microRNAs(miRNAs)是一类小RNA分子,在植物和动物的基因表达调控中发挥着重要作用,miRNAs不参与蛋白质的直接合成,而是转录后基因表达的重要调控因子。它们不仅在身体发育中起着关键作用,也是细胞周期、凋亡和分化的关键调节因子。成熟m...microRNAs(miRNAs)是一类小RNA分子,在植物和动物的基因表达调控中发挥着重要作用,miRNAs不参与蛋白质的直接合成,而是转录后基因表达的重要调控因子。它们不仅在身体发育中起着关键作用,也是细胞周期、凋亡和分化的关键调节因子。成熟miRNAs的产生需要几个关键步骤。首先,在细胞核中经由RNA polymerase II(PolII)转录完成聚腺苷酸化和封顶产生primary mi RNAs(Pri-miRNAs)。Pri-miRNAs通过Drosha/DGCR8复合物进一步加工合成hairpin precursor mi RNAs(pre-miRNAs)。Pre-miRNAs通过输出蛋白5(XPO5)输出到细胞质中,并被Dicer切割,在这一过程进行末端环的切割后形成成熟的miRNAs。miRNAs以互补序列结合靶mRNA,发挥调控作用。研究表明,超过30%的蛋白质编码基因受miRNAs调控。miRNAs的失调和功能障碍与人类疾病有关,miRNAs的异常表达被认为是癌症发生的重要过程。本文就microRNAs在妇科肿瘤发生发展中的研究现状进行综述。展开更多
BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,...BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.展开更多
Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy an...Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy and urine cytology serve as the established diagnostic methods for BC.However,their efficacy is limited by their invasive nature and low sensitivity.Therefore,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved prognosis.microRNAs(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic pathways.Substantially altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC.Investigations into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the disease.Simultaneously,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC.This review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for BC.Additionally,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.展开更多
In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvi...In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvironment.In this review,the authors introduce the following points:(1)The composition and function of exosomal microRNAs(miRNAs)of different cell origins in hepatocellular carcinoma(HCC);(2)the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC;and(3)the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.In addition,the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced.In this review,the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC,which provides a deeper understanding of exosomal miRNAs to the readers.展开更多
MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like ot...MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.展开更多
脑出血后所释放的大量内源性物质和血液中的毒性成分可加剧炎性反应和神经缺损,严重影响脑出血患者预后。microRNAs水平在脑出血后发生变化,可通过多种机制调控神经炎症的功能。文章综述归纳总结了microRNAs对脑出血后神经炎症影响的研...脑出血后所释放的大量内源性物质和血液中的毒性成分可加剧炎性反应和神经缺损,严重影响脑出血患者预后。microRNAs水平在脑出血后发生变化,可通过多种机制调控神经炎症的功能。文章综述归纳总结了microRNAs对脑出血后神经炎症影响的研究进展,旨在为出血性中风患者发现更有效的治疗方法。A large number of endogenous substances and toxic components in blood released after intracerebral hemorrhage can aggravate inflammatory reaction and neurological damage, which seriously affect the prognosis of patients with intracerebral hemorrhage. The level of microRNAs changes after intracerebral hemorrhage, which can regulate the function of neuroinflammation through various mechanisms. This review summarizes the research progress of the effect of microRNAs on neuroinflammation after intracerebral hemorrhage in order to find more effective treatment methods for patients with hemorrhagic stroke.展开更多
Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizoph...Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.展开更多
目的通过microRNAs差异分析、网络药理学及分子对接技术,探讨益母草治疗宫腔粘连(intrauterine adhesion,IUA)的潜在作用靶点及相关机制。方法基于GEO(gene expression omnibus)数据库筛选IUA与健康者的差异miRNA,经multiMiR进行靶基因...目的通过microRNAs差异分析、网络药理学及分子对接技术,探讨益母草治疗宫腔粘连(intrauterine adhesion,IUA)的潜在作用靶点及相关机制。方法基于GEO(gene expression omnibus)数据库筛选IUA与健康者的差异miRNA,经multiMiR进行靶基因预测。通过TCMSP(traditional Chinese medicine systems pharmacology)数据库检索益母草有效活性成分及相关靶点,并与miRNA靶基因取交集。利用String平台进行蛋白质互作分析,利用cytoNCA筛选关键靶点。基于R语言进行基因本体(gene ontology,GO)和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。利用CB-dock2对关键靶点和活性成分进行分子对接。结果共筛选出与IUA相关的差异miRNA 43个,经靶基因预测后与IUA共有13个交集靶点,GO及KEGG富集分析结果显示,益母草治疗IUA作用机制主要与细胞衰老、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、PI3K-Akt信号通路等有关。益母草3个特征性活性成分是花生四烯酸、山奈酚、槲皮素,可与蛋白互作网络中相对应的靶点蛋白细胞周期蛋白依赖性激酶4(cyclin-dependent kinase 4,CDK4)、芳香烃受体(aryl hydrocarbon receptor,AHR)、原癌基因c-myc编码转录因子、血管内皮生长因子(vascular endothelial growth factor,VEGF)进行分子对接,主要活性成分能够与核心靶点结合,并展现出较好的亲和力。结论益母草治疗IUA是多成分、多靶点、多通路相互作用的结果,进一步证实了益母草治疗IUA的科学性及有效性,为后续实验提供了研究思路。展开更多
