Lung disease death predictor gene expression
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE214484 | GEO | 2025/09/03
REPOSITORIES: GEO
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Project description:The development of a biodosimetric assay based on the combined gene expression analysis of ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation has been developed. Gene expression profile signature of human radiation injury into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) has been shown to discriminate 6 radiation dose levels in human PB. Candidate gene lists were first developed assaying human ex vivo and human TBI samples on the Affymetrix platform.
2014-10-21 | GSE58613 | GEO
Project description:In a radiation mass casualty event, exposed populations will suffer dose-dependent toxicity to multiple-organ systems. Although several therapies are FDA-approved for treatment of the hematopoietic acute radiation syndrome (H-ARS), there are no FDA-approved medical countermeasures (MCM) for either acute gastrointestinal injury (GI) or late multi-organ toxicities known as the delayed effects of acute radiation exposure (DEARE). Prior data suggest activation of the alternative renin angiotensin (RAS) enzyme angiotensin-converting enzyme 2 (ACE2) has therapeutic potential for mitigating multi-organ radiation injury, including GI acute radiation syndrome (GI-ARS). Here, we evaluated whether pharmacologic activation of ACE2 mitigates GI-ARS in rodent models and protects against DEARE in GI-ARS survivors.
2025-08-04 | GSE303960 | GEO
Project description:There is a current interest in the development of biodosimetric methods for rapidly assessing radiation exposure in the wake of a large-scale radiological event. The initial focus of this work has largely centered on determining the exposure dose to an individual using biological indicators. Gene expression signatures are showing promise for biodosimetric application, but little is known about how these signatures might translate for the assessment of radiological injury in radiosensitive individuals, who comprise a significant fraction of the general population, and who would likely require treatment following lower doses. Using Parp1-/- mice as a model radiation sensitive genotype, we have investigated the effect of this DNA repair deficiency on the gene expression response to radiation. Although Parp1 is known to play general roles in regulating transcription, the pattern of gene expression changes observed 24 h after exposure to a potentially lethal LD50 dose of radiation was remarkably similar in the two genotypes, and indicated similar levels of activation of both the p53 and NFκB radiation response pathways. In contrast, exposure of wild-type mice to a sub-lethal dose that was equal to the LD50 dose given to the Parp1-/- mice, resulted in a reduced gene expression response. Gene expression classifiers trained on the wild-type data correctly identified all wild-type samples as unexposed, exposed to a sub-lethal dose, or exposed to a potentially lethal dose. All unexposed samples from the Parp1-/- mice were also correctly classified, and 80% of the irradiated samples were identified as exposed to a potentially lethal dose. The results of this study suggest that, at least for some genotypes, gene expression has the potential to accurately detect the extent of radiological injury, rather than being useful only as a surrogate of physical radiation dose.
2018-05-23 | GSE101402 | GEO
Project description:There is a perceived need to develop tools for high-throughput radiation biodosimetry. In the case of an improvised nuclear device or a dirty bomb in a major city, potentially hundreds of thousands of people would have to be screened to assign exposed individuals to appropriate treatment. Gene expression represents an emerging approach to biodosimetry and could potentially provide an estimate of both absorbed dose and individual radiation-induced injury. Mice have been used as an in vivo model to elucidate the radiation response and to construct biodosimetric gene expression profiles. However, while most studies have used mouse strains with “average” radiation sensitivity, 2-4% of humans are thought to be radiosensitive. Such individuals would suffer greater radiological injury at a given dose than members of the general population, so it is of interest to determine how such sensitivity may impact the biodosimetric gene expression signatures being developed. Here, we use wild-type mice and genetically engineered mouse models deficient in two DNA repair pathways that can contribute to radiation sensitivity. Humans with ataxia telangiectasia or Atm-/- mice are deficient in double-strand break repair and show increased radiosensitivity. Atm-/- mice have a LD50/30 of 4 Gy compared with 8 Gy in the parental wild-type (WT) C57BL/6 mice. Humans with SCID, or Prkdcscid mice are deficient in non-homologous end joining, and are also radiosensitive. SCID mice have a LD50/30 of 3 Gy. These animal models represent a “worse-case” scenario, and should be viewed as an extreme of radiation sensitivity. Most radiosensitive members of the population will not have full-blown DNA repair deficiency syndromes, but these extreme models should help to define the maximum impact of DNA repair deficiency on gene expression following radiation exposure.
