Network pharmacology:Changes the treatment mode of"one disease-one target"in cancer treatment

The article concluded that network pharmacology provides new ideas and insights into the molecular mechanism of traditional Chinese medicine(TCM)treatment of cancer.TCM is a new choice and hot spot in the field of cancer treatment.We have also previously published studies on TCM and network pharmacology.In this letter,we summarize the new paradigm of network pharmacology in cancer treatment mechanisms.

Advances in ethnopharmacology,phytochemistry and pharmacology of Erigerontis Herba and its Chinese medicine prescriptions

Erigerontis Herba(EH),the dried whole plant of Erigeron breviscapus,is well-known for circulating blood,activating meridians to alleviate pain,expelling wind,and clearing away cold.It has been extensively utilized in southern China for the treatment of stroke hemiplegia,chest stuffiness and pains,rheumatic arthralgia,headache,and toothache.This review focuses on the botany,ethnopharmacology,phytochemistry,pharmacology and toxicity of EH and its related prescriptions to offer new insights for prospective research of EH.Relevant information about EH was retrieved from ancient records and books,PubMed,China National Knowledge Infrastructure,Chinese Pharmacopoeia,Web of Science,Doctoral and Master’s Theses,and various electronic databases.EH is a member of Compositae family and is mainly grown in southern China.Traditional Chinese medicine records that EH has the effects of circulating blood and removing blood stasis,expelling wind,and removing cold,as well as relieving rigidity of muscle and relieving pain.By now,nearly 200 ingredients have been characterized from EH,including flavonoids,caffeoyls,aromatic acids,coumarins,pentacyclic terpenoids,volatile oil and other compounds.EH extracts,EH related prescriptions(Dengzhan Xixin injection,Dengzhan Shengmai capsules,etc.)or compounds(scutellarin,scutellarein,etc.)possessed obvious therapeutic effects of ischemic stroke,cerebral hemorrhage,myocardial infarction,Alzheimer’s disease,diabetes and its complications,gastric cancer,bone,and joint degenerative diseases.Scutellarin,the major active compound of EH,has been used as a quality marker.And no obvious toxicity of EH has been reported.According to its traditional applications,ethnopharmacology,phytochemistry,pharmacology,and toxicity,EH was applied as a valuable herb for clinical application in food and medicine fields.While several compounds have been shown to possess diverse biological activities,the underlying mechanisms of their actions remain elusive.To fully exploit the medicinal potential of EH,further studies on understanding the effective material basis and mechanisms are warranted.

Unraveling the mechanism of action of Shangxia Liangji formula for treating insomnia:a metabolomics and network pharmacology approach

Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mouse model of insomnia was established by intraperitoneal injection of para-chlorophenylalanine.Forty-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive days.The open field test and pentobarbital-induced sleeping test were conducted.LC-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating insomnia.Finally,key targets were validated using RT-qPCR.Results:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep duration.Metabolomics and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of SXLJF.Specifically,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,respectively.RT-qPCR results supported the role of TH in the mechanism of SXLJF in treating insomnia.Conclusion:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.

Mechanistic insights into the amelioration effects of diabetic cardiomyopathy by berberine:an integrated systems pharmacology study and experimental validation

Background:Diabetic cardiomyopathy(DCM)is a type of cardiomyopathy caused by long-term diabetes,characterized by abnormal myocardial structure and function,which can lead to heart failure.Berberine(BBR),a quaternary ammonium alkaloid isolated from Coptidis Rhizoma,a traditional Chinese medicine,has superior anti-diabetic and heart-protective properties.The purpose of this study is to assess the impact of BBR on DCM.Methods:This study used a systems pharmacology approach to evaluate the related proteins and signalling pathways between BBR and DCM targets,combined with experimental validation using diabetic mouse heart sections.Microstructural and pathological changes were observed using Hematoxylin-eosin,Masson’s trichrome stain and wheat germ agglutinin staining.Immunofluorescence and western blot were used to determine protein expression.Results:The results indicate that BBR and DCM share 21 core relevant targets,with cross-targets predominantly located in mitochondrial,endoplasmic reticulum,and plasma membrane components.BBR exerts its main effects in improving DCM by maintaining mitochondrial integrity,particularly involving the PI3K-AKT-GSK3βand apoptosis signalling pathways.In addition,post-treatment changes in the key targets of BBR,including cysteine aspartate specific protease(Caspase)-3,phosphoinositide 3-kinase(PI3K)and mitochondria-related proteins,are suggestive of its efficacy.Conclusion:BBR crucially improves DCM by maintaining mitochondrial integrity,inhibiting apoptosis,and modulating PI3K-AKT-GSK3βsignaling.Further studies must address animal model limitations and validate clinical efficacy to understand BBR’s mechanisms fully and its potential clinical use.

