Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks
Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our g...
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| Veröffentlicht in: | International journal of molecular sciences 2019-12, Vol.20 (24), p.6348 |
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| creator | Guo, Nancy Lan Poh, Tuang Yeow Pirela, Sandra Farcas, Mariana T Chotirmall, Sanjay H Tham, Wai Kin Adav, Sunil S Ye, Qing Wei, Yongyue Shen, Sipeng Christiani, David C Ng, Kee Woei Thomas, Treye Qian, Yong Demokritou, Philip |
| description | Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. To the best of our knowledge, this is the first study systematically integrating in vivo, transcriptomics, metabolomics, and lipidomics to assess PEPs inhalation exposure-induced disease risks using a rat model. |
| doi_str_mv | 10.3390/ijms20246348 |
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Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. To the best of our knowledge, this is the first study systematically integrating in vivo, transcriptomics, metabolomics, and lipidomics to assess PEPs inhalation exposure-induced disease risks using a rat model.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20246348</identifier><identifier>PMID: 31888290</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Air Pollutants - analysis ; Animals ; Arachidonic acid ; Biomarkers ; Carcinogenesis ; Carcinogens ; Cardiovascular disease ; Cardiovascular system ; Cell division ; Congenital defects ; Diabetes ; Diabetes mellitus ; Disease - genetics ; EKG ; Electrocardiography ; Exposure ; Gene expression ; Genomes ; Heart ; Histidine ; Hypertension ; In vivo methods and tests ; Inhalation ; Inhalation Exposure - adverse effects ; Integrated approach ; Laser printers ; Linoleic acid ; Lipid metabolism ; Lipidomics ; Lipids ; Lung - metabolism ; Lungs ; Male ; Metabolic disorders ; Metabolic syndrome ; Metabolism ; Metabolites ; Metabolomics ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Nanoparticles ; Nanoparticles - adverse effects ; Nanotechnology ; Occupational exposure ; Particulate matter ; Printers ; Printing ; Rats, Sprague-Dawley ; Respiration ; Risk Factors ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Serum - metabolism ; Surveillance ; Toners ; Toxicology ; Transcription ; Transcriptome - genetics ; Ventricle</subject><ispartof>International journal of molecular sciences, 2019-12, Vol.20 (24), p.6348</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-db4292af6fbea5e609ae2c031bd5df8d43d26d02a1ee074b34484c958c471daa3</citedby><cites>FETCH-LOGICAL-c412t-db4292af6fbea5e609ae2c031bd5df8d43d26d02a1ee074b34484c958c471daa3</cites><orcidid>0000-0002-8050-6268 ; 0000-0003-2404-9434 ; 0000-0002-0301-0242 ; 0000-0003-0417-7607 ; 0000-0002-1054-8796 ; 0000-0002-8559-4885 ; 0000-0002-7276-3563</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940784/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940784/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31888290$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Nancy Lan</creatorcontrib><creatorcontrib>Poh, Tuang Yeow</creatorcontrib><creatorcontrib>Pirela, Sandra</creatorcontrib><creatorcontrib>Farcas, Mariana T</creatorcontrib><creatorcontrib>Chotirmall, Sanjay H</creatorcontrib><creatorcontrib>Tham, Wai Kin</creatorcontrib><creatorcontrib>Adav, Sunil S</creatorcontrib><creatorcontrib>Ye, Qing</creatorcontrib><creatorcontrib>Wei, Yongyue</creatorcontrib><creatorcontrib>Shen, Sipeng</creatorcontrib><creatorcontrib>Christiani, David C</creatorcontrib><creatorcontrib>Ng, Kee Woei</creatorcontrib><creatorcontrib>Thomas, Treye</creatorcontrib><creatorcontrib>Qian, Yong</creatorcontrib><creatorcontrib>Demokritou, Philip</creatorcontrib><title>Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. 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adverse effects</subject><subject>Integrated approach</subject><subject>Laser printers</subject><subject>Linoleic acid</subject><subject>Lipid metabolism</subject><subject>Lipidomics</subject><subject>Lipids</subject><subject>Lung - metabolism</subject><subject>Lungs</subject><subject>Male</subject><subject>Metabolic disorders</subject><subject>Metabolic syndrome</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Nanoparticles</subject><subject>Nanoparticles - adverse effects</subject><subject>Nanotechnology</subject><subject>Occupational exposure</subject><subject>Particulate matter</subject><subject>Printers</subject><subject>Printing</subject><subject>Rats, Sprague-Dawley</subject><subject>Respiration</subject><subject>Risk Factors</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Serum - 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Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. 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| ispartof | International journal of molecular sciences, 2019-12, Vol.20 (24), p.6348 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Air Pollutants - analysis Animals Arachidonic acid Biomarkers Carcinogenesis Carcinogens Cardiovascular disease Cardiovascular system Cell division Congenital defects Diabetes Diabetes mellitus Disease - genetics EKG Electrocardiography Exposure Gene expression Genomes Heart Histidine Hypertension In vivo methods and tests Inhalation Inhalation Exposure - adverse effects Integrated approach Laser printers Linoleic acid Lipid metabolism Lipidomics Lipids Lung - metabolism Lungs Male Metabolic disorders Metabolic syndrome Metabolism Metabolites Metabolomics MicroRNAs - genetics MicroRNAs - metabolism miRNA Nanoparticles Nanoparticles - adverse effects Nanotechnology Occupational exposure Particulate matter Printers Printing Rats, Sprague-Dawley Respiration Risk Factors RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Serum - metabolism Surveillance Toners Toxicology Transcription Transcriptome - genetics Ventricle |
| title | Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T23%3A08%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Integrated%20Transcriptomics,%20Metabolomics,%20and%20Lipidomics%20Profiling%20in%20Rat%20Lung,%20Blood,%20and%20Serum%20for%20Assessment%20of%20Laser%20Printer-Emitted%20Nanoparticle%20Inhalation%20Exposure-Induced%20Disease%20Risks&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Guo,%20Nancy%20Lan&rft.date=2019-12-16&rft.volume=20&rft.issue=24&rft.spage=6348&rft.pages=6348-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms20246348&rft_dat=%3Cproquest_pubme%3E2548663036%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2548663036&rft_id=info:pmid/31888290&rfr_iscdi=true |