner. We also found that PM2.5 exposure induced autophagy in HUVECs, as evidenced by:(1) an increased number of double-membrane vesicles;(2) enhanced conversion and punctuation of the microtubule-associated protein light chain 3(LC3); and(3) decreased levels of the selective autophagy substrate p62 in a time-dependent manner.Furthermore, promoting autophagy in PM2.5-exposed HUVECs with rapamycin increased the cell survival rate, whereas inhibiting autophagy via 3-methyladenine significantly decreased cell survival. These results demonstrate that PM2.5 exposure can induce cytotoxicity and autophagy in HUVECs and that autophagy play a protective role against PM2.5-induced cytotoxicity. The findings of the present study imply a direct toxic effect of PM2.5 on HUVECs and provide novel insight into the mechanism of cardiovascular diseases caused by PM2.5 exposure.
