Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification

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.

Prospects of polyglycolic acid sheets for the treatment of esophageal stricture after esophageal endoscopic submucosal dissection

Esophageal cancer is the seventh most common type of cancer and the sixth leading cause of cancer-related mortality worldwide.Endoscopic submucosal dissection(ESD)is widely used for the resection of early esophageal cancer.However,post-ESD esophageal stricture is a common long-term complication,which requires attention.Patients with post-ESD esophageal stricture often experience dysphagia and require multiple dilatations,which greatly affects their quality of life and increases healthcare costs.Therefore,to manage post-ESD esophageal stricture,researchers are actively exploring various strategies,such as pharmaceutical interventions,endoscopic balloon dilation,and esophageal stenting.Although steroids-based therapy has achieved some success,steroids can lead to complications such as osteoporosis and infection.Meanwhile,endoscopic balloon dilatation is effective in the short term,but is prone to recurrence and perforation.Additionally,esophageal stenting can alleviate the stricture,but is associated with discomfort during stenting and the complication of easy displacement also present challenges.Tissue engineering has evolved rapidly in recent years,and hydrogel materials have good biodegradability and biocompatibility.A novel type of polyglycolic acid(PGA)sheets has been found to be effective in preventing esophageal stricture after ESD,with the advantages of a simple operation and low complication rate.PGA membranes act as a biophysical barrier to cover the wound as well as facilitate the delivery of medications to promote wound repair and healing.However,there is still a lack of multicenter,large-sample randomized controlled clinical studies focused on the treatment of post-ESD esophageal strictures with PGA membrane,which will be a promising direction for future advancements in this field.

Unraveling the therapeutic mechanisms of myristic acid and luteolin 7-rutinoside in oral cancer: insights from network pharmacology and molecular docking analysis

Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its structure as a 14-carbon,unsaturated fatty acid.In this investigation,we endeavor to elucidate the putative mechanisms underlying the therapeutic effects of Myristic Acid and Luteolin 7-rutinoside in the context of oral cancer treatment,employing network pharmacology coupled with molecular docking methodologies.Methods:The protein targets of Myristic Acid and Luteolin 7-rutinoside were identified through a search on the Swiss Target Database.Subsequently,a compound-target network was constructed using Cytoscape 3.9.1.Targets associated with OC were retrieved from the OMIM and GeneCards databases.The overlap between compound targets and OC-related targets was determined,and the resulting shared targets were subjected to protein-protein interaction(PPI)network analysis using the STRING database.Additionally,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the identified targets.Molecular docking were performed to investigate the interactions between the core target and the active compound.Results:The component target network comprises 103 nodes and 102 edges.Among the proteins in the protein-protein interaction(PPI)network,those with higher degrees are TNF,PPARG,and TP53.Analysis through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways indicates that the treatment of OC with Myristic Acid and Luteolin 7-rutinoside primarily involves the regulation of miRNA transcription and inflammatory response.The identified signaling pathways include Pathways in cancer,PPAR signaling pathway,EGFR signaling pathway,and TNF signaling pathway.Molecular docking studies reveal that Luteolin 7-rutinoside and Myristic acid exhibit higher affinity towards TNF,PPARG,TP53,and EGFR.Conclusion:This study reveals the potential molecular mechanism of Myristic Acid and Luteolin 7-rutinoside in the treatment of oral cancer,and provides a reference for subsequent basic research.

Boswellic acids: a review on its pharmacological properties, molecular mechanism and bioavailability

Boswellic acids is a general term for a series of pentacyclic triterpenoid compounds that are isolated from the oleogin resin of the Boswellia genus and serve as the main active ingredient.It exhibits a wide range of biological activities,such as anti-inflammatory,anti-cancer,antibacterial,antiviral,hepatoprotective,neuroprotective,anti-diabetic,and anti-thrombotic properties.As a result,it has gained significant recognition among practitioners of traditional Chinese and Indian medicine.These biological effects may be associated with multiple molecular targets and signal transduction pathways.However,the poor pharmacokinetic properties of the substance lead to lower bioavailability,which affects its effectiveness.To address this issue,scientists have proposed a number of strategies,such as solid dispersions,phytosome®technologies,and novel drug delivery systems.This article aims to provide a comprehensive overview for boswellic acids on the phytochemistry,molecular mechanisms,potential therapeutic applications,and strategies to improve bioavailability.

