BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine t...BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.展开更多
OBJECTIVE To explore mecha⁃nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net⁃work pharmacology combined with in vitro experi⁃ment.METHODS Drug targets were predicted using ...OBJECTIVE To explore mecha⁃nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net⁃work pharmacology combined with in vitro experi⁃ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data⁃bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100μmol·L^(-1))on P-gp activity were monitored in hCMEC/D3 in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans⁃mission regulation,neurotransmitter receptor activity,protein kinase regulation activity,G proteincoupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig⁃naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi⁃cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu⁃lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro⁃tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer⁃ence basis for further exploration of the mecha⁃nisms of imperatorin on regulating P-gp in BBB.展开更多
Background:Primary biliary cholangitis(PBC)is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis.Swertia mussotii Franch.(SMF)is a Tibetan medicine with hepatoprotective and anti-infl...Background:Primary biliary cholangitis(PBC)is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis.Swertia mussotii Franch.(SMF)is a Tibetan medicine with hepatoprotective and anti-inflammatory activities.In this study,the therapeutic effect and potential mechanisms of SMF on PBC were investigated by bioinformatics analysis and in vitro experimental validation,with the aim of promoting the progress of SMF and PBC research.Methods:We first explored the therapeutic effects and key targets of SMF on PBC using a network pharmacology approach,further screened the core targets using the GSE79850 dataset,and finally validated the results using molecular docking techniques and in vitro experiments.Results:By bioinformatics analysis,we identified core targets of SMF for PBC treatment(STAT3,JAK2,TNF-α,and IL-1β)and important signaling pathways:JAK-STAT,TNF,and PI3K-AKT.The molecular docking results showed that the significant components of SMF had good binding properties to the core targets.In vitro experiments showed that SMF extracts improved the extent of epithelial-mesenchymal transition in human intrahepatic biliary epithelial cells and had a significant reversal effect on epithelial-mesenchymal transition process markers and potential targets in PBC.Conclusion:SMF may exert its therapeutic effects on PBC by acting on important targets such as STAT3,JAK2,TNF-α,IL-1β,Vimentin,and E-cadherin and the pathways in which they are involved.展开更多
Objective:To explore the key target molecules and potential mechanisms of oridonin against non-small cell lung cancer(NSCLC).Methods:The target molecules of oridonin were retrieved from Similarity Ensemble Approach(SE...Objective:To explore the key target molecules and potential mechanisms of oridonin against non-small cell lung cancer(NSCLC).Methods:The target molecules of oridonin were retrieved from Similarity Ensemble Approach(SEA),Search Tool for Interacting Chemicals(STITCH),SuperPred and TargetPred databases;target genes associated with the treatment of NSCLC were retrieved from GeneCards,DisGeNET and TTD databases.Then,the overlapping target molecules between the drug and the disease were identified.The protein–protein interaction(PPI)was constructed using the STRING database according to overlapping targets,and Cytoscape was used to screen for key targets.Molecular docking verification were performed using Auto Dock Tools and Py MOL software.Using the DAVID database,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were conducted.The impact of oridonin on the proliferation and apoptosis of NSCLC cells was assessed using cell counting kit-8,cell proliferation Ed U image kit,and Annexin V-FITC/PI apoptosis kit respectively.Moreover,real-time quantitative PCR and Western blot were used to verify the potential mechanisms.Results:Fifty-six target molecules and 12 key target molecules of oridonin involved in NSCLC treatment were identified,including tumor protein 53(TP53),Caspase-3,signal transducer and activator of transcription 3(STAT3),mitogen-activated protein kinase kinase 8(MAPK8),and mammalian target of rapamycin(m TOR).Molecular docking showed that oridonin and its key target molecules bind spontaneously.GO and KEGG enrichment analyses revealed cancer,apoptosis,phosphoinositide-3 kinase/protein kinase B(PI3K/Akt),and other signaling pathways.In vitro experiments showed that oridonin inhibited the proliferation,induced apoptosis,downregulated the expression of Bcl-2 and Akt,and upregulated the expression of Caspase-3.Conclusion:Oridonin can act on multiple targets and pathways to exert its inhibitory effects on NSCLC,and its mechanism may be related to upregulating the expression of Caspase-3 and downregulating the expressions of Akt and Bcl-2.展开更多