2018-01-17 | GSE99176 | GEO
Project description:The development of a biodosimetric assay based on the combined gene expression analysis of ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation has been developed. Gene expression profile signature of human radiation injury into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) has been shown to discriminate 6 radiation dose levels in human PB. Candidate gene lists were first developed assaying human ex vivo and human TBI samples on the Affymetrix platform. For the Ex Vivo samples, healthy consented adult donor was randomly assigned to a radiation group and labeled with the target dose of 0 cGy, 150 cGy, 300 cGy, or 600 cGy. In addition to the radiation exposures, the samples were also treated with either no treatment, GCSF, or LPS at time points 6 hours and 24 hours. Radiation expire times from the Cs137 irradiator were calculated to achieve target doses specific for tubes filled with blood and inserted in the roaring test tube holder. The dose rate was 480 cGy/min for the duration of the study. The healthy donors were enrolled to participate in this study following a protocol to collect PB samples that was previously approved by the Duke University Institutional Review Board. For the TBI samples, adult patients, ages 21 to 66, were evaluated at the Duke University Adult Bone Marrow Transplantation Program enrolled in a Duke IRB-approved protocol to collect PB prior to and post TBI conditioning. With approval from the Duke University Institutional Review Board (IRB), between 5-12 mL of peripheral blood was collected from consented patients prior to and 6 hours following TBI with 150-200 cGy as part of their pre-transplantation conditioning. All patients receiving non-myeloablative conditioning were treated with 200 cGy of TBI from a linear accelerator at a dose rate of 20 cGy/min. All patients who underwent TBI-based myeloablative allogeneic or autologous stem-cell transplantation received radiation fractionated at 150 cGy per fraction at 20 cGy/min. All patients had PB collected (50 ml) prior to and 6 hours following exposure to either 200 cGy or 150 cGy radiation treatment. The dose exposure for TBI patients used in this study were 0 cGy, 150 cGy, 450 cGy and 1050 cGy at 0, 6, 30 and 78 hours post irradiation. Total RNA was extracted and assayed on the Affymetrix platform.
2014-10-21 | E-GEOD-58613 | biostudies-arrayexpress
Project description:Maximal aerobic exercise capacity (V̇O2max) is one of the strongest predictors of morbidity and mortality. Aerobic exercise training can increase V̇O2max, but inter-individual variability is marked and unexplained physiologically. The mechanisms underlying this variability have major clinical implications for extending human healthspan. Here, we report the first comprehensive, RNA-seq study of circulating transcriptome signatures related to ΔV̇O2max. We used RNA-seq to characterize transcriptomic predictors of ΔV̇O2max in healthy women who completed a 16-week, randomized controlled trial comparing higher vs. lower aerobic exercise training volume and intensity (four training groups, fully crossed). We found striking baseline gene expression differences in subjects who responded to aerobic exercise training with robust (R) vs. little/no (NR) ΔV̇O2max.
