首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1190310111211000624, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1190243275249390089, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.0351.2025.0126, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1710777600000, receivedDateStr=2024-03-19, revisedDate=null, revisedDateStr=null, acceptedDate=1723651200000, acceptedDateStr=2024-08-15, onlineDate=1761721645404, onlineDateStr=2025-10-29, pubDate=1748361600000, pubDateStr=2025-05-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1761721645404, onlineIssueDateStr=2025-10-29, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1761721645404, creator=13701087609, updateTime=1761721645404, updator=13701087609, issue=Issue{id=1190243275249390089, tenantId=1146029695717560320, journalId=1189873630562394117, year='2025', volume='50', issue='5', pageStart='505', pageEnd='640', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1761705710470, creator=13701087609, updateTime=1765784077922, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1207349188233372409, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1190243275249390089, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1207349188233372410, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1190243275249390089, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=581, endPage=591, ext={EN=ArticleExt(id=1190310111970169651, articleId=1190310111211000624, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Exploring the effects and underlying mechanisms of typhaneoside on lung adenocarcinoma based on network pharmacology and in vitro experiments, columnId=1190310110212751762, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Basic Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the effects and underlying molecular mechanisms of typhaneoside (TYP) on lung adenocarcinoma based on network pharmacology and in vitro experiments. Methods TYP-lung adenocarcinoma-related genes were obtained from the prediction target website SwissTargetPrediction, The Cancer Genome Atlas (TCGA) database, GeneCards database, and Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the obtained TYP-lung adenocarcinoma-related genes. Protein-protein network interactions analysis was carried out using the String database, and molecular docking was conducted with the Vina software. These network pharmacological analysis methods were employed to explore the theoretical action pathways of TYP on lung adenocarcinoma. PC9 cells were divided into control group (normal culture), low-TYP group (treated with 50 μmol/L TYP for 48 h), high-TYP group (treated with 100 μmol/L TYP for 48 h), and ferrostatin-1 (Fer-1)+TYP group (treated with 1 μmol/L Fer-1+100 μmol/L TYP for 48 h). The cell viability was detected by the CCK-8 assay, the cell proliferation ability was detected by the EdU assay, and the cell migration and invasion ability was detected by scratch assay, Transwell migration assay and Transwell invasion assay. The occurrence of ferroptosis was detected by reduced glutathione (GSH) assay kit, reactive oxygen species (ROS) assay kit, mitochondrial membrane potential assay kit, ferrous ion fluorescent probe, and transmission electron microscopy. Protein and mRNA expression levels of ferroptosis-related key molecules, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), were measured by Western blotting and reverse transcription-quantitative PCR (RT-qPCR). PC9 cells were transfected with SLC7A11 overexpression plasmid and divided into vector group (transfected with empty plasmid), vector+TYP group (transfected with empty plasmid and treated with 100 μmol/L TYP for 48 h), OE-SLC7A11 group (transfected with SLC7A11 overexpression plasmid) and OE-SLC7A11+TYP group (transfected with SLC7A11 overexpression plasmid and treated with 100 μmol/L TYP for 48 h). The molecular mechanism of SLC7A11 in the effect of TYP on PC9 was verified by CCK-8 assay, ferrous ion fluorescence probe, and protein expression levels of SLC7A11 and GPX4. Results A total of 73 TYP-lung adenocarcinoma-related target genes were predicted. GO analysis showed that the target genes were mainly involved in biological processes such as positive regulation of kinase activity, and were enriched in cellular components like transferase complex (transferring phosphorus-containing groups), revealing molecular functions such as transmembrane receptor protein tyrosine kinase activity. KEGG analysis identified 124 related pathways, mainly including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance pathway. Protein-protein interaction network analysis obtained 7 core targets such as serine/threonine kinase 1 (Akt1). Molecular docking results showed that the binding energies of TYP with core target genes and the ferroptosis-related proteins (SLC7A11 and GPX4) were all ≤-5.0 kcal/mol, indicating significant binding activity. CCK-8 assay showed that TYP significantly inhibited PC9 cell viability (P<0.05). EdU assay demonstrated that the proportion of proliferating cells in TYP group was significantly lower than that in control group (P<0.05). Scratch assay, Transwell migration assay, and invasion assay revealed that, compared with control group, the migration and invasion abilities of PC9 cells in TYP group significantly decreased (P<0.05), and GSH content and mitochondrial membrane potential in TYP group also significantly decreased (P<0.05), while ROS and Fe2+ contents increased significantly (P<0.01), and protein and mRNA expression levels of SLC7A11 and GPX4 decreased significantly (P<0.05). Transmission electron microscopy results showed that cells in TYP group exhibited specific ferroptosis-related changes such as reduced mitochondrial cristae and increased membrane density, compared with control group. Compared with vector+TYP group, OE-SLC7A11+TYP group had higher cell viability (P<0.05), lower Fe2+ content (P<0.05), and higher protein expression levels of SLC7A11 and GPX4 (P<0.05). Conclusion TYP may induce ferroptosis in lung adenocarcinoma cells and inhibit their malignant behaviors such as proliferation, migration and invasion by regulating the SLC7A11-GPX4 axis.

, correspAuthors=Xue Yan, authorNote=null, correspAuthorsNote=
E-mail:
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Meng-Ru Liu, Xue Yan), CN=ArticleExt(id=1190310395836469771, articleId=1190310111211000624, tenantId=1146029695717560320, journalId=1189873630562394117, language=CN, title=基于网络药理学及体外实验探讨香蒲新苷对肺腺癌的作用及其分子机制, columnId=1190310110472798614, journalTitle=解放军医学杂志, columnName=基础研究, runingTitle=null, highlight=null, articleAbstract=

目的 基于网络药理学及体外实验探讨香蒲新苷(TYP)对肺腺癌的作用及其潜在的分子机制。方法 通过预测靶点网站SwissTargetPrediction、癌症基因组图谱(TCGA)数据库、GeneCards数据库和基因表达综合数据库(GEO)获得TYP-肺腺癌相关靶点基因，对得到的TYP-肺腺癌相关基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析，应用String数据库进行蛋白互作网络分析，应用Vina软件进行分子对接，通过这些网络药理学分析方法探索TYP对肺腺癌的理论作用通路。取PC9细胞，设置对照组(正常培养)、低TYP组(50 μmol/L TYP处理48 h)、高TYP组(100 μmol/L TYP处理48 h)与铁抑制剂-1(Fer-1)+TYP组(1 μmol/L Fer-1+100 μmol/L TYP处理48 h)；采用CCK-8法检测细胞活力，EdU实验检测细胞增殖能力，划痕实验、Transwell迁移及侵袭实验检测细胞迁移和侵袭能力，采用还原型谷胱甘肽(GSH)检测试剂盒、活性氧(ROS)检测试剂盒、线粒体膜电位检测试剂盒、亚铁离子荧光探针、透射电镜检测铁死亡的发生，Western blotting和反转录-定量PCR(RT-qPCR)检测铁死亡关键分子溶质载体家族7成员11(SLC7A11)和谷胱甘肽过氧化物酶4(GPX4)蛋白和mRNA的表达情况。应用SLC7A11过表达质粒转染PC9细胞，设置Vector组(空载质粒转染)、Vector+TYP组(空载质粒转染+100 μmol/L TYP处理48 h)、OE-SLC7A11组(SLC7A11过表达质粒转染)与OE-SLC7A11+TYP组(SLC7A11过表达质粒转染+100 μmol/L TYP处理48 h)，通过CCK-8法、亚铁离子荧光探针、铁死亡关键分子SLC7A11和GPX4蛋白表达情况验证SLC7A11在TYP作用于PC9细胞时的分子机制。结果 通过靶点预测网站SwissTargetPrediction及基因数据库(TCGA、GeneCards和GEO)共预测了73个TYP-肺腺癌相关靶点基因。GO分析结果显示，靶基因主要参与激酶活性的正向调节等生物过程，主要富集于转移酶复合物(转移含磷基团)等细胞组分，揭示了跨膜受体蛋白酪氨酸激酶活性等分子功能；KEGG富集分析共获得124个相关途径，主要包括表皮生长因子受体(EGFR)酪氨酸激酶抑制剂的抗药性等途径。蛋白互作网络分析获得丝氨酸/苏氨酸激酶1(Akt1)等7个核心靶点；分子对接结果显示，TYP与核心靶点基因及铁死亡相关蛋白SLC7A11和GPX4的结合能均≤-5.0 kcal/mol，表明它们具有显著的结合活性。CCK-8法检测结果显示，TYP可明显抑制PC9细胞活力(P<0.05)；EdU实验结果显示，与对照组相比，TYP组增殖期细胞比例明显降低(P<0.05)；划痕实验、Transwell迁移和侵袭实验结果显示，与对照组相比，TYP组细胞迁移和侵袭能力明显降低(P<0.05)；与对照组相比，TYP组细胞GSH含量、线粒体膜电位明显降低(P<0.05)，ROS、Fe2+含量明显增加(P<0.01)，SLC7A11、GPX4蛋白和mRNA表达水平明显降低(P<0.05)；透射电镜观察显示，与对照组相比，TYP组细胞发生了线粒体嵴减少及膜密度增加等铁死亡特异性变化。与Vector+TYP组相比，OE-SLC7A11+TYP组细胞活力明显升高(P<0.05)，Fe2+含量明显降低(P<0.05)，SLC7A11、GPX4蛋白表达水平明显增高(P<0.05)。结论 TYP可能通过调节SLC7A11-GPX4轴诱导肺腺癌细胞发生铁死亡，并抑制肺腺癌细胞的增殖、迁移和侵袭等恶性行为。

, correspAuthors=阎雪, authorNote=null, correspAuthorsNote=
阎雪，E-mail：
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=juMe80trdw5LTDe1h29L6A==, magXml=kJI7vB7wqbL5H3D29cwn8Q==, pdfUrl=null, pdf=Xkn0cTSATK1KeRpxURtX1Q==, pdfFileSize=7018617, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=gsrZ3MNyprsFx/oHlnsMDw==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=nGc7ar12H/bJII4NKARVXw==, mapNumber=null, authorCompany=null, fund=null, authors=