The degradation characteristics of high-purity(HP)magnesium(Mg)orthopedic implants under static and cyclic compressive loads(SCL and CCL)remain inadequately understood.This study developed an in vivo loading device ca...The degradation characteristics of high-purity(HP)magnesium(Mg)orthopedic implants under static and cyclic compressive loads(SCL and CCL)remain inadequately understood.This study developed an in vivo loading device capable of applying single SCL and CCL while shielding against unpredictable host movements.In vitro degradation experiments of HP Mg implants were conducted to verify the experimental protocol,and in vivo experiments in rabbit tibiae to observe the degradation characteristics of the implants.Micro-computed tomography and scanning electron microscope were used for three-dimensional reconstruction and surface morphology analysis,respectively.Compared to in vitro specimens,in vivo specimens exhibited significantly higher corrosion rates and more extensive cracking.Cracks in the in vivo specimens gradually penetrated deeper from the loading surface,eventually leading to a rapid structural deterioration;whereas in vitro specimens exhibited more surface-localized cracking and a relatively uniform corrosion pattern.Compared to SCL,CCL accelerated both corrosion and cracking to some extent.These findings provide new insights into the in vivo degradation behavior of Mg-based implants under compressive loading conditions.展开更多
It has been recognized that alpha-fetoprotein (AFP),as an oncofetal antigen, re-expresses in large amounts inadult tumor cells and serves clinically useful purposes asa tumor marker assay. However, its biological acti...It has been recognized that alpha-fetoprotein (AFP),as an oncofetal antigen, re-expresses in large amounts inadult tumor cells and serves clinically useful purposes asa tumor marker assay. However, its biological activiticsare still far from clear. In thc present study, the ability ofAFP to stimulate tumor cell growth was observed by invitro test system. The new finding indicates that AFPcontributes to the generation and development of tumorand is an important target action site of tumor therapy.展开更多
Objective:To study the anti-HCV activity and mechanism of Hehuan Yin aqueous extract.Methods:Huh7.5.1 cells were used to establish the HCV2a virus infection model.Cell survival rate(%)and Renilla Luciferase Assay Kit(...Objective:To study the anti-HCV activity and mechanism of Hehuan Yin aqueous extract.Methods:Huh7.5.1 cells were used to establish the HCV2a virus infection model.Cell survival rate(%)and Renilla Luciferase Assay Kit(%)were calculated by Celltiter-GLO Assay for evaluating CC50,EC50 and SI values.To observe the drug resistance of the virus to different concentrations of Hehuan Yin within 72 hours by detecting luciferase activity,western-blot was used to detect the protein expression levels of NS5A,NS3 and NS5B.Results:the CC50,EC50 and SI of Hehuan Yin against HCV2a were 132.50g/ml,1.90g/ml and 67.90 respectively.The EC50 after 24h,48h and 72h administration were 18g/ml,5.8g/ml and 2.3g/ml respectively.Within the range of drug concentration,the aqueous extract Hehuan Yin had inhibitory effect on the expression of NS5A and NS5B proteins in a dose-effect relationship,but had no obvious effect on the expression of NS3 protein.Conclusion:The aqueous extract of Hehuan Yin may inhibit the replication of HCV2a virus by changing the protein expression levels of NS5A and NS5B,and the virus has no tolerance to the aqueous extract of Hehuan Yin.展开更多
Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency mo...Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency modulation. The high-frequency part was chosen to select the malignant lesion using the specialties of the tumor: the higher conductivity and dielectric constant of the tumor than its host. The electric field selects the tumor, and the low-frequency amplitude modulation polarizes and excites the transmembrane proteins of the malignant cells. The dominant absorption of the energy by the microscopic clusters of the membrane rafts acts like nanoparticle heating. Exciting the membrane produces various apoptotic signals. The processes were modeled using silico and phantom experiments, which proved the concept. The preclinical verification was made in vitro and in vivo, and in the end, clinical proofs validated the method. Our objective is to follow all the development steps from the laboratory to the clinics in a trilogy of articles. This present is the first part, which deals with in silico, phantom, and in vitro research.展开更多