2022-06-22 | GSE206505 | GEO
Project description:Acute radiation syndrome (ARS) is a severe condition that develops after exposure to high doses of ionizing radiation that features immune suppression and organ failure. Currently, there are no diagnostics to identify the occurrence or severity of radiation exposure. There are also no current treatments or preventative strategies to mitigate ARS. Extracellular vesicles (EVs) are mediators of intercellular communication that contribute to immune dysfunction across diseases. We investigated if EV cargo would be able to identify whole body irradiation (WBIR) exposure and if EVs promote ARS immune dysfunction. We hypothesized that beneficial EVs derived from mesenchymal stem cells (MSC-EVs) would blunt ARS immune dysfunction and might serve as prophylactic radioprotectants. Mice received WBIR (2 or 9 Gy) with assessment of EVs at 3 and 7 days after exposure. LC-MS/MS proteomic analysis of WBIR-EVs found dose-related changes as well as candidate proteins that were increased with both doses and timepoints (34 total) such as Thromboxane-A Synthase and lymphocyte cytosolic protein 2. Suprabasin and Sarcalumenin were increased only after 9 Gy suggesting these proteins may indicate high dose/lethal exposure. Analysis of EV miRNAs identified miR-376 and miR-136, which were increased up to 200- and 60-fold respectively by both levels of WBIR and select miRNAs such as miR-1839 and miR-664 that were increased only with 9 Gy. WBIR-EVs (9 Gy) were biologically active and blunted immune responses to LPS in RAW264.7 macrophages, inhibiting canonical signaling pathways associated with wound healing and phagosome formation. Accordingly, WBIR-EVs also blunted RAW macrophage phagocytosis. When given 3 days after exposure, MSC-EVs slightly modified immune gene expression changes in the spleens of mice in response to WBIR and a combined radiation plus burn injury exposure (RCI). MSC-EVs normalized the expression of certain key immune genes such as NFκBia and Cxcr4 (WBIR), Map4k1, Ccr9 and Cxcl12 (RCI) lowered plasma TNFα cytokine levels after RCI, though most gene changes were not influenced. When given prophylactically (24 and 3 hours before exposure), MSC-EVs prolonged survival to the 9 Gy lethal exposure. Thus, EVs are important participants in ARS. EV cargo might be used to diagnose WBIR exposure, and MSC-EVs might serve as radioprotectants to blunt the impact of toxic radiation exposure.
2023-06-30 | PXD041837 | Pride
Project description:The continuous production of all mature blood cell lineages is maintained by Hematopoietic stem cells (HSCs), but they are highly susceptible to damage by ionizing radiation (IR) that induces death. Therefore, devising the therapeutic strategies that can mitigate hematopoietic toxicity caused by IR would benefit acute radiation syndrome (ARS) victims and radiation therapy patients. Here, we prepared an injectable hydrogel based on RGD-alginate and Laponite by a simple mixing method to release IL-12 (RGD-Alg/Laponite@IL-12) slowly and locally. The localization administration of RGD-Alg/Laponite@IL-12 substantially increased the survival and promoted the hematopoietic recovery of mice following sublethal-dose irradiation. These results suggested that local intra-bone marrow injection of RGD-Alg/Laponite@IL-12 hydrogel can effectively stimulate IL12R-PI3K/AKT signaling axis, which promotes proliferation and hematopoietic growth factors (HGFs) secretion of bone marrow mesenchymal stem/stromal cells (BM-MSCs). This signaling axis facilitates hematopoietic microenvironment repair and plays a pivotal role in hematopoietic reconstitution. In conclusion, our study attempted a biomaterial-sustained release of IL-12 for the treatment of irradiated hematopoietic injury and provided a new therapeutic strategy for hematopoietic acute radiation syndrome (H-ARS).
2024-09-18 | GSE267635 | GEO
Project description:Exposure to high-doses of ionizing radiation (IR) leads to development of a strong acute radiation syndrome (ARS) in mammals. ARS manifests after a latency period and it is important to develop fast prognostic biomarkers for its early detection and assessment. Analysis of chromosomal aberrations in peripheral blood lymphocytes is the gold standard of biological dosimetry, but it fails after high doses of IR. Therefore, it is important to establish novel biomarkers of exposure that are fast and reliable also in the high dose range. Here, we investigated the applicability of miRNA levels in mouse serum.
2025-01-29 | GSE288305 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE6871: Gene expression signatures that predict radiation exposure (human) GSE6873: Gene expression signatures that predict radiation exposure (mouse) Keywords: SuperSeries Refer to individual Series
2010-06-12 | E-GEOD-6874 | biostudies-arrayexpress