{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:39:17Z","timestamp":1779205157137,"version":"3.51.4"},"reference-count":66,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011039","name":"Swiss Centre for Applied Human Toxicology","doi-asserted-by":"publisher","award":["313926"],"award-info":[{"award-number":["313926"]}],"id":[{"id":"10.13039\/501100011039","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Over the last decade, the knowledge in extracellular vesicles (EVs) biogenesis and modulation has increasingly grown. As their content reflects the physiological state of their donor cells, these \u201cintercellular messengers\u201d progressively became a potential source of biomarker reflecting the host cell state. However, little is known about EVs released from the human brain microvascular endothelial cells (HBMECs). The current study aimed to isolate and characterize EVs from HBMECs and to analyze their EVs proteome modulation after paraquat (PQ) stimulation, a widely used herbicide known for its neurotoxic effect. Size distribution, concentration and presence of well-known EV markers were assessed. Identification and quantification of PQ-exposed EV proteins was conducted by data-independent acquisition mass spectrometry (DIA-MS). Signature pathways of PQ-treated EVs were analyzed by gene ontology terms and pathway enrichment. Results highlighted that EVs exposed to PQ have modulated pathways, namely the ubiquinone metabolism and the transcription HIF-1 targets. These pathways may be potential molecular signatures of the PQ-induced toxicity carried by EVs that are reflecting their cell of origin by transporting with them irreversible functional changes.<\/jats:p>","DOI":"10.3390\/ijms22105065","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T11:30:16Z","timestamp":1620732616000},"page":"5065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ubiquinone Metabolism and Transcription HIF-1 Targets Pathway Are Toxicity Signature Pathways Present in Extracellular Vesicles of Paraquat-Exposed Human Brain Microvascular Endothelial Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7410-6148","authenticated-orcid":false,"given":"Tatjana","family":"Vuji\u0107","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Geneva, 1206 Geneva, Switzerland"},{"name":"Swiss Centre for Applied Human Toxicology, 4055 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1133-0462","authenticated-orcid":false,"given":"Domitille","family":"Schvartz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Geneva, 1206 Geneva, Switzerland"},{"name":"Swiss Centre for Applied Human Toxicology, 4055 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Iliuk","sequence":"additional","affiliation":[{"name":"Tymora Analytical Operations, West Lafayette, IN 47906, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Charles","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Geneva, 1206 Geneva, Switzerland"},{"name":"Swiss Centre for Applied Human Toxicology, 4055 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26913","DOI":"10.3402\/jev.v3.26913","article-title":"Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles","volume":"3","author":"Lotvall","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"De Jong, O.G., Verhaar, M.C., Chen, Y., Vader, P., Gremmels, H., Posthuma, G., Schiffelers, R.M., Gucek, M., and van Balkom, B.W. (2012). Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. J. Extracell. Vesicles, 1.","DOI":"10.3402\/jev.v1i0.18396"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41398-019-0459-9","article-title":"The emerging role of exosomes in mental disorders","volume":"9","author":"Saeedi","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Caruso Bavisotto, C., Scalia, F., Marino Gammazza, A., Carlisi, D., Bucchieri, F., Conway de Macario, E., Macario, A.J.L., Cappello, F., and Campanella, C. (2019). Extracellular Vesicle-Mediated Cell(-)Cell Communication in the Nervous System: Focus on Neurological Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020434"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2015.01.002","article-title":"Anatomy and physiology of the blood-brain barrier","volume":"38","author":"Serlin","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2016.03.010","article-title":"The blood-brain barrier in systemic inflammation","volume":"60","author":"Varatharaj","year":"2017","journal-title":"Brain Behav. Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1111\/j.1471-4159.2008.05730.x","article-title":"The human brain endothelial cell line hCMEC\/D3 as a human blood-brain barrier model for drug transport studies","volume":"107","author":"Poller","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2045-8118-10-4","article-title":"Method for isolation and molecular characterization of extracellular microvesicles released from brain endothelial cells","volume":"10","author":"Haqqani","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1152\/physrev.00050.2017","article-title":"Blood-Brain Barrier: From Physiology to Disease and Back","volume":"99","author":"Sweeney","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"225","DOI":"10.15171\/bi.2016.30","article-title":"Blood-brain barrier transport machineries and targeted therapy of brain diseases","volume":"6","author":"Barar","year":"2016","journal-title":"BioImpacts BI"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","article-title":"Blood\u2013brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders","volume":"14","author":"Sweeney","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"116","DOI":"10.2174\/1567205012666150204121719","article-title":"Role of environmental contaminants in the etiology of Alzheimer\u2019s disease: A review","volume":"12","author":"Yegambaram","year":"2015","journal-title":"Curr. Alzheimer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.3233\/JPD-181493","article-title":"The Search for Environmental Causes of Parkinson\u2019s Disease: Moving Forward","volume":"8","author":"Chen","year":"2018","journal-title":"J. Parkinsons Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0076-6879(08)04421-2","article-title":"Chapter 