Effects of some methodological factors on in vitro measures of gas production（GP, mL/g DM）, CH4production（mL/g DM） and proportion（% CH4 on total GP） were investigated by meta-analysis. These factors were conside...Effects of some methodological factors on in vitro measures of gas production（GP, mL/g DM）, CH4production（mL/g DM） and proportion（% CH4 on total GP） were investigated by meta-analysis. These factors were considered：pressure in the GP equipment（0 = constant; 1 = increasing）, incubation time（0 = 24; 1 = ≥ 48 h）, time of rumen fluid collection（0 = before feeding; 1 = after feeding of donor animals）, donor species of rumen fluid（0 = sheep; 1 =bovine）, presence of N in the buffer solution（0 = presence; 1 = absence）, and ratio between amount of buffered rumen fluid and feed sample（BRF/FS; 0 = ≤ 130 mL/g DM; 1 = 130–140 mL/g DM; 2 = ≥ 140 mL/g DM）. The NDF content of feed sample incubated（NDF） was considered as a continuous variable. From an initial database of 105 papers, 58 were discarded because one of the above-mentioned factors was not stated. After discarding 17 papers,the final dataset comprised 30 papers（339 observations）. A preliminary mixed model analysis was carried out on experimental data considering the study as random factor. Variables adjusted for study effect were analyzed using a backward stepwise analysis including the above-mentioned variables. The analysis showed that the extension of incubation time and reduction of NDF increased GP and CH4 values. Values of GP and CH4 also increased when rumen fluid was collected after feeding compared to before feeding（＋26.4 and ＋9.0 mL/g DM, for GP and CH4）,from bovine compared to sheep（＋32.8 and ＋5.2 mL/g DM, for GP and CH4）, and when the buffer solution did not contain N（＋24.7 and ＋6.7 mL/g DM for GP and CH4）. The increase of BRF/FS ratio enhanced GP and CH4production（＋7.7 and ＋3.3 mL/g DM per each class of increase, respectively）. In vitro techniques for measuring GP and CH4 production are mostly used as screening methods, thus a full standardization of such techniques is not feasible. However, a greater harmonization of analytical procedures（i.e., a reduction in the number of available protocols） would be useful to facilitate comparison between results of different experiments.展开更多
The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of ...The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of which overlap with GC targets.Key genes,including ESR1,EGFR,CYP3A4,MAPK14,CYP1A2,and CYP2B6,are linked to poor survival in GC patients.Molecular docking con-firmed strong binding affinity of curcumin to these genes.In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823,suggesting its therapeutic potential in GC through multiple targets and pathways.展开更多
Aims:The aim of this study is to develop a prognostic model for hepatocellular carcinoma(HCC)using stemness-related genes(SRGs),while also pinpointing and validating pivotal genes associated with this process.Methods:...Aims:The aim of this study is to develop a prognostic model for hepatocellular carcinoma(HCC)using stemness-related genes(SRGs),while also pinpointing and validating pivotal genes associated with this process.Methods:Utilizing the TCGA and ICGC database,a prognostic stemness-related scores(SRS)for HCC through a combination of WGCNA and machine learning.Bioinformatics analysis evaluated tumor immune infiltration characteristics and drug sensitivity in different SRS subgroups,identifying the key gene TOMM40L.qRT-PCR and IHC were employed to detect the expression level of TOMM40 L.Kaplan-Meier survival analysis assessed the prognostic value of TOMM40L in HCC.In vitro cell experiments explored the influence of TOMM40L on HCC cell progression and stemness.Results:The prognostic model SRS for HCC was developed and validated,incorporating four SRGs:EIF2B4,CDCA8,TCOF1,and TOMM40L.Distinct variations in tumor immune infiltration profiles and drug sensitivity were noted across different SRS subgroups.Elevated TOMM40L levels are notably detected in malignant tissues in contrast to adjacent tissues,with heightened TOMM40L expression correlating with unfavorable prognostic outcomes.In addition,knockdown of TOMM40L significantly inhibited cell progression and stemness.Conclusion:The newly constructed SRS model is a potential biomarker for assessing HCC prognosis,and the key gene TOMM40L exhibits oncogenic properties.展开更多
BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxida...BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxidase(GPX)and the accumulation of lipid peroxides within cells.Ferroptosis is closely related to the occurrence and development of hepatocellular carcinoma(HCC).Chlorogenic acid(CGA),an important bioactive component found in 61 traditional Chinese medicines such as Eucommia ulmoides,has been extensively studied for its effects on various malignant tumors.However,the specific role and potential mechanism of CGA in HCC remain unclear.AIM To elucidate the anti-tumor characteristics and potential mechanisms of CGA in inducing ferroptosis in HCC cells.METHODS The effects of CGA on the proliferation,migration,and invasion of HCC cells were evaluated through in vitro experiments.Bioinformatics analysis combined with network pharmacology was used to study the potential targets and molecular mechanisms of CGA intervention in HCC ferroptosis.In vitro experiments were conducted to verify and explore the anti-HCC effects and mechanisms of CGA through the ferroptosis pathway.RESULTS In vitro experiments showed that CGA dose-dependently inhibited the proliferation,invasion,and migration of HCC cells.Bioinformatics analysis combined with network pharmacology revealed that the pathway of CGA intervention in HCC cell ferroptosis was mainly enriched in the prostaglandin endoperoxide synthase 2(PTGS2)/aldoketo reductase family 1 member C3(AKR1C3)/GPX4 signaling pathway,which was associated with arachidonic acid.In vitro experiments further confirmed that CGA-induced ferroptosis in HCC cells was related to mitochondrial damage through the reprogramming of arachidonic acid metabolism by regulating the PTGS2/AKR1C3/GPX4 signaling pathway.CONCLUSION This study demonstrates that CGA inhibits HCC cell proliferation,migration,and invasion by inducing ferroptosis through the PTGS2/AKR1C3/GPX4 axis,suggesting its potential as a novel ferroptosis inducer or anti-HCC drug.展开更多
Background:Childhood obesity and asthma represent significant worldwide public health challenges with disproportionate impacts on pediatric populations.Pediatric patients with comorbid obesity and asthma frequently de...Background:Childhood obesity and asthma represent significant worldwide public health challenges with disproportionate impacts on pediatric populations.Pediatric patients with comorbid obesity and asthma frequently demonstrate exacerbated clinical manifestations encompassing heightened immunological activation,dysregulated metabolic pathways,and chronic respiratory tract inflammation.Macrophage polarization,particularly the M1 phenotype,is crucial in the development of obesity-related asthma.Methods:Transcriptome microarray data relevant to obesity,asthma,and exercise were extracted from the GEO database,specifically focusing on human samples.Gene expression variance quantification was conducted utilizing the limma analytical toolkit,applying significance thresholds set at P<0.05 alongside a minimum expression variation threshold of 1.5-fold.Additionally,single-cell transcriptomic data from obese asthmatic children were analyzed for cell annotation,interaction mapping,and pseudotime trajectory using R packages(Limma,Seurat,Dplyr,and Magrittr).In vitro experiments,including CCK-8 proliferation assays,cell migration,ROS oxidative stress measurements,and qRT-PCR,were conducted to assess Selenbp1’s role in macrophage M1 polarization.Results:Differential gene expression analysis identified significant transcriptomic changes in obese asthmatic children,particularly elevated Selenbp1 expression,which was closely associated with macrophage M1 polarization.Single-cell sequencing analysis revealed specific cellular subpopulations and interactions,emphasizing Selenbp1’s role in mediating exercise-induced effects.In vitro experiments confirmed Selenbp1’s involvement in altering macrophage activity,highlighting its contribution to disease progression.Conclusion:Research findings reveal that exercise-regulated Selenbp1-mediated modulation of macrophage M1 polarization constitutes a key mechanism underlying pediatric obesity-associated asthma progression.These findings suggest novel molecular targets and provide insights into the therapeutic potential of exercise for treating obese asthmatic children.展开更多
基金West Light Foundation of the Ningxia Key Research and Development Program,No.2023BEG02015High-level Key Discipline Construction Project of State Administration of Traditional Chinese Medicine,No.2022-226+1 种基金Talent Development Projects of Young Qihuang of National Administration of Traditional Chinese Medicine,No.2020-218National Natural Science Foundation of China,No.82374261.
文摘BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.
