{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:06:22Z","timestamp":1784225182998,"version":"3.55.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Traditional Chinese Medicine Science and Technology Program","award":["2024ZL1150"],"award-info":[{"award-number":["2024ZL1150"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastric cancer (GC) is a widespread global malignancy, frequently diagnosed at advanced stages owing to the subtle nature of early symptoms and low screening rates. Consequently, there is an imperative need to investigate innovative strategies for the treatment of GC. Exosomes, originating from various sources, act as natural nanocarriers enriched with numerous bioactive molecules, showcasing potential as groundbreaking treatments for GC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      In the present study, exosome-like nanoparticles (ELNs) were successfully purified from\n                      <jats:italic>Salvia miltiorrhiza<\/jats:italic>\n                      Bunge (Danshen) utilizing ultracentrifugation. The impact of these ELNs on human gastric cancer cells (HGC-27) was evaluated via a suite of viability assays, encompassing CCK-8, colony formation, flow cytometry, transwell migration, and wound healing assays. Furthermore, miRNA sequencing was conducted to identify and analyze the highly abundant miRNA within Danshen-derived ELNs, along with its potential biological functions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The HGC-27 cells internalized Danshen-derived ELNs (DS-ELNs), which led to a decrease in cell viability. Concurrently, these ELNs exhibited significant inhibitory effects on cell migration, colony formation, and overall progression of GC in vitro. The functional analysis of the miRNAs harbored by these ELNs indicated that they may serve as a potential therapeutic target for GC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In summary, these findings have not only comprehensively characterized the miRNAs present in Danshen-derived exosomes but also provided invaluable insights into the molecular mechanisms by which Danshen exerts its effects in mitigating<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0353354","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:35:44Z","timestamp":1784223344000},"page":"e0353354","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization and functional analysis of miRNAs in Salvia miltiorrhiza-isolated exosome-like nanoparticles for gastric cancer treatment"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5162-3274","authenticated-orcid":true,"given":"Gang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinjuan","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"16","key":"pone.0353354.ref001","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.3748\/wjg.v29.i16.2452","article-title":"Updates on global epidemiology, risk and prognostic factors of gastric cancer","volume":"29","author":"W-J Yang","year":"2023","journal-title":"World J Gastroenterol"},{"issue":"4","key":"pone.0353354.ref002","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3892\/ijo.2024.5629","article-title":"Xenograft and organoid models in developing precision medicine for gastric cancer (Review)","volume":"64","author":"J Xu","year":"2024","journal-title":"Int J Oncol"},{"issue":"5","key":"pone.0353354.ref003","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1136\/jmedgenet-2016-104171","article-title":"Gastric cancer: somatic genetics as a guide to therapy","volume":"54","author":"X-Y Zhang","year":"2017","journal-title":"J Med Genet"},{"issue":"1","key":"pone.0353354.ref004","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/jamasurg.2021.5104","article-title":"Laparoscopic vs open distal gastrectomy for locally advanced gastric cancer: five-year outcomes from the CLASS-01 randomized clinical trial","volume":"157","author":"C Huang","year":"2022","journal-title":"JAMA Surg"},{"issue":"24","key":"pone.0353354.ref005","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.3748\/wjg.v24.i24.2567","article-title":"Tumor heterogeneity of gastric cancer: from the perspective of tumor-initiating cell","volume":"24","author":"J-P Gao","year":"2018","journal-title":"World J Gastroenterol"},{"issue":"22","key":"pone.0353354.ref006","doi-asserted-by":"crossref","first-page":"5615","DOI":"10.3390\/cancers14225615","article-title":"Recent trends and advancements in the diagnosis and management of gastric cancer","volume":"14","author":"E Haque","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"9","key":"pone.0353354.ref007","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1016\/j.cmet.2021.08.006","article-title":"Exosomes as mediators of intercellular crosstalk in metabolism","volume":"33","author":"R Isaac","year":"2021","journal-title":"Cell Metab"},{"key":"pone.0353354.ref008","first-page":"1741","volume-title":"Micro-and nanotechnological delivery platforms for treatment of dysbiosis-related