Exploring the targets and molecular mechanism of glycyrrhetinic acid against diabetic nephropathy based on network pharmacology and molecular docking

BACKGROUND Diabetic nephropathy(DN)stands as the most prevalent chronic microvascular complication of diabetes mellitus.Approximately 50%of DN patients progress to end-stage renal disease,posing a substantial health burden.AIM To employ network pharmacology and molecular docking methods to predict the mechanism by which glycyrrhetinic acid(GA)treats DN,subsequently validating these predictions through experimental means.METHODS The study initially identified GA targets using Pharm Mapper and the TCMSP database.Targets relevant to DN were obtained from the Genecards,OMIM,and TTD databases.The Venny database facilitated the acquisition of intersecting targets between GA and DN.The String database was used to construct a protein interaction network,while DAVID database was used to conducted Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and Gene Ontology(GO)analysis.Molecular docking experiments were performed using Autodock software with selected proteins.Experimental validation was conducted using renal proximal tubular cells(HK-2)as the study subjects.A hyperglycemic environment was simulated using glucose solution,and the effect of GA on cell viability was assessed through the cell counting kit-8 method.Flow cytometry was employed to detect cell cycle and apoptosis,and protein immunoblot(western blot)was used to measure the expression of proteins of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway and insulin resistance pathway,including insulin receptor(INSR),PI3K,p-PI3K,AKT,p-AKT,and glycogen synthase kinase-3(GSK3).RESULTS A total of 186 intersecting targets between GA and DN were identified,which were associated with 144 KEGGrelated enrichment pathways,375 GO biological process entries,45 GO cellular component entries,and 112 GO cellular function entries.Molecular docking demonstrated strong binding of GA to mitogen-activated protein kinase(MAPK)-1,SRC,PIK3R1,HSP90AA1,CASPASE9,HARS,KRAS,and MAPK14.In vitro experiments revealed that GA inhibited HK-2 cell viability,induced cell cycle arrest at the G2/M phase,and reduced apoptosis with increasing drug concentration.Western blot analysis showed that GA differentially up-regulated GSK3 protein expression,up-regulated AKT/p-AKT expression,down-regulated INSR,AKT,p-AKT,PI3K,and p-PI3K protein expression,and reduced p-PI3K/PI3K levels under high glucose conditions.CONCLUSION GA may protect renal intrinsic cells by modulating the PI3K/AKT signaling pathway,thereby inhibiting HK-2 cell viability,reducing HK-2 cell apoptosis,and inducing cell cycle arrest at the G0/G1 phase.

Preparation and Drug-Release Property of Polycaprolactone (PCL)/Polyglycolic Acid (PGA) Composite Masterbatch with Drug of Tea Polyphenols (TPs)

In order to effectively control the drug-release rate of medical textiles,biodegradable polycaprolactone(PCL) and polyglycolic acid(PGA) were blended at various mass ratios to prepare composite masterbatches for medical textiles.The surface morphology and the chemical structure of the masterbatches were analyzed.The crystallization,mass losses,strengths and drug-release rates of the composite masterbatches at different PCL/PGA mass ratios were explored.The results show that the degradation rate of the PGA carrier is obvious higher than that of the PCL carrier,and PCL,PGA and the tea polyphenol(TP) drug just physically mix without chemical reaction.During the degradation,the strength of the composite masterbatches gradually decreases.In addition,the drug-release rates of composite masterbatches at different mass ratios are different,and the more the PGA in the composite masterbatches,the faster the drug release of the composite masterbatches.The drug-release rate of the composite masterbatches can be controlled by adjusting the contents of PCL and PGA.