基金Natural Science Foundation of Hebei Province(H2022206456)Natural Sci⁃ence Foundation of Hebei Province(H2021206449)+1 种基金Undergraduate Innovative Experiment Program of Hebei Medical University(USIP2022173)Undergraduate Innovative Experiment Program of Hebei Medical University(USIP2023107)。
文摘OBJECTIVE To explore mecha⁃nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net⁃work pharmacology combined with in vitro experi⁃ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data⁃bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100μmol·L^(-1))on P-gp activity were monitored in hCMEC/D3 in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans⁃mission regulation,neurotransmitter receptor activity,protein kinase regulation activity,G proteincoupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig⁃naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi⁃cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu⁃lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro⁃tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer⁃ence basis for further exploration of the mecha⁃nisms of imperatorin on regulating P-gp in BBB.
基金supported by the Key project of Chinese Academy of Sciences(Grant No.ZDRW-ZS-2020-2)Innovation Platform Program of Qinghai Province(2021-ZJ-T02),Key Laboratory Project of Qinghai Province(2022-ZJ-Y05)+1 种基金the Natural Science Foundation of China(Grant No.82171863)China Postdoctoral Science Foundation funded project(2021M701642).
文摘Background:Primary biliary cholangitis(PBC)is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis.Swertia mussotii Franch.(SMF)is a Tibetan medicine with hepatoprotective and anti-inflammatory activities.In this study,the therapeutic effect and potential mechanisms of SMF on PBC were investigated by bioinformatics analysis and in vitro experimental validation,with the aim of promoting the progress of SMF and PBC research.Methods:We first explored the therapeutic effects and key targets of SMF on PBC using a network pharmacology approach,further screened the core targets using the GSE79850 dataset,and finally validated the results using molecular docking techniques and in vitro experiments.Results:By bioinformatics analysis,we identified core targets of SMF for PBC treatment(STAT3,JAK2,TNF-α,and IL-1β)and important signaling pathways:JAK-STAT,TNF,and PI3K-AKT.The molecular docking results showed that the significant components of SMF had good binding properties to the core targets.In vitro experiments showed that SMF extracts improved the extent of epithelial-mesenchymal transition in human intrahepatic biliary epithelial cells and had a significant reversal effect on epithelial-mesenchymal transition process markers and potential targets in PBC.Conclusion:SMF may exert its therapeutic effects on PBC by acting on important targets such as STAT3,JAK2,TNF-α,IL-1β,Vimentin,and E-cadherin and the pathways in which they are involved.
文摘Objective:To explore the key target molecules and potential mechanisms of oridonin against non-small cell lung cancer(NSCLC).Methods:The target molecules of oridonin were retrieved from Similarity Ensemble Approach(SEA),Search Tool for Interacting Chemicals(STITCH),SuperPred and TargetPred databases;target genes associated with the treatment of NSCLC were retrieved from GeneCards,DisGeNET and TTD databases.Then,the overlapping target molecules between the drug and the disease were identified.The protein–protein interaction(PPI)was constructed using the STRING database according to overlapping targets,and Cytoscape was used to screen for key targets.Molecular docking verification were performed using Auto Dock Tools and Py MOL software.Using the DAVID database,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were conducted.The impact of oridonin on the proliferation and apoptosis of NSCLC cells was assessed using cell counting kit-8,cell proliferation Ed U image kit,and Annexin V-FITC/PI apoptosis kit respectively.Moreover,real-time quantitative PCR and Western blot were used to verify the potential mechanisms.Results:Fifty-six target molecules and 12 key target molecules of oridonin involved in NSCLC treatment were identified,including tumor protein 53(TP53),Caspase-3,signal transducer and activator of transcription 3(STAT3),mitogen-activated protein kinase kinase 8(MAPK8),and mammalian target of rapamycin(m TOR).Molecular docking showed that oridonin and its key target molecules bind spontaneously.GO and KEGG enrichment analyses revealed cancer,apoptosis,phosphoinositide-3 kinase/protein kinase B(PI3K/Akt),and other signaling pathways.In vitro experiments showed that oridonin inhibited the proliferation,induced apoptosis,downregulated the expression of Bcl-2 and Akt,and upregulated the expression of Caspase-3.Conclusion:Oridonin can act on multiple targets and pathways to exert its inhibitory effects on NSCLC,and its mechanism may be related to upregulating the expression of Caspase-3 and downregulating the expressions of Akt and Bcl-2.
