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.

Non-pharmacological cognitive intervention for aging and dementia:Current perspectives

In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting healthy cognition has become a priority and a necessity for minimizing and preventing individual and societal burdens associated with cognitive dysfunctions in the elderly. The general awareness concerning the efficacy of preventive(e.g., lifestyles) and palliative treatment strategies of cognitive impairments, related to either healthy or unhealthy trajectories in cognitive aging, is continuously rising. There are several therapeutic strategies which can be broadly classified as either pharmacological or non-pharmacological/psychosocial. In face of the modest evidence for success of pharmacological treatments, especially for dementia related impairments, psychosocial interventions are progressively considered as a complementary treatment. Despite the relative spread of psychosocial interventions in clinical settings, research in this area is rather scarce with evidence for success of these therapies remaining controversial. In this work we provide an evidence based perspective on cognitive intervention(s) for healthy aging, pre-dementia(mild cognitive impairment), and dementia populations. Current evidence and future directions for improving cognitive functions in the elderly are discussed as well.

Research on the Mechanism of the treatment of non‑alcoholic fatty liver by Jianwei Gexia Zhuyu Decoction based on network pharmacology and molecular docking

Objective:To analyse the key compounds,targets and pathways of the treatment of non‑alcoholic fatty liver disease(NAFLD)by Jianwei Gexia Zhuyu Decoction based on network pharmacology,in order to explore the molecular mechanism of its therapeutic effects.Methods:The differential genes between sick and normal conditions were screened by GEO‑Datasets,and the heat map and volcano map were drawn.The active compounds in Jianwei Gexia Zhuyu Decoction were searched by TCMSP platform and Drugbank database.OB≥30%and DL≥0.18 were set as thresholds to screen potential active compounds and action targets.The molecular target maps of Jianwei Gexia Zhuyu Decoction and NAFLD differential genes were constructed,and the PPI network and network topology parameters were obtained by STRING database.The PPI network and network topology parameters were visually analyzed by Cytoscape,and the core regulatory genes were screened.At the same time,the SwissDock platform was used to dock the main active components with the target.The main pathways were determined by GO biological function enrichment analysis and KEGG metabolic pathway enrichment analysis by DAVID.Results:After screening,377 differential genes(127 up‑regulated genes and 250 down‑regulated genes),225 active compounds of Jianwei Gexia Zhuyu Decoction,308 corresponding targets were obtained;14 key targets were screened,corresponding to 168 compounds,and the key targets involved MYC,FOSL2,FOS,etc.The results of GO functional enrichment analysis showed that Jianwei Gexia Zhuyu Decoction mainly regulated the activity expression of DNA binding transcriptional activator and the specific transcription of RNA polymeraseⅡ;The results of molecular docking showed that the main active components quercetin and baicalein had good binding activity with VCAM1,HSPB1,MYC,JUN and so on;The results of KEGG enrichment analysis showed that it was mainly involved in IL‑17 signal pathway,Wnt receptor signal pathway,NF‑κB signal pathway,TNF signal pathway and AGE‑RAGE signal pathway in diabetic complications.Conclusion:Through the interaction of multi‑components and multi‑targets,Jianwei Gexia Zhuyu Decoction has achieved the goal of overall treatment of NAFLD from many ways.The application of network pharmacology provides a new research approach and scientific basis for further study on the mechanism of Jianwei Gexia Zhuyu Decoction in the treatment of NAFLD.

Integrating network pharmacology and pharmacological evaluation for deciphering the mechanism of(-)-epigallocatechin-3-gallate alleviating ethanol-induced endothelial cells injury

