BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD...BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.展开更多
Combination therapy is a promising approach to address the challenge of antimicrobial resistance,and computational models have been proposed for predicting drug–drug interactions.Most existing models rely on drug sim...Combination therapy is a promising approach to address the challenge of antimicrobial resistance,and computational models have been proposed for predicting drug–drug interactions.Most existing models rely on drug similarity measures based on characteristics such as chemical structure and the mechanism of action.In this study,we focus on the network structure itself and propose a drug similarity measure based on drug–drug interaction networks.We explore the potential applications of this measure by combining it with unsupervised learning and semi-supervised learning approaches.In unsupervised learning,drugs can be grouped based on their interactions,leading to almost monochromatic group–group interactions.In addition,drugs within the same group tend to have similar mechanisms of action(MoA).In semi-supervised learning,the similarity measure can be utilized to construct affinity matrices,enabling the prediction of unknown drug–drug interactions.Our method exceeds existing approaches in terms of performance.Overall,our experiments demonstrate the effectiveness and practicability of the proposed similarity measure.On the one hand,when combined with clustering algorithms,it can be used for functional annotation of compounds with unknown MoA.On the other hand,when combined with semi-supervised graph learning,it enables the prediction of unknown drug–drug interactions.展开更多
Background:A traditional Chinese medicine formula,Youdujing(YDJ)ointment,is widely used for treatment of human papilloma virus-related diseases,such as cervical cancer.However,the underlying mechanisms by which active...Background:A traditional Chinese medicine formula,Youdujing(YDJ)ointment,is widely used for treatment of human papilloma virus-related diseases,such as cervical cancer.However,the underlying mechanisms by which active compounds of YDJ alleviates cervical cancer are still unclear.Methods:We applied a comprehensive network pharmacology approach to explore the key mechanisms of YDJ by integrating potential target identification,network analysis,and enrichment analysis into classical molecular docking procedures.First,we used network and enrichment analyses to identify potential therapeutic targets.Second,we performed molecular docking to investigate the potential active compounds of YDJ.Finally,we carried out a network-based analysis to unravel potentially effective drug combinations.Results:Network analysis yielded four potential therapeutic targets:ESRI,NFKB1,TNF,and AKT1.Molecular docking highlighted that these proteins may interact with four potential active compounds of YDJ:E4,Y2,Y20,and Y21.Finally,we found that Y2 or Y21 can act alone or together with E4 to trigger apoptotic cascades via the mitochondrial apoptotic pathway and estrogen receptors.Conclusion:Our study not only explained why YDJ is effective for cervical cancer treatment,but also lays a strong foundation for future clinical studies based on this traditional medicine.展开更多
基金The study was reviewed and approved by the Fourth Hospital of Hebei Medical University Institutional Review Board(Approval No.2019082).
文摘BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.
基金National Natural Science Foundation of China,Grant/Award Number:62372208,61772226Science and Technology Development Program of Jilin Province,Grant/Award Number:20210204133YY。
文摘Combination therapy is a promising approach to address the challenge of antimicrobial resistance,and computational models have been proposed for predicting drug–drug interactions.Most existing models rely on drug similarity measures based on characteristics such as chemical structure and the mechanism of action.In this study,we focus on the network structure itself and propose a drug similarity measure based on drug–drug interaction networks.We explore the potential applications of this measure by combining it with unsupervised learning and semi-supervised learning approaches.In unsupervised learning,drugs can be grouped based on their interactions,leading to almost monochromatic group–group interactions.In addition,drugs within the same group tend to have similar mechanisms of action(MoA).In semi-supervised learning,the similarity measure can be utilized to construct affinity matrices,enabling the prediction of unknown drug–drug interactions.Our method exceeds existing approaches in terms of performance.Overall,our experiments demonstrate the effectiveness and practicability of the proposed similarity measure.On the one hand,when combined with clustering algorithms,it can be used for functional annotation of compounds with unknown MoA.On the other hand,when combined with semi-supervised graph learning,it enables the prediction of unknown drug–drug interactions.
基金This research received funding support from the National Science and Technology Major Project(2018ZX10201002).
文摘Background:A traditional Chinese medicine formula,Youdujing(YDJ)ointment,is widely used for treatment of human papilloma virus-related diseases,such as cervical cancer.However,the underlying mechanisms by which active compounds of YDJ alleviates cervical cancer are still unclear.Methods:We applied a comprehensive network pharmacology approach to explore the key mechanisms of YDJ by integrating potential target identification,network analysis,and enrichment analysis into classical molecular docking procedures.First,we used network and enrichment analyses to identify potential therapeutic targets.Second,we performed molecular docking to investigate the potential active compounds of YDJ.Finally,we carried out a network-based analysis to unravel potentially effective drug combinations.Results:Network analysis yielded four potential therapeutic targets:ESRI,NFKB1,TNF,and AKT1.Molecular docking highlighted that these proteins may interact with four potential active compounds of YDJ:E4,Y2,Y20,and Y21.Finally,we found that Y2 or Y21 can act alone or together with E4 to trigger apoptotic cascades via the mitochondrial apoptotic pathway and estrogen receptors.Conclusion:Our study not only explained why YDJ is effective for cervical cancer treatment,but also lays a strong foundation for future clinical studies based on this traditional medicine.