基金supported by National Natural Science Foundation of China[51975317].
文摘The degradation characteristics of high-purity(HP)magnesium(Mg)orthopedic implants under static and cyclic compressive loads(SCL and CCL)remain inadequately understood.This study developed an in vivo loading device capable of applying single SCL and CCL while shielding against unpredictable host movements.In vitro degradation experiments of HP Mg implants were conducted to verify the experimental protocol,and in vivo experiments in rabbit tibiae to observe the degradation characteristics of the implants.Micro-computed tomography and scanning electron microscope were used for three-dimensional reconstruction and surface morphology analysis,respectively.Compared to in vitro specimens,in vivo specimens exhibited significantly higher corrosion rates and more extensive cracking.Cracks in the in vivo specimens gradually penetrated deeper from the loading surface,eventually leading to a rapid structural deterioration;whereas in vitro specimens exhibited more surface-localized cracking and a relatively uniform corrosion pattern.Compared to SCL,CCL accelerated both corrosion and cracking to some extent.These findings provide new insights into the in vivo degradation behavior of Mg-based implants under compressive loading conditions.
文摘It has been recognized that alpha-fetoprotein (AFP),as an oncofetal antigen, re-expresses in large amounts inadult tumor cells and serves clinically useful purposes asa tumor marker assay. However, its biological activiticsare still far from clear. In thc present study, the ability ofAFP to stimulate tumor cell growth was observed by invitro test system. The new finding indicates that AFPcontributes to the generation and development of tumorand is an important target action site of tumor therapy.
基金Natural Foundation of Guangdong Province(No.2018A030313308)。
文摘Objective:To study the anti-HCV activity and mechanism of Hehuan Yin aqueous extract.Methods:Huh7.5.1 cells were used to establish the HCV2a virus infection model.Cell survival rate(%)and Renilla Luciferase Assay Kit(%)were calculated by Celltiter-GLO Assay for evaluating CC50,EC50 and SI values.To observe the drug resistance of the virus to different concentrations of Hehuan Yin within 72 hours by detecting luciferase activity,western-blot was used to detect the protein expression levels of NS5A,NS3 and NS5B.Results:the CC50,EC50 and SI of Hehuan Yin against HCV2a were 132.50g/ml,1.90g/ml and 67.90 respectively.The EC50 after 24h,48h and 72h administration were 18g/ml,5.8g/ml and 2.3g/ml respectively.Within the range of drug concentration,the aqueous extract Hehuan Yin had inhibitory effect on the expression of NS5A and NS5B proteins in a dose-effect relationship,but had no obvious effect on the expression of NS3 protein.Conclusion:The aqueous extract of Hehuan Yin may inhibit the replication of HCV2a virus by changing the protein expression levels of NS5A and NS5B,and the virus has no tolerance to the aqueous extract of Hehuan Yin.
文摘Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency modulation. The high-frequency part was chosen to select the malignant lesion using the specialties of the tumor: the higher conductivity and dielectric constant of the tumor than its host. The electric field selects the tumor, and the low-frequency amplitude modulation polarizes and excites the transmembrane proteins of the malignant cells. The dominant absorption of the energy by the microscopic clusters of the membrane rafts acts like nanoparticle heating. Exciting the membrane produces various apoptotic signals. The processes were modeled using silico and phantom experiments, which proved the concept. The preclinical verification was made in vitro and in vivo, and in the end, clinical proofs validated the method. Our objective is to follow all the development steps from the laboratory to the clinics in a trilogy of articles. This present is the first part, which deals with in silico, phantom, and in vitro research.
