Serum pharmacochemistry of traditional Chinese medicine has become a more accurate and rapidly developing reasonable way to analyze the effective material basis of traditional Chinese medicine in recent years. Through...Serum pharmacochemistry of traditional Chinese medicine has become a more accurate and rapidly developing reasonable way to analyze the effective material basis of traditional Chinese medicine in recent years. Through this method, we can select very complex Chinese medicine components and clarify the effective substances consistent with the main functions, and then separate and purify effective ingredients in traditional Chinese medicine, so as to explain the material basis of the drug effect and prove the rationality and principle of action of Chinese medicine compounds. It can show the multi-component and multi-target characteristic of traditional Chinese medicine, and after analyzing the migrating components of serum, we can explore the direct effective substances that act on the patient’s body, so as to accelerate and accurately complete the in-depth study of the effective substances of Chinese medicine.展开更多
Background:The Qingjiehuagong decoction(QJHGD),which has been used in clinical trials to treat acute pancreatitis(AP),has demonstrated encouraging results.Methods:In this particular investigation,we used both metabolo...Background:The Qingjiehuagong decoction(QJHGD),which has been used in clinical trials to treat acute pancreatitis(AP),has demonstrated encouraging results.Methods:In this particular investigation,we used both metabolomics and network pharmacology to investigate the fundamental processes and targets that QJHGFD employs to cure AP.Results:Using a cerulein-induced rat model of AP,we showed that QJHGD effectively improved pancreatic tissue damage and reduced serum levels of AMY,LPS,IL-1β,IL-6,IL-8 and TNF-α.In total,28 blood entry compounds derived from QJHGD were identified by ultra-performance liquid chromatography-high resolution mass spectrometry technology.The intersecting target genes of 108 genes associated with identified compounds in QJHGD and AP disease genes were identified using a network pharmacology approach.The protein interaction network revealed AKT1,TNF-α,IL-6,VEGFA,and TP53 as important targets.Gene ontology analysis showed that response to stimulus,molecular function regulator and organelle part were the main functions,and Kyoto Encyclopedia of Genes and Genomes analysis showed that 20 pathways such as AGE-RAGE signaling pathway in diabetic complications and the IL-17 signaling pathway were the main pathways involved in the anti-AP effects of QJHGD.Thirty-two potential metabolic markers and 13 possible metabolic pathways were identified by metabolomics analysis.Combined network pharmacological analysis revealed that QJHGD affects four metabolic pathways(tryptophan metabolism;glycolysis and gluconeogenesis metabolism;valine,leucine and isoleucine degradation metabolism;the urea cycle and metabolism of arginine,proline,glutamate,aspartate and asparagine),five metabolites(indole-3-acetate,pyruvate,methylmalonate,L-citrulline,N-acetyl-l-glutamate)and four related targets(AKT1,ALDH2,NOS2,NOS3)to combat inflammation.The strong affinity of QJHGD’s interactions with its primary targets was established by molecular docking and molecular dynamics simulations.Conclusion:This research investigate the critical targets and mechanisms of QJHGFD for treating AP.The results of this investigation provide novel tactics and complementary techniques for the clinical treatment of AP.展开更多
Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid no...Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.展开更多
In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cas...In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weighted correlation network analysis provide the basis of this integration[11-13].The occurrence of strong correlations between classified metabolites and co-expression transcripts implies either various roles of metabolites or linkages between metabolic pathways and the immune system.展开更多
BACKGROUND Rectal carcinoma(RC),one of the most common malignancies globally,presents an increasing incidence and mortality year by year,especially among young people,which seriously affects the prognosis and quality ...BACKGROUND Rectal carcinoma(RC),one of the most common malignancies globally,presents an increasing incidence and mortality year by year,especially among young people,which seriously affects the prognosis and quality of life of patients.At present,dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters and serum carbohydrate antigen 19-9(CA19-9)and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC.However,the accuracy of these evaluation modalities still needs further research.This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC.AIM To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers(TMs)in assessing pathological processes and prognosis of RC patients.METHODS A retrospective analysis was performed on 104 RC patients treated at Yantai Yuhuangding Hospital from May 2018 to January 2022.Patients were categorized into stages T1,T2,T3,and T4,depending on their T stage and differentiation degree.In addition,they were assigned to low(L group)and moderate-high differentiation(M+H group)groups based on their differentiation degree.The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared.In addition,the value of DCE-MRI parameters[volume transfer constant(Ktrans),rate constant(Kep),and extravascular extracellular volume fraction(Ve)in assessing the differentiation and T staging of RC patients was discussed.Furthermore,the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed.RESULTS Ktrans,Ve,CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M+H Group,respectively(P<0.05).The areas under the