BACKGROUND Hepatocellular carcinoma(HCC)is a malignant disease with high incidence and mortality worldwide.This study focuses on the TP53 target protein to investigate the potential therapeutic effect of tetrahydrocur...BACKGROUND Hepatocellular carcinoma(HCC)is a malignant disease with high incidence and mortality worldwide.This study focuses on the TP53 target protein to investigate the potential therapeutic effect of tetrahydrocurcumin(THC)on HCC and its mechanism of action.The research hypothesis is that THC can inhibit the proliferation,migration,and invasion of HCC cells,and promote their apoptosis by regulating the TP53 target protein.AIM To explore the mechanism by which THC inhibits HCC cell proliferation via the TP53 signaling pathway.METHODS Potential targets of THC and HCC were identified from multiple databases.The core targets were subjected to analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases,and visualization processing,using the online platform Metascape to identify the key molecules and signaling pathways involved in the action of THC against HCC.The molecular mechanisms of action of THC against TP53 in the inhibition of HCC cells were verified using cell counting kit-8,Transwell,apoptosis,and western blotting assays.RESULTS Molecular docking results showed that THC had a high score for the TP53 target protein.In vitro experiments indicated that THC effectively inhibited the proliferation and migration of HCC cells,and affected the expression levels of TP53,MDM2,cyclin B,Bax,Bcl-2,caspase-9,and caspase-3.CONCLUSION THC induces the apoptosis of HCC cells through the TP53 signaling pathway,thereby inhibiting their proliferation and migration.展开更多
Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function ...Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 k Da viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.展开更多
Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damag...Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.展开更多
The anonymity of the darknet makes it attractive to secure communication lines from censorship.The analysis,monitoring,and categorization of Internet network traffic are essential for detecting darknet traffic that ca...The anonymity of the darknet makes it attractive to secure communication lines from censorship.The analysis,monitoring,and categorization of Internet network traffic are essential for detecting darknet traffic that can generate a comprehensive characterization of dangerous users and assist in tracing malicious activities and reducing cybercrime.Furthermore,classifying darknet traffic is essential for real-time applications such as the timely monitoring of malware before attacks occur.This paper presents a two-stage deep network chain for detecting and classifying darknet traffic.In the first stage,anonymized darknet traffic,including VPN and Tor traffic related to hidden services provided by darknets,is detected.In the second stage,traffic related to VPNs and Tor services is classified based on their respective applications.The methodology of this paper was verified on a benchmark dataset containing VPN and Tor traffic.It achieved an accuracy of 96.8%and 94.4%in the detection and classification stages,respectively.Optimization and parameter tuning were performed in both stages to achieve more accurate results,enabling practitioners to combat alleged malicious activities and further detect such activities after outbreaks.In the classification stage,it was observed that the misclassifications were due to the audio and video streaming commonly used in shared real-time protocols.However,in cases where it is desired to distinguish between such activities accurately,the presented deep chain classifier can accommodate additional classifiers.Furthermore,additional classifiers could be added to the chain to categorize specific activities of interest further.展开更多
Objective:To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma(HCC)by network pharmacology and experimental in vitro validation.Methods:The predicti...Objective:To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma(HCC)by network pharmacology and experimental in vitro validation.Methods:The predictive targets of curcumin or HCC were collected from several databases.the identified overlapping targets were crossed with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)platform.Two of the candidate pathways were selected to conduct an experimental verification.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium(MTT)assay was used to determine the effect of curcumin on the viability of Hep G2 and LO2 cells.The apoptosis and autophagy of Hep G2 cells were respectively detected by flow cytometry and transmission electron microscopy.Besides,western blot and real-time polymerase chain reaction(PCR)were employed to verify the p53 apoptotic pathway and adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)autophagy pathway.Hep G2 cells were pretreated with pifithrin-α(PFT-α)and GSK690693 for further investigation.Results:The 167 pathways analyzed by KEGG included apoptosis,autophagy,p53,and AMPK pathways.The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug,regulation of apoptotic pathway,and so on.The in vitro experiments also confirmed that curcumin can inhibit the growth of Hep G2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway.Furthermore,the protein and messenger RNA(m RNA)of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group.The damage-regulated autophagy modulator(DRAM)in the PFT-α-pretreated group was downregulated,and p62 in the GSK690693-pretreated group was upregulated.Conclusions:Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1(ULK1)autophagy pathway,in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.展开更多
