Notch信号通路——对健康和疾病的机械论观点

The Notch signaling pathway is evolutionarily conserved across metazoan species and plays key roles in many physiological processes.The Notch receptor is activated by two families of canonical ligands(Deltalike and Serrate/Jagged)where both ligands and receptors are single-pass transmembrane proteins usually with large extracellular domains,relative to their intracellular portions.Upon interaction of the core binding regions,presented on opposing cell surfaces,formation of the receptor/ligand complex initiates force-mediated proteolysis,ultimately releasing the transcriptionally-active Notch intracellular domain.This review focuses on structural features of the extracellular receptor/ligand complex,the role of posttranslational modifications in tuning this complex,the contribution of the cell membrane to ligand function,and insights from acquired and genetic diseases.

Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

Inhibitory effect of saffron on head and neck squamous cell carcinoma via targeting of ESR1 and CCND1 by its active compound crocetin

Background:Traditional Chinese medicine is promising for managing challenging and complex disorders,including cancer,and in particular,saffron is applied in treating various cancer types.However,its potential therapeutic efficacy and active components in managing squamous cell carcinoma of the head and neck(HNSCC)remain unclear yet.Methods:Using network pharmacology approaches,active ingredients of saffron,their target genes,and HNSCC-related genes were identified.Enrichment analyses were conducted for determining molecular functions and pathways enriched by genes that overlapped between the saffron target gene set and the HNSCC gene set.Among the four known active ingredients of saffron,crocetin was found to have the strongest inhibitory impact on HNSCC,based on the findings of cell viability and migration assays.Therefore,the potential target genes of crocetin in HNSCC cells were examined using molecular docking experiments and were confirmed by qPCR.Result s:Four active ingredients of saffron and 184 of their target genes were identified.Further,a total of 34 overlapping saffron-/HNSCC-associated targets related to the four active ingredients were screened,and crocetin was chosen for further investigation because it had the strongest inhibitory effect on HNSCC cells.Molecular docking experiments indicated that ESR1 and CCND1 were the target genes of crocetin.These results were confirmed through qPCR analysis,in which crocetin was found to lower the expression of the ESR1 and CCND1 genes in AMC-HN-8 and FaDu cells.Conclusion:According to our results,crocetin is a primary active anti-cancer component of saffron that may have potential in the development of novel HNSCC-treating medications.However,more thorough molecular research is necessary for confirming these results and elucidating the anti-cancer mechanism underlying saffron.

Lignans are the main active components of Schisandrae Chinensis Fructus for liver disease treatment:a review

As a traditional Chinese herbal medicine,Schisandrae Chinensis Fructus(SC)has been used in medicine and food industry due to its health care and therapeutic effects.Over the past 20 years,the use of SC and its active ingredient lignans in the prevention and treatment of liver diseases has been increasing,and their hepatoprotective effects has increased the interest of the public and academia.Therefore,in the present work,we first determined the effectiveness of SC in the treatment of liver diseases such as metabolic associated fatty liver disease,alcoholic liver disease,cholestatic liver disease and acute liver injury.Subsequently,the pharmacological effects and molecular mechanisms of lignans,the active components of SC,for liver disease treatment were comprehensively summarized for the first time.The results showed that the lignans in SC could achieve hepatoprotective effects by regulating lipid metabolism,anti-fibrosis,anti-inflammation,anti-oxidation,anti-tumor and regulating bile acid metabolism.The mechanism mainly involved adenosine 5’-monophosphate-activated protein kinase,endoplasmic reticulum stress,sterol regulatory element binding protein 1c,autophagy,transforming growth factor-β,mitogen-activated protein kinase,microRNA,nuclear factor kappa-B,nuclear factor erythroid-2-related factor 2,heat shock proteins and pregnane X receptor signaling pathways.These results can lay a scientific foundation for the development of hepatoprotective drugs or functional foods from SC/lignans.

Trigonelline mitigates bleomycin-induced idiopathic pulmonary fibrosis in mice

Objective:To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis(IPF)and to explore its underlying mechanisms using network pharmacology.Methods:IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin(5 mg/kg).Trigonelline was administered at doses of 25,50,and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th day.In IPF-induced mice,lung coefficient,immune cell infiltration in bronchoalveolar lavage fluid,and oxidative stress were measured.Histological alterations in lung tissues were also assessed.Moreover,network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of IPF.Results:Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration,and mitigated physiological changes in the lung tissues of mice.Moreover,trigonelline alleviated bleomycin-induced histological alterations in lung tissues.Network pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets,such as NFKB1,HDAC2,HIF1A,and TLR4.Conclusions:The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating IPF.It may be considered an antifibrotic agent for further clinical development.