curve(AUCs)of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages,respectively,and 0.672 and 0.725 in diagnosing moderate-high and low differentiation,respectively.The AUC of DCE-MRI parameters(Ktrans+Ve)in the diagnosis of high and low stages was 0.742,and the AUC in diagnosing moderate-high and low differentiation was 0.769.The AUCs of CA19-9 and CA-125 were 0.773 and 0.802 in the diagnosis of high and low stages,respectively,and 0.834 and 0.796 in diagnosing moderate-high and low differentiation,respectively.Then,we combined DCE-MRI(Ktrans+Ve)parameters with CA19-9 and CA-125 and found that the AUC of DCE-MRI parameters plus serum TMs was 0.836 in the diagnosis of high and low stages and 0.946 in the diagnosis of moderate-high and low differentiation.According to the Delong test,the AUC of DCE-MRI parameters plus serum TMs increased significantly compared with serum TMs alone in the diagnosis of T stage and differentiation degree(P<0.001).CONCLUSION The levels of the DCE-MRI parameters Ktrans and Ve and the serum TMs CA19-9 and CA125 all increase with increasing T stage and decreasing differentiation degree of RC and can be used as indices to evaluate the differentiation degree of RC in clinical practice.Moreover,the combined evaluation of the above indices has a better effect and more obvious clinical value,providing important guiding importance for clinical condition judgment and treatment selection.展开更多
Background: Following coronary artery bypass grafting (CABG), delirium emerges as a prevalent complication. This study aimed to assess the correlation between elevated serum cortisol levels and the occurrence of posto...Background: Following coronary artery bypass grafting (CABG), delirium emerges as a prevalent complication. This study aimed to assess the correlation between elevated serum cortisol levels and the occurrence of postoperative delirium subsequent to off-pump CABG. Methods: Conducted in the Department of Cardiac Surgery at BSMMU from October 2020 to September 2022, this comparative cross-sectional study included a total of 44 participants. Subjects, meeting specific criteria, were purposefully assigned to two groups based on off-pump CABG. Group A (n = 22) consisted of patients with normal serum cortisol levels, while Group B (n = 22) comprised individuals with high serum cortisol levels on the first postoperative day. Delirium onset was assessed at the bedside in the ICU on the 1st, 2nd, 3rd, 4th, and 5th postoperative days using standard tools, namely the Richmond Agitation Sedation score (RASS) and The Confusion Assessment Method (CAM-ICU). Data were collected based on the presence or absence of delirium. Statistical analysis utilized SPSS version 26.0, employing an independent Student’s t-test for continuous data and chi-square and Fischer’s exact test for categorical data. A p-value ≤ 0.05 was considered statistically significant. Results: Group-A had a mean age of 54.50 ± 17.97, and Group-B had a mean age of 55.22 ± 15.45, both with a male predominance (81.81% and 86.36% respectively). The mean serum cortisol level was significantly higher in Group B (829.71 ± vs. 389.98 ± 68.77). Postoperative delirium occurred in 27.3% of Group B patients, statistically significant compared to the 4.5% in Group A. However, patients in Group B who developed delirium experienced significantly longer postoperative ICU and hospital stays (79.29 ± 12.27 vs. 11.44 ± 2.85, p ≤ 0.05). There was one mortality in Group B, which was statistically not significant. Conclusion: This study observed a significant association between elevated serum cortisol levels in the postoperative period and the occurrence of postoperative delirium after off-pump coronary artery bypass grafting.展开更多
In this study,the impacts of egg consumption on mice model of metabolic syndrome(Met S)were comparatively investigated.Mice were divided into five groups(n=8):normal diet group(ND),high-fat diet group(HFD),HFD with wh...In this study,the impacts of egg consumption on mice model of metabolic syndrome(Met S)were comparatively investigated.Mice were divided into five groups(n=8):normal diet group(ND),high-fat diet group(HFD),HFD with whole egg group(WE),HFD with free-yolk egg substitute group(YFES),and HFD with lovastatin group(Lov).Main biochemical indexes and a non-targeted lipidomic analysis were employed to insight the lipid profile changes in serum.It was revealed that WE could significantly improve serum biochemical indexes by reducing body weight,low-density lipoprotein cholesterol(LDL-C)and total cholesterol(TC),while increasing high-density lipoprotein cholesterol.YFES exhibited remarkably better performance in increasing phosphatidylglycerol and phosphatidic acids,while decreasing phosphatidylinositol than WE.A total of 50 differential lipids biomarkers tightly related to glycerophospholipids metabolism were screened out.Carnitine C18:2 and C12:1,SM(d18:0/12:0),and SM(d18:1/14:1)were significantly upregulated in YFES compared to WE.YFES reduced expression of SREBP-1c and Cpt1a,while did not affect the expression of PPAR-α.Sphingomyelin biomarkers were positively related to the TC(|r|>0.6),while PPAR-αwas negatively correlated with triglyceride and LDL-C levels.To sum up,YFES attenuated HFD-induced Met S by improving the serum phospholipids,which account for its modulation of glycerophospholipid metabolism.展开更多
BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal ...BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.展开更多
BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,...BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.展开更多
Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrha...Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrhage.This study aims to investigate the treatment mechanism of BHD to provide a basis for its clinical application in hypertension treatment.Methods:Network pharmacology analysis and cell culture experiments were performed to explore the potential proteins and mechanisms of action of BHD against hypertension.Bioactive compounds related to BHD were screened,and relevant targets associated with hypertension and BHD were retrieved.Molecular docking technology was used to identify the effective signaling pathway based on the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network cores.Lastly,the effects and mechanisms of BHD on salt-sensitive hypertensive endothelial cells were investigated.Results:Ninety-three potential therapeutic targets for BHD and salt-sensitive hypertension were found to be closely associated with the PI3K/Akt/eNOS signaling pathway and oxidative stress.Cell experiments further indicated the pivotal role of endothelial cells in hypertension,and validation analysis showed that BHD significantly preserved cell morphology,suppressed oxidative stress reactions,activated the PI3K/Akt/eNOS signaling pathways,preserved normal endothelial cell function,and reduced cell apoptosis.Conclusion:BHD effectively activates the PI3K/Akt/VEGF signaling pathway,attenuates oxidative stress-induced injury in endothelial cells exposed to high salt levels,and mitigates apoptosis,supporting the use of traditional Chinese medicine BHD in the treatment of salt-sensitive hypertension.展开更多
BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To in...BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.展开更多
BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationsh...BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationship between the serum BA profile and colonic polyps.AIM To study the serum BA profile detection results of patients with colonic polyps,and analyze the correlation between BA and colonic polyps.METHODS From January 1,2022,to June 1,2023,204 patients with colonic polyps who were diagnosed and treated at Zhongda Hospital Southeast University were chosen as the study subjects,and 135 non-polyp people who underwent physical examination were chosen as the control group.Gathering all patients'clinical information,typical biochemical indicators,and BA profile.RESULTS Compared with the control group,the serum levels of taurocholic acid,glycocholic acid,glycochenodeoxycholic acid,and taurochenodeoxycholic acid in the colonic polyp group were significantly higher than those in the control group,while the content of deoxycholic acid(DCA)was lower than that in the control group(P<0.05).When colonic polyps were analyzed as subgroups,it was shown that there was a strong correlation between changes in the BA profile and polyp diameter,location,morphology,pathological kind,etc.CONCLUSION The serum BA profile showed significant changes in patients with colonic polyps,with a significant increase in primary conjugated BA content and a decrease in secondary free bile acid DCA content.There is a certain correlation between primary free BA and pathological parameters of polyps.展开更多
Objective: This study aims to investigate the potential targets of diosgenin for the treatment of Alzheimer's disease (AD) and Coronavirus Disease 2019 (COVID-19) through the utilization of bioinformatics, network...Objective: This study aims to investigate the potential targets of diosgenin for the treatment of Alzheimer's disease (AD) and Coronavirus Disease 2019 (COVID-19) through the utilization of bioinformatics, network pharmacology, and molecular docking techniques. Methods: Differential expression genes (DEGs) shared by AD and COVID-19 were enriched by bioinformatics. Additionally, regulatory networks were analyzed to identify key genes in the Transcription Factor (TF) of both diseases. The networks were visualized using Cytoscape. Utilizing the DGIdb database, an investigation was conducted to identify potential drugs capable of treating both Alzheimer's disease (AD) and COVID-19. Subsequently, a Venn diagram analysis was performed using the drugs associated with AD and COVID-19 in the CTD database, leading to the identification of diosgenin as a promising candidate for the treatment of both AD and COVID-19.SEA, SuperPred, Swiss Target Prediction and TCMSP were used to predict the target of diosgenin in the treatment of AD and COVID-19, and the target of diosgenin in the treatment of AD and COVID-19 was determined by Wayne diagram intersection analysis with the differentially expressed genes of AD and COVID- 19. Their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed jointly. Genomes The Protein Protein Interaction (PPI) network of these drug targets was constructed, and core targets with the highest correlation were screened out. The binding of diosgenin to these core targets was analyzed by molecular docking. Results: Through enrichment and cluster analysis, it was found that the biological processes, pathways and diseases enriched by DEGs in AD and COVID-19 were all related to inflammation and immune regulation. These common DEGs and Trust databases were used to construct AD and COVID-19 TFs regulatory networks. Diosgenin was predicted as a potential drug for the treatment of AD and COVID-19 by network pharmacology, and 36 targets of diosgenin for the treatment of AD and 27 targets for COVID-19 were revealed. The six core targets with the highest correlation were selected for molecular docking with diosgenin using CytohHubba to calculate the scores. Conclusions: This study firstly revealed that the common TFs regulatory network of AD and COVID-19, and predicted and verified diosgenin as a potential drug for the treatment of AD and COVID-19. The binding of diosgenin to the core pharmacological targets for the treatment of AD and COVID-19 was determined by molecular docking, which provides a theoretical basis for developing a new approach to clinical treatment of AD and COVID-19.