The adhesion of endothelial progenitor cells(EPCs) on endothelial cells(ECs) is one of the critical physiological processes for the regenesis of vascular vessels and the prevention of serious cardiovascular diseases.H...The adhesion of endothelial progenitor cells(EPCs) on endothelial cells(ECs) is one of the critical physiological processes for the regenesis of vascular vessels and the prevention of serious cardiovascular diseases.Here,the rolling and adhesion behavior of EPCs on ECs was studied numerically.A two-dimensional numerical model was developed based on the immersed boundary method for simulating the rolling and adhesion of cells in a channel flow.The binding force arising from the catch bond of a receptor and ligand pair was modeled with stochastic Monte Carlo method and Hookean spring model.The effect of tumor necrosis factor alpha(TNF-α) on the expression of the number of adhesion molecules in ECs was analyzed experimentally.A flow chamber system with CCD camera was set up to observe the top view of the rolling of EPCs on the substrate cultivated with ECs.Numerical results prove that the adhesion of EPC on ECs is closely related to membrane stiff-ness of the cell and shear rate of the flow.It also suggests that the adhesion force between EPC and EC by P-selectin glycoprotein ligand-1 only is not strong enough to bond the cell onto vessel walls unless contributions of other catch bond are considered.Experimental results demonstrate that TNF-α enhanced the expressions of VCAM,ICAM,P-selectin and E-selectin in ECs,which supports the numerical results that the rolling velocity of EPC on TNF-α treated EC substrate decreases obviously compared with its velocity on the untreated one.It is found that because the adhesion is affected by both the rolling velocity and the deformability of the cell,an optimal stiffness of EPC may exist at a given shear rate of flow for achieving maximum adhesion rates.展开更多
Objective Jiedu Recipe(JR),a Chinese herbal remedy,has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma(HCC).This work investigated the...Objective Jiedu Recipe(JR),a Chinese herbal remedy,has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma(HCC).This work investigated the mechanism of JR in HCC treatment.Methods The chemical constituents of JR were detected using liquid chromatography-mass spectrometry.The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid(mRNA)microarray chip assay,followed by experimental validation in human HCC cells(SMMC-7721 and Huh7)in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo.HCC cell characteristics of proliferation,migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide,wound healing and Transwell assays,respectively.Image-i^(TM)Hypoxia Reagent was added to reveal hypoxic conditions.Stem cell sphere formation assay was used to detect the stemness.Epithelial-mesenchymal transition(EMT)markers like E-cadherin,vimentin andα-smooth muscle actin,and pluripotent transcription factors including nanog homeobox,octamer-binding transcription factor 4,and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction.Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway.Results According to network pharmacology and mRNA microarray chip analysis,JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway.In vitro and in vivo experiments showed that JR significantly decreased hypoxia,and suppressed HCC cell features of proliferation,migration and invasion;furthermore,the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR.Results based on the co-administration of JR and an agonist(LiCl)or inhibitor(IWR-1-endo)verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway.Conclusion JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions.展开更多
Tumor microenvironment(TME) has received more and more attention as modern medical research has begun to understand its importance in tumorigenesis. The occurrence, development, metastasis and drug resistance of tumor...Tumor microenvironment(TME) has received more and more attention as modern medical research has begun to understand its importance in tumorigenesis. The occurrence, development, metastasis and drug resistance of tumors are closely related to TME. TME is a complicated system, including nontumor cells, their secreted cytokines, extracellular matrix, among other components. The concepts of wholism and multitarget regulation in traditional Chinese medicine(TCM) make it well suited to the regulation of TME. In this paper, the authors reviewed the progress of TME research and the effect of TCM on TME, providing some views of Chinese medicine in antitumor research.展开更多
Objective:Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma(HCC),and Chinese herbal medicine has also been used to manage advanced HCC.The present work evaluates the effectiven...Objective:Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma(HCC),and Chinese herbal medicine has also been used to manage advanced HCC.The present work evaluates the effectiveness and safety of Jiedu(JD)Granule,a compound of traditional Chinese herbal medicine,side-by-side with sorafenib for the treatment of advance HCC.Methods:Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018.The primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS)and safety.Propensity score matching(PSM)analysis was used to control for possible selection bias from the study group allocation process.Results:Of the 325 patients included,161 received JD Granule and 164 received sorafenib.No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib(P>0.05).Median OS of the two study groups was 6.83 months(95%confidence interval[CI]:5.83–9.47)in the group receiving JD Granule and 8 months(95%CI:6.67–9.80)in the group receiving sorafenib,with half-,1-and 2-year survival rates of 53.6%,31.2%and 13.2%vs 60.1%,35.5%and 14.2%,respectively.Even after PSM,the median survival time did not differ between the JD Granule group(9.03 months;95%CI:6.37–14.2)and the sorafenib group(7.93 months;95%CI:6.5–9.97),with comparable half-,1-and 2-year survival rates.The most common adverse events(AEs)were diarrhea(13.7%)and fatigue(5.6%)in the JD Granule group,and hand-foot skin reaction(46.3%)and diarrhea(36.6%)in the sorafenib group.The JD Granule was more cost-effective than sorafenib treatment for advanced HCC.Conclusion:Compared to sorafenib,JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.展开更多
基金supported by the National Natural Science Foundation of China (10732070, 11072155)Shanghai Pujiang Program (09PJ1405800)
文摘The adhesion of endothelial progenitor cells(EPCs) on endothelial cells(ECs) is one of the critical physiological processes for the regenesis of vascular vessels and the prevention of serious cardiovascular diseases.Here,the rolling and adhesion behavior of EPCs on ECs was studied numerically.A two-dimensional numerical model was developed based on the immersed boundary method for simulating the rolling and adhesion of cells in a channel flow.The binding force arising from the catch bond of a receptor and ligand pair was modeled with stochastic Monte Carlo method and Hookean spring model.The effect of tumor necrosis factor alpha(TNF-α) on the expression of the number of adhesion molecules in ECs was analyzed experimentally.A flow chamber system with CCD camera was set up to observe the top view of the rolling of EPCs on the substrate cultivated with ECs.Numerical results prove that the adhesion of EPC on ECs is closely related to membrane stiff-ness of the cell and shear rate of the flow.It also suggests that the adhesion force between EPC and EC by P-selectin glycoprotein ligand-1 only is not strong enough to bond the cell onto vessel walls unless contributions of other catch bond are considered.Experimental results demonstrate that TNF-α enhanced the expressions of VCAM,ICAM,P-selectin and E-selectin in ECs,which supports the numerical results that the rolling velocity of EPC on TNF-α treated EC substrate decreases obviously compared with its velocity on the untreated one.It is found that because the adhesion is affected by both the rolling velocity and the deformability of the cell,an optimal stiffness of EPC may exist at a given shear rate of flow for achieving maximum adhesion rates.
