{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T07:34:59Z","timestamp":1777534499299,"version":"3.51.4"},"reference-count":90,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T00:00:00Z","timestamp":1576454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Institute for Occupational Safety and Health and the Consumer Protection Safety Commission","award":["1007514R"],"award-info":[{"award-number":["1007514R"]}]},{"name":"NTU-Harvard School of Public Health Initiative for Sustainable Nanotechnology","award":["NTU-HSPH 17001"],"award-info":[{"award-number":["NTU-HSPH 17001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms20246348","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T02:59:01Z","timestamp":1576551541000},"page":"6348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"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"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8050-6268","authenticated-orcid":false,"given":"Nancy Lan","family":"Guo","sequence":"first","affiliation":[{"name":"West Virginia University Cancer Institute\/School of Public Health, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuang Yeow","family":"Poh","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Pirela","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T. 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Chan School of Public Health, Harvard University, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2404-9434","authenticated-orcid":false,"given":"Mariana T.","family":"Farcas","sequence":"additional","affiliation":[{"name":"Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-7607","authenticated-orcid":false,"given":"Sanjay H.","family":"Chotirmall","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wai Kin","family":"Tham","sequence":"additional","affiliation":[{"name":"Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8559-4885","authenticated-orcid":false,"given":"Sunil S.","family":"Adav","sequence":"additional","affiliation":[{"name":"Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1054-8796","authenticated-orcid":false,"given":"Qing","family":"Ye","sequence":"additional","affiliation":[{"name":"West Virginia University Cancer Institute\/School of Public Health, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongyue","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Lab for Modern Toxicology, Department of Epidemiology and Biostatistics and Ministry of Education (MOE), School of Public Health, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sipeng","family":"Shen","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0301-0242","authenticated-orcid":false,"given":"David C.","family":"Christiani","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7276-3563","authenticated-orcid":false,"given":"Kee Woei","family":"Ng","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T. 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Chan School of Public Health, Harvard University, Boston, MA 02115, USA"},{"name":"School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore"},{"name":"Environmental Chemistry and Materials Centre, Nanyang Environment &amp; Water Research Institute, Singapore 637141, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Treye","family":"Thomas","sequence":"additional","affiliation":[{"name":"Office of Hazard Identification and Reduction, U.S. Consumer Product Safety Commission, Rockville, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Qian","sequence":"additional","affiliation":[{"name":"Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Demokritou","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T. 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Chan School of Public Health, Harvard University, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.nano.2019.03.003","article-title":"Inactivation of common hospital acquired pathogens on surfaces and in air utilizing engineered water nanostructures (EWNS) based nano-sanitizers","volume":"18","author":"Vaze","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1021\/acsnano.8b03074","article-title":"Reducing Intestinal Digestion and Absorption of Fat Using a Nature-Derived Biopolymer: Interference of Triglyceride Hydrolysis by Nanocellulose","volume":"12","author":"DeLoid","year":"2018","journal-title":"ACS Nano"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.copbio.2016.11.012","article-title":"Nanotechnology to the rescue: Using nano-enabled approaches in microbiological food safety and quality","volume":"44","author":"Eleftheriadou","year":"2017","journal-title":"Curr. 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