Dataset Information

Global gene expression profiling of blast lung injury of goats exposed to shock wave.

ABSTRACT: PURPOSE:Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear. METHODS:In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression. RESULTS:Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing. CONCLUSION:Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

SUBMITTER: Wang H

PROVIDER: S-EPMC7567904 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Global gene expression profiling of blast lung injury of goats exposed to shock wave.

Wang Hong H Zhang Wen-Juan WJ Gao Jun-Hong JH Liu Jin-Ren JR Liu Zhi-Yong ZY Xia Bao-Qing BQ Fan Xiao-Lin XL Li Cun-Zhi CZ Qian Ai-Rong AR

Chinese journal of traumatology = Zhonghua chuang shang za zhi 20200821 5

<h4>Purpose</h4>Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear.<h4>Methods</h4>In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control g ...[more]

PMID: 32917472

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Project description:Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by two pathological hallmarks: Tau-containing neurofibrillary tangles and amyloid-? protein (A?)-containing neuritic plaques. The goal of this study is to understand mild traumatic brain injury (mTBI)-related brain proteomic changes and tau-related biochemical adaptations that may contribute to AD-like neurodegeneration. We found that both phosphorylated tau (p-tau) and the ratio of p-tau/tau were significantly increased in brains of mice collected at 3 and 24 h after exposure to 82-kPa low-intensity open-field blast. Neurological deficits were observed in animals at 24 h and 7 days after the blast using Simple Neuroassessment of Asymmetric imPairment (SNAP) test, and axon/dendrite degeneration was revealed at 7 days by silver staining. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to analyze brain tissue labeled with isobaric mass tags for relative protein quantification. The results from the proteomics and bioinformatic analysis illustrated the alterations of axonal and synaptic proteins in related pathways, including but not being limited to substantia nigra development, cortical cytoskeleton organization, and synaptic vesicle exocytosis, suggesting a potential axonal damage caused by blast-induced mTBI. Among altered proteins found in brains suffering blast, microtubule-associated protein 1B, stathmin, neurofilaments, actin binding proteins, myelin basic protein, calcium/calmodulin-dependent protein kinase, and synaptotagmin I were representative ones involved in altered pathways elicited by mTBI. Therefore, TBI induces elevated phospho-tau, a pathological feature found in brains of AD, and altered a number of neurophysiological processes, supporting the notion that blast-induced mTBI as a risk factor contributes to AD pathogenesis. LC/MS-based profiling has presented candidate target/pathways that could be explored for future therapeutic development.

Project description:Long-term molecular changes in the brain resulting from blast exposure may be mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation, that regulate gene expression. Aberrant regulation of gene expression is associated with behavioral abnormalities, where DNA methylation bridges environmental signals to sustained changes in gene expression. We assessed DNA methylation changes in the brains of rats exposed to three 74.5 kPa blast overpressure events, conditions that have been associated with long-term anxiogenic manifestations weeks or months following the initial exposures. Rat frontal cortex eight months post-exposure was used for cell sorting of whole brain tissue into neurons and glia. We interrogated DNA methylation profiles in these cells using Expanded Reduced Representation Bisulfite Sequencing. We obtained data for millions of cytosines, showing distinct methylation profiles for neurons and glia and an increase in global methylation in neuronal versus glial cells (p<10(-7)). We detected DNA methylation perturbations in blast overpressure-exposed animals, compared with sham blast controls, within 458 and 379 genes in neurons and glia, respectively. Differentially methylated neuronal genes showed enrichment in cell death and survival and nervous system development and function, including genes involved in transforming growth factor β and nitric oxide signaling. Functional validation via gene expression analysis of 30 differentially methylated neuronal and glial genes showed a 1.2 fold change in gene expression of the serotonin N-acetyltransferase gene (Aanat) in blast animals (p<0.05). These data provide the first genome-based evidence for changes in DNA methylation induced in response to multiple blast overpressure exposures. In particular, increased methylation and decreased gene expression were observed in the Aanat gene, which is involved in converting serotonin to the circadian hormone melatonin and is implicated in sleep disturbance and depression associated with traumatic brain injury.

Project description:Measurement issues leading to the acquisition of artifact-free shock wave pressure-time profiles are discussed. We address the importance of in-house sensor calibration and data acquisition sampling rate. Sensor calibration takes into account possible differences between calibration methodology in a manufacturing facility, and those used in the specific laboratory. We found in-house calibration factors of brand new sensors differ by less than 10% from their manufacturer supplied data. Larger differences were noticeable for sensors that have been used for hundreds of experiments and were as high as 30% for sensors close to the end of their useful lifetime. These observations were despite the fact that typical overpressures in our experiments do not exceed 50 psi for sensors that are rated at 1,000 psi maximum pressure. We demonstrate that sampling rate of 1,000?kHz is necessary to capture the correct rise time values, but there were no statistically significant differences between peak overpressure and impulse values for low-intensity shock waves (Mach number <2) at lower rates. We discuss two sources of experimental errors originating from mechanical vibration and electromagnetic interference on the quality of a waveform recorded using state-of-the-art high-frequency pressure sensors. The implementation of preventive measures, pressure acquisition artifacts, and data interpretation with examples, are provided in this paper that will help the community at large to avoid these mistakes. In order to facilitate inter-laboratory data comparison, common reporting standards should be developed by the blast TBI research community. We noticed the majority of published literature on the subject limits reporting to peak overpressure; with much less attention directed toward other important parameters, i.e., duration, impulse, and dynamic pressure. These parameters should be included as a mandatory requirement in publications so the results can be properly compared with others.

Dataset Information

Global gene expression profiling of blast lung injury of goats exposed to shock wave.

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Global gene expression profiling of blast lung injury of goats exposed to shock wave.

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