刘梦茹，硕士研究生，主要从事肺癌发病机制方面的研究

, authorsList=刘梦茹, 阎雪)}, authors=[Author(id=1190330692539093584, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1190330692618785362, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, authorId=1190330692539093584, language=EN, stringName=Meng-Ru Liu, firstName=Meng-Ru, middleName=null, lastName=Liu, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=Department of Respiratory Medicine, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1190330692685894227, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, authorId=1190330692539093584, language=CN, stringName=刘梦茹, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=锦州医科大学附属第一医院呼吸内科，辽宁锦州 121000, bio={"content":"

刘梦茹，硕士研究生，主要从事肺癌发病机制方面的研究

"}, bioImg=null, bioContent=

刘梦茹，硕士研究生，主要从事肺癌发病机制方面的研究

, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1190330692451013196, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, xref=null, ext=[AuthorCompanyExt(id=1190330692459401805, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, companyId=1190330692451013196, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Respiratory Medicine, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China), AuthorCompanyExt(id=1190330692471984718, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, companyId=1190330692451013196, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=锦州医科大学附属第一医院呼吸内科，辽宁锦州 121000)])]), Author(id=1190330692748808789, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=yanxue@jzmu.edu.cn, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1190330692836889175, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, authorId=1190330692748808789, language=EN, stringName=Xue Yan, firstName=Xue, middleName=null, lastName=Yan, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=*, address=Department of Respiratory Medicine, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1190330692899803736, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, authorId=1190330692748808789, language=CN, stringName=阎雪, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=*, address=锦州医科大学附属第一医院呼吸内科，辽宁锦州 121000, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1190330692451013196, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, xref=null, ext=[AuthorCompanyExt(id=1190330692459401805, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, companyId=1190330692451013196, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Respiratory Medicine, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China), AuthorCompanyExt(id=1190330692471984718, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, companyId=1190330692451013196, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=锦州医科大学附属第一医院呼吸内科，辽宁锦州 121000)])])], keywords=[Keyword(id=1190330693021438553, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, orderNo=1, keyword=ferroptosis), Keyword(id=1190330693075964506, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, orderNo=2, keyword=typhaneoside), Keyword(id=1190330693138879067, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, orderNo=3, keyword=lung adenocarcinoma), Keyword(id=1190330693193405020, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, orderNo=4, keyword=network pharmacology), Keyword(id=1190330693260513885, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, orderNo=5, keyword=molecular docking), Keyword(id=1190330693319234142, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, orderNo=1, keyword=铁死亡), Keyword(id=1190330693386343007, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, orderNo=2, keyword=香蒲新苷), Keyword(id=1190330693453451872, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, orderNo=3, keyword=肺腺癌), Keyword(id=1190330693528949345, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, orderNo=4, keyword=网络药理), Keyword(id=1190330693587669602, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, orderNo=5, keyword=分子对接)], refs=[Reference(id=1190330695009538677, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2024, volume=49, issue=7, pageStart=761, pageEnd=769, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=石兴文, 尹鸿涛, 刘进进, journalName=解放军医学杂志, refType=null, unstructuredReference=石兴文, 尹鸿涛, 刘进进, 等. 兰州市城关区中老年人群恶性肿瘤发病与死亡情况及其危险因素的队列研究[J]. 解放军医学杂志, 2024, 49(7): 761-769., articleTitle=兰州市城关区中老年人群恶性肿瘤发病与死亡情况及其危险因素的队列研究, refAbstract=null), Reference(id=1190330695076647542, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2021, volume=71, issue=3, pageStart=209, pageEnd=249, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=Sung H, Ferlay J, Siegel RL, journalName=CA Cancer J Clin, refType=null, unstructuredReference=Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249., articleTitle=Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, refAbstract=null), Reference(id=1190330695139562103, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=11, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=Jiang J, Zhang Y, Wang J, journalName=PeerJ, refType=null, unstructuredReference=Jiang J, Zhang Y, Wang J, et al. Identification of CDT1 as a prognostic marker in human lung adenocarcinoma using bioinformatics approaches[J]. PeerJ, 2023, 11: e16166., articleTitle=Identification of CDT1 as a prognostic marker in human lung adenocarcinoma using bioinformatics approaches, refAbstract=null), Reference(id=1190330695219253880, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2012, volume=149, issue=5, pageStart=1060, pageEnd=1072, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=Dixon SJ, Lemberg KM, Lamprecht MR, journalName=Cell, refType=null, unstructuredReference=Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072., articleTitle=Ferroptosis: an iron-dependent form of nonapoptotic cell death, refAbstract=null), Reference(id=1190330695273779833, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=10, issue=null, pageStart=2173, pageEnd=2185, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=Xing K, Bian X, Shi D, journalName=J Hepatocell Carcinoma, refType=null, unstructuredReference=Xing K, Bian X, Shi D, et al. miR-612 enhances RSL3-induced ferroptosis of hepatocellular carcinoma cells via mevalonate pathway[J]. J Hepatocell Carcinoma, 2023, 10: 2173-2185., articleTitle=miR-612 enhances RSL3-induced ferroptosis of hepatocellular carcinoma cells via mevalonate pathway, refAbstract=null), Reference(id=1190330695332500090, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=13, issue=1, pageStart=226, pageEnd=null, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=Zhang Q, Luo Y, Peng L, journalName=Cell Biosci, refType=null, unstructuredReference=Zhang Q, Luo Y, Peng L, et al. Ferroptosis in cardiovascular diseases: role and mechanism[J]. Cell Biosci, 2023, 13(1): 226., articleTitle=Ferroptosis in cardiovascular diseases: role and mechanism, refAbstract=null), Reference(id=1190330696343327355, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=48, issue=3, pageStart=249, pageEnd=257, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=陈丹丹, 徐涛, 薛姝婧, journalName=解放军医学杂志, refType=null, unstructuredReference=陈丹丹, 徐涛, 薛姝婧, 等. Toll样受体4在热射病大鼠心功能损伤及心肌铁死亡中的作用[J]. 解放军医学杂志, 2023, 48(3): 249-257., articleTitle=Toll样受体4在热射病大鼠心功能损伤及心肌铁死亡中的作用, refAbstract=null), Reference(id=1190330696406241916, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=11, issue=null, pageStart=1297024, pageEnd=null, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=An F, Zhang J, Gao P, journalName=Front Cell Dev Biol, refType=null, unstructuredReference=An F, Zhang J, Gao P, et al. New insight of the pathogenesis in osteoarthritis: the intricate interplay of ferroptosis and autophagy mediated by mitophagy/chaperone-mediated autophagy[J]. Front Cell Dev Biol, 2023, 11: 1297024., articleTitle=New insight of the pathogenesis in osteoarthritis: the intricate interplay of ferroptosis and autophagy mediated by mitophagy/chaperone-mediated autophagy, refAbstract=null), Reference(id=1190330696473350781, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=579, issue=null, pageStart=216465, pageEnd=null, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=Cai S, Zhang B, Huang C, journalName=Cancer Lett, refType=null, unstructuredReference=Cai S, Zhang B, Huang C, et al. CTRP6 protects against ferroptosis to drive lung cancer progression and metastasis by destabilizing SOCS2 and augmenting the xCT/GPX4 pathway[J]. Cancer Lett, 2023, 579: 216465., articleTitle=CTRP6 protects against ferroptosis to drive lung cancer progression and metastasis by destabilizing SOCS2 and augmenting the xCT/GPX4 pathway, refAbstract=null), Reference(id=1190330696548848254, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=66, issue=5, pageStart=1071, pageEnd=1081, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=Du J, Krishnamoorthy K, Ramabhai V, journalName=Mol Biotechnol, refType=null, unstructuredReference=Du J, Krishnamoorthy K, Ramabhai V, et al. Targeting ferroptosis as a therapeutic implication in lung cancer treatment by a novel naphthoquinone inducer: juglone[J]. Mol Biotechnol, 2023, 66(5): 1071-1081., articleTitle=Targeting ferroptosis as a therapeutic implication in lung cancer treatment by a novel naphthoquinone inducer: juglone, refAbstract=null), Reference(id=1190330696615957119, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=9, issue=1, pageStart=453, pageEnd=null, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=Ning N, Shang Z, Liu Z, journalName=Cell Death Discov, refType=null, unstructuredReference=Ning N, Shang Z, Liu Z, et al. A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling[J]. Cell Death Discov, 2023, 9(1): 453., articleTitle=A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling, refAbstract=null), Reference(id=1190330696683065984, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=38, issue=3, pageStart=1173, pageEnd=1190, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=Nie A, Shen C, Zhou Z, journalName=Phytother Resm, refType=null, unstructuredReference=Nie A, Shen C, Zhou Z, et al. Ferroptosis: potential opportunities for natural products in cancer therapy[J]. Phytother Resm, 2023, 38(3): 1173-1190., articleTitle=Ferroptosis: potential opportunities for natural products in cancer therapy, refAbstract=null), Reference(id=1190330696745980545, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=48, issue=1, pageStart=58, pageEnd=63, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=李昕, 栗东海, 高小明, journalName=解放军医学杂志, refType=null, unstructuredReference=李昕, 栗东海, 高小明, 等. 重楼皂苷通过p53/SLC7A11信号轴促进三阴性乳腺癌细胞铁死亡的机制研究[J]. 解放军医学杂志, 2023, 48(1): 58-63., articleTitle=重楼皂苷通过p53/SLC7A11信号轴促进三阴性乳腺癌细胞铁死亡的机制研究, refAbstract=null), Reference(id=1190330696808895106, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2019, volume=516, issue=4, pageStart=1265, pageEnd=1271, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=Zhu HY, Huang ZX, Chen GQ, journalName=Biochem Biophys Res Commun, refType=null, unstructuredReference=Zhu HY, Huang ZX, Chen GQ, et al. Typhaneoside prevents acute myeloid leukemia (AML) through suppressing proliferation and inducing ferroptosis associated with autophagy[J]. Biochem Biophys Res Commun, 2019, 516(4): 1265-1271., articleTitle=Typhaneoside prevents acute myeloid leukemia (AML) through suppressing proliferation and inducing ferroptosis associated with autophagy, refAbstract=null), Reference(id=1190330696880198275, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=39, issue=12, pageStart=2305, pageEnd=2313, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=游赣花, 何恋, 李凯, journalName=中国药理学通报, refType=null, unstructuredReference=游赣花, 何恋, 李凯, 等. 八角莲醇提物抑制MAPK信号通路引起肾癌细胞凋亡的作用机制[J]. 中国药理学通报, 2023, 39(12): 2305-2313., articleTitle=八角莲醇提物抑制MAPK信号通路引起肾癌细胞凋亡的作用机制, refAbstract=null), Reference(id=1190330696947307140, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=16, issue=12, pageStart=1734, pageEnd=null, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=Zhou H, Zhang M, Cao H, journalName=Pharmaceuticals (Basel), refType=null, unstructuredReference=Zhou H, Zhang M, Cao H, et al. Research progress on the synergistic anti-tumor effect of natural anti-tumor components of Chinese herbal medicine combined with chemotherapy drugs[J]. Pharmaceuticals (Basel), 2023, 16(12): 1734., articleTitle=Research progress on the synergistic anti-tumor effect of natural anti-tumor components of Chinese herbal medicine combined with chemotherapy drugs, refAbstract=null), Reference(id=1190330697014416005, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=9, issue=12, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=Song W, Chen Y, Qin L, journalName=Heliyon, refType=null, unstructuredReference=Song W, Chen Y, Qin L, et al. Oxidative stress drives vascular smooth muscle cell damage in acute Stanford type A aortic dissection through HIF-1α/HO-1 mediated ferroptosis[J]. Heliyon, 2023, 9(12): e22857., articleTitle=Oxidative stress drives vascular smooth muscle cell damage in acute Stanford type A aortic dissection through HIF-1α/HO-1 mediated ferroptosis, refAbstract=null), Reference(id=1190330697081524870, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=13, issue=1, pageStart=18302, pageEnd=null, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=Shan Q, Zhang C, Li Y, journalName=Sci Rep, refType=null, unstructuredReference=Shan Q, Zhang C, Li Y, et al. SLC7A11, a potential immunotherapeutic target in lung adenocarcinoma[J]. Sci Rep, 2023, 13(1): 18302., articleTitle=SLC7A11, a potential immunotherapeutic target in lung adenocarcinoma, refAbstract=null), Reference(id=1190330697148633735, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, doi=null, pmid=null, pmcid=null, year=2023, volume=388, issue=null, pageStart=110835, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=Ruan Q, Wang C, Zhang Y, journalName=Chem Biol Interact, refType=null, unstructuredReference=Ruan Q, Wang C, Zhang Y, et al. Ruscogenin attenuates cartilage destruction in osteoarthritis through suppressing chondrocyte ferroptosis via Nrf2/SLC7A11/GPX4 signaling pathway[J]. Chem Biol Interact, 2023, 388: 110835., articleTitle=Ruscogenin attenuates cartilage destruction in osteoarthritis through suppressing chondrocyte ferroptosis via Nrf2/SLC7A11/GPX4 signaling pathway, refAbstract=null)], funds=[Fund(id=1190330694808212083, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, awardId=JYTJCZR2020057, language=EN, fundingSource=Science and Technology Research Project of Education Department of Liaoning Province(JYTJCZR2020057), fundOrder=null, country=null), Fund(id=1190330694875320948, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, awardId=JYTJCZR2020057, language=CN, fundingSource=辽宁省教育厅科学技术研究项目(JYTJCZR2020057), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1190330692451013196, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, xref=null, ext=[AuthorCompanyExt(id=1190330692459401805, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, companyId=1190330692451013196, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Respiratory Medicine, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China), AuthorCompanyExt(id=1190330692471984718, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, companyId=1190330692451013196, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=锦州医科大学附属第一医院呼吸内科，辽宁锦州 121000)])], figs=[ArticleFig(id=1190330693742858851, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, label=Fig.1, caption=Results of bioinformatics analysis on the target genes of typhaneoside with lung adenocarcinoma, figureFileSmall=xQBwRdoBkEVGYmpDLvOvSg==, figureFileBig=qgNWJSlUjQf3T9rV/86KSQ==, tableContent=null), ArticleFig(id=1190330693822550628, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, label=图1, caption=TYP与肺腺癌相关靶点基因的生物信息学分析结果