Objective To investigate the potential therapeutic targets and pharmacological mechanism of(-)-epigallocatechin-3-gallate(EGCG)based on network pharmacology and experimental verification.METHODS The druggability of EGCG was measured by the traditional Chinese medicine systems pharmacology(TCMSP)server,and potential targets of EGCG were identified by Pharm Mapper and Drug Repositioning and Adverse drug Reaction via Chemical-Protein Interactome(DRAR-CPI).The potential targets were imported into GeneMANIA database to obtain the protein-protein direct interaction network,and target physical interaction,co-expression,prediction,genetic interaction,and shared protein domains.The biological process,molecular functions,cellular components and KEGG signaling pathways of potential targets were analyzed using DAVID database.For further study,ethanol was used to establish a model of endothelial injury in vitro.The cell viability was assayed by MTT method,the cellular apoptosis was stained by Annexin V/PI,and the expression levels of Bcl-2,Bax and cleved-caspase-3 were tested by Western blotting.Then,JC-1 and nuclear translocation of NF-κB experiments were used to study the mitochondrial membrane potential and nuclear translocation.RESULTS The oral availability of EGCG was 55.09%(≥30%)and drug-like index was 0.77(≥0.18),which were considered pharmacokinetically active.17 potential targetable proteins of EGCG were predicted by Pharm Mapper and DRAR-CPI.Further research showed that 68.13%displayed similar co-expression characteristics,26.11%physical interactions,and 2.74%shared the same protein domain.The depth network analysis results showed that the biofunctions of EGCG were mainly by regulating glutathione derivative biosynthetic process,glutathione metabolic process,nitrogen compound metabolic process etc..via drug binding,catalytic activity,glutathione transferase activity,anion binding etc..in sarcoplasmic reticulum,spindle pole,microtubule cytoskeleton and cytoplasm.KEGG enrichment analysis showed that Glutathione metabolism,IL^(-1)7 signaling pathway,EGFR tyrosine kinase inhibitor resistance,PI3K-Akt signaling pathway and other pathways were involves in the biofunction of EGCG.The above analyses indicated that EGCG exerts its biofunction through antioxidant and anti-inflammatory mechanisms.The experimental results showed that ethanol 20.0 mmol·L^(-1) decreased cell viability,Bcl-2 expression,and increased cell apoptosis,the intracellular ROS,as well as the expression of Bax and cleaved-caspase-3 of human endothelial cells.However,treatment of the cells with EGCG can significantly alleviate ethanol induced endothelial cells injury.Further study showed that EGCG significantly alleviates ethanol induced mitochondrial depolarization and nuclear translocation of NF-κB.CONCLUSIONS EGCG exerts pharmacological efficacies on ethanol induced endothelial cell injury through multi-target,multi-function and multi-pathway mode.Protective effect of EGCG on ethanol induced cell injury was mainly through alteration of mitochondrial function and NF-κB translocation.Therefore,EGCG have great potential in protecting against endothelial dysfunction of the persons who are chronically abuse of ethanol.This study also provides a new understanding of EGCG in clinical application on cardiovascular and cerebrovascular diseases.

Systematic pharmacology analysis of Sodium 8-(((carboxymethyl)amino)methyl)-4',7-bishydroxy-isoflavone-3'-sulfonate

The purpose of this study is to use the newly synthesized molecule Sodium 8-(((carboxymethyl)amino)methyl)-4',7-bishydroxy-isoflavone-3'-sulfonate(M)as a research object,the pharmacological mechanism of the molecule was analyzed by using a series of Systematic pharmacology methods.The results show that the M molecule has a higher drug-like DL value of 0.59 and better molecular property parameters,namely Hdon=4,Hacc=10 and AlogP=0.94;A total of 11 M molecules related targets,namely F2,ESR1,AR,F10,CA2,DPP4,CCNA2,PRSS1,CDK2,GSK3B and PTPN1;A total of 140 diseases are associated with M molecule targets,and these diseases are mainly related to cancer and cardiovascular diseases;A total of 52 pathways involve the pharmacological mechanisms of M molecules,which are mainly related to cancer and other related diseases;GO-enriched analysis showed that these targets are closely related to the regulation of peptidase activity and biological processes such as blood coagulation and hemostasis.This article clearly demonstrated the pharmacological mechanism of M molecule,which provides references for exploring the pharmacological mechanism of new compounds.

Non-pharmacological intervention for posterior cortical atrophy

Posterior cortical atrophy(PCA) is a rare neurodegene-rative condition characterized by progressive visual-perceptual deficits. Although the neurocognitive profile of PCA is a growing and relatively well-established field, non-pharmacological care remains understudied and to be widely established in clinical practice. In the present work we review the available literature on non-pharmacological approaches for PCA, such as cognitive rehabilitation including individual cognitive exercises and compensatory techniques to improve autonomy in daily life, and psycho-education aiming to inform people with PCA about the nature of their visual deficits and limits of cognitive rehabilitation. The reviewed studies represented a total of 7 patients. There is a scarcity of the number of studies, and mostly consisting of case studies. Results suggest non-pharmacological intervention to be a potentially beneficial approach for the partial compensation of deficits, improvement of daily functionality and improvement of quality of life. Clinical implications and future directions are also highlighted for the advancement of the field, in order to clarify the possible role of non-pharmacological interventions, and its extent, in PCA.