In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cas...In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weighted correlation network analysis provide the basis of this integration[11-13].The occurrence of strong correlations between classified metabolites and co-expression transcripts implies either various roles of metabolites or linkages between metabolic pathways and the immune system.展开更多
Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underl...Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.展开更多
BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal ...BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.展开更多
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 ...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.展开更多
文摘microRNAs(miRNAs)是一类小RNA分子,在植物和动物的基因表达调控中发挥着重要作用,miRNAs不参与蛋白质的直接合成,而是转录后基因表达的重要调控因子。它们不仅在身体发育中起着关键作用,也是细胞周期、凋亡和分化的关键调节因子。成熟miRNAs的产生需要几个关键步骤。首先,在细胞核中经由RNA polymerase II(PolII)转录完成聚腺苷酸化和封顶产生primary mi RNAs(Pri-miRNAs)。Pri-miRNAs通过Drosha/DGCR8复合物进一步加工合成hairpin precursor mi RNAs(pre-miRNAs)。Pre-miRNAs通过输出蛋白5(XPO5)输出到细胞质中,并被Dicer切割,在这一过程进行末端环的切割后形成成熟的miRNAs。miRNAs以互补序列结合靶mRNA,发挥调控作用。研究表明,超过30%的蛋白质编码基因受miRNAs调控。miRNAs的失调和功能障碍与人类疾病有关,miRNAs的异常表达被认为是癌症发生的重要过程。本文就microRNAs在妇科肿瘤发生发展中的研究现状进行综述。
基金supported by the National Natural Science Foundation of China(82172182 and 82102311)Natural Science Foundation of Jiangsu Province(BK20211136)+2 种基金China Postdoctoral Science Foundation(2018M643890 and 2020M683718)Xuzhou Science and Technology Project(KC21215 and KC22136)Development Fund Project of Affiliated Hospital of Xuzhou Medical University(XYFY202232)。
文摘BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.
基金supported by the China Postdoctoral Science Foundation(Grant No.2022M721404)the Natural Science Foundation of Jiangsu Province(Grant No.BK20220737)+1 种基金the Social Development Foundation of Clinical Frontier Technology of Jiangsu Province(Grant No.BE2017763)the Medical Research Project of Jiangsu Province Health Committee(Grant No.K2019020).
文摘Bladder cancer(BC)is the tenth most prevalent malignancy globally,presenting significant clinical and societal challenges because of its high incidence,rapid progression,and frequent recurrence.Presently,cystoscopy and urine cytology serve as the established diagnostic methods for BC.However,their efficacy is limited by their invasive nature and low sensitivity.Therefore,the development of highly specific biomarkers and effective noninvasive detection strategies is imperative for achieving a precise and timely diagnosis of BC,as well as for facilitating an optimal tumor treatment and an improved prognosis.microRNAs(miRNAs),short noncoding RNA molecules spanning around 20–25 nucleotides,are implicated in the regulation of diverse carcinogenic pathways.Substantially altered miRNAs form robust functional regulatory networks that exert a notable influence on the tumorigenesis and progression of BC.Investigations into aberrant miRNAs derived from blood,urine,or extracellular vesicles indicate their potential roles as diagnostic biomarkers and prognostic indicators in BC,enabling miRNAs to monitor the progression and predict the recurrence of the disease.Simultaneously,the investigation centered on miRNA as a potential therapeutic agent presents a novel approach for the treatment of BC.This review comprehensively analyzes biological roles of miRNAs in tumorigenesis and progression,and systematically summarizes their potential as diagnostic and prognostic biomarkers,as well as therapeutic targets for BC.Additionally,we evaluate the progress made in laboratory techniques within this field and discuss the prospects.
基金Supported by the National Natural Science Foundation of China,No.82303441Natural Science Foundation of Shanghai Municipality,No.21ZR1459100 and No.22ZR1457900+1 种基金Science and Technology Commission of Shanghai Municipality,No.20DZ2254500Shanghai Anticancer Association EYAS Project.
文摘In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.Small extracellular vesicles(exosomes)play important roles in the tumor microenvironment.In this review,the authors introduce the following points:(1)The composition and function of exosomal microRNAs(miRNAs)of different cell origins in hepatocellular carcinoma(HCC);(2)the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC;and(3)the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.In addition,the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced.In this review,the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC,which provides a deeper understanding of exosomal miRNAs to the readers.
文摘MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.
