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
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
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
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
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
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
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
BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related deaths worldwide.As liver cancer often presents no noticeable symptoms in its early stages,most patients are diagnosed at an advance...BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related deaths worldwide.As liver cancer often presents no noticeable symptoms in its early stages,most patients are diagnosed at an advanced stage,complicating treatment.Therefore,the identification of new biomarkers is crucial for the early detection and treatment of HCC.Research on exportin-5(XPO5)could offer new avenues for early diagnosis and improve treatment strategies.AIM To explore the role of XPO5 in HCC progression and its potential as a prognostic biomarker.METHODS This study assessed XPO5 mRNA expression in HCC using The Cancer Genome Atlas,TIMER,and International Cancer Genome Consortium databases,correlating it with clinical profiles and disease progression.We performed in vitro experiments to examine the effect of XPO5 on liver cell growth.Gene Set Enrichment Analysis,Kyoto Encyclopedia of Genes and Genomes,and Gene Ontology were used to elucidate the biological roles and signaling pathways.We also evaluated XPO5’s impact on immune cell infiltration and validated its prognostic potential using machine learning.RESULTS XPO5 was significantly upregulated in HCC tissues,correlating with tumor grade,T-stage,and overall survival,indicating poor prognosis.Enrichment analyses linked high XPO5 expression with tumor immunity,particularly CD4 T cell memory activation and macrophage M0 infiltration.Drug sensitivity tests identified potential therapeutic agents such as MG-132,paclitaxel,and WH-4-023.Overexpression of XPO5 in HCC cells,compared to normal liver cells,was confirmed by western blotting and quantitative real-time polymerase chain reaction.The lentiviral transduction-mediated knockdown of XPO5 significantly reduced cell proliferation and metastasis.Among the various machine learning algorithms,the C5.0 decision tree algorithm achieved accuracy rates of 95.5%in the training set and 92.0%in the validation set.CONCLUSION Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is significantly associated with immune cell infiltration.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
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 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 phytoestrogen puerarin has been shown to protect neurons and astrocytes in the brain, and is therefore an attractive drug in the treatment of Alzheimer’s disease, Parkinson’s disease and cerebral ischemia. Wheth...The phytoestrogen puerarin has been shown to protect neurons and astrocytes in the brain, and is therefore an attractive drug in the treatment of Alzheimer’s disease, Parkinson’s disease and cerebral ischemia. Whether puerarin exhibits the same biological processes in neurons and astro-cytesin vitro has rarely been reported. In this study, cortical neurons and astrocytes of newborn Sprague-Dawley rats were separated, identiifed and co-cultured in a system based on Transwell membranes. The retention time and distribution of puerarin in each cell type was detected by lfuorescence spectrophotometry and lfuorescence microscope. The concentration of puerarin in both co-cultured and separately cultured neurons was greater than that of astrocytes. Puerarin concentration reached a maximum 20 minutes after it was added. At 60 minutes after its addi-tion, a scant amount of drug was detected in astrocytes; however in both separately cultured and co-cultured neurons, the concentration of puerarin achieved a stable level of about 12.8 ng/mL. The results indicate that puerarin had a higher concentration and longer retention time in neu-rons than that observed in astrocytes.展开更多
The locking plate and percutaneous crossing metallic screws and crossing absorbable screws have been used clinically to treat intra-articular calcaneal fractures, but little is known about the biomechanical difference...The locking plate and percutaneous crossing metallic screws and crossing absorbable screws have been used clinically to treat intra-articular calcaneal fractures, but little is known about the biomechanical differences between them. This study compared the biomechanical stability of calcaneal fractures fixed using a locking plate and crossing screws. Three-dimensional finite-element models of intact and fractured calcanei were developed based on the CT images of a cadaveric sample. Surgeries were simulated on models of Sanders type III calcaneal fractures to produce accurate postoperative models fixed by the three implants. A vertical force was applied to the superior surface of the subtalar joint to simulate the stance phase of a walking gait. This model was validated by an in vitro experiment using the same calcaneal sample. The intact calcaneus showed greater stiffness than the fixation models. Of the three fixations, the locking plate produced the greatest stiffness and the highest von Mises stress peak. The micromotion of the fracture fixated with the locking plate was similar to that of the fracture fixated with the metallic screws but smaller than that fixated with the absorbable screws. Fixation with both plate and crossing screws can be used to treat intra-articular calcaneal fractures. In general, fixation with crossing metallic screws is preferable because it provides sufficient stability with less stress shielding.展开更多
Artificial gut models including both the gastric and intestinal phases have been used in poultry research for decades to predict the digestibility of nutrients,the efficacy of feed enzymes and additives,and caecal fer...Artificial gut models including both the gastric and intestinal phases have been used in poultry research for decades to predict the digestibility of nutrients,the efficacy of feed enzymes and additives,and caecal fermentation.However,the models used in the past are static and cannot be used to predict interactions between the feed,gut environment and microbiome.It is imperative that a standard artificial gut model for poultry is established,to enable these interactions to be examined without continual reliance on animals.To ensure the validity of an artificial model,it should be validated with in vivo studies.This review describes current practices in the use of artificial guts in research,their importance in poultry nutrition studies and highlights an opportunity to develop a dynamic gut model for poultry to reduce the number of in vivo experiments.展开更多
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.
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.
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.