TCGA. 癌症基因组图谱；TYP. 香蒲新苷；GO. 基因本体论；KEGG. 京都基因与基因组百科全书；PI3K. 磷脂酰肌醇3-激酶；Akt. 丝氨酸/苏氨酸激酶；FoxO. 叉头框蛋白；AGE-RAGE. 晚期糖基化终产物及其受体；A. 从TCGA数据库、GeneCards数据库和GSE116959数据集中筛选肺腺癌相关靶点基因；B. TYP预测靶点与肺腺癌相关靶点基因的交集；C. 交集基因的蛋白互作网络；D. GO分析结果各分支的前10个项目；E. KEGG富集分析结果的前20条通路

, figureFileSmall=xQBwRdoBkEVGYmpDLvOvSg==, figureFileBig=qgNWJSlUjQf3T9rV/86KSQ==, tableContent=null), ArticleFig(id=1190330693914825317, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, label=Fig.2, caption=Visualization of molecular docking of TYP with core target genes related to lung adenocarcinoma, figureFileSmall=Y0pid447V7cMbcV9TovBeg==, figureFileBig=C+rBmgvL9ir/b3DVMRDaSQ==, tableContent=null), ArticleFig(id=1190330693965156966, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, label=图2, caption=TYP与肺腺癌相关核心靶点基因分子对接的可视化

TYP. 香蒲新苷；Akt1. 丝氨酸/苏氨酸激酶1；MMP9. 基质金属蛋白酶9；EGFR. 表皮生长因子受体；PIK3R1. 磷脂酰肌醇3-激酶调节亚基1；SRC. 非受体酪氨酸激酶；PTGS2. 前列腺素E合酶2；TNF. 肿瘤坏死因子；SLC7A11. 溶质载体家族7成员11；GPX4. 谷胱甘肽过氧化物酶4

, figureFileSmall=Y0pid447V7cMbcV9TovBeg==, figureFileBig=C+rBmgvL9ir/b3DVMRDaSQ==, tableContent=null), ArticleFig(id=1190330694015488615, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, label=Fig.3, caption=Effects of TYP on proliferation of PC9 cells, figureFileSmall=XMiS6tVtj6nvV+G1QvyzGw==, figureFileBig=LbNwnn/tePeZmVTOorplNg==, tableContent=null), ArticleFig(id=1190330694070014568, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, label=图3, caption=TYP对PC9细胞增殖的影响

TYP. 香蒲新苷；EdU. 5-乙炔基-2'-脱氧尿嘧啶核苷；A. TYP的化学结构；B. 不同浓度TYP处理PC9细胞48或72 h后，采用CCK-8法检测细胞活力；与0 μmol/L TYP比较，(1)P<0.05，(2)P<0.01；与48 h比较，(3)P<0.05；C. EdU实验检测细胞增殖情况；与对照组相比，(4)P<0.05

, figureFileSmall=XMiS6tVtj6nvV+G1QvyzGw==, figureFileBig=LbNwnn/tePeZmVTOorplNg==, tableContent=null), ArticleFig(id=1190330694132929129, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, label=Fig.4, caption=Effects of TYP on migration and invasion of PC9 cells, figureFileSmall=RamLCs7xqpok1u/Tmvb6OA==, figureFileBig=RsFdkv6XYl/J6I8MCg5dNg==, tableContent=null), ArticleFig(id=1190330694195843690, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, label=图4, caption=TYP对PC9细胞迁移和侵袭能力的影响

TYP. 香蒲新苷；N-cadherin. 神经钙黏蛋白；MMP9. 基质金属蛋白酶9；MMP2. 基质金属蛋白酶2；Vimentin. 波形蛋白；GAPDH. 甘油醛-3-磷酸脱氢酶；A. Transwell迁移和侵袭实验检测PC9细胞的迁移和侵袭能力(×200)；B. 划痕实验检测PC9细胞的迁移能力；C. Western blotting检测各组N-cadherin、MMP9、MMP2、Vimentin蛋白的表达；D. RT-qPCR检测各组N-cadherin、MMP9、MMP2、Vimentin mRNA的表达；与对照组相比，(1)P<0.05，(2)P<0.01；与低TYP组相比，(3)P<0.05，(4)P<0.01

, figureFileSmall=RamLCs7xqpok1u/Tmvb6OA==, figureFileBig=RsFdkv6XYl/J6I8MCg5dNg==, tableContent=null), ArticleFig(id=1190330694254563947, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, label=Fig.5, caption=Effects of TYP on ferroptosis of PC9 cells, figureFileSmall=lkjqz69dI6xhtLkSA4X9uQ==, figureFileBig=7SN8b2lswLyXFKrQmv5IGQ==, tableContent=null), ArticleFig(id=1190330694317478508, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, label=图5, caption=TYP对PC9细胞铁死亡的影响

TYP. 香蒲新苷；FerrOrange. 一种橙色亚铁离子荧光探针；GSH. 还原型谷胱甘肽；ROS. 活性氧；JC-1. 一种用于检测线粒体膜电位的荧光探针；A. CCK-8法检测各组PC9细胞活力；B. GSH试剂盒检测各组细胞内GSH含量；C. 亚铁离子探针检测各组Fe2+含量；D. ROS检测试剂盒测定各组ROS含量；E. 线粒体膜电位检测试剂盒测定各组的线粒体膜电位；F. 透射电子显微镜观察各组细胞的线粒体超微结构；与对照组相比，(1)P<0.01；与低TYP组相比，(2)P<0.05，(3)P<0.01；与高TYP组相比，(4)P<0.05，(5)P<0.01