基金This study was supported by the National Natural Science Foundation of China(No.81803929 and 82074138)the Natural Science Foundation of Shanghai(No.21ZR1479500).
文摘Objective Jiedu Recipe(JR),a Chinese herbal remedy,has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma(HCC).This work investigated the mechanism of JR in HCC treatment.Methods The chemical constituents of JR were detected using liquid chromatography-mass spectrometry.The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid(mRNA)microarray chip assay,followed by experimental validation in human HCC cells(SMMC-7721 and Huh7)in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo.HCC cell characteristics of proliferation,migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide,wound healing and Transwell assays,respectively.Image-i^(TM)Hypoxia Reagent was added to reveal hypoxic conditions.Stem cell sphere formation assay was used to detect the stemness.Epithelial-mesenchymal transition(EMT)markers like E-cadherin,vimentin andα-smooth muscle actin,and pluripotent transcription factors including nanog homeobox,octamer-binding transcription factor 4,and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction.Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway.Results According to network pharmacology and mRNA microarray chip analysis,JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway.In vitro and in vivo experiments showed that JR significantly decreased hypoxia,and suppressed HCC cell features of proliferation,migration and invasion;furthermore,the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR.Results based on the co-administration of JR and an agonist(LiCl)or inhibitor(IWR-1-endo)verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway.Conclusion JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions.
基金supported by the National Natural Science Foundation of China(No.81430101)the Special Fund for the Development of Traditional Chinese Medicine in Anhui Province in 2015
文摘Tumor microenvironment(TME) has received more and more attention as modern medical research has begun to understand its importance in tumorigenesis. The occurrence, development, metastasis and drug resistance of tumors are closely related to TME. TME is a complicated system, including nontumor cells, their secreted cytokines, extracellular matrix, among other components. The concepts of wholism and multitarget regulation in traditional Chinese medicine(TCM) make it well suited to the regulation of TME. In this paper, the authors reviewed the progress of TME research and the effect of TCM on TME, providing some views of Chinese medicine in antitumor research.
基金supported by Shanghai Municipal Commission of Health and Family Planning(No.ZY 2018-2020-CCCX-4003and No.ZYBZ-2017028)the National Natural Science Foundation of China(No.81430101)。
文摘Objective:Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma(HCC),and Chinese herbal medicine has also been used to manage advanced HCC.The present work evaluates the effectiveness and safety of Jiedu(JD)Granule,a compound of traditional Chinese herbal medicine,side-by-side with sorafenib for the treatment of advance HCC.Methods:Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018.The primary endpoint was overall survival(OS).The secondary endpoints were progression-free survival(PFS)and safety.Propensity score matching(PSM)analysis was used to control for possible selection bias from the study group allocation process.Results:Of the 325 patients included,161 received JD Granule and 164 received sorafenib.No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib(P>0.05).Median OS of the two study groups was 6.83 months(95%confidence interval[CI]:5.83–9.47)in the group receiving JD Granule and 8 months(95%CI:6.67–9.80)in the group receiving sorafenib,with half-,1-and 2-year survival rates of 53.6%,31.2%and 13.2%vs 60.1%,35.5%and 14.2%,respectively.Even after PSM,the median survival time did not differ between the JD Granule group(9.03 months;95%CI:6.37–14.2)and the sorafenib group(7.93 months;95%CI:6.5–9.97),with comparable half-,1-and 2-year survival rates.The most common adverse events(AEs)were diarrhea(13.7%)and fatigue(5.6%)in the JD Granule group,and hand-foot skin reaction(46.3%)and diarrhea(36.6%)in the sorafenib group.The JD Granule was more cost-effective than sorafenib treatment for advanced HCC.Conclusion:Compared to sorafenib,JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.