基金Supported by the Scientific Research Project of Jiangsu Health Committee,No.M2022083Natural Science Foundation of Jiangsu Province,No.BK20230742+1 种基金Open Project of Key Laboratory of Environmental Medicine Engineering of Ministry of Education,No.2022EME001Laboratory of Jiangsu Provincial Medical Key Discipline,No.ZDXK202249.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related deaths worldwide.As liver cancer often presents no noticeable symptoms in its early stages,most patients are diagnosed at an advanced stage,complicating treatment.Therefore,the identification of new biomarkers is crucial for the early detection and treatment of HCC.Research on exportin-5(XPO5)could offer new avenues for early diagnosis and improve treatment strategies.AIM To explore the role of XPO5 in HCC progression and its potential as a prognostic biomarker.METHODS This study assessed XPO5 mRNA expression in HCC using The Cancer Genome Atlas,TIMER,and International Cancer Genome Consortium databases,correlating it with clinical profiles and disease progression.We performed in vitro experiments to examine the effect of XPO5 on liver cell growth.Gene Set Enrichment Analysis,Kyoto Encyclopedia of Genes and Genomes,and Gene Ontology were used to elucidate the biological roles and signaling pathways.We also evaluated XPO5’s impact on immune cell infiltration and validated its prognostic potential using machine learning.RESULTS XPO5 was significantly upregulated in HCC tissues,correlating with tumor grade,T-stage,and overall survival,indicating poor prognosis.Enrichment analyses linked high XPO5 expression with tumor immunity,particularly CD4 T cell memory activation and macrophage M0 infiltration.Drug sensitivity tests identified potential therapeutic agents such as MG-132,paclitaxel,and WH-4-023.Overexpression of XPO5 in HCC cells,compared to normal liver cells,was confirmed by western blotting and quantitative real-time polymerase chain reaction.The lentiviral transduction-mediated knockdown of XPO5 significantly reduced cell proliferation and metastasis.Among the various machine learning algorithms,the C5.0 decision tree algorithm achieved accuracy rates of 95.5%in the training set and 92.0%in the validation set.CONCLUSION Our analysis shows that XPO5 expression is a reliable prognostic indicator for patients with HCC and is significantly associated with immune cell infiltration.
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.
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.
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 the National Natural Science Foundation of China,No.31402237,81473549the Fundamental Research Funds for Central Universities in China,No.XDJK2014C058,XDJK2014D023,XDJK2015D016+2 种基金a grant from the National Key New Drug Development Project of China,No.2014ZX09304-306-04the Fundamental and Front Research Funds of Chongqing of China,No.CSTC2014jcyj A80023a grant from the Natural Science Foundation of Chongqing of China,No.CSTC2012jj A10012
文摘The phytoestrogen puerarin has been shown to protect neurons and astrocytes in the brain, and is therefore an attractive drug in the treatment of Alzheimer’s disease, Parkinson’s disease and cerebral ischemia. Whether puerarin exhibits the same biological processes in neurons and astro-cytesin vitro has rarely been reported. In this study, cortical neurons and astrocytes of newborn Sprague-Dawley rats were separated, identiifed and co-cultured in a system based on Transwell membranes. The retention time and distribution of puerarin in each cell type was detected by lfuorescence spectrophotometry and lfuorescence microscope. The concentration of puerarin in both co-cultured and separately cultured neurons was greater than that of astrocytes. Puerarin concentration reached a maximum 20 minutes after it was added. At 60 minutes after its addi-tion, a scant amount of drug was detected in astrocytes; however in both separately cultured and co-cultured neurons, the concentration of puerarin achieved a stable level of about 12.8 ng/mL. The results indicate that puerarin had a higher concentration and longer retention time in neu-rons than that observed in astrocytes.
基金supported by the Shanghai Municipal Commission of Health and Family Planning(20144Y0250,20134Y207)the National Natural Science Foundation of China(11302154,11272273)The Hong Kong Research Grant Council GRF(PolyU152216/14E,PolyU5326/11E)
文摘The locking plate and percutaneous crossing metallic screws and crossing absorbable screws have been used clinically to treat intra-articular calcaneal fractures, but little is known about the biomechanical differences between them. This study compared the biomechanical stability of calcaneal fractures fixed using a locking plate and crossing screws. Three-dimensional finite-element models of intact and fractured calcanei were developed based on the CT images of a cadaveric sample. Surgeries were simulated on models of Sanders type III calcaneal fractures to produce accurate postoperative models fixed by the three implants. A vertical force was applied to the superior surface of the subtalar joint to simulate the stance phase of a walking gait. This model was validated by an in vitro experiment using the same calcaneal sample. The intact calcaneus showed greater stiffness than the fixation models. Of the three fixations, the locking plate produced the greatest stiffness and the highest von Mises stress peak. The micromotion of the fracture fixated with the locking plate was similar to that of the fracture fixated with the metallic screws but smaller than that fixated with the absorbable screws. Fixation with both plate and crossing screws can be used to treat intra-articular calcaneal fractures. In general, fixation with crossing metallic screws is preferable because it provides sufficient stability with less stress shielding.
文摘Artificial gut models including both the gastric and intestinal phases have been used in poultry research for decades to predict the digestibility of nutrients,the efficacy of feed enzymes and additives,and caecal fermentation.However,the models used in the past are static and cannot be used to predict interactions between the feed,gut environment and microbiome.It is imperative that a standard artificial gut model for poultry is established,to enable these interactions to be examined without continual reliance on animals.To ensure the validity of an artificial model,it should be validated with in vivo studies.This review describes current practices in the use of artificial guts in research,their importance in poultry nutrition studies and highlights an opportunity to develop a dynamic gut model for poultry to reduce the number of in vivo experiments.