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but...BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but its therapeutic mech-anisms have not been systematically investigated.AIM Radix Salviae(Danshen in pinin),a traditional Chinese medicine(TCM),is widely used to treat DPN in China.However,the mechanism through which Radix Salviae treats DPN remains unclear.Therefore,we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology.METHODS The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform.The genes associated with DPN were obtained from the Gene Cards and OMIM databases,a drug-com-position-target-disease network was constructed,and a protein–protein inter-action network was subsequently constructed to screen the main targets.Gene Ontology(GO)functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes(KEGG)using Bioconductor.RESULTS A total of 56 effective components,108 targets and 4581 DPN-related target genes of Radix Salviae were screened.Intervention with Radix Salviae for DPN mainly involved 81 target genes.The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways.CONCLUSION These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway.Therefore,Danshen may affect DPN by regulating inflammation and apoptosis.展开更多
Background:Sanhua decoction has significant effects in the treatment of stroke.The study of the Sanhua decoction material benchmark was carried out to analyze the value transfer relationship between the Chinese herbal...Background:Sanhua decoction has significant effects in the treatment of stroke.The study of the Sanhua decoction material benchmark was carried out to analyze the value transfer relationship between the Chinese herbal pieces and the substance benchmark.Methods:Network pharmacology was employed to investigate the potential active components and molecular mechanisms of Sanhua decoction in the treatment of stroke.15 batches of Sanhua decoction lyophilized powder were prepared using traditional formulas and subjected to high-performance liquid chromatography analysis to generate fingerprints of the Sanhua decoction substance benchmarks.Then,a multi-component quantitative analysis method was established,allowing for the simultaneous determination of ten components,to study the transfer of quantity values between pieces and substance benchmarks.Results:60 active ingredients were screened from Sanhua decoction by network pharmacology,of which gallic acid,magnolol honokiol,physcion,and aloe-emodin may have a greater effect than other active components.63 key targets and 134 pathways were predicted as the potential mechanism of Sanhua decoction in treating stroke.The fingerprint similarity of the Sanhua decoction substance benchmarks was found to be good among the 15 batches,confirming the 19 common peaks.The content of the 10 components was basically consistent.The components’transfer rates were within 30%of their respective means.Conclusions:This study provided a comprehensive and reliable strategy for the quality evaluation of Sanhua decoction substance benchmarks and held significant importance in improving its application value.展开更多
Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sit...Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.展开更多
Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enter...Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.展开更多
[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to ...[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO databases.The Chinese medicine compound-target network was constructed by Cytoscape software.Besides,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also performed.Afterward,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the databases.After the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating keloids.Hub genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling pathways.The molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling pathways.The present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.展开更多
BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated...BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.展开更多
Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal ex...Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.展开更多
基金Supported by University Continuing Education Teaching Reform Project(2019jxjj67)Provincial quality engineering project of"Traditional Chinese Medicine Technique and Skilled Master Studio"of Anhui Provincial Department of Education in 2020(2020dsgzs23)+3 种基金Key Natural Science Research Project of Higher Learning Institutions in Anhui Province in 2018(KJ2018A0884)Key Natural Science Research Projects of Colleges and Universities in Anhui Province in 2020(KJ2020A1014)Key Project of 2020 Applied Technology Research and Collaborative Innovation Center of Bozhou Vocational and Technical College(BZZX202001)Key Research Project of Bozhou Vocational and Technical College in 2020(BYK2002)。
文摘Serum pharmacochemistry of traditional Chinese medicine has become a more accurate and rapidly developing reasonable way to analyze the effective material basis of traditional Chinese medicine in recent years. Through this method, we can select very complex Chinese medicine components and clarify the effective substances consistent with the main functions, and then separate and purify effective ingredients in traditional Chinese medicine, so as to explain the material basis of the drug effect and prove the rationality and principle of action of Chinese medicine compounds. It can show the multi-component and multi-target characteristic of traditional Chinese medicine, and after analyzing the migrating components of serum, we can explore the direct effective substances that act on the patient’s body, so as to accelerate and accurately complete the in-depth study of the effective substances of Chinese medicine.