基金financed by the project “ARCHAEA- Feeding strategies to reduce methane emissions from dairy cows,”Veneto Region Rural Development Programme (RDP) 2007–2013 “Progetto di Ateneo cod. CPDA 155250”, University of Padova, Italy
文摘Effects of some methodological factors on in vitro measures of gas production（GP, mL/g DM）, CH4production（mL/g DM） and proportion（% CH4 on total GP） were investigated by meta-analysis. These factors were considered：pressure in the GP equipment（0 = constant; 1 = increasing）, incubation time（0 = 24; 1 = ≥ 48 h）, time of rumen fluid collection（0 = before feeding; 1 = after feeding of donor animals）, donor species of rumen fluid（0 = sheep; 1 =bovine）, presence of N in the buffer solution（0 = presence; 1 = absence）, and ratio between amount of buffered rumen fluid and feed sample（BRF/FS; 0 = ≤ 130 mL/g DM; 1 = 130–140 mL/g DM; 2 = ≥ 140 mL/g DM）. The NDF content of feed sample incubated（NDF） was considered as a continuous variable. From an initial database of 105 papers, 58 were discarded because one of the above-mentioned factors was not stated. After discarding 17 papers,the final dataset comprised 30 papers（339 observations）. A preliminary mixed model analysis was carried out on experimental data considering the study as random factor. Variables adjusted for study effect were analyzed using a backward stepwise analysis including the above-mentioned variables. The analysis showed that the extension of incubation time and reduction of NDF increased GP and CH4 values. Values of GP and CH4 also increased when rumen fluid was collected after feeding compared to before feeding（＋26.4 and ＋9.0 mL/g DM, for GP and CH4）,from bovine compared to sheep（＋32.8 and ＋5.2 mL/g DM, for GP and CH4）, and when the buffer solution did not contain N（＋24.7 and ＋6.7 mL/g DM for GP and CH4）. The increase of BRF/FS ratio enhanced GP and CH4production（＋7.7 and ＋3.3 mL/g DM per each class of increase, respectively）. In vitro techniques for measuring GP and CH4 production are mostly used as screening methods, thus a full standardization of such techniques is not feasible. However, a greater harmonization of analytical procedures（i.e., a reduction in the number of available protocols） would be useful to facilitate comparison between results of different experiments.
基金Supported by The College Students’Innovation and Entrepreneurship Competition,No.2024cxcy504 and No.202410459164.
文摘The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of which overlap with GC targets.Key genes,including ESR1,EGFR,CYP3A4,MAPK14,CYP1A2,and CYP2B6,are linked to poor survival in GC patients.Molecular docking con-firmed strong binding affinity of curcumin to these genes.In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823,suggesting its therapeutic potential in GC through multiple targets and pathways.
基金supported by the National Natural Science Foundation of China(No.82370608)Natural Science Foundation of Anhui Province(No.2208085MH204)+5 种基金Natural Science Foundation of Education Department of Anhui Province(No.2022AH040160)Anhui Provincial Special Fund for Clinical Medical Research Transformation(No.202304295107020040)Suzhou Health Commission“Suzhou Health Young Talent”National Mentor Training Program(No.Qngg2023046)Kunshan Social Development Science and Technology Special Fund(No.KS1719)New Coronavirus Pneumonia Research Project of Kunshan First People’s Hospital(First Batch,No.XGF202018)Kunshan First People’s Hospital Medical and Health Science and Technology Innovation Special Project(No.KETDCX202424).
文摘Aims:The aim of this study is to develop a prognostic model for hepatocellular carcinoma(HCC)using stemness-related genes(SRGs),while also pinpointing and validating pivotal genes associated with this process.Methods:Utilizing the TCGA and ICGC database,a prognostic stemness-related scores(SRS)for HCC through a combination of WGCNA and machine learning.Bioinformatics analysis evaluated tumor immune infiltration characteristics and drug sensitivity in different SRS subgroups,identifying the key gene TOMM40L.qRT-PCR and IHC were employed to detect the expression level of TOMM40 L.Kaplan-Meier survival analysis assessed the prognostic value of TOMM40L in HCC.In vitro cell experiments explored the influence of TOMM40L on HCC cell progression and stemness.Results:The prognostic model SRS for HCC was developed and validated,incorporating four SRGs:EIF2B4,CDCA8,TCOF1,and TOMM40L.Distinct variations in tumor immune infiltration profiles and drug sensitivity were noted across different SRS subgroups.Elevated TOMM40L levels are notably detected in malignant tissues in contrast to adjacent tissues,with heightened TOMM40L expression correlating with unfavorable prognostic outcomes.In addition,knockdown of TOMM40L significantly inhibited cell progression and stemness.Conclusion:The newly constructed SRS model is a potential biomarker for assessing HCC prognosis,and the key gene TOMM40L exhibits oncogenic properties.