21 Paraquat-induced production of reactive oxygen species in brain mitochondria","volume":"456","author":"Drechsel","year":"2009","journal-title":"Methods Enzymol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s002040050316","article-title":"Effects of paraquat on mitochondrial electron transport system and catecholamine contents in rat brain","volume":"70","author":"Tawara","year":"1996","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0940-2993(11)80056-4","article-title":"Mechanism of cytotoxicity of paraquat: III. The effects of acute paraquat exposure on the electron transport system in rat mitochondria","volume":"46","author":"Fukushima","year":"1994","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/labinvest.2015.161","article-title":"Multifactorial theory applied to the neurotoxicity of paraquat and paraquat-induced mechanisms of developing Parkinson\u2019s disease","volume":"96","author":"Zhang","year":"2016","journal-title":"Lab. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.neuro.2017.04.010","article-title":"Potential mechanisms of development-dependent adverse effects of the herbicide paraquat in 3D rat brain cell cultures","volume":"60","author":"Broyer","year":"2017","journal-title":"Neurotoxicology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.neuro.2006.05.012","article-title":"Paraquat exposure as an etiological factor of Parkinson\u2019s disease","volume":"27","author":"Carmo","year":"2006","journal-title":"Neurotoxicology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1289\/ehp.8095","article-title":"Pesticides and Parkinson\u2019s disease--is there a link?","volume":"114","author":"Brown","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14186","DOI":"10.1074\/jbc.M700827200","article-title":"Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain","volume":"282","author":"Castello","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1021\/acs.jproteome.8b00459","article-title":"Highly Efficient Phosphoproteome Capture and Analysis from Urinary Extracellular Vesicles","volume":"17","author":"Wu","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1021\/acs.jproteome.0c00151","article-title":"Plasma-Derived Extracellular Vesicle Phosphoproteomics through Chemical Affinity Purification","volume":"19","author":"Iliuk","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1038\/s41467-019-11534-w","article-title":"Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS","volume":"10","author":"Men","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yoshioka, Y., Konishi, Y., Kosaka, N., Katsuda, T., Kato, T., and Ochiya, T. (2013). Comparative marker analysis of extracellular vesicles in different human cancer types. J. Extracell. Vesicles, 2.","DOI":"10.3402\/jev.v2i0.20424"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D516","DOI":"10.1093\/nar\/gky1029","article-title":"Vesiclepedia 2019: A compendium of RNA, proteins, lipids and metabolites in extracellular vesicles","volume":"47","author":"Pathan","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fonseka, P., Pathan, M., Chitti, S.V., Kang, T., and Mathivanan, S. (2020). FunRich enables enrichment analysis of OMICs datasets. J. Mol. Biol., 166747.","DOI":"10.1016\/j.jmb.2020.166747"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3389\/fphys.2017.00275","article-title":"Endothelial Extracellular Vesicles-Promises and Challenges","volume":"8","author":"Hromada","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1302705","DOI":"10.1080\/20013078.2017.1302705","article-title":"Characterisation of extracellular vesicle-subsets derived from brain endothelial cells and analysis of their protein cargo modulation after TNF exposure","volume":"6","author":"Dozio","year":"2017","journal-title":"J. Extracell. Vesicles"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1131804","DOI":"10.1080\/21688370.2015.1131804","article-title":"Extracellular vesicles of the blood-brain barrier","volume":"4","author":"Toborek","year":"2016","journal-title":"Tissue Barriers"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Simeone, P., Bologna, G., Lanuti, P., Pierdomenico, L., Guagnano, M.T., Pieragostino, D., Del Boccio, P., Vergara, D., Marchisio, M., and Miscia, S. (2020). Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072514"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mir, B., and Goettsch, C. (2020). Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo. Cells, 9.","DOI":"10.3390\/cells9071601"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1002\/pmic.200800109","article-title":"Proteomic profiling of exosomes: Current perspectives","volume":"8","author":"Simpson","year":"2008","journal-title":"Proteomics"},{"key":"ref_37","first-page":"1641","article-title":"LOXL2 upregulates hypoxia-inducible factor-1\u03b1 signaling through Snail-FBP1 axis in hepatocellular carcinoma cells","volume":"43","author":"Fan","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"C1321","DOI":"10.1152\/ajpcell.00079.2005","article-title":"Hypoxia of endothelial cells leads to MMP-2-dependent survival and death","volume":"289","author":"Miller","year":"2005","journal-title":"Am J. Physiol. Cell Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41419-018-0661-3","article-title":"Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment","volume":"9","author":"Yang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/jcmm.12769","article-title":"HIF-1\u03b1 regulates EMT via the Snail and \u03b2-catenin pathways in paraquat poisoning-induced early pulmonary fibrosis","volume":"20","author":"Zhu","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1289\/ehp.845537","article-title":"Paraquat: Model for oxidant-initiated toxicity","volume":"55","author":"Bus","year":"1984","journal-title":"Environ. Health Perspect."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.taap.2004.04.019","article-title":"Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10","volume":"201","author":"McCarthy","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_43","unstructured":"Vuji\u0107, T., Schvartz, D., and Sanchez, J.