, figureFileSmall=lkjqz69dI6xhtLkSA4X9uQ==, figureFileBig=7SN8b2lswLyXFKrQmv5IGQ==, tableContent=null), ArticleFig(id=1190330694372004461, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, label=Fig.6, caption=Molecular mechanisms of TYP-induced ferroptosis in PC9 cell, figureFileSmall=kLEmbNK6a4NapRliXuzwuQ==, figureFileBig=TYD8IVf2RCXwMHqs9tgdZA==, tableContent=null), ArticleFig(id=1190330694430724718, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, label=图6, caption=TYP诱导PC9细胞铁死亡的分子机制

TYP. 香蒲新苷；GAPDH. 甘油醛-3-磷酸脱氢酶；SLC7A11. 溶质载体家族7成员11；GPX4. 谷胱甘肽过氧化物酶4；FerrOrange. 一种橙色亚铁离子荧光探针；A. Western blotting检测各组细胞SLC7A11和GPX4蛋白的表达；B. RT-qPCR法检测各组细胞SLC7A11和GPX4 mRNA的表达；与对照组相比，(1)P<0.05，(2)P<0.01；与低TYP组相比，(3)P<0.05；与高TYP组相比，(4)P<0.01；C. CCK-8法检测SLC7A11过表达后各组细胞活力；D. 亚铁离子探针检测SLC7A11过表达后各组细胞Fe2+含量；E. Western blotting检测SLC7A11过表达后各组细胞SLC7A11和GPX4蛋白的表达；与Vector组相比，(5)P<0.05，(6)P<0.01；与Vector+TYP组相比，(7)P<0.05，(8)P<0.01；与OE-SLC7A11组相比，(9)P<0.01

, figureFileSmall=kLEmbNK6a4NapRliXuzwuQ==, figureFileBig=TYD8IVf2RCXwMHqs9tgdZA==, tableContent=null), ArticleFig(id=1190330694489444975, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, label=Tab.1, caption=

Primer sequences for RT-qPCR

, figureFileSmall=null, figureFileBig=null, tableContent=
基因引物序列(5'-3')
GAPDH上游：CACCCACTCCTCCACCTTTGAC
下游：GTCCACCACCCTGTTGCTGTAG
MMP2上游：ATGACGATGAGCTATGGACCTT
下游：TATCAGTGCAGCTGTTGTACTCC
MMP9上游：ACTTTGACAGCGACAAGAAGTG
下游：AGTGAAGCGGTACATAGGGTACA
N-cadherin上游：TGAAGTTCCTGAGAACAGGGTAG
下游：CACTGATTCTGTACACTGCGTTC
Vimentin上游：GTCACCTTCGTGAATACCAAGAC
下游：GAAAAGTTTGGAAGAGGCAGAG
SLC7A11上游：ACGGTGGTGTGTTTGCTGTCTC
下游：GCTGGTAGAGGAGTGTGCTTGC
GPX4上游：CCGCTGTGGAAGTGGATGAAGATC
下游：CTTGTCGATGAGGAACTGTGGAGAG
), ArticleFig(id=1190330694543970928, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, label=表1, caption=

RT-qPCR引物序列

, figureFileSmall=null, figureFileBig=null, tableContent=
基因引物序列(5'-3')
GAPDH上游：CACCCACTCCTCCACCTTTGAC
下游：GTCCACCACCCTGTTGCTGTAG
MMP2上游：ATGACGATGAGCTATGGACCTT
下游：TATCAGTGCAGCTGTTGTACTCC
MMP9上游：ACTTTGACAGCGACAAGAAGTG
下游：AGTGAAGCGGTACATAGGGTACA
N-cadherin上游：TGAAGTTCCTGAGAACAGGGTAG
下游：CACTGATTCTGTACACTGCGTTC
Vimentin上游：GTCACCTTCGTGAATACCAAGAC
下游：GAAAAGTTTGGAAGAGGCAGAG
SLC7A11上游：ACGGTGGTGTGTTTGCTGTCTC
下游：GCTGGTAGAGGAGTGTGCTTGC
GPX4上游：CCGCTGTGGAAGTGGATGAAGATC
下游：CTTGTCGATGAGGAACTGTGGAGAG
), ArticleFig(id=1190330694602691185, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=EN, label=Tab.2, caption=

Molecular docking results of TYP with core target genes related to lung adenocarcinoma

, figureFileSmall=null, figureFileBig=null, tableContent=
分子对接方式结合能(kcal/mol)
TYP-Akt1-9.0
TYP-MMP9-8.2
TYP-EGFR-8.7
TYP-PIK3R1-9.8
TYP-SRC-7.3
TYP-PTGS2-9.4
TYP-TNF-6.8
TYP-SLC7A11-9.6
TYP-GPX4-6.5
), ArticleFig(id=1190330694669800050, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1190310111211000624, language=CN, label=表2, caption=

TYP与肺腺癌相关的核心靶点基因分子对接结果

, figureFileSmall=null, figureFileBig=null, tableContent=
分子对接方式结合能(kcal/mol)
TYP-Akt1-9.0
TYP-MMP9-8.2
TYP-EGFR-8.7
TYP-PIK3R1-9.8
TYP-SRC-7.3
TYP-PTGS2-9.4
TYP-TNF-6.8
TYP-SLC7A11-9.6
TYP-GPX4-6.5
)], attaches=null, journal=Journal(id=1146441329971666965, delFlag=0, nameCn=解放军医学杂志, nameEn=Medical Journal of Chinese People’s Liberation Army, nameHistory1=null, nameHistory2=null, issn=0577-7402, eissn=null, cn=11-1056/R, coden=null, periodic=0, language=CN, oaType=是, ccby=CC BY-NC-ND, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=6srot5PcoYX30Oa4xeTmeg==, journalPrice=null, startedYear=null, abbrevIsoEn=null, journalRemark=null, publicationField=null, createdTime=1751262512917, updatedTime=1761735725513, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=M, firstLetterEn=M, subjectCode=Life Sciences, subjectName=Life Sciences, subjectCodeEn=Life Sciences, subjectNameEn=null, picCn=6srot5PcoYX30Oa4xeTmeg==, picEn=ELwBh5xqrSTlIs7HmSNt2Q==, jcr=null, cjcr=null, exts=[JournalExt(id=1190369167564968109, language=CN, name=解放军医学杂志, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1761735725537, updatedTime=1761735725537, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=#, submissionEditorUrl=#, submissionReviewUrl=#, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1190369167615299758, language=EN, name=Medical Journal of Chinese People’s Liberation Army, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1761735725549, updatedTime=1761735725549, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=#, submissionEditorUrl=#, submissionReviewUrl=#, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1189873630562394117, websiteList=[Website(id=1189873845923287108, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1189873630562394117, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/jfjyxzz/CN, language=CN, createTime=1761617631655, createBy=18614031015, updateTime=1761622010471, updateBy=18614031015, name=解放军医学杂志-中文, tplId=1146099689490845704, title=解放军医学杂志, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1189924939378520839, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=articleTextType, value=kx, createTime=1761629813284, updateTime=1761629813284, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924939353355012, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=banner, value=null, createTime=1761629813278, updateTime=1761629813278, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924939399492362, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=grayFlag, value=0, createTime=1761629813289, updateTime=1761629813289, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924939344966403, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=logo, value=https://castjournals.cast.org.cn/joweb/jfjyxzz/CN/file/pic?fileId=+zXjYVhun8ZOAA6+aKx2hw==, createTime=1761629813276, updateTime=1761629813276, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924939412075276, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=minRunFlag, value=0, createTime=1761629813292, updateTime=1761629813292, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924939374326534, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/jfjyxzz/CN/file/pic, createTime=1761629813283, updateTime=1761629813283, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924939407880971, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=silenceFlag, value=0, createTime=1761629813291, updateTime=1761629813291, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924939361743621, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1761629813280, updateTime=1761629813280, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924939386909448, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=themeColor, value=null, createTime=1761629813286, updateTime=1761629813286, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924939395298057, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873845923287108, code=themeStyle, value=null, createTime=1761629813288, updateTime=1761629813288, creator=18614031015, updator=18614031015)]), Website(id=1189873846057504839, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1189873630562394117, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/jfjyxzz/EN, language=EN, createTime=1761617631687, createBy=18614031015, updateTime=1761622030030, updateBy=18614031015, name=解放军医学杂志-英文, tplId=1146101810881728533, title=Medical Journal of Chinese People’s Liberation Army, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1189924968168223505, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=articleTextType, value=kx, createTime=1761629820148, updateTime=1761629820148, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924968147251982, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=banner, value=null, createTime=1761629820143, updateTime=1761629820143, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924968185000724, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=grayFlag, value=0, createTime=1761629820152, updateTime=1761629820152, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924968138863373, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=logo, value=https://castjournals.cast.org.cn/joweb/jfjyxzz/EN/file/pic?fileId=+zXjYVhun8ZOAA6+aKx2hw==, createTime=1761629820141, updateTime=1761629820141, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924968197583638, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=minRunFlag, value=0, createTime=1761629820155, updateTime=1761629820155, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924968159834896, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/jfjyxzz/EN/file/pic, createTime=1761629820146, updateTime=1761629820146, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924968193389333, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=silenceFlag, value=0, createTime=1761629820154, updateTime=1761629820154, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924968155640591, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1761629820145, updateTime=1761629820145, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924968172417810, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=themeColor, value=null, createTime=1761629820149, updateTime=1761629820149, creator=18614031015, updator=18614031015), WebsiteProps(id=1189924968180806419, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1189873846057504839, code=themeStyle, value=null, createTime=1761629820151, updateTime=1761629820151, creator=18614031015, updator=18614031015)])], journalTitle=解放军医学杂志, weixinUrl=null, journalUrl=http://zh.jfjyxzz.org.cn/, iacademicId=null, status=1, seqNo=null, journalTitleEn=Medical Journal of Chinese People’s Liberation Army, journalPhotoCn=6srot5PcoYX30Oa4xeTmeg==, journalPhotoEn=ELwBh5xqrSTlIs7HmSNt2Q==, journalFirstLetter=M, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false), detailUrlCn=https://castjournals.cast.org.cn/joweb/jfjyxzz/CN/10.11855/j.issn.0577-7402.0351.2025.0126, detailUrlEn=https://castjournals.cast.org.cn/joweb/jfjyxzz/EN/10.11855/j.issn.0577-7402.0351.2025.0126, pdfUrlCn=https://castjournals.cast.org.cn/joweb/jfjyxzz/CN/PDF/10.11855/j.issn.0577-7402.0351.2025.0126, pdfUrlEn=https://castjournals.cast.org.cn/joweb/jfjyxzz/EN/PDF/10.11855/j.issn.0577-7402.0351.2025.0126, aliStartDate=null, aliEndDate=null, collectionFlag=false, citedCount=null, citedUrl=null, reference=null)
收藏切换
基于网络药理学及体外实验探讨香蒲新苷对肺腺癌的作用及其分子机制
收藏切换
PDF下载
刘梦茹 , 阎雪 *
解放军医学杂志 | 基础研究 2025,50(5): 581-591
收起
收藏切换
解放军医学杂志 | 基础研究 2025, 50(5): 581-591
基于网络药理学及体外实验探讨香蒲新苷对肺腺癌的作用及其分子机制
全屏
刘梦茹, 阎雪*
作者信息
  • 锦州医科大学附属第一医院呼吸内科，辽宁锦州 121000