文摘Background:The Qingjiehuagong decoction(QJHGD),which has been used in clinical trials to treat acute pancreatitis(AP),has demonstrated encouraging results.Methods:In this particular investigation,we used both metabolomics and network pharmacology to investigate the fundamental processes and targets that QJHGFD employs to cure AP.Results:Using a cerulein-induced rat model of AP,we showed that QJHGD effectively improved pancreatic tissue damage and reduced serum levels of AMY,LPS,IL-1β,IL-6,IL-8 and TNF-α.In total,28 blood entry compounds derived from QJHGD were identified by ultra-performance liquid chromatography-high resolution mass spectrometry technology.The intersecting target genes of 108 genes associated with identified compounds in QJHGD and AP disease genes were identified using a network pharmacology approach.The protein interaction network revealed AKT1,TNF-α,IL-6,VEGFA,and TP53 as important targets.Gene ontology analysis showed that response to stimulus,molecular function regulator and organelle part were the main functions,and Kyoto Encyclopedia of Genes and Genomes analysis showed that 20 pathways such as AGE-RAGE signaling pathway in diabetic complications and the IL-17 signaling pathway were the main pathways involved in the anti-AP effects of QJHGD.Thirty-two potential metabolic markers and 13 possible metabolic pathways were identified by metabolomics analysis.Combined network pharmacological analysis revealed that QJHGD affects four metabolic pathways(tryptophan metabolism;glycolysis and gluconeogenesis metabolism;valine,leucine and isoleucine degradation metabolism;the urea cycle and metabolism of arginine,proline,glutamate,aspartate and asparagine),five metabolites(indole-3-acetate,pyruvate,methylmalonate,L-citrulline,N-acetyl-l-glutamate)and four related targets(AKT1,ALDH2,NOS2,NOS3)to combat inflammation.The strong affinity of QJHGD’s interactions with its primary targets was established by molecular docking and molecular dynamics simulations.Conclusion:This research investigate the critical targets and mechanisms of QJHGFD for treating AP.The results of this investigation provide novel tactics and complementary techniques for the clinical treatment of AP.
基金The College Students’ Innovative Entrepreneurial Training Plan Program [202110594024]Science and Technology Plan Projects of Liuzhou [2022CAC0299]
文摘Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.
文摘In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weighted correlation network analysis provide the basis of this integration[11-13].The occurrence of strong correlations between classified metabolites and co-expression transcripts implies either various roles of metabolites or linkages between metabolic pathways and the immune system.
文摘BACKGROUND Rectal carcinoma(RC),one of the most common malignancies globally,presents an increasing incidence and mortality year by year,especially among young people,which seriously affects the prognosis and quality of life of patients.At present,dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)parameters and serum carbohydrate antigen 19-9(CA19-9)and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC.However,the accuracy of these evaluation modalities still needs further research.This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC.AIM To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers(TMs)in assessing pathological processes and prognosis of RC patients.METHODS A retrospective analysis was performed on 104 RC patients treated at Yantai Yuhuangding Hospital from May 2018 to January 2022.Patients were categorized into stages T1,T2,T3,and T4,depending on their T stage and differentiation degree.In addition,they were assigned to low(L group)and moderate-high differentiation(M+H group)groups based on their differentiation degree.The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared.In addition,the value of DCE-MRI parameters[volume transfer constant(Ktrans),rate constant(Kep),and extravascular extracellular volume fraction(Ve)in assessing the differentiation and T staging of RC patients was discussed.Furthermore,the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed.RESULTS Ktrans,Ve,CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M+H Group,respectively(P<0.05).The areas under the curve(AUCs)of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages,respectively,and 0.672 and 0.725 in diagnosing moderate-high and low differentiation,respectively.The AUC of DCE-MRI parameters(Ktrans+Ve)in the diagnosis of high and low stages was 0.742,and the AUC in diagnosing moderate-high and low differentiation was 0.769.The AUCs of CA19-9 and CA-125 were 0.773 and 0.802 in the diagnosis of high and low stages,respectively,and 0.834 and 0.796 in diagnosing moderate-high and low differentiation,respectively.Then,we combined DCE-MRI(Ktrans+Ve)parameters with CA19-9 and CA-125 and found that the AUC of DCE-MRI parameters plus serum TMs was 0.836 in the diagnosis of high and low stages and 0.946 in the diagnosis of moderate-high and low differentiation.According to the Delong test,the AUC of DCE-MRI parameters plus serum TMs increased significantly compared with serum TMs alone in the diagnosis of T stage and differentiation degree(P<0.001).CONCLUSION The levels of the DCE-MRI parameters Ktrans and Ve and the serum TMs CA19-9 and CA125 all increase with increasing T stage and decreasing differentiation degree of RC and can be used as indices to evaluate the differentiation degree of RC in clinical practice.Moreover,the combined evaluation of the above indices has a better effect and more obvious clinical value,providing important guiding importance for clinical condition judgment and treatment selection.