Effect of polyglycolic acid sheet plus esophageal stent placement in preventing esophageal stricture after endoscopic submucosal dissection in patients with earlystage esophageal cancer: A randomized, controlled trial

AIM To assess the effect of polyglycolic acid(PGA) plus stent placement compared with stent placement alone in the prevention of post-endoscopic submucosal dissection(ESD) esophageal stricture in early-stage esophageal cancer(EC) patients. METHODS Seventy EC patients undergoing ESD were enrolled in this randomized, controlled study. Patients were allocated randomly at a 1:1 ratio into two groups as follows:(1) PGA plus stent group(PGA sheet-coated stent placement was performed); and(2) Stent group(only stent placement was performed). This study was registered on http://www.chictr.org.cn(No. chictrinr-16008709). RESULTS The occurrence rate of esophageal stricture in the PGA plus stent group was 20.5%(n = 7), which was lower than that in the stent group(46.9%, n = 15)(P = 0.024). The mean value of esophageal stricture time was 59.6 ± 16.1 d and 70.7 ± 28.6 d in the PGA plus stent group and stent group(P = 0.174), respectively. Times of balloon dilatation in the PGA plus stent group were less than those in the stent group [4(2-5) vs 6(1-14), P = 0.007]. The length(P = 0.080) and diameter(P = 0.061) of esophageal strictures were numerically decreased in the PGA plus stent group, whereas no difference in location(P = 0.232) between the two groups was found. Multivariate logistic analysis suggested that PGA plus stent placement(P = 0.026) was an independent predictive factor for a lower risk of esophageal stricture, while location in the middle third(P = 0.034) and circumferential range = 1/1(P = 0.028) could independently predict a higher risk of esophageal stricture in EC patients after ESD. CONCLUSION PGA plus stent placement is more effective in preventing post-ESD esophageal stricture compared with stent placement alone in EC patients with earlystage disease.

Purification Process,Content Determination,Pharmacological Activity and Molecular Mechanism of Neogambogic Acid

Neogambogic acid is characterized by broad antitumor spectrum,good antitumor effect and low toxicity and side effects.This paper reviews the purification process,content determination and pharmacologic activity of neogambogic acid,in order to provide a theoretical reference for the research and application of neogambogic acid.

Research advances in phytochemistry,pharmacology and toxicology of oleanolic acid

Oleanolic acid(OA)is a pentacyclic triterpenoid chemical component that exists in natural plants with a molecular formula of C30H48O3 and a molecular weight at 456.71 g·mol-1.OA is widespread in traditional Chinese herbal medicine(Ligustri Lucidi Fructus,Achyranthis Bidentate Radix,Red Sage)and berries(blueberries,grapes).In recent years,because of the extensive pharmacological effects of OA,its advantages in disease treatment have become increasingly prominent and gradually attracted the attention of pharmaceutical researchers.OA has effective therapeutic effects on a series of chronic diseases such as inflammation,cancer,diabetes,and cardiovascular diseases through multiple signaling pathways and various targets.Especially in cancers,such as colorectal cancer,liver cancer,gastric cancer,lung cancer,breast cancer and other malignancies,OA presents substantial efficacy.However,its poor aqueous solubility,needy bioavailability,and unsatisfactory pharmacological activity excessively restrict its clinical application.More importantly,the improper utilization of OA can cause adverse reactions,toxic effects and even damage to organs in some specific situations.With the discovery of various pharmacological effects,the complex action mechanisms of OA,the continuous progress in structural modification of OA,as well as the synthesis of OA derivatives,its application is expanding gradually.Among numerous studies,there is a clear indication that OA and its derivatives,if fully developed,may provide an alternative and cheaper treatment for a variety of chronic diseases.However,the specific molecular mechanisms of OA and its derivatives as an alternative therapy and supplementary therapy for cancer,diabetes,cardiovascular disease and other chronic diseases remain to be clarified.Therefore,it is necessary to further study the pharmacokinetics,pharmacological activity,specific targets and related mechanisms of OA to lay a solid foundation for drug development and the application of OA in clinical settings.