    • 刘梦茹，硕士研究生，主要从事肺癌发病机制方面的研究

通讯作者:

阎雪，E-mail：
Exploring the effects and underlying mechanisms of typhaneoside on lung adenocarcinoma based on network pharmacology and in vitro experiments
Meng-Ru Liu, Xue Yan*
Affiliations
  • Department of Respiratory Medicine, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China
出版时间: 2025-05-28 doi: 10.11855/j.issn.0577-7402.0351.2025.0126
文章导航
收藏切换
摘要
收起

目的 基于网络药理学及体外实验探讨香蒲新苷(TYP)对肺腺癌的作用及其潜在的分子机制。方法 通过预测靶点网站SwissTargetPrediction、癌症基因组图谱(TCGA)数据库、GeneCards数据库和基因表达综合数据库(GEO)获得TYP-肺腺癌相关靶点基因，对得到的TYP-肺腺癌相关基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析，应用String数据库进行蛋白互作网络分析，应用Vina软件进行分子对接，通过这些网络药理学分析方法探索TYP对肺腺癌的理论作用通路。取PC9细胞，设置对照组(正常培养)、低TYP组(50 μmol/L TYP处理48 h)、高TYP组(100 μmol/L TYP处理48 h)与铁抑制剂-1(Fer-1)+TYP组(1 μmol/L Fer-1+100 μmol/L TYP处理48 h)；采用CCK-8法检测细胞活力，EdU实验检测细胞增殖能力，划痕实验、Transwell迁移及侵袭实验检测细胞迁移和侵袭能力，采用还原型谷胱甘肽(GSH)检测试剂盒、活性氧(ROS)检测试剂盒、线粒体膜电位检测试剂盒、亚铁离子荧光探针、透射电镜检测铁死亡的发生，Western blotting和反转录-定量PCR(RT-qPCR)检测铁死亡关键分子溶质载体家族7成员11(SLC7A11)和谷胱甘肽过氧化物酶4(GPX4)蛋白和mRNA的表达情况。应用SLC7A11过表达质粒转染PC9细胞，设置Vector组(空载质粒转染)、Vector+TYP组(空载质粒转染+100 μmol/L TYP处理48 h)、OE-SLC7A11组(SLC7A11过表达质粒转染)与OE-SLC7A11+TYP组(SLC7A11过表达质粒转染+100 μmol/L TYP处理48 h)，通过CCK-8法、亚铁离子荧光探针、铁死亡关键分子SLC7A11和GPX4蛋白表达情况验证SLC7A11在TYP作用于PC9细胞时的分子机制。结果 通过靶点预测网站SwissTargetPrediction及基因数据库(TCGA、GeneCards和GEO)共预测了73个TYP-肺腺癌相关靶点基因。GO分析结果显示，靶基因主要参与激酶活性的正向调节等生物过程，主要富集于转移酶复合物(转移含磷基团)等细胞组分，揭示了跨膜受体蛋白酪氨酸激酶活性等分子功能；KEGG富集分析共获得124个相关途径，主要包括表皮生长因子受体(EGFR)酪氨酸激酶抑制剂的抗药性等途径。蛋白互作网络分析获得丝氨酸/苏氨酸激酶1(Akt1)等7个核心靶点；分子对接结果显示，TYP与核心靶点基因及铁死亡相关蛋白SLC7A11和GPX4的结合能均≤-5.0 kcal/mol，表明它们具有显著的结合活性。CCK-8法检测结果显示，TYP可明显抑制PC9细胞活力(P<0.05)；EdU实验结果显示，与对照组相比，TYP组增殖期细胞比例明显降低(P<0.05)；划痕实验、Transwell迁移和侵袭实验结果显示，与对照组相比，TYP组细胞迁移和侵袭能力明显降低(P<0.05)；与对照组相比，TYP组细胞GSH含量、线粒体膜电位明显降低(P<0.05)，ROS、Fe2+含量明显增加(P<0.01)，SLC7A11、GPX4蛋白和mRNA表达水平明显降低(P<0.05)；透射电镜观察显示，与对照组相比，TYP组细胞发生了线粒体嵴减少及膜密度增加等铁死亡特异性变化。与Vector+TYP组相比，OE-SLC7A11+TYP组细胞活力明显升高(P<0.05)，Fe2+含量明显降低(P<0.05)，SLC7A11、GPX4蛋白表达水平明显增高(P<0.05)。结论 TYP可能通过调节SLC7A11-GPX4轴诱导肺腺癌细胞发生铁死亡，并抑制肺腺癌细胞的增殖、迁移和侵袭等恶性行为。

铁死亡  /  香蒲新苷  /  肺腺癌  /  网络药理  /  分子对接

Objective To investigate the effects and underlying molecular mechanisms of typhaneoside (TYP) on lung adenocarcinoma based on network pharmacology and in vitro experiments. Methods TYP-lung adenocarcinoma-related genes were obtained from the prediction target website SwissTargetPrediction, The Cancer Genome Atlas (TCGA) database, GeneCards database, and Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the obtained TYP-lung adenocarcinoma-related genes. Protein-protein network interactions analysis was carried out using the String database, and molecular docking was conducted with the Vina software. These network pharmacological analysis methods were employed to explore the theoretical action pathways of TYP on lung adenocarcinoma. PC9 cells were divided into control group (normal culture), low-TYP group (treated with 50 μmol/L TYP for 48 h), high-TYP group (treated with 100 μmol/L TYP for 48 h), and ferrostatin-1 (Fer-1)+TYP group (treated with 1 μmol/L Fer-1+100 μmol/L TYP for 48 h). The cell viability was detected by the CCK-8 assay, the cell proliferation ability was detected by the EdU assay, and the cell migration and invasion ability was detected by scratch assay, Transwell migration assay and Transwell invasion assay. The occurrence of ferroptosis was detected by reduced glutathione (GSH) assay kit, reactive oxygen species (ROS) assay kit, mitochondrial membrane potential assay kit, ferrous ion fluorescent probe, and transmission electron microscopy. Protein and mRNA expression levels of ferroptosis-related key molecules, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), were measured by Western blotting and reverse transcription-quantitative PCR (RT-qPCR). PC9 cells were transfected with SLC7A11 overexpression plasmid and divided into vector group (transfected with empty plasmid), vector+TYP group (transfected with empty plasmid and treated with 100 μmol/L TYP for 48 h), OE-SLC7A11 group (transfected with SLC7A11 overexpression plasmid) and OE-SLC7A11+TYP group (transfected with SLC7A11 overexpression plasmid and treated with 100 μmol/L TYP for 48 h). The molecular mechanism of SLC7A11 in the effect of TYP on PC9 was verified by CCK-8 assay, ferrous ion fluorescence probe, and protein expression levels of SLC7A11 and GPX4. Results A total of 73 TYP-lung adenocarcinoma-related target genes were predicted. GO analysis showed that the target genes were mainly involved in biological processes such as positive regulation of kinase activity, and were enriched in cellular components like transferase complex (transferring phosphorus-containing groups), revealing molecular functions such as transmembrane receptor protein tyrosine kinase activity. KEGG analysis identified 124 related pathways, mainly including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance pathway. Protein-protein interaction network analysis obtained 7 core targets such as serine/threonine kinase 1 (Akt1). Molecular docking results showed that the binding energies of TYP with core target genes and the ferroptosis-related proteins (SLC7A11 and GPX4) were all ≤-5.0 kcal/mol, indicating significant binding activity. CCK-8 assay showed that TYP significantly inhibited PC9 cell viability (P<0.05). EdU assay demonstrated that the proportion of proliferating cells in TYP group was significantly lower than that in control group (P<0.05). Scratch assay, Transwell migration assay, and invasion assay revealed that, compared with control group, the migration and invasion abilities of PC9 cells in TYP group significantly decreased (P<0.05), and GSH content and mitochondrial membrane potential in TYP group also significantly decreased (P<0.05), while ROS and Fe2+ contents increased significantly (P<0.01), and protein and mRNA expression levels of SLC7A11 and GPX4 decreased significantly (P<0.05). Transmission electron microscopy results showed that cells in TYP group exhibited specific ferroptosis-related changes such as reduced mitochondrial cristae and increased membrane density, compared with control group. Compared with vector+TYP group, OE-SLC7A11+TYP group had higher cell viability (P<0.05), lower Fe2+ content (P<0.05), and higher protein expression levels of SLC7A11 and GPX4 (P<0.05). Conclusion TYP may induce ferroptosis in lung adenocarcinoma cells and inhibit their malignant behaviors such as proliferation, migration and invasion by regulating the SLC7A11-GPX4 axis.