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii.Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components,namely quercetin,β-sitosterol,stigmasterol,7-Omethylluteolin-6-C-beta-glucoside_qt,atropine,and glycitein,were identified to have potency in improving exercise fatigue via multiple pathways,such as the PI3K-Akt,neuroactive ligand-receptor interaction,IL-17,TNF,and MAPK signaling pathways.The immunofluorescence results indicated that quercetin,a significant active component in Fructus lycii,increased the mean staining area of 2-NBDG,TMRM,and MitoTracker,and decreased the area of CellRox compared to the control.Furthermore,the protein expression levels of p-38 MAPK,p-MAPK,p-JNK,p-PI3K,and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways.Among these,quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress.The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

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.

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

Fufang E’jiao Jiang’s effect on immunity,hematopoiesis,and angiogenesis via a systematic“compound-effect-target”analysis

Fufang E’jiao Jiang(FEJ)as a healthy food consisting of medicine food homology materials approved by China’s Ministry of Health has been extensively applied to replenish qi and nourish blood,and it has a positive impact on women’s health.To find out the material basis and mechanism of FEJ,a systematic“compoundeffect-target”analysis including chemical composition resolution,zebrafish,network pharmacology,molecular docking,transcriptome,and bibliometric analysis was adopted.124 chemical components including ginsenosides,and phenylethanoid glycosides in FEJ were discovered,and effects of FEJ on promoting the generation of immune cells,erythropoiesis and angiogenesis in zebrafish were exhibited.Based on network pharmacology,molecular docking and in vivo activity assay,6 compounds including jionoside A1,isoacteoside,echinacoside,acteoside,lobetyolin,and rehmannioside D were identified as active components of FEJ.Transcriptome data showed that several pathways such as complement and coagulation cascades,ECM-receptor interaction,and PI3K-Akt signaling pathway were associated with proangiogenic effect of FEJ.19 common targets were obtained through combined analysis of network pharmacology and transcriptomics,and 5 targets of them were verified by PCR.The bibliometric analysis of these common targets revealed that FEJ was related to energy metabolism,pathway in cancer,etc.,which was consistent with the results of network pharmacology and transcriptome.The studies suggested that FEJ could replenish qi and nourish blood through multi-compound and multi-targets.

Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

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.

Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation

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.

Curcumin for gastric cancer:Mechanism prediction via network pharmacology,docking,and in vitro experiments

BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.

Evaluation of the famous classic formula Sanhua decoction based on network pharmacology and multi-component quantitative analysis

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.

Modern technology-based exploration of mechanism of traditional Chinese medicine in prevention and treatment of gastric cancer

This review comments on the article“To explore the mechanism of Yigong San anti-gastric cancer and immune regulation”.We are interested that the article applied network pharmacology and bioinformatics techniques to elucidate the mechanism of action of Yigong Sang,a traditional Chinese medicine(TCM),in the treatment of gastric cancer(GC).The mechanism of action of Yigong Sang in the treatment of GC has not yet been elucidated because it is composed of multiple Chinese medicines with multiple components and multiple targets.The emergence of network pharmacology and bioinformatics analysis helps explain the mechanism of action of TCM in preventing and treating GC,and provides a possibility for TCM to transform from empirical to evidence-based medicine.This is of great significance for the application of TCM in oncology,new drug development,formula optimization,and the improvement of clinical efficacy.

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Qizhu prescription for treating breast cancer

Objective To investigate the mechanism underlying the effects exerted by the Qizhu prescription(QZP)in breast cancer(BC),and the respective targets.Methods Expression data from the ArrayExpress and The Cancer Genome Atlas(TCGA)were used to identify differentially expressed genes(DEGs)in BC.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the DEGs to identify genes involved in protein–protein interactions.Molecular docking was used to explore the dynamic relationship between active molecules and targets.Cell function experiments and animal studies were conducted to evaluate the effects of hub genes and active QZP compounds on BC cell behavior.Results Among the 25 evaluated BC-related targets of QZP,matrix metalloproteinase-1(MMP1)and epidermal growth factor receptor(EGFR)exhibited the highest degrees of dysregulation.GO and KEGG enrichment analyses revealed that the anti-BC targets of QZP primarily affected drug responses and pathways in cancer cells.Molecular docking analysis suggested potential interactions between EGFR and quercetin/luteolin,as well as between MMP1 and luteolin/kaempferol/quercetin.Quercetin significantly reduced BC cell proliferation,migration,invasion,and tumor development in vivo.Treatment of BC cells with quercetin decreased the expression or activation of several associated proteins.Conclusion The findings of our study provide new insights into the therapeutic potential of traditional Chinese medicine against BC,with particular reference to QZP.

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.

Recent advances in managing obstructive sleep apnea

Obstructive sleep apnea(OSA)is a rapidly increasing global concern.If it remains untreated,it can lead to cardiovascular,metabolic,and psychiatric complications and may result in premature death.The efficient and effective management of OSA can have a beneficial effect and help reduce the financial burden on the health sector.There has been constant development in OSA management,and numerous options are available.The mainstay of therapy is still the conventional measures and behavioral modifications.However,in cases of failure of these modalities,surgical therapy is the only option.Numerous studies have shown that proper management of OSA has beneficial effects with good long-term outcomes.

Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer

BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.