White blood cells(WBCs)are a vital part of the immune system that protect the body from different types of bacteria and viruses.Abnormal cell growth destroys the body’s immune system,and computerized methods play a v...White blood cells(WBCs)are a vital part of the immune system that protect the body from different types of bacteria and viruses.Abnormal cell growth destroys the body’s immune system,and computerized methods play a vital role in detecting abnormalities at the initial stage.In this research,a deep learning technique is proposed for the detection of leukemia.The proposed methodology consists of three phases.Phase I uses an open neural network exchange(ONNX)and YOLOv2 to localize WBCs.The localized images are passed to Phase II,in which 3D-segmentation is performed using deeplabv3 as a base network of the pre-trained Xception model.The segmented images are used in Phase III,in which features are extracted using the darknet-53 model and optimized using Bhattacharyya separately criteria to classify WBCs.The proposed methodology is validated on three publically available benchmark datasets,namely ALL-IDB1,ALL-IDB2,and LISC,in terms of different metrics,such as precision,accuracy,sensitivity,and dice scores.The results of the proposed method are comparable to those of recent existing methodologies,thus proving its effectiveness.展开更多
Objective:Myocardial ischemia/reperfusion injury(MIRI)is an obstacle to the success of cardiac reperfusion therapy.This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.Methods...Objective:Myocardial ischemia/reperfusion injury(MIRI)is an obstacle to the success of cardiac reperfusion therapy.This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.Methods:Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery,and administered luteolin.The myocardial infarct size,myocardial enzyme levels,and cardiac function were measured.Latent targets and signaling pathways were screened using network pharmacology and molecular docking.Then,proteins related to the p53 signaling pathway,apoptosis and oxidative stress were measured.Hypoxia/reoxygenation(HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro.In addition,a p53 agonist and an inhibitor were used to investigate the mechanism.Results:Luteolin reduced the myocardial infarcted size and myocardial enzymes,and restored cardiac function in MIRI mice.Network pharmacology identified p53 as a hub target.The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties.Additionally,luteolin halted the activation of p53,and prevented both apoptosis and oxidative stress in myocardial tissue in vivo.Furthermore,luteolin inhibited cell apoptosis,JC-1 monomer formation,and reactive oxygen species elevation in HR-incubated HL1 cells in vitro.Finally,the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model,and both luteolin and the p53 inhibitor pifithrin-a demonstrated a similar therapeutic effect in the MIRI mice.Conclusion:Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway.Please cite this article as:Zhai P,Ouyang XH,Yang ML,Lin L,Li JY,Li YM,Cheng X,Zhu R,Hu DS.Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway.J Integr Med.2024;22(6):652–664.展开更多
Background:Xihuang pill is a kind of traditional Chinese medicine,which has been widely used in the treatment of kinds of cancer.However,there is still a lack of systematic understanding of the molecular mechanism of ...Background:Xihuang pill is a kind of traditional Chinese medicine,which has been widely used in the treatment of kinds of cancer.However,there is still a lack of systematic understanding of the molecular mechanism of Xihuang pill in the treatment of liver cancer.In this work,we aim to explore the molecular mechanism of Xihuang pill in treating liver cancer.Methods:The functional components in Xihuang pill were collected from Traditional Chinese Medicine Database and Analysis Platform.The target genes of these components were also collected using Traditional Chinese Medicine Database and Analysis Platform.The target genes of liver cancer were predicted using GeneCards database.The intersecting genes were then analyzed with Venn diagrams.Kyoto Encyclopedia of Genes and Genomes and Database for Annotation,Visualization,and Integrated Discovery were used to analyze the pathway.Then,cell counting kit-8 was used to measure the half-maximal inhibitory concentration of Xihuang