Efficacy of non-pharmacological interventions in controlling type 2 diabetes in patients of African descent: A systematic review

Purpose: The purpose of this review is to systematically assess the potential effectiveness of targeted educational and other non-pharmacological interventions on diabetes control in populations of African descent in developed countries. Such information can inform intervention strategies and highlight evidence-based approaches to deal with this significant problem in this population. Methods: A systematic review and a meta-analysis of random controlled trials and cohort studies evaluating the influence of education and other non-pharmacological interventions on HbA1Cconcentrations in patients of African descent with diabetes. A comprehensive search of PubMed, EMBASE, CINAHL, ZETOC, SIGLE databases was carried out. Results: Although nine studies (8 randomised controlled trials and 1 cohort study) met the inclusion criteria, relevant HbA1Cdata were available for 6 of the studies for the subsequent meta-analysis. Heterogeneity of meta-analysis was high (I2 = 92%), the random effects pooled standard mean difference favoured the intervention -0.66 (-1.15, -0.17), p = 0.009. After sensitivity analysis, I2 remained moderate to high at 69%. The random effects pooled standard mean difference continued to favour the intervention -0.48 (-0.81, -0.16), p = 0.009. Conclusion: There is evidence supporting the efficacy of educational and other non-pharmacological interventions in diabetes control in populations of African descent in English speaking developed countries. This conclusion is tempered by the significant heterogeneity of selected interventions and paucity of high quality research in the target population.

A Non-Invasive Skin Treatment Combining LED with Pharmacologic and Ultrasonic Technologies for Facial Rejuvenation

Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each patient’s unique skin type and condition. RATIONALE Epinova is a non-invasive skin treatment that combines the correct concentrations and combinations of topicals and modalities to elicit facial rejuvenation with no down-time or side effects. Purpose: This paper focuses on facial rejuvenation improvements combining the RATIONALE Essential Six skincare system (RATIONALE, Victoria, Australia) to protect and repair the skin with the RATIONALE Epinova facial treatment every 4-6 weeks—which uses non-invasive technologies and professional strength active ingredients to deliver visible changes to skin tone and texture. Methods: Subjects underwent a RATIONALE consultation, including taking a skin history and skin imaging, followed by a data analysis and diagnosis of skin condition and prescription of a customized RATIONALE treatement (Epinova), including appropriate pharmacologic agents and treatment with personalized photo/sono therapeutic devices. Results: Subjects reported increased skin hydration, tactile improvements, skin firmness and visible radiance following the RATIONALE Epinova treatment. Further investigations will be initiated to explore the potential for longer term improvements, including connenctive tissue deposition, reduction of erythema etc. Treatments should be performed every 4-6 weeks for patients under 40 and every 3-4 weeks for patients over 40, to support cell differentiation, migration and desquamation to achieve non-invasive facial rejuvenation. Conclusion: This study demonstrated that the synergy of pharmacologic, LED light therapy and ultrasonic technologies when prescribed and administered by a trained skin therapist, can lead to a visible improvement in the signs of facial ageing and photodamage, restoring the appearance of healthy, radiant skin. .

肥胖儿童non-HDL-C、remnant cholesterol与亚临床动脉粥样硬化的关系

目的:了解non-HDL-C和remnant cholesterol与肥胖儿童亚临床动脉粥样硬化(AS)的关系。方法:根据甘油三酯(TG)水平将65例肥胖儿童(肥胖组)分为I组(TG≥2.3 mmol/L)32例,II组(TG<2.3 mmol/L)33例,与肥胖组儿童性别年龄相匹配的正常体质量儿童30例为III组(对照组)。比较3组儿童血脂指标,对肥胖组各项血脂指标与血浆致动脉粥样硬化指数(AIP)进行相关性分析,肥胖患儿体质指数、血脂指标与颈动脉内径、内膜-中层厚度(c-IMT)、血流参数进行相关性分析。结果:I组、II组的TG、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、non-HDL-C、remnant cholesterol、AIP均较对照组升高,高密度脂蛋白胆固醇(HDL-C)较对照组降低,且I组的remnant cholesterol、AIP均较II组升高。肥胖组儿童AIP与TG、non-HDL-C、remnant cholesterol呈正相关,与HDL-C呈负相关。37例行颈动脉超声检查的肥胖儿童的c-IMT较正常儿童的增厚。结论:non-HDL-C、remnant cholesterol在肥胖儿童亚临床AS中有重要作用,在肥胖儿童血脂异常的治疗中应关注non-HDL-C、remnant cholesterol的变化。

Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced non-small cell lung cancer： a meta-analysis

Objective： To evaluate the clinical efficacy of Shenqi Fuzheng injection combined with gemcitabine plus cisplatin（GP） in the treatment of advanced non-small cell lung cancer （NSCLC）. Methods： we performed a systematicsearch in the electronic databases such as Cochrane Library, Pubmed, Embase, Chinese Journal Full-text Database,Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Full-text Database andWanfang Database up to 30 January 2017. Randomized controlled trials （RCT） of Shenqi Fuzheng Injectioncombined with GP chemotherapy in the treatment of advanced NSCLC were searched, and all the RCTs wereconducted on methodological quality assessment. Data extraction and data analysis were according to standards ofCochrane systematic review. Results： Eight trials were included including a total of 701 patients. Meta-analysisresults： Shenqi Fuzheng injection combined with GP chemotherapy could significantly improve the functionalstatus of patients with NSCLC （OR = 3.44, 95% CI [2.26, 5.25], P 〈 0.0001） and clinical treatment efficacy （OR =（OR = 0.31, 95%CI [0.20, 0.47], P 〈 0.0001. The rate of leukopenia （OR = .31, 95%CI [0.20,0.47], P 〈 0.0001）,thrombocytopenia （OR = 0.58, 95%CI [0.37, 0.91], P = 0.020）, hemoglobin decline （（OR = 0.31, 95%CI [0.16,0.59], P = 0.0004） and incidence of gastrointestinal reactions （OR = 0.58,P 〈 0.05） could be reduced. Conclusion：Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced NSCLC obtainedsignificantly clinical efficacy. The quality of the literature incorporated is low, the conclusion requires high-qualityresearch to further prove.

1994-2022年中医非药物疗法治疗功能性便秘研究文献可视化分析

目的探索中医非药物疗法治疗功能性便秘的研究热点及发展趋势,为后续研究提供参考。方法检索中国知识资源总库(CNKI)、中国学术期刊数据库(万方数据)、中文科技期刊数据库(VIP)1994年6月15日-2022年12月31日中医非药物疗法治疗功能型便秘研究文献。采用CiteSpace6.2.R2软件对作者、机构、关键词进行可视化分析。结果共纳入文献1716篇,年发文量整体呈上升趋势,发文量较高的作者是李瑛、于永铎、刘志顺、罗芳丽,发文量最高的研究机构是成都中医药大学。高频关键词有“针刺治疗”“临床疗效”“便秘”“电针治疗”等,关键词聚类为9类;“穴位贴敷”“肠道菌群”成为近3年突现关键词。结论该领域尚未形成核心作者群体,机构间合作较少;目前,中医非药物疗法治疗功能型便秘聚焦于针刺、艾灸、推拿等疗法临床疗效,穴位敷贴疗法及肠道菌群机制研究可能成为下一阶段的研究热点。

Current and emerging pharmacological therapy for nonalcoholic fatty liver disease

The main treatment of patients with non-alcoholic fatty liver disease(NAFLD) is life style modification including weight reduction and dietary regimen.Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis(NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an antioxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.

Analysis of Numerical Results in High Temperature Congealment and Chemistry Non-equilibrium Flow Field

Using the air plasma ignition technique, physicochemical process of burning can be accelerated; concentration limit ofretrofires both can be extended; reliability of retrofires and stability of burning can be improved. In this paper, using internalequivalent heat area in place of electric are that created Ohm heat, the flow fields of thermodynamic equilibrium chemistry con-gealment and chemistry non-equilibrium in the plasma generator were simulated. The influences of the inlet prerotation angleof air, the inlet total pressure of air and the airflow compression angle of spray nozzle on the temperature on the surface of elec-

Turbulent Flow Action of Pulp in Wet - Laid Non - Woven Processes

The paper deals with the fluid field of web forming in wet-laid non-woven production.The influence of the turbulent flow on blending fiber and occluded fluid produced in pulp flow has been discussed in theory and practice.The suitable use of the imported velocity of pulp is very important in producing wet-laid products of good quality.

