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Urine miRNAs as potential biomarkers for systemic reactions induced by exposure to embedded metal

ABSTRACT: Urine miRNAs as potential biomarkers for systemic reactions induced by exposure to embedded metal

PROVIDER: PRJNA705654 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13812100.fastq.gz	Fastqsanger.gz
	SRR13812101.fastq.gz	Fastqsanger.gz
	SRR13812102.fastq.gz	Fastqsanger.gz
	SRR13812103.fastq.gz	Fastqsanger.gz
	SRR13812104.fastq.gz	Fastqsanger.gz

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Urine miRNAs as potential biomarkers for systemic reactions induced by exposure to embedded metal

Project description:Many veterans live with military grade heavy metal fragments retained in soft tissue. Retained heavy metal fragments may negatively impact health in various organ systems and can manifest as gastrointestinal, neurocognitive, pulmonary and renal disturbances. As such, a better understanding of the long-term effects of retained metals and identification of biomarkers indicative of detrimental health outcomes would benefit clinical decision making. In this study, we analyzed urine microRNAs from rats with military-relevant pure metals implanted in the gastrocnemius muscle for 1, 3, 6, and 12 months. Our results provide potential tissue targets affected by metal exposure and a list of unique or common urine microRNA biomarkers indicative of exposure to one or more metals, highlighting a complex systemic response.

2021-09-28 | GSE167948 | GEO

Early biomarkers of renal damage due to prolonged exposure to embedded metal.

Project description:Background: Prolonged exposure to toxic heavy metals leads to deleterious health outcomes such as kidney injury and irreversible progression to chronic kidney disease. For example, veterans return from the battlefield with increasing amounts of retained metal fragments. Certain community water sources in the US are contaminated with varying levels of heavy metals, including uranium and lead. One of the key challenges is to detect damage to kidney tissue before glomerular filtration rate is affected. Methods: High-throughput transcriptomics (HTT) has recently been demonstrated have high sensitivity and specificity as a rapid and cost-effective assay for detecting tissue toxicity. To better understand the molecular signature of early kidney damage, we performed RNA-seq analysis on renal tissue using a rat model of soft tissue-embedded metal exposure. We them performed small RNA-seq analysis on serum samples from the same animals in an effort to identify miRNA biomarkers of kidney damage. Results: We found that metals, especially lead and depleted uranium, induces oxidative damage that mainly cause dysregulated mitochondrial gene expression. Utilizing publicly available single-cell RNA-seq datasets, we demonstrate that deep learning-based cell type decomposition effectively identified cells within the kidney that were affected by metal exposure. By combining random forest feature selection and statistical methods, we further identify miRNA-423 as a promising early systemic marker of kidney injury. Conclusion: Our data suggests that combining HTT and deep learning represents a promising approach for identifying cell injury in kidney tissue. We propose miRNA-423 as a potential serum biomarker for early detection of kidney injury.

2022-12-01 | GSE203624 | GEO

Early biomarkers of renal damage due to prolonged exposure to embedded metal.

Project description:Early biomarkers of renal damage due to prolonged exposure to embedded metal.

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Time course analysis of the effect of embedded metal on skeletal muscle gene expression [Array]

Project description:As a consequence of military operations, many veterans suffer from penetrating wounds and long-term retention of military grade heavy metal fragments. Fragments vary in size and location, and complete surgical removal may not be feasible or beneficial in all cases. Increasing evidence suggests retention of heavy metal fragments may have serious biological implications, including increased risks for malignant transformation. Previous studies assessed the tumorigenic effects of metal alloys in rats, demonstrating combinations of metals are sufficient to induce tumor formation after prolonged retention in skeletal muscle tissue. In this study, we analyzed transcriptional changes in skeletal muscle tissue in response to eight different military-relevant pure metals over 12 months. We found that most transcriptional changes occur at 1 and 3 months after metal pellets are embedded in skeletal muscle and these effects resolve at 6 and 12 months. We also report significant immunogenic effects of nickel and cobalt and suppressive effects of lead and depleted uranium on gene expression. Overall, skeletal muscle exhibits a remarkable capacity to adapt to and recover from internalized metal fragments; however, the cellular response to chronic exposure may be restricted to the metal-tissue interface. This data suggests that unless affected regions are specifically captured by biopsy, it would be difficult to reliably detect changes in muscle gene expression that would be indicative of long-term adverse health outcomes.

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Time course analysis of the effect of embedded metal on skeletal muscle gene expression [RNA-seq]

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Time course analysis of the effect of embedded metal on skeletal muscle gene expression

Project description:Time course analysis of the effect of embedded metal on skeletal muscle gene expression

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Identification of gene expression biomarkers in urine for the non-invasive detection of bladder cancer

Project description:Fifty patient urine samples diagnosed as high-grade urothelial carcinoma (HGUC) or benign were evaluated for bladder cancer via urine cytology. RNA was isolated and analyzed by microarray to identify a panel of biomarkers differentially expressed in HGUC and benign.

2018-04-17 | GSE68020 | GEO

Time course analysis of the effect of embedded metal on skeletal muscle gene expression [Array]

Project description:Time course analysis of the effect of embedded metal on skeletal muscle gene expression [Array]

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Project description:To identify urinary RNA from prospective urine as non-invasive biomarkers for kidney transplant patients

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