Genome-wide analysis of the therapeutic effect of NeuroD on irradiation-induced intestinal injury
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ABSTRACT: The objective was to investigate the therapeutic effect of NeuroD on irradiation-induced intestinal injury at gene expression level. Gene expression profilings between NeuroD and EGFP treated mice which were received 9 Gy total body irradiation were compared. All mice were given 9 Gy radiation and divided into two groups (3 mice per group). After radiation, mice were immediately administered with an intraperitoneal injection of 0.1 mM EGFP or NeuroD-EGFP. EGFP treated mice were served as controls. 12 hours post radiation, mice jejunum tissues were isolated. Total RNA obtained from jejunum tissues and subjected to gene expression profiling assays.
Project description:The objective was to investigate the therapeutic effect of NeuroD on irradiation-induced intestinal injury at gene expression level. Gene expression profilings between NeuroD and EGFP treated mice which were received 9 Gy total body irradiation were compared.
Project description:C57BL/6 wild type mice were exposed to 12 Gy whole-body irradiation. Before irradiation (t=0) and at t=24, 48 and 96 hours after irradiation, mice (n=10 per time point) were euthanized. From n=5 mice per time point RNA was isolated from small-intestinal (jejunum) tissue, from n=5 mice per time point RNA was isolated from EDTA-isolated epithelial cells from small-intestinal tissue (jejunum).
Project description:The objective was to investigate the therapeutic effect of VND3207 on irradiation-induced intestinal injury at gene expression level. Gene expression profilings between VND3207 and vehicle treated mice which were received 9 Gy total body irradiation were compared.
Project description:Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 Gy or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation and cholesterol metabolism. We found significantly enhanced expression of pro-inflammatory cytokines (TNF-, TGF-, IL-1 and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low density lipoprotein (LDL) and oxidized LDL was increased whereas that of high density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.
Project description:Transcriptional profiling of intestinal epithelial cells expressing either Negative, Sublow, Low or High levels of the Sox9-EGFP reporter transgene FACS-isolated from jejunum of non-irradiated mice or at 5 days after 14Gy abdominal irradiation. 4 distinct cell populations, FACS-isolated based on expression levels of the Sox9-EGFP reporter transgene (Sox9-EGFP Negative, Sublow, Low and High cells); 2 conditions: Non-irradiated vs Irradiated; Biological replicates: 7 independent non-irradiated mice and 3 independent irradiated (studied at day 5 post-irradiation) mice
Project description:Cranial and craniospinal irradiation are the oldest central nervous system prophylaxis treatments considered for pediatric patients with lymphoblastic leukemia (ALL). However, survivors of childhood ALL that received cranial radiotherapy are at increased risk for deficits in neurocognitive skills. The continuous and dynamic response of normal tissue after irradiation has been identified as one of the causative factors for cognitive changes after cranial radiation therapy. The aim of our study was to investigate the radiation effects on social behavior and neuronal morphology in the hippocampus of adult mice. Twenty-one-day-old male C57BL/6 mice were irradiated with the small-animal radiation research platform (SARRP). Animals were given a single 10-Gy dose of radiation of X-ray cranial radiation. One month following irradiation, animals underwent behavioral testing in the Three-Chamber Sociability paradigm. Radiation affected social discrimination during the third stage eliciting an inability to discriminate between the familiar and stranger mouse, while sham successfully spent more time exploring the novel stranger. Proteomic analysis revealed dysregulation of metabolic and signaling pathways associated with neurocognitive dysfunction such as mitochondrial dysfunction, Rac 1 signaling, and synaptogenesis signaling. We observed significant decreases in mushroom spine density in the Cornu Ammonis 2 of the hippocampus, which is associated sociability processing.
Project description:Transcriptional profiling of intestinal epithelial cells expressing either Negative, Sublow, Low or High levels of the Sox9-EGFP reporter transgene FACS-isolated from jejunum of non-irradiated mice or at 5 days after 14Gy abdominal irradiation.
Project description:Healthy adult male C57BL/6 mice (8 weeks of age) were randomly divided into sham irradiation group (sham) and cranial ir-radiation group (5 Gy 4 d). For the 5 Gy 4 d group, the head of mice were received 20 Gy X-rays (RAD Source RS 2000 series, Suwanee, USA), applied as four doses of 5 Gy in consecutive 4 days at a dose rate of 2.33 Gy/ min. The rest of mouse’s body was completely protected by a 2-cm thick lead shield. For the sham group, the mice were maintained in the same procedure except X-ray irradiation. No radiation leakage through the shield occurred in the present study, as verified by dose measurement of testis under shielding and morphological structure of peripheral main organs. Meanwhile, Monte Carlo simulation was used to calculate the absorbed dose of the peripheral main organs when mice head was irradiated with 20 Gy X-rays. The results showed that the absorbed dose of testis under shielding was 0.018 Gy, which was only 0.9‰ of cranial absorbed dose. Tandem mass tag (TMT) quantitative proteomic analysis of testis at 4 W after cranial irradiation was carried out by LC-BIO Co., Ltd (Hangzhou, China). The differentially expressed proteins (DEPs) were screened and obtained using the cutoffs of fold change > 1.2 and P < 0.05. For bioinformatics analysis, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed using the DAVID 6.8 database (https://david.ncifcrf.gov/).
Project description:In this study, we measured mRNA and lncRNA profiles of gastric tissues following 0, 6 and 12 Gy irradiation. The stomach of C57 mice were exposed to 0, 6 and 12 Gy X-ray irradiation at a dose rate of 2 Gy/min. The mice were sacrificed 7 days after irradiation and gastric tissues were collected. RNA was extracted and quantified. mRNA and lncRNA profilings of each groups were analyzed by microarray.
Project description:The mammalian brain is especially sensitive to ionizing radiation during development, as shown by the increased occurrence of mental retardation and small head size in children who were in utero exposed to ionizing radiation after the atomic bombings of Hiroshima and Nagasaki. These effects of prenatal irradiation can be mimicked by irradiation of mouse embryos during the organogenesis period. In order to better understand the early effects of ionizing radiation on the embryonic brain and immature neurons, we performed a microarray analysis on brains from mice irradiated with different doses (0.0, 0.1, 0.2, 0.5 and 1.0 Gy) at E11. RNA was extracted at either 2 or 24 h post-irradiation.