ferroptosis  /  typhaneoside  /  lung adenocarcinoma  /  network pharmacology  /  molecular docking
刘梦茹, 阎雪. 基于网络药理学及体外实验探讨香蒲新苷对肺腺癌的作用及其分子机制. 解放军医学杂志, 2025 , 50 (5) : 581 -591 . DOI: 10.11855/j.issn.0577-7402.0351.2025.0126
Meng-Ru Liu, Xue Yan. Exploring the effects and underlying mechanisms of typhaneoside on lung adenocarcinoma based on network pharmacology and in vitro experiments[J]. Medical Journal of Chinese People’s Liberation Army, 2025 , 50 (5) : 581 -591 . DOI: 10.11855/j.issn.0577-7402.0351.2025.0126
正文
收起
肺癌是全球癌症死亡的主要原因之一，占癌症死亡总数的18.0%；其发病率和病死率居高不下[1]，5年生存率仅10%~20%[2]。肺腺癌是非小细胞肺癌常见的组织学亚型[3]，由于患者的异质性、靶向药物耐药、免疫相关毒性等导致其临床治疗效果有限，患者预后不理想，因此亟须寻找新的治疗靶点和治疗方式来改善肺腺癌患者的预后及生存质量。铁死亡是2012年由Dixon等[4]提出的有别于细胞凋亡和坏死的一种铁依赖性的伴有脂质活性氧(reactive oxygen species，ROS)产生的细胞死亡形式。多项研究表明，铁死亡可参与肿瘤[5]、心脑血管疾病[6-7]、炎症性疾病[8]等多种疾病的进展。有研究发现，铁死亡与肺癌的发生关系密切[9]，可作为肺癌治疗的新靶点[10]。溶质载体家族7成员11(solute carrier family 7 member 11，SLC7A11)是铁死亡通路的关键因子，研究表明，通过调控其表达来调节铁死亡的发生是治疗癌症的新思路[11]。近年来从中药中提取活性成分来治疗癌症已成为研究的热点，并取得了一定的效果。目前已发现多种天然药物可诱导肺癌细胞铁死亡，且具有多通路、多靶点的特点，因此天然药物干预铁死亡的机制有待进一步探索[12-13]。香蒲新苷(typhaneoside，TYP)是传统中药蒲黄的一种活性成分，具有较强的药理作用，可通过抑制细胞增殖和诱导与自噬相关的铁死亡来预防急性髓系白血病(acute myeloid leukaemia，AML)[14]，但其对肺癌的作用研究鲜见。本研究基于网络药理学及体外实验探讨TYP对肺腺癌的作用及其潜在的分子机制，以期为TYP在肺腺癌临床治疗中的应用提供依据。
1 材料与方法
收起
1.1 生物信息学分析
1.1.1 TYP靶点预测
从PubChem数据库(https://pubchem.ncbi.nlm.nih.gov)中获取TYP的Canonical SMILES信息‍，通过SwissTargetPrediction数据库(http://swisstargetprediction.ch/)进行靶点预测[15]。
1.1.2 肺腺癌相关靶点基因筛选
从癌症基因组图谱(The Cancer Genome Atlas，TCGA)数据库(https://portal.gdc.cancer.gov/)中筛选肺腺癌组织与正常组织差异表达的基因，筛选标准为∣log2差异倍数(fold change，FC)∣>1和错误发现率(false discovery rate，FDR)<0.05；在GeneCards数据库(https://www.genecards.org/)中检索“lung adenocarcinoma”，筛选GeneCards相关性得分>5分的基因；在基因表达综合数据库(Gene Expression Omnibus data base，GEO，https://dcc.icgc.org)的GSE116959数据集中，利用GEO2R分析工具以∣log2FC∣>1和FDR<0.05的标准筛选肺腺癌组织与正常组织差异表达的基因。将3个数据库中得到的差异表达基因取并集得到肺腺癌相关靶点基因。
1.1.3 TYP-肺腺癌相关靶点基因分析
将TYP预测靶点与肺腺癌相关靶点基因取交集，获得TYP-肺腺癌相关基因，对得到的交集基因进行基因本体论(Gene Ontology，GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)分析，并通过String数据库(https://cn.string-db.org/)进行蛋白网络互作分析。
1.1.4 分子对接
从PubChem数据库中下载TYP的2D结构，导入ChemBioOffice Ultra软件将2D结构转换为3D结构。从布鲁克海文蛋白质数据库(the BrookHaven Protein Data Bank，PDB，https://www.rcsb.org)中下载相应的3D蛋白结构，使用PyMOL软件删除蛋白结构中的水分子和小分子配体；用AutoDockTools软件进行加氢处理，选择Grid BOX确定活性口袋的位置并尽量扩大搜索范围；应用Vina软件进行分子对接，选择自由能最低的对接构象作为最终对接构象，并用PyMOL软件可视化对接结果。
1.2 体外细胞实验
1.2.1 试剂及抗体
TYP(HPLC≥98%，B21367；上海源叶生物科技有限公司)；铁抑制剂-1(ferrostatin-1，Fer-1；上海阿拉丁生化科技有限公司)。体外实验中TYP和Fer-1均溶于DMSO中，于-20 ℃储存备用。带有苯甲基磺酰氟(PMSF)的RIPA裂解液、转染试剂Lipo6000、离心柱式RNA抽提试剂盒(上海碧云天生物技术有限公司)；BCA蛋白测定试剂盒、含JC-1的线粒体膜电位检测试剂盒(北京索莱宝科技有限公司)；甘油醛-3-磷酸脱氢酶(glyceraldehyde-3-phosphate dehydrogenase，GAPDH)、基质金属蛋白酶2(matrix metallopeptidase 2，MMP2)、MMP9、神经钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)一抗，以及ROS检测试剂盒、还原型谷胱甘肽(reduced glutathione，GSH)含量检测试剂盒(沈阳万类生物科技有限公司)；SLC7A11、谷胱甘肽过氧化物酶4(glutathione peroxidase 4，GPX4)一抗(美国Affinity公司)；HRP羊抗兔IgG (H+L)二抗(美国APExBIO公司)；ECL化学发光超敏显色试剂盒(福建荷瑞生物科技有限公司)；CCK-8试剂盒(南京恩晶生物科技有限公司)；FeRhoNox-1亚铁离子荧光探针(上海懋康生物科技有限公司)；SLC7A11过表达质粒(苏州吉玛基因股份有限公司)；EdU-488细胞增殖检测试剂盒(武汉赛维尔生物科技有限公司)；RNA反转录试剂盒、SYBR Premix Ex Taq(苏州近岸蛋白质科技股份有限公司)；胎牛血清(浙江天杭生物科技股份有限公司)；1%青霉素-链霉素(武汉普诺赛生命科技有限公司)。
1.2.2 细胞培养
人肺腺癌PC9细胞系由中科院上海细胞库提供，在含有10%胎牛血清和1%青霉素-链霉素的DMEM培养基中于37 ℃、5% CO2条件下培养。取对数生长期细胞进行实验。
1.2.3 CCK-8法检测细胞活力
将PC9细胞以3000个/孔的密度接种于96孔板中，4 h贴壁后，在37 ℃下饥饿24 h。然后分别用不同浓度(0、12.5、25、50、100、200 μmol/L)的TYP与PC9细胞共培养48 h和72 h，达到培养时间后每孔加入10 μl CCK-8试剂，黑暗中孵育1.5 h。采用酶标仪检测450 nm处的吸光度值，计算细胞活力。
1.2.4 EdU实验检测细胞增殖情况
取PC9细胞，设置对照组(正常培养)与TYP组(100 μmol/L TYP处理48 h)，使用EdU-488细胞增殖检测试剂盒测定两组处于增殖期的细胞比例，具体操作按照说明书进行，荧光显微镜拍照记录。
1.2.5 Transwell迁移和侵袭实验检测细胞的迁移和侵袭能力
取PC9细胞，设置对照组(正常培养)、低TYP组(50 μmol/L TYP处理48 h)与高TYP组(100 μmol/L TYP处理48 h)。(1)迁移能力：在每个小室上层中铺5000个PC9细胞及200 μl不含血清的培养基，小室下层加入600 μl完全培养基。48 h后将小室取出，擦去上层小室细胞，4%多聚甲醛溶液固定30 min，结晶紫染色30 min，显微镜拍照并计数。(2)侵袭能力：将基质胶4 °C过夜解冻，按照1:8的比例加入DMEM培养基稀释，每个小室中加入60 μl稀释液，37 °C成胶3 h后，向小室中加入100 μl DMEM培养基37 °C水化30 min，每个小室上层中铺5000个PC9细胞及200 μl不含血清的培养基，小室下层加入600 μl完全培养基。48 h后将小室取出，擦去上层小室细胞，4%多聚甲醛溶液固定30 min，结晶紫染色30 min，显微镜拍照计数。
1.2.6 划痕实验检测细胞迁移率
将PC9细胞接种在6孔板中，使用200 μl枪头进行划痕，洗净漂浮细胞，设置对照组(正常培养)与TYP组(100 μmol/L TYP处理)，在0、24和48 h对同一划痕位置进行显微镜成像。使用ImageJ软件确定迁移面积变化并计算细胞迁移率。
1.2.7 GSH、ROS、Fe2+含量及线粒体膜电位检测
取PC9细胞，设置对照组(正常培养)、低TYP组(50 μmol/L TYP处理48 h)、高TYP组(100 μmol/L TYP处理48 h)与Fer-1+TYP组(1 μmol/L Fer-1+100 μmol/L TYP处理48 h)。采用CCK-8法检测细胞活力；应用GSH检测试剂盒检测各组细胞内GSH含量，设置空白孔、标准孔和待测孔，按说明书步骤操作；ROS检测试剂盒测定各组细胞内ROS含量，按说明书步骤操作，荧光显微镜拍照记录；亚铁离子探针检测细胞内Fe2+含量，按照说明书步骤将探针稀释成1 μmol/L，37 ℃孵育1 h，荧光显微镜拍照记录；含JC-1的线粒体膜电位检测试剂盒测定各组细胞内线粒体膜电位，具体操作按照说明书进行，荧光显微镜拍照记录。
1.2.8 透射电镜观察线粒体超微结构
取PC9细胞，设置对照组(正常培养)与TYP组(100 μmol/L TYP处理48 h)，电镜固定液固定，刮取法收集细胞。由武汉赛维尔生物科技有限公司进行透射电子显微镜拍照，观察线粒体超微结构。
1.2.9 Western blotting检测MMP2、MMP9、N-cadherin、Vimentin、SLC7A11、GPX4蛋白表达水平