-C. Quantitative Data-Independent Acquisition (DIA) analysis unraveled paraquat-induced cholesterol biosynthesis dysregulation in human brain microvascular endothelial cells, Unpublished, manuscript in preparation."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jconrel.2017.07.001","article-title":"Extracellular vesicles: Novel promising delivery systems for therapy of brain diseases","volume":"262","author":"Albuquerque","year":"2017","journal-title":"J. Control Release"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jconrel.2020.04.017","article-title":"Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders","volume":"323","author":"Upadhya","year":"2020","journal-title":"J. Control Release"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Leitolis, A., Suss, P.H., Roderjan, J.G., Angulski, A.B.B., da Costa, F.D.A., Stimamiglio, M.A., and Correa, A. (2019). Human Heart Explant-Derived Extracellular Vesicles: Characterization and Effects on the In Vitro Recellularization of Decellularized Heart Valves. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061279"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1348885","DOI":"10.1080\/20013078.2017.1348885","article-title":"A rigorous method to enrich for exosomes from brain tissue","volume":"6","author":"Vella","year":"2017","journal-title":"J. Extracell. Vesicles"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.etap.2011.12.027","article-title":"Astrocyte mediated protection of fetal cerebral cortical neurons from rotenone and paraquat","volume":"33","author":"Rathinam","year":"2012","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1073\/pnas.83.10.3189","article-title":"Superoxide mediates the toxicity of paraquat for Chinese hamster ovary cells","volume":"83","author":"Bagley","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1023\/A:1022497319548","article-title":"Paraquat-induced free radical reaction in mouse brain microsomes","volume":"23","author":"Yang","year":"1998","journal-title":"Neurochem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wang, X., Luo, F., and Zhao, H. (2014). Paraquat-Induced Reactive Oxygen Species Inhibit Neutrophil Apoptosis via a p38 MAPK\/NF-\u03baB\u2013IL-6\/TNF-\u03b1 Positive-Feedback Circuit. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093837"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12974-018-1204-7","article-title":"Inflammation leads to distinct populations of extracellular vesicles from microglia","volume":"15","author":"Yang","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1038\/s41467-020-15305-w","article-title":"Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment","volume":"11","author":"Chan","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.blre.2012.12.002","article-title":"Extracellular vesicles in physiological and pathological conditions","volume":"27","author":"Yuana","year":"2013","journal-title":"Blood Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7609","DOI":"10.1111\/jcmm.15397","article-title":"Extracellular vesicles enhance oxidative stress through P38\/NF-kB pathway in ketamine-induced ulcerative cystitis","volume":"24","author":"Xi","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"eabe5085","DOI":"10.1126\/sciadv.abe5085","article-title":"Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome","volume":"7","author":"Kim","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"881","DOI":"10.2217\/nnm-2015-0009","article-title":"Cetuximab treatment alters the content of extracellular vesicles released from tumor cells","volume":"11","author":"Coimbra","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.ygyno.2007.08.064","article-title":"Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM","volume":"107","author":"Runz","year":"2007","journal-title":"Gynecol. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nbt.2886","article-title":"Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor","volume":"32","author":"Im","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7312","DOI":"10.1073\/pnas.1220998110","article-title":"Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development","volume":"110","author":"Kucharzewska","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1161\/CIRCRESAHA.118.314601","article-title":"Mitochondria Are a Subset of Extracellular Vesicles Released by Activated Monocytes and Induce Type I IFN and TNF Responses in Endothelial Cells","volume":"125","author":"Puhm","year":"2019","journal-title":"Circ. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1635420","DOI":"10.1080\/20013078.2019.1635420","article-title":"Mitochondrial protein enriched extracellular vesicles discovered in human melanoma tissues can be detected in patient plasma","volume":"8","author":"Jang","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1177\/1535370213498978","article-title":"Expression and significance of HIF-1\u03b1 in pulmonary fibrosis induced by paraquat","volume":"238","author":"Xie","year":"2013","journal-title":"Exp. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Alural, B., Ozerdem, A., Allmer, J., Genc, K., and Genc, S. (2015). Lithium protects against paraquat neurotoxicity by NRF2 activation and miR-34a inhibition in SH-SY5Y cells. Front. Cell. Neurosci., 9.","DOI":"10.3389\/fncel.2015.00209"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3232869","DOI":"10.1155\/2020\/3232869","article-title":"The Role of Exosomal microRNAs and Oxidative Stress in Neurodegenerative Diseases","volume":"2020","author":"Wang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1186\/s12974-018-1371-6","article-title":"Profiling the proteomic inflammatory state of human astrocytes using DIA mass spectrometry","volume":"15","author":"Dozio","year":"2018","journal-title":"J. Neuroinflamm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:59:06Z","timestamp":1760162346000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/10\/5065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,11]]},"references-count":66,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22105065"],"URL":"https:\/\/doi.org\/10.3390\/ijms22105065","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,11]]}}}