CYFRA 21-1 as an early predictor of first line chemotherapy response in advanced non small cell lung cancer

Objective： In an era of ever evolving, promising new therapies for advanced non small cell lung cancer （NSCLC）, early predictors of response to therapy, are needed. We evaluated early variations in CYFRA 21-1 serum levels of patients with advanced NSCLC receiving first line chemotherapy and correlated the results with objective tumor response. Methods： 29 consecutive, previously untreated, patients of advanced non small cell lung cancer, with measurable disease on CT scan were evaluated. All patients were treated with conventional systemic chemotherapy, although the choice of chemotherapy was left to the discretion of the treating physicians. Serum samples were obtained immediately before the start of 1st and 2nd cycles of chemotherapy. CYFRA 21-1 was measured with an electrochemiluminescense immunoassay on an automatic analyzer （Elecsys 2000; Roche Diagnostics）. Response was evaluated using Response evaluation criteria in solid tumors （RECIST） criteria. Results： 10 patients had partial response, 9 patients had stable disease and 9 had progressive disease. None of the patients had complete response. 21/29 （72%） patients had an elevated baseline value of CYFRA 21-1.62% patients （18/29） had a decrease in CYFRA 21-1 after 1 cycle of chemotherapy. The average reduction in the 2nd reading was irrespective of whether baseline value was normal or not. The average reduction was statistically significant （P = 0.002; 95% CI, from 0.8369 to 3.49464; t test）. 8 out of 10 （80%） patients with partial response had a reduction in their 2nd reading of. CYFRA （P = 0.019; 95% CI, from 0.81965 to 7.20035; t test） which was significant. We also observed that 6/9 （66%） patients whose disease remains stable also had a decrease in their subsequent reading （P = 0.0106; 95% CI, from -0.44942 to 3.82720; t test）, though it was not significant statistically. Although 5 out of 9 （55%） patients, who had an increase in their CYFRA 21-1 level, had progressive disease, but it was not statistically significant （P = 0.537; 95% CI, from -1.20021 to 2.13354; ttest）. 14 out of 19 （73%） who either had partial response or had stable disease, had a reduction in their 2nd value of CYFRA 21-1 and was significant statistically （P = 0.004; 95% CI, from 0.74792 to 3.50208; t test）. We also observed that except for 1 patient, all patients who had a decrease of 42% or more in their subsequent CYFRA 21-1 level, were those who had either responded to chemotherapy or had stable disease （P = 0.001）, which was statistically significant. Conclusion： We can conclude that monitoring of serum marker CYFRA 21-1, early dudng first-line chemotherapy may be a useful prognostic tool for evaluation of early tumor response in patients with advanced NSCLC.

MiR-16-5p plays an inhibitory role in human non-small cell lung cancer through Fermitin family member 2

Increasing evidence indicates that aberrant expressions of some microRNAs are associated with cancer progression.However,the roles and biological mechanisms of miRNA-16-5p in human non-small cell lung cancer(NSCLC)are not to be well studied.Here,we validated that the expression of miR-16-5p was decreased significantly in NSCLC samples and cell lines.The correlation between the clinicopathological features of NSCLC and the miR-16-5p expression showed that the expression of miR-16-5p in non-small cell lung cancer was linked with the advanced TNM stage,positive lymph node metastasis,with short overall survival(OS).Also,a negative correlation between miR-16-5p and Fermitin family member 2(FERMT2)was observed,implying there may be a potential link about their regulation.The hypothesis was further confirmed by in-silico analysis and dual-luciferase reporter assay.Moreover,we demonstrated that the transfections of miR-16-5p mimics could alter some biological characteristics of NSCLC cells remarkably accomplished by the expression variance of FERMT2 in vitro and in vivo assays.Summarily,this study demonstrated that miR-16-5p,as a tumor suppression factor in NSCLC by targeting FERMT2,could serve as one promising biomarker in the prediction for NSCLC patients.