取PC9细胞，分组及处理同1.2.5和1.2.7。收集各组细胞，在含有PMSF的RIPA裂解液中冰上裂解30 min，离心后收集上清液，BCA蛋白检测试剂盒测定总蛋白浓度并上样。采用10% SDS-PAGE凝胶电泳分离等量的蛋白质，然后转移到PVDF膜上。在室温下用快速封闭液封闭15 min，将膜与相应一抗MMP2(1:1000)、MMP9(1:1000)、N-cadherin(1:750)、Vimentin(1:750)、SLC7A11(1:1000)、GPX4(1:1000)和GAPDH(1:1000)4 °C孵育过夜，然后将膜与相应的HRP羊抗兔IgG二抗(H+L)孵育2 h。使用ECL化学发光超敏显色试剂盒检测蛋白条带，以GAPDH为内参，使用ImageJ软件定量蛋白表达水平。
1.2.10 反转录-定量PCR(RT-qPCR)检测MMP2、MMP9、N-cadherin、Vimentin、SLC7A11、GPX4 mRNA表达水平
取PC9细胞，设置对照组(正常培养)与TYP组(100 μmol/L TYP处理48 h)，使用离心柱式RNA抽提试剂盒提取总RNA，然后使用反转录试剂盒合成cDNA。使用SYBR Premix Ex Taq进行实时荧光定量PCR，以GAPDH为内参基因，采用2-ΔΔCt法分析目的基因的表达水平。引物序列见表1。
1.2.11 SLC7A11过表达转染
应用Lipo6000将SLC7A11过表达质粒转染至PC9细胞，采用Western blotting检测转染效果。使用不同浓度的TYP处理转染后的细胞，设置Vector组(空载质粒转染)、Vector+TYP组(空载质粒转染+100 μmol/L TYP处理48 h)、OE-SLC7A11组(SLC7A11过表达质粒转染)与OE-SLC7A11+TYP组(SLC7A11过表达质粒转染+100 μmol/L TYP处理48 h)，验证SLC7A11在TYP作用于PC9细胞时的相关分子机制。
1.3 统计学处理
采用GraphPad Prism 8.0软件进行统计分析。所有实验数据均符合正态分布，以$\bar{x}±s$表示，两组间比较采用t检验，多组间比较采用单因素方差分析，进一步两两比较采用LSD-t检验。P<0.05为差异有统计学意义。
2 结果
收起
2.1 生物信息学分析结果
根据TYP的Canonical SMILES在SwissTargetPrediction网站进行靶点预测，共获得103个靶基因。从TCGA数据库、GeneCards数据库和GSE116959数据集中获取肺腺癌相关靶点基因，取并集后共获得7652个肺腺癌相关靶点基因(图1A)。将它们取交集，获得TYP—肺腺癌相关靶点基因73个(图1B)。将交集基因导入String数据库，设置最低要求交互得分为0.700，并选择“隐藏网络中断开连接的节点”项，建立了一个含73个节点、149条边、平均节点度为4.08的蛋白互作网络，如图1C所示。
将交集基因进行GO和KEGG富集分析，其中GO分析共获得生物过程1567个、细胞组分50个和分子功能126个。靶基因主要参与激酶活性的正向调节、细胞对化学应激的反应、对氧化应激的反应、蛋白质自身磷酸化、细胞对氧化应激的反应等生物过程；主要富集于转移酶复合物(转移含磷基团)、蛋白激酶复合物、丝氨酸/苏氨酸蛋白激酶复合体、膜外成分和膜筏等细胞组分；揭示了跨膜受体蛋白酪氨酸激酶活性、酪氨酸激酶活性、跨膜受体蛋白激酶活性、丝氨酸/苏氨酸激酶活性和碳酸脱水酶活性等分子功能。根据P值(P<0.05)筛选出各分支的前10个项目制作条形图进行可视化(图1D)。KEGG富集分析共获得124个相关途径，根据P<0.05筛选列出前20条通路(图1E)，主要包括表皮生长因子受体(epidermal growth factor receptor，EGFR)酪氨酸激酶抑制剂的抗药性、卵巢类固醇生成、氮代谢、化学致癌物-活性氧、癌症中的蛋白聚糖和磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase，PI3K)-丝氨酸/苏氨酸激酶(serine/threonine kinase，Akt)信号通路等。
根据蛋白互作网络分析结果，以Degree参数值>10为筛选条件获得Akt1、MMP9、EGFR、磷脂酰肌醇3-激酶调节亚基1(phosphoinositide-3-kinase regulatory subunit 1，PIK3R1)、非受体酪氨酸激酶(SRC proto-oncogene， non-receptor tyrosine kinase，SRC)、前列腺素E合酶2(prostaglandin-endoperoxide synthase 2，PTGS2)、肿瘤坏死因子(tumor necrosis factor，TNF)共7个核心靶点进行分子对接，另外根据文献及GO和KEGG结果分析发现TYP与铁死亡有一定的关系，因此进行TYP与铁死亡相关蛋白SLC7A11和GPX4的分子对接(图2)。通过分子对接来评估分子与蛋白的结合能力，当结合能≤-5.0 kcal/mol时，表明分子间具有显著的结合活性。TYP与相关蛋白的结合力如表2所示。
2.2 细胞实验
2.2.1 TYP对PC9细胞增殖、迁移及侵袭的影响
TYP的化学结构如图3A所示。CCK-8法检测结果显示，处理48 h时，与0 μmol/L TYP相比，25、50、100、200 μmol/L TYP处理均可明显抑制PC9细胞的活力(P<0.05或P<0.01B)；处理72 h时，与0 μmol/L TYP相比，50、100、200 μmol/L TYP处理均可明显抑制PC9细胞的活力(P<0.01)；与处理48 h相比，200 μmol/L TYP处理72 h的PC9细胞活力明显降低(P<0.05)；TYP处理48 h和72 h的IC50分别为188.70 μmol/L和69.35 μmol/L(图3B)。EdU实验结果显示，与对照组相比，TYP组增殖期细胞比例明显降低(P<0.05，图3C)。
Transwell迁移和侵袭实验结果显示，与对照组相比，低TYP组、高TYP组迁移和侵袭细胞数均明显减少(P<0.01)；与低TYP组相比，高TYP组侵袭细胞数明显减少(P<0.01，图4A)。划痕实验结果显示，与对照组相比，TYP处理24 h和48 h后细胞迁移率均明显降低(P<0.01，图4B)。Western blotting检测结果显示，与对照组相比，低TYP组N-cadherin、MMP2蛋白表达水平明显降低(P<0.05)，高TYP组N-cadherin、MMP9、MMP2、Vimentin蛋白表达水平明显降低(P<0.05或P<0.01)；与低TYP组相比，高TYP组N-cadherin蛋白表达水平明显降低(P<0.05，图4C)。RT-qPCR检测结果显示，与对照组比较，TYP组N-cadherin、MMP9、MMP2、Vimentin mRNA表达水平均明显降低(P<0.01，图4D)。
2.2.2 TYP对PC9细胞铁死亡的影响
CCK-8法检测结果显示，与对照组相比，高TYP组细胞活力明显降低(P<0.01)；与高TYP组相比，Fer-1+TYP组细胞活力明显升高(P<0.01，图5A)。
与对照组相比，低TYP组Fe2+、ROS含量明显增加(P<0.01)，线粒体膜电位明显降低(P<0.01)，高TYP组GSH含量、线粒体膜电位明显降低(P<0.01)，Fe2+、ROS含量明显增加(P<0.01)。与低TYP组相比，高TYP组GSH含量明显降低(P<0.05)，Fe2+、ROS含量明显增加(P<0.01)。与高TYP组相比，Fer-1+TYP组GSH含量、线粒体膜电位明显增加(P<0.05、P<0.01)，Fe2+、ROS含量明显降低(P<0.01)(图5B-E)。
透射电子显微镜观察显示，对照组PC9细胞线粒体双层膜正常，嵴完整；与对照组相比，TYP组PC9细胞发生了铁死亡的特异性变化，即线粒体嵴减少及膜密度增加(图5F)。
2.2.3 TYP诱导PC9细胞发生铁死亡的分子机制
Western blotting检测结果显示，与对照组相比，低TYP组SLC7A11、GPX4蛋白表达水平明显降低(P<0.01，P<0.05)，高TYP组SLC7A11、GPX4蛋白表达水平明显降低(P<0.01)；与低TYP组相比，高TYP组GPX4蛋白表达水平明显降低(P<0.05)；与高TYP组相比，Fer-1+TYP组SLC7A11、GPX4蛋白表达水平明显升高(P<0.01，图6A)。RT-qPCR检测结果显示，与对照组比较，TYP组SLC7A11、GPX4 mRNA表达水平均明显降低(P<0.01，图6B)。
CCK-8法检测结果显示，与Vector组相比，Vector+TYP组PC9细胞活力明显降低(P<0.01)；与Vector+TYP组相比，OE-SLC7A11+TYP组PC9细胞活力明显升高(P<0.05)；与OE-SLC7A11组相比，OE-SLC7A11+TYP组PC9细胞活力明显降低(P<0.01，图6C)。细胞亚铁离子探针检测结果显示，与Vector组相比，Vector+TYP组Fe2+含量明显增加(P<0.01)；与Vector组相比，OE-SLC7A11组Fe2+含量明显降低(P<0.05)；与Vector+TYP组相比，OE-SLC7A11+TYP组Fe2+含量明显降低(P<0.01，图6D)。Western blotting检测结果显示，与Vector组相比，Vector+TYP组SLC7A11、GPX4蛋白表达水平明显降低(P<0.05或P<0.01)；与Vector组相比，OE-SLC7A11组SLC7A11蛋白表达水平明显升高(P<0.01)；与Vector+TYP组相比，OE-SLC7A11+TYP组SLC7A11、GPX4蛋白表达水平明显升高(P<0.05或P<0.01，图6E)。
3 讨论
收起
肺癌是一种高死亡率的全球性疾病，肺腺癌是其常见组织学亚型。从中药中提取活性成分来治疗肺癌是目前研究的重要方向，已发现多种中药活性成分在抗癌方面具有独特价值[16]。TYP是中药蒲黄的一种活性成分，可通过诱导铁死亡来预防AML[14]，然而其在肺腺癌中的应用价值尚不清楚。本研究通过网络药理学及体外实验探讨TYP对肺腺癌的作用，以及铁死亡通路SLC7A11-GPX4在其中可能发挥的作用。
本研究首先通过网络药理学方法分析TYP对肺腺癌的作用靶点及通路，使用SwissTargetPrediction网站预测TYP的作用靶点，将获得的靶点基因与肺腺癌相关靶点基因取交集获得TYP-肺腺癌相关基因，并进行GO、KEGG和蛋白互作网络分析，结果表明TYP与侵袭、迁移及氧化应激通路关系密切，其中氧化应激与铁死亡密切相关[17]；进一步通过分子对接探索TYP与核心靶点基因及SLC7A11、GPX4之间的结合能力，发现TYP对这些蛋白均具有良好的结合活性。