基于Python和Selenium的期刊论文施引侧数据挖掘程序设计

为了研究中文科技期刊被国际期刊“施引侧”的引用行为,采用Python+Selenium+Chrome组合框架设计了WhoCiteMe程序,提出一种期刊论文施引侧引用信息的数据挖掘方法.文章提出了WhoCiteMe程序的设计思路,并分析了广东省10种中文科技期刊被国际期刊引用次数、学科分布、施引期刊的分区等特征.结果表明:提出的算法和设计的数据挖掘程序,可以获取国际期刊施引文献清单及引用数据,为评价中文科技期刊的国际影响力提供个性化数据,为办刊决策提供数据支撑.

基于Selenium的Ajax异步加载页面的数据采集技术

互联网中的许多网站均为Ajax站点,而Ajax页面的原始源代码中并无通过异步加载方式呈现到页面中的数据,因此其数据的采集颇为困难。针对此问题,介绍一种基于Selenium的Ajax页面数据采集方案,并通过具体的实例说明其关键技术。

基于Selenium的智慧职教平台RPA系统的设计与实现

针对智慧职教平台日常管理中需要执行大量且重复性工作的问题,提出了一种基于Selenium的RPA系统解决方案。通过分析智慧职教平台特点和RPA技术应用价值,设计并实现了一个能够自动化完成课程管理、特定范式信息录入、舆情监控、AI互动助学等任务的RPA系统,并在实践中验证了其效果和性能。

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.

Selenium Differentially Regulates Flavonoid Accumulation and Antioxidant Capacities in Sprouts of Twenty Diverse Mungbean(Vigna radiata(L.)Wilczek)Genotypes

Seed germination with selenium(Se)is promising for producing Se-biofortified foods.Mungbean(Vigna radiata(L.)Wilczek)sprout is freshly eaten as a salad dressed with sauce,making it superior for Se biofortification.Since the Se safety range for the human body is extremely narrow,it is imperative to evaluate the genotypic responses of mungbean sprouts to Se.This study evaluated the Se enrichment capacity and interaction withflavonoids and antioxidant systems in sprouts of 20 mungbean germplasms.Selenium treatment was done by immersing mung-bean seeds in 20μM sodium selenite solution for 8 h.Afterward,the biomass,Se amounts,flavonoid(particularly vitexin and isovitexin)contents,antioxidant capacity,and key biosynthetic gene expressions were measured.Sprout Se content was 2.0-7.0μg g^(-1) DW among the 20 mungbean germplasms.Selenium treatment differentially affected the biomass,totalflavonoid,vitexin,isovitexin,antioxidant enzyme activities,and antioxidant capacities of the mungbean germplasms.Eight germplasms showed increased biomass(p<0.05),the highest increasing by 127%,but 13 did not phenotypically respond to Se treatment.Seven and six germplasms showed varied levels of vitexin and isovitexin increment after Se treatment,the highest measuring 2.67-and 2.87-folds for vitexin and isovitexin,respectively.Two mungbeanflavonoid biosynthesis genes,chalcone synthase(VrCHS)and chalcone isomerase(VrCHI)were significantly up-regulated in the germplasms with increased vitexin and isovitexin levels(p<0.05).Moreover,Se enrichment capacity was significantly correlated with the vitexin,isovitexin,and antiox-idant capacities.In conclusion,mungbean sprouts could be a useful Se-biofortified food,but the Se enrichment capacity and nutritional response must be determined for each germplasm before commercialization.

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.

Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

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.

融合ChatGPT的智能化Selenium网络爬虫设计与实现

针对现代信息社会海量数据的提取难度,开发一种集成ChatGPT的自动化网络爬虫系统。将信息呈现给用户,降低了使用门槛,结合系统的设计和实施,展示其在实际运用中的效果,实验结果证明,利用Selenium技术自动执行爬取操作,降低数据提取难度,提升数据信息抓取的准确性。功能测试结果显示,该系统有效提高了数据的使用率,为普通用户从网络中提取信息提供了新的途径。用户的信息挖掘和知识获取需求,促进自动化网络爬虫技术的发展和应用。

基于Selenium的Web智能测试研究

回归测试需要大量的测试成本,如果无法很好地跟进测试脚本的修改,将导致测试跟不上系统更新的速度,这就需要解决测试脚本的易读性与易迭代性,研究重点集中在测试脚本的框架结构优化上,以实现测试最少的人工参与、最低的熟悉代码成本及高效的脚本迭代率。

Status and distribution of selenium in selenium-enriched peanut sprouts

Selenium is one of the essential trace elements in human body,however,due to the limitation of geographic factors,the intake of selenium is seriously insufficient in most regions.In this study,selenium-enriched peanut sprouts with high selenium content were prepared by soaking peanut seeds in sodium selenite.The content and distribution of selenium in germinated peanuts were investigated.The results showed that 200μmol/L sodium selenite and germination for 6 days resulted in the highest total selenium,organic selenium content,and organic selenium conversion in peanut sprouts.Selenium exists in peanut sprouts mainly in organic selenium form,of which selenoproteins are the most critical organic selenium carriers.ABTS free radical scavenging capacity and reducing power assays showed that alkali-soluble protein had the highest antioxidant activity among the four soluble proteins,attributed to its high selenium binding level.Radicle and cotyledons of peanut seedlings were significantly enriched with selenium compared to hypocotyl.Amino acid analysis and SDS-PAGE results showed that selenium increases significantly after peanut germination and selenium enrichment.This study provides a simple,environmentally friendly,and effective way of selenium enrichment and offers a theoretical basis for applying selenium-enriched foods in food and medicine.