pills.The living dead cell staining method was used to observe the survival of cells.HepG2 cell apoptosis was tested by flow cytometry with fluorescein isothiocyanate/propidium iodide double staining method,and then the mitochondrial damage was also detected by flow cytometry.The expression of target genes was detected by quantitative real-time polymerase chain reaction.Results:A total of 130 compounds and 198 genes were identified as potential active ingredients and putative liver cancer‑related targets.We obtained 1,899 disease targets and 297 transcriptome targets from the database.Six drug-disease intersecting genes,CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3 were obtained.They are enrichment in apoptosis,PI3K-AKT signaling pathway,MAPK signaling pathway,pathways in cancer and p53 signaling pathway.Besides,it was found that the apoptosis rate of the HepG2 cells in Xihuang pill treated group was significantly higher than that of the control group.And the apoptosis rate gradually increased in a dose dependent manner of Xihuang pill treatment.Xihuang pill also induced the mitochondrial membrane potential damage.Compared with the control group,the expression level of CCNB1 and BIRC5 was induced,while the expression level of IGF2 was reduced after Xihuang pill treatment.Conclusion:Xihuang pill may act on six proteins(CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3)and cover multiple pathways to form a therapeutic network to treat liver cancer.展开更多
The main purpose of YOLOv3,aiming to improve the detection speed and accuracy from current detection models,is to predict the center coordinates of(x,y)from the Bounding Box and its length,width through multiple layer...The main purpose of YOLOv3,aiming to improve the detection speed and accuracy from current detection models,is to predict the center coordinates of(x,y)from the Bounding Box and its length,width through multiple layers of VGG Convolutional Neural Network(VGG-CNN)and uses the Darknet lightweight framework to process images at a faster speed.More specifically,our model has been reduced part of YOLOv3's complex and computationally intensive procedures and improved its algorithms to maintain the efficiency and accuracy of object detection.By this method,it performs a higher quality on mass object detection tasks with fewer detection errors.展开更多
基金The Central Government Guides Local Science and Technology Development Fund,No.2023JH6/100100021Liaoning Province Education Department Foundation of China,No.JYTMS20231393 and No.LJ212410164032+2 种基金Scientific Research Project of the Liaoning Province Education Department,No.SYYX2019015Science and Technology Foundation of Shenyang Medical College,No.20171004the Science and Technology Innovation Fund for Master Students of Shenyang Medical College,No.Y20220509.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a malignant disease with high incidence and mortality worldwide.This study focuses on the TP53 target protein to investigate the potential therapeutic effect of tetrahydrocurcumin(THC)on HCC and its mechanism of action.The research hypothesis is that THC can inhibit the proliferation,migration,and invasion of HCC cells,and promote their apoptosis by regulating the TP53 target protein.AIM To explore the mechanism by which THC inhibits HCC cell proliferation via the TP53 signaling pathway.METHODS Potential targets of THC and HCC were identified from multiple databases.The core targets were subjected to analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases,and visualization processing,using the online platform Metascape to identify the key molecules and signaling pathways involved in the action of THC against HCC.The molecular mechanisms of action of THC against TP53 in the inhibition of HCC cells were verified using cell counting kit-8,Transwell,apoptosis,and western blotting assays.RESULTS Molecular docking results showed that THC had a high score for the TP53 target protein.In vitro experiments indicated that THC effectively inhibited the proliferation and migration of HCC cells,and affected the expression levels of TP53,MDM2,cyclin B,Bax,Bcl-2,caspase-9,and caspase-3.CONCLUSION THC induces the apoptosis of HCC cells through the TP53 signaling pathway,thereby inhibiting their proliferation and migration.
基金supported by the National Natural Science Foundation of China (No. 81601762)the National Science and Technology Major Project of Infectious Diseases (No. 2017ZX10304402)+1 种基金the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2017ZX09101005-005-003)the Scientific Research Foundation of State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics (No. 2016ZY005)
文摘Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 k Da viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.
基金Project supported by the National Natural Science Foundation of China (Grant No. 10875049)the Key Project of Chinese Ministry of Education (Grant No. 108096)the Programme of Introducing Talents of Discipline to Universities (Grant No. B08033)
文摘Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.