文摘Background: Following coronary artery bypass grafting (CABG), delirium emerges as a prevalent complication. This study aimed to assess the correlation between elevated serum cortisol levels and the occurrence of postoperative delirium subsequent to off-pump CABG. Methods: Conducted in the Department of Cardiac Surgery at BSMMU from October 2020 to September 2022, this comparative cross-sectional study included a total of 44 participants. Subjects, meeting specific criteria, were purposefully assigned to two groups based on off-pump CABG. Group A (n = 22) consisted of patients with normal serum cortisol levels, while Group B (n = 22) comprised individuals with high serum cortisol levels on the first postoperative day. Delirium onset was assessed at the bedside in the ICU on the 1st, 2nd, 3rd, 4th, and 5th postoperative days using standard tools, namely the Richmond Agitation Sedation score (RASS) and The Confusion Assessment Method (CAM-ICU). Data were collected based on the presence or absence of delirium. Statistical analysis utilized SPSS version 26.0, employing an independent Student’s t-test for continuous data and chi-square and Fischer’s exact test for categorical data. A p-value ≤ 0.05 was considered statistically significant. Results: Group-A had a mean age of 54.50 ± 17.97, and Group-B had a mean age of 55.22 ± 15.45, both with a male predominance (81.81% and 86.36% respectively). The mean serum cortisol level was significantly higher in Group B (829.71 ± vs. 389.98 ± 68.77). Postoperative delirium occurred in 27.3% of Group B patients, statistically significant compared to the 4.5% in Group A. However, patients in Group B who developed delirium experienced significantly longer postoperative ICU and hospital stays (79.29 ± 12.27 vs. 11.44 ± 2.85, p ≤ 0.05). There was one mortality in Group B, which was statistically not significant. Conclusion: This study observed a significant association between elevated serum cortisol levels in the postoperative period and the occurrence of postoperative delirium after off-pump coronary artery bypass grafting.
基金supported by the Applied Basic Research of Shanxi Province(201901D211381)the Innovation-driven Development Capacity Enhancement Fund of Shanxi Province(SXYBKY2019041)+2 种基金National Key Research and Development Program(2021YFD1600604-03)Shanxi Scholarship Council of China(2021-068)Shanxi Agricultural University High-Level Talent Project(2021XG013)。
文摘In this study,the impacts of egg consumption on mice model of metabolic syndrome(Met S)were comparatively investigated.Mice were divided into five groups(n=8):normal diet group(ND),high-fat diet group(HFD),HFD with whole egg group(WE),HFD with free-yolk egg substitute group(YFES),and HFD with lovastatin group(Lov).Main biochemical indexes and a non-targeted lipidomic analysis were employed to insight the lipid profile changes in serum.It was revealed that WE could significantly improve serum biochemical indexes by reducing body weight,low-density lipoprotein cholesterol(LDL-C)and total cholesterol(TC),while increasing high-density lipoprotein cholesterol.YFES exhibited remarkably better performance in increasing phosphatidylglycerol and phosphatidic acids,while decreasing phosphatidylinositol than WE.A total of 50 differential lipids biomarkers tightly related to glycerophospholipids metabolism were screened out.Carnitine C18:2 and C12:1,SM(d18:0/12:0),and SM(d18:1/14:1)were significantly upregulated in YFES compared to WE.YFES reduced expression of SREBP-1c and Cpt1a,while did not affect the expression of PPAR-α.Sphingomyelin biomarkers were positively related to the TC(|r|>0.6),while PPAR-αwas negatively correlated with triglyceride and LDL-C levels.To sum up,YFES attenuated HFD-induced Met S by improving the serum phospholipids,which account for its modulation of glycerophospholipid metabolism.
基金Natural Science Foundation of Hebei Province,No.H2018307071Traditional Chinese Medicine Research Plan Project in Hebei Province,No.2022122Hebei Provincial Science and Technology Program,No.17397763D.
文摘BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.
基金supported by the National Natural Science Foundation of China(82172182 and 82102311)Natural Science Foundation of Jiangsu Province(BK20211136)+2 种基金China Postdoctoral Science Foundation(2018M643890 and 2020M683718)Xuzhou Science and Technology Project(KC21215 and KC22136)Development Fund Project of Affiliated Hospital of Xuzhou Medical University(XYFY202232)。
文摘BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.