基于UPLC-Q-TOF-MS联合网络药理学和分子对接技术探讨益气养阴方治疗非小细胞肺癌的潜在作用机制

目的:通过超高效液相色谱-高分辨质谱联用方法 (UPLC-Q-TOF-MS)联合网络药理学和分子对接技术探讨益气养阴方治疗非小细胞肺癌(NSCLC)的潜在作用机制。方法:采用UPLC-Q-TOF-MS对益气养阴方样品进行质谱数据采集,分析其有效化学活性成分及对应靶点;通过TTD、Gene-Cards、DrugBank等数据库筛选出NSCLC相关靶点;借助韦恩图将药物靶点与疾病靶点相交集取得到益气养阴方干预NSCLC的潜在作用靶点;运用STRING数据库构建蛋白-蛋白相互作用网络(PPI),并采用Cytoscape 3.9.1软件得到核心靶点网络图;通过运用Metascape数据库对核心靶点进行GO基因本体论和KEGG基因百科全书富集功能分析。利用AutoDock Tools进行活性成分与核心靶点的分子对接验证。结果:获得益气养阴方45个有效活性成分,794个药物成分靶点基因和5 951个疾病靶点基因,两者交集后得到484个交集靶点基因。网络分析显示益气养阴方干预NSCLC的关键活性成分包括异牡荆苷、奎宁酸、毛蕊异黄酮、芒柄花素、没食子酸等。获得5个Hub靶基因,包括神经母细胞瘤RAS病毒致癌基因同源物(NRAS)、 v-Ha-rasHarvey鼠肉瘤病毒癌基因同源物(HRAS)、磷酸肌醇3激酶调控亚基1 (PIK3R1)、磷脂酰肌醇-3-激酶α (PIK3CA)、生长因子受体结合蛋白2 (GRB2)。GO分析和KEGG富集分析显示益气养阴方干预NSCLC的主要通路包括PI3K-Akt信号通路、MAPK信号通路、Ras信号通路、Rap1信号通路等。分子对接结果表明有效活性成分与核心靶点之间具有较好的结合性。结论:本研究初步探讨揭示了益气养阴方干预NSCLC的多成分、多靶点、多通路的潜在作用机制,可为后续研究提供一定的理论依据和参考。

基于网络药理学与体外实验探讨淫羊藿素抗非小细胞肺癌EGFR-TKIs耐药的分子机制

目的基于网络药理学与体外实验探讨淫羊藿素抗非小细胞肺癌(NSCLC)表皮生长因子受体-酪氨酸酶抑制剂(EGFR-TKIs)耐药的分子机制。方法利用PubChem和化合物靶点预测(Swiss Target Prediction)数据库下载淫羊藿素的简化分子线性输入规范(SMILES)号及作用靶点,通过人类基因(GeneCards)和在线人类孟德尔遗传(OMIM)数据库收集NSCLC耐药疾病靶点,将药物与疾病交集靶点导入STRING数据库分析蛋白质-蛋白质相互作用(PPI)情况,运用Cytoscape 3.9.1软件内置插件计算节点拓扑参数值并筛选核心靶点,采用生物信息学分析平台(DAVID)数据库进行京都基因与基因组百科全书(KEGG)和基因本体(GO)富集分析,构建“淫羊藿素-关键靶点-疾病-通路”图。使用Pymol和Autodock Tools 1.5.7软件进行分子对接。体外实验选用NSCLC耐药株PC9OR研究淫羊藿素对细胞增殖、集落形成、迁移、侵袭和凋亡能力的影响,并对富集得到的核心靶点及关键通路进行验证。结果共筛选到淫羊藿素治疗NSCLC耐药的潜在作用靶点1952个。通过PPI网络节点拓扑参数值筛选得到13个核心靶点,涉及蛋白激酶B(AKT1)、雌激素受体α(ESR1)、B淋巴细胞瘤2(BCL2)、表皮生长因子受体(EGFR)等基因。KEGG通路富集分析显示,癌症相关通路、磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-AKT)信号通路、EGFR-TKIs耐药通路等可能在淫羊藿素治疗NSCLC EGFR-TKIs耐药的过程中起关键作用。GO富集分析显示,细胞功能涉及信号传导、凋亡过程的负调控、DNA转录的正调控等。分子对接显示淫羊藿素与各核心靶点均具有较强的结合能力。细胞实验表明,淫羊藿素抑制耐药细胞的增殖、集落形成、迁移、侵袭及促进细胞凋亡,并下调ESR1、AKT1、EGFR等mRNA表达水平以及PI3K-AKT通路磷酸化磷脂酰肌醇-3-激酶(p-PI3K)、磷酸化蛋白激酶B(p-AKT)的关键蛋白水平。结论淫羊藿素可能通过多靶点调控PI3K-AKT通路抑制EGFR-TKIs耐药细胞的增殖、集落形成、迁移、侵袭及促进细胞凋亡,从而发挥抗NSCLC EGFR-TKIs耐药的作用。