文摘The anonymity of the darknet makes it attractive to secure communication lines from censorship.The analysis,monitoring,and categorization of Internet network traffic are essential for detecting darknet traffic that can generate a comprehensive characterization of dangerous users and assist in tracing malicious activities and reducing cybercrime.Furthermore,classifying darknet traffic is essential for real-time applications such as the timely monitoring of malware before attacks occur.This paper presents a two-stage deep network chain for detecting and classifying darknet traffic.In the first stage,anonymized darknet traffic,including VPN and Tor traffic related to hidden services provided by darknets,is detected.In the second stage,traffic related to VPNs and Tor services is classified based on their respective applications.The methodology of this paper was verified on a benchmark dataset containing VPN and Tor traffic.It achieved an accuracy of 96.8%and 94.4%in the detection and classification stages,respectively.Optimization and parameter tuning were performed in both stages to achieve more accurate results,enabling practitioners to combat alleged malicious activities and further detect such activities after outbreaks.In the classification stage,it was observed that the misclassifications were due to the audio and video streaming commonly used in shared real-time protocols.However,in cases where it is desired to distinguish between such activities accurately,the presented deep chain classifier can accommodate additional classifiers.Furthermore,additional classifiers could be added to the chain to categorize specific activities of interest further.
基金supported by the General Project of Shaanxi Science and Technology Plan(No.2021JM-472)the Key Laboratory Project of Education Department of Shaanxi Province(Nos.21JS014 and 21JS007)+1 种基金the Subject Innovation Team of Shaanxi University of Chinese Medicine(No.2019YL14)the Postgraduate Student’s Innovation Project of Shaanxi University of Chinese Medicine(No.2021-09),China。
文摘Objective:To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma(HCC)by network pharmacology and experimental in vitro validation.Methods:The predictive targets of curcumin or HCC were collected from several databases.the identified overlapping targets were crossed with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)platform.Two of the candidate pathways were selected to conduct an experimental verification.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium(MTT)assay was used to determine the effect of curcumin on the viability of Hep G2 and LO2 cells.The apoptosis and autophagy of Hep G2 cells were respectively detected by flow cytometry and transmission electron microscopy.Besides,western blot and real-time polymerase chain reaction(PCR)were employed to verify the p53 apoptotic pathway and adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)autophagy pathway.Hep G2 cells were pretreated with pifithrin-α(PFT-α)and GSK690693 for further investigation.Results:The 167 pathways analyzed by KEGG included apoptosis,autophagy,p53,and AMPK pathways.The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug,regulation of apoptotic pathway,and so on.The in vitro experiments also confirmed that curcumin can inhibit the growth of Hep G2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway.Furthermore,the protein and messenger RNA(m RNA)of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group.The damage-regulated autophagy modulator(DRAM)in the PFT-α-pretreated group was downregulated,and p62 in the GSK690693-pretreated group was upregulated.Conclusions:Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1(ULK1)autophagy pathway,in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.
基金This research was supported by Korea Institute for Advancement of Technology(KIAT)grant funded by the Korea Government(MOTIE)(P0012724,The Competency Development Program for Industry Specialist)the Soonchunhyang University Research Fund.
文摘White blood cells(WBCs)are a vital part of the immune system that protect the body from different types of bacteria and viruses.Abnormal cell growth destroys the body’s immune system,and computerized methods play a vital role in detecting abnormalities at the initial stage.In this research,a deep learning technique is proposed for the detection of leukemia.The proposed methodology consists of three phases.Phase I uses an open neural network exchange(ONNX)and YOLOv2 to localize WBCs.The localized images are passed to Phase II,in which 3D-segmentation is performed using deeplabv3 as a base network of the pre-trained Xception model.The segmented images are used in Phase III,in which features are extracted using the darknet-53 model and optimized using Bhattacharyya separately criteria to classify WBCs.The proposed methodology is validated on three publically available benchmark datasets,namely ALL-IDB1,ALL-IDB2,and LISC,in terms of different metrics,such as precision,accuracy,sensitivity,and dice scores.The results of the proposed method are comparable to those of recent existing methodologies,thus proving its effectiveness.