Novel concept of endoscopic device delivery station system for rapid and tight attachment of polyglycolic acid sheet

AIM To evaluate appropriate and rapid polyglycolic acid sheet(PGAs) covering time using device delivery station system(DDSS).METHODS This pilot basic study was conducted to evaluate the potential of accurate and rapid PGAs delivery using DDSS. Three 11-month-old female Beagle dogs were used in this study. Two endoscopic submucosal dissections(ESDs) 4 cm in diameter were performed in lesser curvature of middle gastric body and greater curvature of antrum(total 6 ESDs performed). DDSS(3 cm length, 12 mm in outer diameter) has 2 chambers which 16 cm^2 large 2 PGAs were stored, and DDSS was attached post ESD ulcers, respectively. Beriplast P?(CSL Behring K.K., Tokyo, Japan)(combination of fibringlue and thrombin) was applied equally to the artificial ulcer, and tight attachment of 2 PGAs with DDSS were completed. The evaluation items were covering times, post ESD bleeding and perforation during ESD.RESULTS The covering time of PGAs(defined as the duration from the beginning of endoscope insertion into the mouth to the end of the fibrin glue coating process) was 6.07(4.86-8.29) min. There was no postESD bleeding(1-7 d after ESD), and there was no perforation during ESD.CONCLUSION DDSS was very useful for rapid delivering and tight attachment of PGAs, and has potentials of multipurpose delivery station system.

Potassium Dichromate Surface Modification of Polyglycolic Acid (PGA) Multifilament

For improving its hydrophilicity and biocompatibility,and preserving filament mechanical properties at the same time,polyglycolic acid( PGA) filament was modified by potassium dichromate solution with different processing time. Breaking force and water contact angle were tested. Surface changes before and after surface modifications were tested with scanning electron microscopy(SEM). Furthermore,differential scanning calorimeter(DSC) and Fourier transform infrared spectrometry(FTIR) were used to analyze the changes of molecular structure and functional group. Experimental results showed that 6 min was the most suitable time for improving hydrophilicity of PGA filament and preserving its mechanical properties.

Surface Modification of Polyglycolic Acid Fibers by Hydrogen Peroxide for Enhancing Hydrophilicity and Cytocompatibility

Hydrogen peroxide( H_2O_2) is applied for surface modification of polyglycolic acid( PGA) fibers in order to enhance the hydrophilicity and cytocompatibility of PGA fibers effectively,and maintain the breaking strength as the same time. PGA fibers are dipped in H_2O_2 solution a certain time for modification. Scanning electron microscopy( SEM) was used to observe the surface morphology of PGA fibers before and after modification. The varying of PGA macromolecule was examined with Fourier transform infrared spectroscopy( FTIR) analyses. X-ray diffraction( XRD) and differential scanning calorimetry( DSC) analysis showed that crystallinity slightly decreases. Mechanical performance test showed tensile force of modified PGA fiber was increased. The water contact angle test indicated the improving of hydrophilic. A cell proliferation assay showed that fibroblast cells attach and proliferate well on the fibers, which meant the modified fibers possess good cytocompatibility. These results suggest that H_2O_2 surface modification is easy to operate and a advantageous modification method for PGA fibers.

Pharmacologic inducers of the uric acid exporter ABCG2 as potential drugs for treatment of gouty arthritis

Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of production and the rate of excretion,the latter occurring in urine(kidney),bile(liver)and feces(intestinal tract).Reabsorption in kidney is also an important component of this process.Both excretion and reabsorption are mediated by specific transporters.Disruption of the balance between production and excretion leads to hyperuricemia,which increases the risk of uric acid crystallization as monosodium urate with subsequent deposition of the crystals in joints causing gouty arthritis.Loss-of-function mutations in the transporters that mediate uric acid excretion are associated with gout.The ATP-Binding Cassette exporter ABCG2 is important in uric acid excretion at all three sites:kidney(urine),liver(bile),and intestine(feces).Mutations in this transporter cause gout and these mutations occur at significant prevalence in general population.However,mutations that are most prevalent result only in partial loss of transport function.Therefore,if the expression of these partially defective transporters could be induced,the increased number of the transporter molecules would compensate for the mutation-associated decrease in transport function and hence increase uric acid excretion.As such,pharmacologic agents with ability to induce the expression of ABCG2 represent potentially a novel class of drugs for treatment of gouty arthritis.