基金the National Natural Science Foundation of China,No.82074425Natural Foundation of Hunan Province,No.2023JJ30364 and No.2023JJ30361+1 种基金Hunan Provincial Key R&D Program,No.2023SK2057Key Project of Hunan Provincial Administration of Traditional Chinese Medicine,No.A2023042.
文摘BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxidase(GPX)and the accumulation of lipid peroxides within cells.Ferroptosis is closely related to the occurrence and development of hepatocellular carcinoma(HCC).Chlorogenic acid(CGA),an important bioactive component found in 61 traditional Chinese medicines such as Eucommia ulmoides,has been extensively studied for its effects on various malignant tumors.However,the specific role and potential mechanism of CGA in HCC remain unclear.AIM To elucidate the anti-tumor characteristics and potential mechanisms of CGA in inducing ferroptosis in HCC cells.METHODS The effects of CGA on the proliferation,migration,and invasion of HCC cells were evaluated through in vitro experiments.Bioinformatics analysis combined with network pharmacology was used to study the potential targets and molecular mechanisms of CGA intervention in HCC ferroptosis.In vitro experiments were conducted to verify and explore the anti-HCC effects and mechanisms of CGA through the ferroptosis pathway.RESULTS In vitro experiments showed that CGA dose-dependently inhibited the proliferation,invasion,and migration of HCC cells.Bioinformatics analysis combined with network pharmacology revealed that the pathway of CGA intervention in HCC cell ferroptosis was mainly enriched in the prostaglandin endoperoxide synthase 2(PTGS2)/aldoketo reductase family 1 member C3(AKR1C3)/GPX4 signaling pathway,which was associated with arachidonic acid.In vitro experiments further confirmed that CGA-induced ferroptosis in HCC cells was related to mitochondrial damage through the reprogramming of arachidonic acid metabolism by regulating the PTGS2/AKR1C3/GPX4 signaling pathway.CONCLUSION This study demonstrates that CGA inhibits HCC cell proliferation,migration,and invasion by inducing ferroptosis through the PTGS2/AKR1C3/GPX4 axis,suggesting its potential as a novel ferroptosis inducer or anti-HCC drug.
基金funding from Ningxia Hui Autonomous Region’s Key R&D Initiative(Project No.2023BEG03001)alongside provincial-level Natural Science Foundation grants(Project No.2024AAC03444).
文摘Background:Childhood obesity and asthma represent significant worldwide public health challenges with disproportionate impacts on pediatric populations.Pediatric patients with comorbid obesity and asthma frequently demonstrate exacerbated clinical manifestations encompassing heightened immunological activation,dysregulated metabolic pathways,and chronic respiratory tract inflammation.Macrophage polarization,particularly the M1 phenotype,is crucial in the development of obesity-related asthma.Methods:Transcriptome microarray data relevant to obesity,asthma,and exercise were extracted from the GEO database,specifically focusing on human samples.Gene expression variance quantification was conducted utilizing the limma analytical toolkit,applying significance thresholds set at P<0.05 alongside a minimum expression variation threshold of 1.5-fold.Additionally,single-cell transcriptomic data from obese asthmatic children were analyzed for cell annotation,interaction mapping,and pseudotime trajectory using R packages(Limma,Seurat,Dplyr,and Magrittr).In vitro experiments,including CCK-8 proliferation assays,cell migration,ROS oxidative stress measurements,and qRT-PCR,were conducted to assess Selenbp1’s role in macrophage M1 polarization.Results:Differential gene expression analysis identified significant transcriptomic changes in obese asthmatic children,particularly elevated Selenbp1 expression,which was closely associated with macrophage M1 polarization.Single-cell sequencing analysis revealed specific cellular subpopulations and interactions,emphasizing Selenbp1’s role in mediating exercise-induced effects.In vitro experiments confirmed Selenbp1’s involvement in altering macrophage activity,highlighting its contribution to disease progression.Conclusion:Research findings reveal that exercise-regulated Selenbp1-mediated modulation of macrophage M1 polarization constitutes a key mechanism underlying pediatric obesity-associated asthma progression.These findings suggest novel molecular targets and provide insights into the therapeutic potential of exercise for treating obese asthmatic children.
