{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:30:07Z","timestamp":1769128207790,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Joint Program Committee-7\/Radiation Health Effects Research Program (RHERP)","award":["1I80 VP00262-01"],"award-info":[{"award-number":["1I80 VP00262-01"]}]},{"name":"Joint Program Committee-7\/Radiation Health Effects Research Program (RHERP)","award":["AFR-B4-10978"],"award-info":[{"award-number":["AFR-B4-10978"]}]},{"name":"Joint Program Committee-7\/Radiation Health Effects Research Program (RHERP)","award":["AFR-12080"],"award-info":[{"award-number":["AFR-12080"]}]},{"name":"Uniformed Services University of the Health Sciences\/Armed Forces Radiobiology Research Institute","award":["1I80 VP00262-01"],"award-info":[{"award-number":["1I80 VP00262-01"]}]},{"name":"Uniformed Services University of the Health Sciences\/Armed Forces Radiobiology Research Institute","award":["AFR-B4-10978"],"award-info":[{"award-number":["AFR-B4-10978"]}]},{"name":"Uniformed Services University of the Health Sciences\/Armed Forces Radiobiology Research Institute","award":["AFR-12080"],"award-info":[{"award-number":["AFR-12080"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Development of radiation medical countermeasures under the U.S. Food and Drug Administration Animal Rule requires the capability to translate an effective animal-to-human drug dose. One method of human dose translation is using a biomarker and determining drug doses that modulate the biomarker to the desired level. BIO 300 Oral Powder (BIO 300) is a prophylactic radiation medical countermeasure that is currently being developed following the Animal Rule. The present study aimed to identify biomarkers that can be used for human dose conversion by conducting transcriptomics of whole blood collected from BIO 300-treated CD2F1 mice in the presence and absence of total-body irradiation (TBI). Unirradiated mice were treated with vehicle or 50, 100, or 200 mg\/kg BIO 300, and irradiated mice were treated with 200 mg\/kg or BIO 300 or vehicle prior to TBI. Whole-blood samples were collected after the last dose of the drug and after irradiation. RNA sequencing demonstrated 100 and 200 mg\/kg of BIO 300 doses caused significantly more differential gene expression at 48 h after drug dose compared to 50 mg\/kg of BIO 300 (7648, 7680, and 55 significantly differently expressed genes, respectively). Interestingly, following TBI, there were no significantly differentially expressed genes between vehicle- and BIO 300-treated mice. Despite the lack of significant changes in gene expression, the transcriptomic profiles in both groups indicated differential changes in signaling pathways. Pathway analysis of the transcriptome profile from vehicle-treated\/TBI mice revealed that many inflammatory signaling pathways were activated in these animals. Signaling pathways enriched in BIO 300-treated\/TBI mice were involved in cellular stress and immune response and were predicted to be inhibited. In all, four signaling pathways of interest were identified that were differentially enriched in irradiated animals treated with BIO 300: pathogen-induced cytokine storm signaling, S100 family signaling, pulmonary fibrosis idiopathic signaling, and wound-healing signaling. These pathways should be explored to identify potential biomarkers of BIO 300 that can be used for human dose translation.<\/jats:p>","DOI":"10.3390\/ijms25168818","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T05:23:27Z","timestamp":1723613007000},"page":"8818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["BIO 300 Attenuates Whole Blood Transcriptome Changes in Mice Exposed to Total-Body Radiation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2683-4383","authenticated-orcid":false,"given":"Artur A.","family":"Serebrenik","sequence":"first","affiliation":[{"name":"Humanetics Corporation, Minneapolis, MN 55435, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7942-2497","authenticated-orcid":false,"given":"Oluseyi O.","family":"Fatanmi","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen Y.","family":"Wise","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2645-7570","authenticated-orcid":false,"given":"Sarah A.","family":"Petrus","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Kaytor","sequence":"additional","affiliation":[{"name":"Humanetics Corporation, Minneapolis, MN 55435, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6631-3849","authenticated-orcid":false,"given":"Vijay K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1080\/09553002.2017.1332438","article-title":"A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures","volume":"93","author":"Singh","year":"2017","journal-title":"Int. J. Radiat. 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