基金the Liaoning Provincial Science and Technology Plan Project(2023-MSLH-178)the Project Fund of Liaoning Provincial Department of Education(LJKMZ20221315,L202025)+1 种基金the Special Fund of Liaoning Provincial Department of Science and Technology for Central Guidance of Local Science and Technology Development(2018416016)the Project Fund of Liaoning Provincial Department of Human Resources and Social Security"Millions of Talents Program"(2020921097).
文摘Background:Buyang Huanwu decoction(BHD)is a traditional Chinese medicine herbal formula used for treating hypertension,particularly in the later stages of hypertension when it is associated with intracerebral hemorrhage.This study aims to investigate the treatment mechanism of BHD to provide a basis for its clinical application in hypertension treatment.Methods:Network pharmacology analysis and cell culture experiments were performed to explore the potential proteins and mechanisms of action of BHD against hypertension.Bioactive compounds related to BHD were screened,and relevant targets associated with hypertension and BHD were retrieved.Molecular docking technology was used to identify the effective signaling pathway based on the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network cores.Lastly,the effects and mechanisms of BHD on salt-sensitive hypertensive endothelial cells were investigated.Results:Ninety-three potential therapeutic targets for BHD and salt-sensitive hypertension were found to be closely associated with the PI3K/Akt/eNOS signaling pathway and oxidative stress.Cell experiments further indicated the pivotal role of endothelial cells in hypertension,and validation analysis showed that BHD significantly preserved cell morphology,suppressed oxidative stress reactions,activated the PI3K/Akt/eNOS signaling pathways,preserved normal endothelial cell function,and reduced cell apoptosis.Conclusion:BHD effectively activates the PI3K/Akt/VEGF signaling pathway,attenuates oxidative stress-induced injury in endothelial cells exposed to high salt levels,and mitigates apoptosis,supporting the use of traditional Chinese medicine BHD in the treatment of salt-sensitive hypertension.
基金Supported by Ningxia Science and Technology Benefiting People Program,No.2022CMG03064National Natural Science Foundation of China,No.82260879Ningxia Natural Science Foundation,No.2022AAC03144 and 2022AAC02039.
文摘BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.
文摘BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationship between the serum BA profile and colonic polyps.AIM To study the serum BA profile detection results of patients with colonic polyps,and analyze the correlation between BA and colonic polyps.METHODS From January 1,2022,to June 1,2023,204 patients with colonic polyps who were diagnosed and treated at Zhongda Hospital Southeast University were chosen as the study subjects,and 135 non-polyp people who underwent physical examination were chosen as the control group.Gathering all patients'clinical information,typical biochemical indicators,and BA profile.RESULTS Compared with the control group,the serum levels of taurocholic acid,glycocholic acid,glycochenodeoxycholic acid,and taurochenodeoxycholic acid in the colonic polyp group were significantly higher than those in the control group,while the content of deoxycholic acid(DCA)was lower than that in the control group(P<0.05).When colonic polyps were analyzed as subgroups,it was shown that there was a strong correlation between changes in the BA profile and polyp diameter,location,morphology,pathological kind,etc.CONCLUSION The serum BA profile showed significant changes in patients with colonic polyps,with a significant increase in primary conjugated BA content and a decrease in secondary free bile acid DCA content.There is a certain correlation between primary free BA and pathological parameters of polyps.
基金Research and Development and Industrialization Demonstration of Xinjiang Special Medicinal Materials,Antiinfective Drugs and Disinfection Products-Construction of Xinjiang Special Resource Antiinfective Drug Research and Development Platform(No.2021A03002-4)。
文摘Objective: This study aims to investigate the potential targets of diosgenin for the treatment of Alzheimer's disease (AD) and Coronavirus Disease 2019 (COVID-19) through the utilization of bioinformatics, network pharmacology, and molecular docking techniques. Methods: Differential expression genes (DEGs) shared by AD and COVID-19 were enriched by bioinformatics. Additionally, regulatory networks were analyzed to identify key genes in the Transcription Factor (TF) of both diseases. The networks were visualized using Cytoscape. Utilizing the DGIdb database, an investigation was conducted to identify potential drugs capable of treating both Alzheimer's disease (AD) and COVID-19. Subsequently, a Venn diagram analysis was performed using the drugs associated with AD and COVID-19 in the CTD database, leading to the identification of diosgenin as a promising candidate for the treatment of both AD and COVID-19.SEA, SuperPred, Swiss Target Prediction and TCMSP were used to predict the target of diosgenin in the treatment of AD and COVID-19, and the target of diosgenin in the treatment of AD and COVID-19 was determined by Wayne diagram intersection analysis with the differentially expressed genes of AD and COVID- 19. Their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed jointly. Genomes The Protein Protein Interaction (PPI) network of these drug targets was constructed, and core targets with the highest correlation were screened out. The binding of diosgenin to these core targets was analyzed by molecular docking. Results: Through enrichment and cluster analysis, it was found that the biological processes, pathways and diseases enriched by DEGs in AD and COVID-19 were all related to