基于HPLC-Q-Exactive MS和网络药理学探讨红花清肝十三味丸治疗非酒精性脂肪肝的药效物质基础及作用机制

目的利用高分辨液相色谱-质谱联用仪,快速准确地对红花清肝十三味丸中复杂的化学成分进行分析鉴定,旨在明确其缓解非酒精性脂肪肝的有效成分,同时结合网络药理学和分子对接,探索红花清肝十三味丸潜在的作用机制。方法使用甲醇和含有0.1%甲酸的水溶液作为流动相,进行梯度洗脱;采用正负离子交替扫描模式切换扫描,扫描范围m/z 110~1200;通过与对照品、参考文献与自建数据库比对后对复方中化合物进行识别鉴定;基于液质联用数据,通过中药系统药理学数据库与分析平台(TCMSP)数据库进一步筛选活性化合物,并利用SwissTargetPrediction、GeneCards等在线数据库预测分析红花清肝十三味丸在治疗非酒精性脂肪肝可能的靶点并进行KEGG与GO的富集分析;利用蛋白质-蛋白质相互作用网络筛选核心靶点;最后运用分子对接技术验证活性化合物与靶点的潜在结合活力。结果从红花清肝十三味丸中共鉴定出75个化合物,其中黄酮类化合物31个,有机酸类化合物17个,鞣质类化合物9个,环烯醚萜类化合物8个,木质素类化合物3个及其他类化合物7个。利用网络药理学方法筛选出核心靶点5个:丝氨酸/苏氨酸蛋白激酶1(AKT1)、表皮生长因子受体(EGFR)、人表皮生长因子受体2/酪氨酸激酶受体2(HER2/ERBB2)、磷脂酰肌醇-3-激酶调节亚基1(PI3KR1)及非受体酪氨酸激酶Src。KEGG富集通路主要为:PI3K-AKT信号通路、EGFR酪氨酸激酶抑制剂抵抗通路、ERBB信号通路。结论对红花清肝十三味的复杂化学成分进行了快速准确地分析鉴定,同时探讨其治疗非酒精性脂肪肝的可能作用机制,为红花清肝的质量控制及后续研究提供科学参考。

基于超高液相色谱-四级杆-飞行时间串联质谱法与网络药理学技术分析参葛颗粒治疗非酒精性脂肪性肝病的活性成分及作用机制

目的运用超高压液相色谱-四级杆-飞行时间串联质谱(UPLC-Q-TOF-MS/MS)技术结合网络药理学技术探究参葛颗粒治疗非酒精性脂肪性肝病的活性成分及作用机制。方法通过UPLC-Q-TOF-MS/MS技术鉴定参葛颗粒中的化学成分,结合中药系统药理学数据库(TCMSP)、PubChem数据库以及SwissTargetPrediction数据库筛选参葛颗粒的活性成分和靶点,在GeneCards等数据库检索非酒精性脂肪性肝病的疾病靶点,在Venny 2.1.0在线作图平台绘制药物-疾病韦恩图,将交集靶点导入String数据库,再利用Cytoscape 3.10.0软件进行可视化处理,同时基于交集靶点通过DAVID数据库进行GO和KEGG通路富集。利用Cytoscape 3.10.0软件构建核心靶点网络图以及疾病-通路-靶点-成分-药物网络图。结果质谱解析化合物75个,筛选得到药物活性成分29个,药物靶点499个,疾病靶点4776个,共同靶点353个,关键基因10个,分别为TP53、CASP3、HIF1A、JUN、BCL2L1、SRC、MTOR、HRAS、TNF、ALB,关键活性成分8个,分别为丹酚酸B、葛根素、Puerol B、芒柄花苷、葛苷A、丹参素、大豆苷、染料木素苷。结论参葛颗粒治疗非酒精性脂肪性肝病具有多成分、多靶点、多通路的特点,主要通过减少肝脏脂肪堆积、调节内分泌减缓炎症以及细胞凋亡,从而发挥治疗非酒精性脂肪肝病的作用。