本研究通过体外实验进一步探索了TYP在肺腺癌细胞中的作用机制。CCK-8法检测结果显示TYP可抑制PC9细胞的活力，EdU实验证实TYP使增殖期细胞的比例明显降低，宏观上提示了TYP治疗肺腺癌具有一定的应用前景。迁移与侵袭能力是癌细胞恶性生物学行为的重要基础，划痕实验、Transwell迁移及侵袭实验结果表明，TYP可抑制PC9细胞的迁移与侵袭能力，并降低间充质标志物N-cadherin、MMP9、MMP2、Vimentin蛋白和mRNA的表达，提示TYP可抑制肺腺癌细胞的迁移与侵袭，进而抑制肺腺癌细胞的恶性行为。
铁死亡是一种有别于凋亡和坏死的铁依赖性的非凋亡细胞死亡形式。SLC7A11是近年来公认的铁死亡相关基因[17]，在肺腺癌中高表达，可作为肺腺癌患者的预后因子，SLC7A11高表达患者的生存期更短[18]。为探讨铁死亡是否参与了TYP对肺腺癌的作用，本研究使用铁死亡抑制剂Fer-1进行实验，结果表明，TYP可使PC9细胞中Fe2+、ROS含量增加，GSH含量、线粒体膜电位以及SLC7A11、GPX4的表达降低，且这些结果可被Fer-1逆转。此外，透射电子显微镜观察显示TYP处理可使PC9细胞线粒体出现嵴减少及膜密度增加的铁死亡特征表现。上述结果提示TYP可诱导PC9细胞发生铁死亡。
GPX4是SLC7A11下游通路因子[19]，细胞内GSH含量受二者的调控。本研究使用SLC7A11过表达质粒探索SLC7A11-GPX4通路是否参与了TYP诱导的铁死亡，结果显示，SLC7A11过表达可部分逆转TYP对PC9细胞活力的抑制作用，且细胞内Fe2+含量、GPX4表达均有一定程度的恢复。基于分子对接和体外实验结果推测，TYP可能通过SLC7A11-GPX4通路诱导PC9细胞发生铁死亡。
综上所述，本研究结果表明，TYP可能通过调节SLC7A11-GPX4轴诱导肺腺癌细胞发生铁死亡，并抑制肺腺癌细胞的增殖、迁移和侵袭等恶性行为。该结果为TYP在肺腺癌临床治疗中的应用和药物开发提供了理论依据。但本研究也存在一些不足之处，如仅使用PC9细胞进行实验，结果需要在更多类型的肺腺癌细胞中进行验证；虽然在体外实验中取得了显著的结果，但体外不能模拟体内的复杂环境，TYP在体内的实验效果仍需进一步探索；TYP在肺腺癌中的作用机制复杂且涉及多种信号通路，后续仍需深入探讨。
基金
收起
  • 辽宁省教育厅科学技术研究项目(JYTJCZR2020057)
文献
收起
参考文献 引证文献
排序方式：
[1]
石兴文, 尹鸿涛, 刘进进, 等. 兰州市城关区中老年人群恶性肿瘤发病与死亡情况及其危险因素的队列研究[J]. 解放军医学杂志, 2024, 49(7): 761-769.
[2]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[3]
Jiang J, Zhang Y, Wang J, et al. Identification of CDT1 as a prognostic marker in human lung adenocarcinoma using bioinformatics approaches[J]. PeerJ, 2023, 11: e16166.
[4]
Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072.
[5]
Xing K, Bian X, Shi D, et al. miR-612 enhances RSL3-induced ferroptosis of hepatocellular carcinoma cells via mevalonate pathway[J]. J Hepatocell Carcinoma, 2023, 10: 2173-2185.
[6]
Zhang Q, Luo Y, Peng L, et al. Ferroptosis in cardiovascular diseases: role and mechanism[J]. Cell Biosci, 2023, 13(1): 226.
[7]
陈丹丹, 徐涛, 薛姝婧, 等. Toll样受体4在热射病大鼠心功能损伤及心肌铁死亡中的作用[J]. 解放军医学杂志, 2023, 48(3): 249-257.
[8]
An F, Zhang J, Gao P, et al. New insight of the pathogenesis in osteoarthritis: the intricate interplay of ferroptosis and autophagy mediated by mitophagy/chaperone-mediated autophagy[J]. Front Cell Dev Biol, 2023, 11: 1297024.
[9]
Cai S, Zhang B, Huang C, et al. CTRP6 protects against ferroptosis to drive lung cancer progression and metastasis by destabilizing SOCS2 and augmenting the xCT/GPX4 pathway[J]. Cancer Lett, 2023, 579: 216465.
[10]
Du J, Krishnamoorthy K, Ramabhai V, et al. Targeting ferroptosis as a therapeutic implication in lung cancer treatment by a novel naphthoquinone inducer: juglone[J]. Mol Biotechnol, 2023, 66(5): 1071-1081.
[11]
Ning N, Shang Z, Liu Z, et al. A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling[J]. Cell Death Discov, 2023, 9(1): 453.
[12]
Nie A, Shen C, Zhou Z, et al. Ferroptosis: potential opportunities for natural products in cancer therapy[J]. Phytother Resm, 2023, 38(3): 1173-1190.
[13]
李昕, 栗东海, 高小明, 等. 重楼皂苷通过p53/SLC7A11信号轴促进三阴性乳腺癌细胞铁死亡的机制研究[J]. 解放军医学杂志, 2023, 48(1): 58-63.
[14]
Zhu HY, Huang ZX, Chen GQ, et al. Typhaneoside prevents acute myeloid leukemia (AML) through suppressing proliferation and inducing ferroptosis associated with autophagy[J]. Biochem Biophys Res Commun, 2019, 516(4): 1265-1271.
[15]
游赣花, 何恋, 李凯, 等. 八角莲醇提物抑制MAPK信号通路引起肾癌细胞凋亡的作用机制[J]. 中国药理学通报, 2023, 39(12): 2305-2313.
[16]
Zhou H, Zhang M, Cao H, et al. Research progress on the synergistic anti-tumor effect of natural anti-tumor components of Chinese herbal medicine combined with chemotherapy drugs[J]. Pharmaceuticals (Basel), 2023, 16(12): 1734.
[17]
Song W, Chen Y, Qin L, et al. Oxidative stress drives vascular smooth muscle cell damage in acute Stanford type A aortic dissection through HIF-1α/HO-1 mediated ferroptosis[J]. Heliyon, 2023, 9(12): e22857.
[18]
Shan Q, Zhang C, Li Y, et al. SLC7A11, a potential immunotherapeutic target in lung adenocarcinoma[J]. Sci Rep, 2023, 13(1): 18302.
[19]
Ruan Q, Wang C, Zhang Y, et al. Ruscogenin attenuates cartilage destruction in osteoarthritis through suppressing chondrocyte ferroptosis via Nrf2/SLC7A11/GPX4 signaling pathway[J]. Chem Biol Interact, 2023, 388: 110835.
2025年第50卷第5期
PDF下载
282
118
引用本文
BibTeX
文章信息
doi: 10.11855/j.issn.0577-7402.0351.2025.0126
  • 接收时间：2024-03-19
  • 首发时间：2025-10-29
  • 出版时间：2025-05-28
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2024-03-19
  • 录用日期：2024-08-15
基金
Science and Technology Research Project of Education Department of Liaoning Province(JYTJCZR2020057)
辽宁省教育厅科学技术研究项目(JYTJCZR2020057)
作者信息
    锦州医科大学附属第一医院呼吸内科，辽宁锦州 121000

通讯作者:

阎雪，E-mail：
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/jfjyxzz/CN/10.11855/j.issn.0577-7402.0351.2025.0126
分享至
全文二维码

扫描看全文

引用本文
BibTeX
本文的引用情况
2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
相关链接
论文
最新文章
热读文章
热点专题
内参
蓝皮书
产业发展报告
传播力报告
期刊分级目录
资讯
学术新闻
行业新闻
学术会议
行业会议
关于
关于我们
联系我们
北京市海淀区学院南路86号
100081
010-62199257
qkjq@cast.org.cn

中国科学技术协会版权所有 京ICP 备10216604号-4 海淀分局备案 1101084647
科技导报社主办 中国科协信息中心技术支持