inflammatory bowel disease","author":"D Long","year":"2021"},{"issue":"5","key":"pone.0353354.ref009","doi-asserted-by":"crossref","first-page":"742","DOI":"10.3390\/biom10050742","article-title":"Blueberry-derived exosome-like nanoparticles counter the response to TNF-\u03b1-induced change on gene expression in EA.hy926 cells","volume":"10","author":"M De Robertis","year":"2020","journal-title":"Biomolecules"},{"issue":"15","key":"pone.0353354.ref010","doi-asserted-by":"crossref","first-page":"4725","DOI":"10.1021\/acs.jafc.1c07306","article-title":"Characterization of the MicroRNA profile of ginger exosome-like nanoparticles and their anti-inflammatory effects in intestinal Caco-2 cells","volume":"70","author":"L Yin","year":"2022","journal-title":"J Agric Food Chem"},{"issue":"16","key":"pone.0353354.ref011","doi-asserted-by":"crossref","first-page":"7520","DOI":"10.1039\/D3FO01094E","article-title":"Garlic-derived exosome-like nanovesicles alleviate dextran sulphate sodium-induced mouse colitis via the TLR4\/MyD88\/NF-\u03baB pathway and gut microbiota modulation","volume":"14","author":"Z Zhu","year":"2023","journal-title":"Food Funct"},{"issue":"4","key":"pone.0353354.ref012","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.3390\/nu15041031","article-title":"Treatment effects of natural products on inflammatory bowel disease in vivo and their mechanisms: based on animal experiments","volume":"15","author":"Y Zhou","year":"2023","journal-title":"Nutrients"},{"key":"pone.0353354.ref013","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.jconrel.2024.01.060","article-title":"Brucea javanica derived exosome-like nanovesicles deliver miRNAs for cancer therapy","volume":"367","author":"G Yan","year":"2024","journal-title":"J Control Release"},{"issue":"16","key":"pone.0353354.ref014","doi-asserted-by":"crossref","first-page":"8986","DOI":"10.3390\/ijms25168986","article-title":"Ethyl acetate fractions of Salvia miltiorrhiza Bunge (Danshen) crude extract modulate fibrotic signals to ameliorate diabetic kidney injury","volume":"25","author":"Y-C Hsu","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"7","key":"pone.0353354.ref015","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.3390\/molecules29071599","article-title":"Establishing Salvia miltiorrhiza-derived exosome-like nanoparticles and elucidating their role in angiogenesis","volume":"29","author":"S Zhang","year":"2024","journal-title":"Molecules"},{"issue":"1","key":"pone.0353354.ref016","doi-asserted-by":"crossref","first-page":"100131","DOI":"10.1016\/j.ocarto.2020.100131","article-title":"A bioinformatics approach to microRNA-sequencing analysis","volume":"3","author":"P Potla","year":"2020","journal-title":"Osteoarthr Cartil Open"},{"key":"pone.0353354.ref017","doi-asserted-by":"crossref","first-page":"123987","DOI":"10.1016\/j.ijbiomac.2023.123987","article-title":"Estrogen-mediated oar-miR-485-5p targets PPP1R13B to regulate myoblast proliferation in sheep","volume":"236","author":"S Liu","year":"2023","journal-title":"Int J Biol Macromol"},{"key":"pone.0353354.ref018","doi-asserted-by":"crossref","first-page":"145206","DOI":"10.1016\/j.gene.2020.145206","article-title":"Identification and characterization of miRNA expression profiles across five tissues in giant panda","volume":"769","author":"C Wang","year":"2021","journal-title":"Gene"},{"key":"pone.0353354.ref019","doi-asserted-by":"crossref","first-page":"124373","DOI":"10.1016\/j.talanta.2023.124373","article-title":"A light-up fluorescence platform based DNA: RNA hybrid G-quadruplet for detecting single nucleotide variant of ctDNA and miRNA-21","volume":"257","author":"G Cao","year":"2023","journal-title":"Talanta"},{"issue":"2","key":"pone.0353354.ref020","doi-asserted-by":"crossref","first-page":"869","DOI":"10.26599\/FSHW.2022.9250074","article-title":"Characterization of blueberry exosome-like nanoparticles and miRNAs with potential cross-kingdom human gene targets","volume":"13","author":"Y Leng","year":"2024","journal-title":"Food Sci Hum Wellness"},{"issue":"12","key":"pone.0353354.ref021","first-page":"1798","article-title":"Small RNA targets: advances in prediction tools and high-throughput profiling","volume":"11","author":"K Gre\u0161ov\u00e1","year":"2022","journal-title":"Biology (Basel)"},{"issue":"1","key":"pone.0353354.ref022","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3390\/biomedicines12010201","article-title":"Anticancer drug discovery based on natural products: from computational approaches to clinical studies","volume":"12","author":"P Chunarkar-Patil","year":"2024","journal-title":"Biomedicines"},{"issue":"1","key":"pone.0353354.ref023","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.hoc.2023.05.013","article-title":"State of cancer control in South America: challenges and advancement strategies","volume":"38","author":"I Riano","year":"2024","journal-title":"Hematol Oncol Clin North Am"},{"issue":"4","key":"pone.0353354.ref024","first-page":"717","article-title":"A