Preclinical Model of Military Burn Pit Exposure Reveals Altered Inflammatory and Metabolic Pathways in the Rat Lung-Brain Axis
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PROVIDER: PRJNA1186574 | ENA |
REPOSITORIES: ENA
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Project description:Military personnel deployed to combat zones in Iraq and Afghanistan were exposed to toxic emissions from open-air burn pits, raising concerns about long-term health effects. Burn pit exposures are linked to a wide range of pulmonary and extra-pulmonary morbidities. This study aimed to model military burn pit exposure and investigate its impact on lung-brain axis signaling. Rats were exposed to carbon black nanoparticles and naphthalene (CBN) via whole body inhalation chamber for six hours to simulate burn pit exposure. Gene expression and inflammatory protein changes in lung and brain tissue were examined 24 hours post-exposure using next-generation RNA sequencing, Meso Scale Discovery biomarker assays, and western blot. Multiple inflammatory pathway proteins were significantly altered in plasma, lung and brain. Gene Set Enrichment Analysis (GSEA) in lung and brain revealed significant alterations in molecular processes in lung tissue, including increased cell cycle activity, lipid balance disruption, and enhanced inflammatory responses. Conversely, processes such as adipogenesis, oxidative phosphorylation, and epithelial to mesenchymal transition were suppressed. An elastic net penalized regression model identified a set of 104 genes in lung tissue that could indicate CBN exposure in lung. We focus on the nine genes with the greatest contribution to this model. These genes, including Tiam1, Cpsf3, and Tgfrb1, are involved in various cellular processes such as inflammation, cell signaling, and tissue remodeling. We observed significant increases in lung, brain and peripheral inflammation as well as signaling changes in lung and brain that demonstrate disruption of tissue homeostasis. Our findings demonstrate notable gene expression changes that may represent similarities to Veterans suffering from Deployment-Related Respiratory Disease (DRRD). This study provides insights into the molecular mechanisms underlying lung and brain response to burn pit-like exposures and identifies potential biomarkers for further investigation of the lung-brain axis. These results contribute to our understanding of the health impacts of military burn pit exposures and may inform future diagnostic and therapeutic strategies.
2025-08-20 | GSE281993 | GEO
Project description:#G017 Burn/Trauma Study. This is a Glue Grant Study comparison between gene expression analyses performed in eight trauma/burn subjects using either a buffy coat isolation of whole blood or using the PAXgene system Keywords: other
2004-04-24 | GSE1343 | GEO
Project description:Post-Traumatic Stress Disorder is a mental health condition that may develop after exposure to a traumatic event. The diagnosis of PTSD is based on clinical signs and symptoms; there is increasing evidence that biological markers aid in the diagnosis of PTSD. In a Dutch military cohort, we compared blood-based transcriptomic profiles of individuals susceptible and resilient to developing PTSD symptoms after combat-trauma exposure. Whole blood samples were collected from susceptible (n=20) and resilient (n=20) military personnel deployed to Afghanistan, 6 months after returning from military deployment.
2024-11-30 | E-MTAB-13185 | biostudies-arrayexpress
Project description:Animal experiments were performed with male Sprague-Dawley rats (Charles River Laboratories, Boston, MA) weighing 150 ? 200 grams. All experimental protocols used in this study were approved by the Subcommittee on Research Animal Care, Massachusetts General Hospital. Rats were individually housed in a temperature-controlled (25oC) and light-controlled room (12h light-dark cycle) and allowed to adjust to their new surroundings for at least 5 days prior to the experiment. Water and rat chow were provided ad libitum to the animals. On the day of the treatment, the animals were randomly divided into two groups, burned and sham-burned. The burn injury consisted of a full-skin-thickness scald burn of the dorsum, calculated to be ~ 20% of the rat?s total body surface area (TBSA), induced by immersing the designated area in boiling water for 10 s (45). Rats were resuscitated with an intra-peritoneal injection of sterile saline solution (1.5 mL/Kg body weight/% TBSA) immediately after burn. The mortality rate of this treatment was negligible. At each time point (1, 2, 4, and 7d), three animals belonging to each group were sacrificed, the liver and serum collected, and stored at ?80oC after being inflicted with 20% TBSA burn injury. Sham-burn rats (n=3) considered as the control were treated identically except that they were immersed into a 37oC water bath and immediately sacrificed to collect the livers. Keywords = Burn Liver microarray genechip time course Keywords: time-course
2005-10-11 | GSE1860 | GEO
Project description:The aim of the study is to evaluate Pit-1-induced genes in the MCF-7 cell line The Pit-1 transcription factor (also known as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumors elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node positive breast cancer and may represent a new therapeutic target (Journal of Clinical Investigation 2010, 120:4289-4302)
2014-12-12 | GSE64101 | GEO
Project description:Burn wound blister fluid is a valuable matrix for understanding the biological pathways associated with burn injury. In this study, 152 blister fluid samples collected from paediatric burn wounds at two different hospitals were analysed using mass spectrometry proteomic techniques. The protein abundance profile at different days post-burn indicated that there were more proteins associated with cellular damage/repair in the first 24 hours, whereas after this point there were more proteins associated with antimicrobial defence and inflammation. The inflammatory proteins persisted at a high level in the blister fluid for more than 7 days. This may indicate that removal of burn blisters prior to two days post-burn is optimal to prevent excessive or prolonged inflammation in the wound environment. Additionally, many proteins associated with the neutrophil extracellular trap (NET) pathway were increased post-burn, further implicating NETs in the post-burn inflammatory response. NET inhibitors may therefore be a potential treatment to reduce post-burn inflammation and coagulation pathology and enhance burn wound healing outcomes.