基金financially supported by grants from the National Natural Science Foundation of China(No.82104488,81974249,82274317,and 82161138003)。
文摘Objective:Myocardial ischemia/reperfusion injury(MIRI)is an obstacle to the success of cardiac reperfusion therapy.This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.Methods:Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery,and administered luteolin.The myocardial infarct size,myocardial enzyme levels,and cardiac function were measured.Latent targets and signaling pathways were screened using network pharmacology and molecular docking.Then,proteins related to the p53 signaling pathway,apoptosis and oxidative stress were measured.Hypoxia/reoxygenation(HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro.In addition,a p53 agonist and an inhibitor were used to investigate the mechanism.Results:Luteolin reduced the myocardial infarcted size and myocardial enzymes,and restored cardiac function in MIRI mice.Network pharmacology identified p53 as a hub target.The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties.Additionally,luteolin halted the activation of p53,and prevented both apoptosis and oxidative stress in myocardial tissue in vivo.Furthermore,luteolin inhibited cell apoptosis,JC-1 monomer formation,and reactive oxygen species elevation in HR-incubated HL1 cells in vitro.Finally,the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model,and both luteolin and the p53 inhibitor pifithrin-a demonstrated a similar therapeutic effect in the MIRI mice.Conclusion:Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway.Please cite this article as:Zhai P,Ouyang XH,Yang ML,Lin L,Li JY,Li YM,Cheng X,Zhu R,Hu DS.Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway.J Integr Med.2024;22(6):652–664.
文摘Background:Xihuang pill is a kind of traditional Chinese medicine,which has been widely used in the treatment of kinds of cancer.However,there is still a lack of systematic understanding of the molecular mechanism of Xihuang pill in the treatment of liver cancer.In this work,we aim to explore the molecular mechanism of Xihuang pill in treating liver cancer.Methods:The functional components in Xihuang pill were collected from Traditional Chinese Medicine Database and Analysis Platform.The target genes of these components were also collected using Traditional Chinese Medicine Database and Analysis Platform.The target genes of liver cancer were predicted using GeneCards database.The intersecting genes were then analyzed with Venn diagrams.Kyoto Encyclopedia of Genes and Genomes and Database for Annotation,Visualization,and Integrated Discovery were used to analyze the pathway.Then,cell counting kit-8 was used to measure the half-maximal inhibitory concentration of Xihuang pills.The living dead cell staining method was used to observe the survival of cells.HepG2 cell apoptosis was tested by flow cytometry with fluorescein isothiocyanate/propidium iodide double staining method,and then the mitochondrial damage was also detected by flow cytometry.The expression of target genes was detected by quantitative real-time polymerase chain reaction.Results:A total of 130 compounds and 198 genes were identified as potential active ingredients and putative liver cancer‑related targets.We obtained 1,899 disease targets and 297 transcriptome targets from the database.Six drug-disease intersecting genes,CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3 were obtained.They are enrichment in apoptosis,PI3K-AKT signaling pathway,MAPK signaling pathway,pathways in cancer and p53 signaling pathway.Besides,it was found that the apoptosis rate of the HepG2 cells in Xihuang pill treated group was significantly higher than that of the control group.And the apoptosis rate gradually increased in a dose dependent manner of Xihuang pill treatment.Xihuang pill also induced the mitochondrial membrane potential damage.Compared with the control group,the expression level of CCNB1 and BIRC5 was induced,while the expression level of IGF2 was reduced after Xihuang pill treatment.Conclusion:Xihuang pill may act on six proteins(CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3)and cover multiple pathways to form a therapeutic network to treat liver cancer.
文摘The main purpose of YOLOv3,aiming to improve the detection speed and accuracy from current detection models,is to predict the center coordinates of(x,y)from the Bounding Box and its length,width through multiple layers of VGG Convolutional Neural Network(VGG-CNN)and uses the Darknet lightweight framework to process images at a faster speed.More specifically,our model has been reduced part of YOLOv3's complex and computationally intensive procedures and improved its algorithms to maintain the efficiency and accuracy of object detection.By this method,it performs a higher quality on mass object detection tasks with fewer detection errors.