Selenium,Type-2 Diabetes,and the Possible Protective Role of Vitamin D

Diabetes is a pervasive and serious global health issue.According to the International Diabetes Federation report,463 million adults worldwide were living with diabetes in 2019,and this number is projected to reach 700 million in 2045^([1]).

Enhanced protective effect of selenium-biofortified peptide RYNA(Se)MNDYT compared with its native peptide RYNAMNDYT in lipopolysaccharide-injured murine gut microbiota

Selenopeptides may be a valuable bioactive compound to promote gut microbiota-targeted therapeutic methods for intestinal disease and hepatopathy.However,limited information is available on the utilization of selenopeptides by gut microbiota,especially Selenium(Se)function.For this purpose,the present study aimed to investigate the protective effect of selenopeptide(RYNA(Se)MNDYT,Se-P2,purity of≥95%)and its original peptide(RYNAMNDYT,P2,purity of≥95%)in vivo by the microbiota-metabolite axis and further analyze the potential contribution of Se biofortification to Se-P2 bioactivity.The results showed that Se-P2 exhibits a higher protective effect on lipopolysaccharide(LPS)-induced inflammation than P2,including pathology of the colon and liver,which suggested that the bioactivity of P2 was promoted by the organic combination of Se.Notably,gut microbiota composition tended to be a healthy structure by Se-P2 pretreatment in LPS-injured mice,which had a positive effect on LPS-induced gut microbiota dysbacteriosis.Additionally,only Se-P2 promoted an increase in the relative abundance of Lactobacillus,Alistipes,and Roseburia and a decrease in the relative abundance of Akkermansia,Erysipelatoclostridium,and Bacteroides in LPS-injured mice.The changes in gut microbiota were obviously correlated with the changes in metabolites and affected the metabolic pathways of valine,leucine,isoleucine,phenylalanine,tyrosine,and tryptophan biosynthesis and phenylalanine metabolism.This may be one of the key reasons for Se-P2 to exert bioactivity through the microbiota-metabolite axis.Furthermore,Se-biofortification in Se-enriched Cordyceps militaris affected the parental proteins of Se-P2 to modulate mitogen-activated protein kinase,GPI anchored protein,and carbohydrate metabolism,translation,folding,sorting and degradation,which may contribute to the bioactivity of Se-P2.Our study provides information on the effect of Se on selenopeptides in vivo,which further promotes the prospective applications of selenopeptides as dietary supplements.

Fundamental Understanding on Selenium Electrochemistry:From Electrolytic Cell to Advanced Energy Storage

Selenium(Se),as an important quasi-metal element,has attracted much attention in the fields of thin-film solar cells,electrocatalysts and energy storage applications,due to its unique physical and chemical properties.However,the electrochemical behavior of Se in different systems from electrolytic cell to battery are complex and not fully understood.In this article,we focus on the electrochemical processes of Se in aqueous solutions,molten salts and ionic liquid electrolytes,as well as the application of Se-containing materials in energy storage.Initially,the electrochemical behaviors of Se-containing species in different systems are comprehensively summarized to understand the complexity of the kinetic processes and guide the Se electrodeposition.Then,the relationship between the deposition conditions and resulting structure and morphology of electrodeposited Se is discussed,so as to regulate the morphology and composition of the products.Finally,the advanced energy storage applications of Se in thin-film solar cells and secondary batteries are reviewed,and the electrochemical reaction processes of Se are systematically comprehended in monovalent and multivalent metal-ion batteries.Based on understanding the fundamental electrochemistry mechanism,the future development directions of Se-containing materials are considered in view of the in-depth review of reaction kinetics and energy storage applications.

基于Selenium框架+随机森林模型的农产品价格分析

农产品作为中国市场经济体制中的重要战略资源,其价格波动不仅会给消费者带来影响,还会影响生产经营活动。在大数据技术赋能农业发展的背景下,研究构建了一个基于Selenium框架+随机森林模型,用于实时采集、可视化分析以及序列预测的地方农产品大数据平台系统。将该预测系统和决策树模型、支持向量机(support vector machines,SVM)模型的预测效果进行对比分析,研究发现:该平台的数据采集实时性强,预测效果较决策树模型和SVM模型更好。

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.