2024-03-04 | PXD050003 | Pride
Project description:Epigenetic profiles in peripheral blood samples from 59 subjects (in two separate U.S. Military training sessions) were screened using Illumina Infinium MethylationEPIC BeadChips, session 2 (31 subjects) were also screened post-exposure to a controlled, low-level blast during a 3-day explosive breaching course. Participants had varying numbers of exposures to blast over their military careers (empirically defined as high ≥ 40, and conversely, low < 39 breaching exposures) at baseline. Daily self-reported physiological symptoms were recorded.
2020-08-24 | GSE155426 | GEO
Project description:Burn injury remains a major clinical challenge to both survival and to quality of life. Its progressive, aberrant inflammation underlies the lethal dysfunction of various organs and the pain it induces is excruciating and notoriously difficult to manage. While it is known that burn injury’s complex local and disseminating pathology is orchestrated from the burned tissue, few studies have sought to characterise the local signalling environment. An enhanced understanding of the local and acutely temporally-dynamic processes defining burn injury and its progression is required for the development of novel therapeutic interventions. Microdialysis was used as an interstitial sampling technique, conducted over three hours post-burn. Samples were analysed by metabolomics and a multiplex cytokine immunoassay. Next-Generation sequencing libraries of the burn and control microdialysis sites were prepared to measure transcriptional changes potentially underlying the interstitial profile characterising burn injury.
2018-08-31 | GSE102811 | GEO
Project description:The socioeconomic burden of snakebite in India is largely attributed to the ‘big four’ snakes, completely neglecting the considerable impact of envenoming by many other snake species. Bites from the so-called ‘neglected many’ are often treated with a polyvalent antivenom that is manufactured against the ‘big four’ snakes - a strategy that has been widely documented to fail. Yet, specific antivenoms are not commercially manufactured against these snakes. While the medical importance of various species of cobras, saw-scaled vipers, and kraits is very well-known, the clinical impact of pit vipers from the rainforests of the Western Ghats, northeastern India, and Andaman and Nicobar islands has remained elusive. Amongst the 90+ species of snakes found in the Western Ghats, the hump-nosed (Hypnale hypnale), Malabar (Craspedocephalus malabaricus) and bamboo (Craspedocephalus gramineus) pit vipers can potentially inflict clinically severe envenoming in humans. To evaluate the severity of toxicity inflicted by these snakes, we characterised their venom composition, biochemical and pharmacological activities, and toxicity- and morbidity-inducing potentials. Our findings highlight the therapeutic inadequacies of the generic Indian and Hypnale-specific Sri Lankan polyvalent antivenoms in neutralising morbidity and mortality resulting from pit viper envenomings and underscore the need for a regional antivenom therapy in India.
2023-07-20 | PXD039139 | Pride
Project description:The aim of the study is to evaluate Pit-1-induced genes in the MCF-7 cell line The Pit-1 transcription factor (also known as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumors elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node positive breast cancer and may represent a new therapeutic target (Journal of Clinical Investigation 2010, 120:4289-4302) MCF-7 cells were transfected with the pcDNA3 (control, two samples as condition, named C1 and C2) or the pcDNA3-Pit-1 overexpression vector (two samples as condition, named 1+ and 2+) for 48 hours.
2014-12-12 | E-GEOD-64101 | biostudies-arrayexpress