inflammation and immune regulation. These common DEGs and Trust databases were used to construct AD and COVID-19 TFs regulatory networks. Diosgenin was predicted as a potential drug for the treatment of AD and COVID-19 by network pharmacology, and 36 targets of diosgenin for the treatment of AD and 27 targets for COVID-19 were revealed. The six core targets with the highest correlation were selected for molecular docking with diosgenin using CytohHubba to calculate the scores. Conclusions: This study firstly revealed that the common TFs regulatory network of AD and COVID-19, and predicted and verified diosgenin as a potential drug for the treatment of AD and COVID-19. The binding of diosgenin to the core pharmacological targets for the treatment of AD and COVID-19 was determined by molecular docking, which provides a theoretical basis for developing a new approach to clinical treatment of AD and COVID-19.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but its therapeutic mech-anisms have not been systematically investigated.AIM Radix Salviae(Danshen in pinin),a traditional Chinese medicine(TCM),is widely used to treat DPN in China.However,the mechanism through which Radix Salviae treats DPN remains unclear.Therefore,we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology.METHODS The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform.The genes associated with DPN were obtained from the Gene Cards and OMIM databases,a drug-com-position-target-disease network was constructed,and a protein–protein inter-action network was subsequently constructed to screen the main targets.Gene Ontology(GO)functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes(KEGG)using Bioconductor.RESULTS A total of 56 effective components,108 targets and 4581 DPN-related target genes of Radix Salviae were screened.Intervention with Radix Salviae for DPN mainly involved 81 target genes.The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways.CONCLUSION These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway.Therefore,Danshen may affect DPN by regulating inflammation and apoptosis.
基金supported by grants from the Special Project for Transformation of Scientific and Technological Achievements in Qinghai Province(No.2021-SF-150)the National Natural Science Foundation of China(No.82173929).
文摘Background:Sanhua decoction has significant effects in the treatment of stroke.The study of the Sanhua decoction material benchmark was carried out to analyze the value transfer relationship between the Chinese herbal pieces and the substance benchmark.Methods:Network pharmacology was employed to investigate the potential active components and molecular mechanisms of Sanhua decoction in the treatment of stroke.15 batches of Sanhua decoction lyophilized powder were prepared using traditional formulas and subjected to high-performance liquid chromatography analysis to generate fingerprints of the Sanhua decoction substance benchmarks.Then,a multi-component quantitative analysis method was established,allowing for the simultaneous determination of ten components,to study the transfer of quantity values between pieces and substance benchmarks.Results:60 active ingredients were screened from Sanhua decoction by network pharmacology,of which gallic acid,magnolol honokiol,physcion,and aloe-emodin may have a greater effect than other active components.63 key targets and 134 pathways were predicted as the potential mechanism of Sanhua decoction in treating stroke.The fingerprint similarity of the Sanhua decoction substance benchmarks was found to be good among the 15 batches,confirming the 19 common peaks.The content of the 10 components was basically consistent.The components’transfer rates were within 30%of their respective means.Conclusions:This study provided a comprehensive and reliable strategy for the quality evaluation of Sanhua decoction substance benchmarks and held significant importance in improving its application value.
基金Emergency Research Project for Novel Coronavirus(2019-nCoV)Prevention and Control in Shanxi Province(No.202003D31012/GZ)Jingfang Fuyang Key Laboratory of Shanxi Province(No.202104010910011)Shanxi Provincial Health Commission Key Laboratory Construction Project。
文摘Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.
基金supported by National Science Fund for Young Scholars of China (Grant No.82204594).
文摘Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.
基金Supported by Central Government Funds of Guiding Local Scientific and Technological Development for Sichuan Province(2021ZYD0057).
文摘[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO databases.The Chinese medicine compound-target network was constructed by Cytoscape software.Besides,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also performed.Afterward,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the databases.After the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating keloids.Hub genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling pathways.The molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling pathways.The present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.
基金Supported by National Natural Science Foundation of China,No.81573695,No.81860894,and No.81674096Ningxia Key Research and Development Plan Project,No.2021BEG03106.
文摘BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.
基金funding from the Basic Research Project of the Education Department of Shaanxi Province(21JC010,21JP035)the Young and Middle-Aged Scientific Research and Innovation Team of the Shaanxi Provincial Administration of Traditional Chinese Medicine(2022SLRHLJ001)the 2023 Central Financial Transfer Payment Local Project“Innovation and Improvement of Five Types of Hospital Preparations,Such as Roumudan Granules”.
文摘Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.