Pharmacological research progress of ursolic acid for the treatment of liver diseases

Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory,hepatoprotective,antitumor,and hypoglycemic activity.This natural product is widely present in many common Chinese herbal medicines such as Hedyotis diffusa and Prunella vulgaris.The present review highlights the pharmacological research progress of ursolic acid in liver disease,with a focus on providing directions for future research and clinical practice of ursolic acid.Modern studies have demonstrated that ursolic acid can adjust the activities of enzymes such as superoxide dismutase and NADPH oxidase to balance oxidative stress,reduce inflammation,as well as to repair damaged liver.Research also showed that ursolic acid targeted lipid metabolic genes,activating autophagy and reducing lipid deposition in hepatocytes,further preventing the progress of fatty liver.Besides,the combination of ursolic acid with caspase-3 was able to prevent apoptosis and relieve liver injury.Furthermore,ursolic acid was showed to target the intestine by alleviating mucosal injury and restoring the balance of the intestinal microecology and protect liver through the enterohepatic axis.In terms of antitumor activity,ursolic acid targeted several tumor suppressor genes including gene of phosphate and tension homology deleted on chromsome ten and p53,and affected the expression of cyclin and apoptosis-related proteins involving Bax,Bcl-2,and Bcl-x,which acted on signal transduction pathways including phosphatidylinositol-3-kinase/protein kinase B,extracellular regulated protein kinases and proteina fosforilata 21 wide-type actiated factorlp 1.The same compound interacted with caspases,resulting in inhibition of cell proliferation and induction of apoptosis.In addition,ursolic acid also exerted anticancer activity through inhibiting angiogenesis,tumor invasion and metastasis,and improving immunity.Other studies have noted the importance of nano-preparations of ursolic acid for its clinical applications.This review provides essential information on the role of ursolic acid in liver protection.Further research on the mechanisms of action of ursolic acid would be useful for its pharmaceutical development and clinical application.

Study on the effect of Danbei Yifei formula on pulmonary fibrosis based on network pharmacology and molecular docking technology

Objective:To determine the pharmacodynamic material basis and mechanism of Danbei Yifei formula on pulmonary fibrosis.Methods:Starting with the clear absorbed components of Danbei Yifei formula or the potential effective components in line with the five rules of Ribinsky,the network pharmacology method and technology of traditional Chinese medicine were used to predict and analyze the action targets of Danbei Yifei formula in vivo,such as Salvia miltiorrhiza,PINBEI,Taoren,etc.On the basis of enrichment analysis,the core pathway of Danbei Yifei formula in the treatment of pulmonary fibrosis was identified,and the binding energy of drug ligand and protein target was determined through molecular docking technology simulation and verification,and its affinity and stability were evaluated.To clarify the material basis and mechanism of Danbei Yifei formula in the treatment of pulmonary fibrosis.Result:The results of network pharmacology prediction of traditional Chinese medicine showed that Danbei Yifei formula contained 72 potential pharmacodynamic components and 26 corresponding targets,including CHRM1、MAPK14、CCL2、ADRB1、PTGS1、PPARG、ALOX5、Pde3a、CHRM2、Adrb2、TNF、JUN、Adora2a、LTA4H、CYP1A2、OPRD1、CHRM3、DRD2、OPRM1、ARG1、EDNRA、Il6st、TACR1、MMP1、MMP8、Ptgs2,which were related to pulmonary fibrosis and pulmonary fibrosis Lung related diseases are highly correlated.There were 26 Go items(P<0.05)in go functional enrichment analysis,including 22 biological process(BP),9 cellular component(CC)and 3 molecular function(MF)categories.The results of network pharmacology showed that many components,such as protocatechuic acid and aminosuccinic acid,had direct effects on known targets of pulmonary fibrosis.Conclusion:Danbei Yifei formula contains many effective components which have inhibitory effect on pulmonary fibrosis,and it may play its role through the mechanism of multi-component and multi-target synergistic effect.