文摘脑出血后所释放的大量内源性物质和血液中的毒性成分可加剧炎性反应和神经缺损,严重影响脑出血患者预后。microRNAs水平在脑出血后发生变化,可通过多种机制调控神经炎症的功能。文章综述归纳总结了microRNAs对脑出血后神经炎症影响的研究进展,旨在为出血性中风患者发现更有效的治疗方法。A large number of endogenous substances and toxic components in blood released after intracerebral hemorrhage can aggravate inflammatory reaction and neurological damage, which seriously affect the prognosis of patients with intracerebral hemorrhage. The level of microRNAs changes after intracerebral hemorrhage, which can regulate the function of neuroinflammation through various mechanisms. This review summarizes the research progress of the effect of microRNAs on neuroinflammation after intracerebral hemorrhage in order to find more effective treatment methods for patients with hemorrhagic stroke.
文摘Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.
文摘目的通过microRNAs差异分析、网络药理学及分子对接技术,探讨益母草治疗宫腔粘连(intrauterine adhesion,IUA)的潜在作用靶点及相关机制。方法基于GEO(gene expression omnibus)数据库筛选IUA与健康者的差异miRNA,经multiMiR进行靶基因预测。通过TCMSP(traditional Chinese medicine systems pharmacology)数据库检索益母草有效活性成分及相关靶点,并与miRNA靶基因取交集。利用String平台进行蛋白质互作分析,利用cytoNCA筛选关键靶点。基于R语言进行基因本体(gene ontology,GO)和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析。利用CB-dock2对关键靶点和活性成分进行分子对接。结果共筛选出与IUA相关的差异miRNA 43个,经靶基因预测后与IUA共有13个交集靶点,GO及KEGG富集分析结果显示,益母草治疗IUA作用机制主要与细胞衰老、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、PI3K-Akt信号通路等有关。益母草3个特征性活性成分是花生四烯酸、山奈酚、槲皮素,可与蛋白互作网络中相对应的靶点蛋白细胞周期蛋白依赖性激酶4(cyclin-dependent kinase 4,CDK4)、芳香烃受体(aryl hydrocarbon receptor,AHR)、原癌基因c-myc编码转录因子、血管内皮生长因子(vascular endothelial growth factor,VEGF)进行分子对接,主要活性成分能够与核心靶点结合,并展现出较好的亲和力。结论益母草治疗IUA是多成分、多靶点、多通路相互作用的结果,进一步证实了益母草治疗IUA的科学性及有效性,为后续实验提供了研究思路。
文摘In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weighted correlation network analysis provide the basis of this integration[11-13].The occurrence of strong correlations between classified metabolites and co-expression transcripts implies either various roles of metabolites or linkages between metabolic pathways and the immune system.
文摘Background: Celastrol is an active ingredient extracted from Traditional Chinese Medicine (TCM), which can restrain the progression of lung cancer, whereas its underlying mechanism is unclear. In our study, the underlying mechanism of celastrol in the treatment of lung adenocarcinoma (LUAD) with metastasis was investigated by network pharmacology and molecular docking. Method: Potential targets of celastrol were collected from TCMSP, Batman-TCM and GeneCard database, and its potential targets were predicted using the STP platform and the TargetNet server. Metastasis marker genes (MGs) were obtained from the HCMDB. The genes correlated with LUAD were gathered from the GeneCard and OMIM database. And the common targets among celastrol potential targets, MGs and LUAD were analyzed. The protein-protein interaction (PPI) networks were obtained from the STRING database. SangerBox and the Xiantao bioinformatics tool were applied to visualize GO and KEGG analysis. Molecular docking tested the binding affinity between celastrol and core genes. Result: A total of 107 targets of celastrol against metastasis LUAD were obtained. The core targets were obtained from the PPI network, namely AKT1, JUN, MYC, STAT3, IL6, TNF, NFKB1, BCL2, IL1B, and HIF1A. GO and KEGG enrichment analysis indicated celastrol for the treatment of metastasis LUAD most refers to cellular response to chemical stress, DNA-binding transcription factor binding, transcription regulator complex and pathways in cancer. And some of these targets are associated with differential expressions and survival rates in LUAD. Moreover, Molecular docking shows celastrol can bind with BCL2 well by hydrogen bond and hydrophobic interaction. Conclusion: This finding roundly expounded the core genes and potential mechanisms of celastrol for the treatment of metastasis LUAD, offering the theoretical basis and antitumor mechanism of TCM in the treatment of lung cancer.
基金Natural Science Foundation of Hebei Province,No.H2018307071Traditional Chinese Medicine Research Plan Project in Hebei Province,No.2022122Hebei Provincial Science and Technology Program,No.17397763D.
文摘BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.
基金funded by the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources(Guangxi Normal University)(CMEMR2022-B11)the Natural Science Research of Jiangsu Higher education Institution of China(22KJB360018)Jiangsu Province University Student Innovation and Entrepreneurial Training Program(202311117019Z).
文摘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.