comprehensive review on anticancer natural drugs","volume":"13","author":"P Darji","year":"2024","journal-title":"World J Pharm Pharm Sci"},{"issue":"7","key":"pone.0353354.ref025","doi-asserted-by":"crossref","first-page":"848","DOI":"10.2174\/0929867330666230502113150","article-title":"Natural Anticancer agents: their therapeutic potential, challenges and promising outcomes","volume":"31","author":"S Tauro","year":"2024","journal-title":"Curr Med Chem"},{"key":"pone.0353354.ref026","doi-asserted-by":"crossref","first-page":"106314","DOI":"10.1016\/j.jff.2024.106314","article-title":"Structural characteristics and anti-tumor effect of low molecular weight Dendrobium officinale polysaccharides by reconstructing tumor microenvironment","volume":"119","author":"Y He","year":"2024","journal-title":"J Funct Foods"},{"issue":"8","key":"pone.0353354.ref027","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20201807","article-title":"Tanshinone IIA induces ferroptosis in gastric cancer cells through p53-mediated SLC7A11 down-regulation","volume":"40","author":"Z Guan","year":"2020","journal-title":"Biosci Rep"},{"key":"pone.0353354.ref028","doi-asserted-by":"crossref","first-page":"155093","DOI":"10.1016\/j.phymed.2023.155093","article-title":"Salvianolic acid F suppresses KRAS-dependent lung cancer cell growth through the PI3K\/AKT signaling pathway","volume":"121","author":"X Hou","year":"2023","journal-title":"Phytomedicine"},{"issue":"288","key":"pone.0353354.ref029","article-title":"More than just a fruit: grapefruit-derived nanovectors deliver cancer drugs","volume":"7","author":"AZ Wang","year":"2015","journal-title":"Sci Transl Med"},{"issue":"4","key":"pone.0353354.ref030","doi-asserted-by":"crossref","first-page":"428","DOI":"10.2174\/1871520620666200918100833","article-title":"Anti-cancer effect of gingerol in cancer prevention and treatment","volume":"21","author":"S Nafees","year":"2021","journal-title":"Anticancer Agents Med Chem"},{"issue":"6","key":"pone.0353354.ref031","first-page":"804","article-title":"Overview and update on extracellular vesicles: considerations on exosomes and their application in modern medicine","volume":"11","author":"MA Di Bella","year":"2022","journal-title":"Biology (Basel)"},{"issue":"11","key":"pone.0353354.ref032","doi-asserted-by":"crossref","first-page":"4879","DOI":"10.7150\/thno.72812","article-title":"Extracellular vesicles as bioactive nanotherapeutics: an emerging paradigm for regenerative medicine","volume":"12","author":"M Li","year":"2022","journal-title":"Theranostics"},{"key":"pone.0353354.ref033","doi-asserted-by":"crossref","first-page":"586564","DOI":"10.3389\/fnut.2021.586564","article-title":"Potential mechanisms linking food-derived microRNAs, gut microbiota and intestinal barrier functions in the context of nutrition and human health","volume":"8","author":"E D\u00edez-Sainz","year":"2021","journal-title":"Front Nutr"},{"issue":"44","key":"pone.0353354.ref034","doi-asserted-by":"crossref","first-page":"16568","DOI":"10.1021\/acs.jafc.3c04150","article-title":"Broccoli-derived exosome-like nanoparticles alleviate loperamide-induced constipation, in correlation with regulation on gut microbiota and tryptophan metabolism","volume":"71","author":"T Duan","year":"2023","journal-title":"J Agric Food Chem"},{"key":"pone.0353354.ref035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jare.2024.04.001","article-title":"Ginger exosome-like nanoparticle-derived miRNA therapeutics: a strategic inhibitor of intestinal inflammation","volume":"69","author":"L Yan","year":"2025","journal-title":"J Adv Res"},{"key":"pone.0353354.ref036","doi-asserted-by":"crossref","first-page":"116979","DOI":"10.1016\/j.biopha.2024.116979","article-title":"MicroRNA-based interventions in aberrant cell cycle diseases: therapeutic strategies for cancers, central nervous system disorders and comorbidities","volume":"177","author":"X Tang","year":"2024","journal-title":"Biomed Pharmacother"},{"key":"pone.0353354.ref037","doi-asserted-by":"crossref","first-page":"105179","DOI":"10.1016\/j.phrs.2020.105179","article-title":"The P53\/microRNA network: a potential tumor suppressor with a role in anticancer therapy","volume":"160","author":"J Sargolzaei","year":"2020","journal-title":"Pharmacol Res"},{"issue":"4","key":"pone.0353354.ref038","doi-asserted-by":"crossref","first-page":"102057","DOI":"10.1016\/j.xcrm.2025.102057","article-title":"Challenges and opportunities in microRNA-based cancer therapeutics","volume":"6","author":"J Ju","year":"2025","journal-title":"Cell Rep Med"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0353354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:35:52Z","timestamp":1784223352000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0353354"}},"subtitle":[],"editor":[{"given":"Minhui","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0353354","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]}}}