Evaluation of Angelicae sinensis radix as a promising treatmentoption for hyperlipidemia based on network pharmacology

Background: Angelicae sinensis radix has been widely applied in traditional Chinese medicine while little isexplored in its potential mechanism. This study aims to elucidate the effective components and defattingmechanism based on network pharmacology. Methods: Traditional Chinese Medicine Systems PharmacologyDatabase and Analysis Platform was screened to collect the possible active ingredients and their CAS and SMILESwas searched in Pubchem, which further used for reverse molecular docking in Swiss Target Prediction database toobtain potential targets. Hyperlipidemia-related molecules were obtained from GeneCards database, and thepredicted targets of Angelicae sinensis radix for hyperlipidemia treatment were selected by Wayne diagram. Formechanism analysis, the protein-protein interactions were constructed with String, the Gene Oncology enrichmentanalysis and Kyoto Encyclopedia of Genes and Genomes analysis were conducted in DAVID. Results: Usingnetwork-based systems biology analysis, we predicted that 5 active ingredients in Angelicae sinensis radix hasantilipemic effects with 71 potential targets. Through Gene Oncology and Kyoto Encyclopedia of Genes andGenomes analysis, we found that the related signaling pathways mainly involved in arachidonic acid metabolism,and regulation of lipolysis in adipocytes. The related genes are ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2,ADRB1, and ADRB3. Conclusion: Angelicae sinensis radix may alleviate hyperlipidemia through arachidonic acidmetabolism, and regulation of lipolysis in adipocytes. ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2, ADRB1, andADRB3 may be new targets for treatment.

Investigating mechanism of Jiang-zhi-dai-pao-cha for treatment of hyperlipidemia by network pharmacology

Objective:To collect the main components and targets of Jiang-zhi-dai-pao-cha(JZDPC)and investigate the mechanism of JZDPC for the treatment of hyperlipidemia by network pharmacology.Methods:The components and targets of JZDPC were searched from ETCM databases,the targets related to hyperlipidemia were searched from DisGeNET and GeneCards databases,and then the intersection targets and corresponding key components were obtained.Cytoscape 3.8.2 software was used to construct and analyze networks,and then Metascape online database was applied for gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of core putative targets.Results:There were 99 overlapping targets between JZDPC and hyperlipidemia,among which NR3C1,ESR1,NR1I2,NFKB1,ESR2,ALOX5,PTGS1,PPARA,RXRA,LPL,PLA2G1B,PYGM,CYP2C9 were the core putative targets,and many members of nuclear receptor 1(NR1)subfamily were included.The core components of JZDPC,such as Ursolic Acid,β-Sitosterol,Resveratrol,Arirubic Acid,Alisol A,Oleanolic Acid,Rhein,Chrysophanol and Emodin,can regulate blood lipid by regulating a series of signaling pathways including the above core potential targets,such as non-alcoholic fatty liver disease(NAFLD)signaling pathway,pathways in cancer,arachidonic acid(AA)metabolism signaling pathway and peroxisome proliferator activated receptor(PPAR)signaling pathway,Starch and sucrose metabolism signaling pathway,etc.They play many roles in the treatment of hyperlipidemia by participating in lipid synthesis and metabolism,anti inflammation,anti oxidative stress,regulating hormone levels and carbohydrate metabolism.Conclusion:Network pharmacology provides a theoretical basis for investigating the mechanism of action of JZDPC,and the NAFLD signaling pathway is one of the most valuable pathways.

Mechanism of Wumei Pill in the Treatment of Non-Erosive reflux disease from the Perspective of Network Pharmacology and Molecular docking

Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei Pill by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and collected NERD related targets through Genecards,PharmGKB,Drugbank,DisGeNET,OMIM,CTD and TTD databases.Intersection targets of Wumei Pill targets and NERD related targets were the potential targets of Wumei Pill in the treatment of NERD.We imported the intersection targets into the STRING database to obtain the PPI network,and obtained the hub targets.The network diagram of"Drugs-Potential active ingredients-Potential targets"was constructed by Cytoscape 3.7.2 software.We used R software to perform Gene Ontology function enrichment analysis(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis(KEGG)on hub targets,and then performed molecular docking verification.Results:There were 129 active ingredients and 213 drug targets of Wumei Pill of which 114 were the intersection targets.1587 GO enrichment items were identified(P<0.05),including 1,491 biological processes,11 cell components,and 85 molecular functions.143 KEGG pathways(P<0.05),mainly related to Kaposi sarcoma-associated herpesvirus infection,IL-17 signaling pathway,the TNF signaling pathway,MAPK signaling pathway.Results of molecular docking showed that the potential active ingredients in Wumei Pill had relatively stable binding activity to the key targets.Conclusion:Wumei pill for the treatment of non-erosive reflux disease are main active ingredients quercetin,kaempferol,beta sitosterol,Isocorypalmine,Stigmasterol,rutaecarpine,etc,the main targets is JUN,TP53,AKT1,may inhibit excessive inflammation,antioxidant therapy effect into full play.This provided a certain theoretical basis for clinical application.

改性聚乙醇酸暂堵剂研发及其在河南油田的应用

酸溶性暂堵剂对地层伤害较大,解堵较麻烦,油溶性暂堵剂不适合高含水的油层;河南油田低渗透油藏地层温度为50~120℃,注水驱油见水快,常规水溶性聚乙醇酸暂堵剂和聚乳酸暂堵剂水解温度大于80℃,不能完全满足低渗透油藏暂堵压裂的需求。结合颗粒类水溶性聚乙醇酸暂堵剂和聚乳酸暂堵剂的特性和暂堵原理,采用催化剂和抑制剂使聚乙醇酸和聚乳酸发生酯化反应,生成聚乙醇酸和聚乳酸融合物,再加入成核剂及结晶促进剂,可得到改性聚乙醇酸暂堵剂。经测试,改性聚乙醇酸暂堵剂在50~120℃温度下具有常规聚乙醇酸暂堵剂的溶解性能和暂堵强度;当改性聚乙醇酸暂堵剂的总用量占比达到18%、粗粒径与细粒径质量配比接近1:1时,其封堵强度大于40 MPa,暂堵性能良好。现场试验7井次,加入改性聚乙醇酸暂堵剂后,单井施工压力最高增加了6.1 MPa,日增油5.3 t,取得了明显的增油效果。

基于网络药理学与实验验证探讨肉桂酸治疗慢性心力衰竭的作用机制

目的采用网络药理学、分子对接及体外实验验证的方法,探讨肉桂酸治疗慢性心力衰竭(chronic heart failure,CHF)的潜在靶点及作用机制。方法通过网络药理学在线数据库预测肉桂酸靶点及CHF靶点,取交集靶点于String数据库构建蛋白互作网络,通过Cytoscape 3.7.2软件进行可视化分析,筛选出核心靶点,使用Metascape数据库进行GO和KEGG富集分析,预测肉桂酸治疗CHF的作用机制,采用分子对接技术及体外实验验证上述结果。结果网络药理学分析结果发现,肉桂酸潜在靶点187个,与6094个CHF疾病靶点相交,得到132个交集靶点,涉及CASP3、JUN、PTGS2、MMP9、TLR4等10个核心靶点。GO和KEGG富集分析显示,肉桂酸治疗CHF的作用主要与细胞对活性氧的反应、对氧化应激的反应等生物过程有关,涉及细胞凋亡等信号通路。分子对接结果显示,肉桂酸与10个核心靶点均具有良好的结合活性。体外实验结果显示,肉桂酸能显著降低心肌细胞H9c2凋亡率及活性氧水平(P<0.05),降低c-Jun、PTGS2、MMP9、TLR4 mRNA表达水平(P<0.05)和caspase-9、caspase-3、Bax蛋白表达水平(P<0.05),升高Bcl-2蛋白表达水平(P<0.05);使用乙酰半胱氨酸后,细胞凋亡率、活性氧水平及Bax蛋白表达水平显著降低(P<0.05),Bcl-2蛋白表达水平显著升高(P<0.05),与肉桂酸作用一致。结论肉桂酸能够调节多个信号靶点、抑制心肌细胞氧化应激损伤及细胞凋亡,发挥治疗CHF的作用,肉桂酸是苓桂术甘汤防治CHF的重要物质基础之一。