Urine miRNAs as potential biomarkers for systemic reactions induced by exposure to embedded metal
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE167948 | GEO | 2021/09/28
REPOSITORIES: GEO
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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 serum microRNAs from rats with military-relevant pure metals implanted in the gastrocnemius muscle for 1, 3, 6, and 12 months in order to identify potential microRNA biomarkers that are indicative of exposure to one or more metals.
2023-05-01 | GSE168757 | GEO
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.
2020-09-16 | GSE157929 | GEO
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.
2020-09-16 | GSE157921 | GEO
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
Project description:Background: The high number of heavy metal resistance genes in the soil bacterium Cupriavidus metallidurans CH34 makes it an interesting model organism to study microbial responses to heavy metals. Results: In this study the transcriptional response of this bacterium was measured after challenging it to a wide range of sub-lethal concentrations of various essential or toxic metals. Considering the global transcriptional responses for each challenge as well as by identifying the overlap in upregulated genes between different metal responses, the sixteen metals could be clustered in three different groups. Additionally, next to the assessment of the transcriptional response of already known metal resistance genes, new metal response gene clusters were identified. The majority of the metal response loci showed similar expression profiles when cells were exposed to different metals, suggesting complex cross-talk at transcriptional level between the different metal responses. The highly redundant nature of these metal resistant regions – illustrated by the large number of paralogous genes – combined with the phylogenetic distribution of these metal response regions within evolutionary related and other metal resistant bacteria, provides important insights on the recent evolution of this naturally soil dwelling bacterium towards a highly metal-resistant strain found in harsh and anthropogenic environments. Conclusions: The metal-resistant soil bacterium Cupriavidus metallidurans CH34 displays myriads of gene expression patterns when exposed to a wide range of heavy metals at non-lethal concentrations. The interplay between the different gene expression clusters points towards a complex cross-regulated regulatory network governing heavy metal resistance in C. metallidurans CH34. Keywords: Cupriavidus metallidurans CH34, transcriptional regulation, heavy metal resistance Two-condition experiments. Comparing samples after induction with heavy metals versus non-induced samples. Biological duplicate or triplicate. Each array contains 3 or 4 technical replicates.
2011-06-28 | E-GEOD-23876 | biostudies-arrayexpress
Project description:Background: The high number of heavy metal resistance genes in the soil bacterium Cupriavidus metallidurans CH34 makes it an interesting model organism to study microbial responses to heavy metals. Results: In this study the transcriptional response of this bacterium was measured after challenging it to a wide range of sub-lethal concentrations of various essential or toxic metals. Considering the global transcriptional responses for each challenge as well as by identifying the overlap in upregulated genes between different metal responses, the sixteen metals could be clustered in three different groups. Additionally, next to the assessment of the transcriptional response of already known metal resistance genes, new metal response gene clusters were identified. The majority of the metal response loci showed similar expression profiles when cells were exposed to different metals, suggesting complex cross-talk at transcriptional level between the different metal responses. The highly redundant nature of these metal resistant regions – illustrated by the large number of paralogous genes – combined with the phylogenetic distribution of these metal response regions within evolutionary related and other metal resistant bacteria, provides important insights on the recent evolution of this naturally soil dwelling bacterium towards a highly metal-resistant strain found in harsh and anthropogenic environments. Conclusions: The metal-resistant soil bacterium Cupriavidus metallidurans CH34 displays myriads of gene expression patterns when exposed to a wide range of heavy metals at non-lethal concentrations. The interplay between the different gene expression clusters points towards a complex cross-regulated regulatory network governing heavy metal resistance in C. metallidurans CH34. Keywords: Cupriavidus metallidurans CH34, transcriptional regulation, heavy metal resistance
2011-06-28 | GSE23876 | GEO
Project description:We hypothesize that microarray-based analysis of Lycopersicon esculentum is a sensitive tool for the early detection of potential toxicity of heavy metals, as well as an effective tool for identifying the heavy metal-specific genes. To test the hypothesis, the Agilent whole-genome cDNA microarrays were used to assess the effects of heavy metal on L. esculentum at relatively low concentrations (1/10 LC50 of heavy metals). Results showed that the characteristic gene expression profiles induced by Cd, Cr, Hg and Pb were not only distinct from the control but also distinct from one another, demonstrating the feasibility of discriminating between the effects of these four heavy metals present at relatively low concentrations. Moreover, heavy metal-specific genes were identified by microarray analysis. These findings support the above hypothesis.
2014-11-06 | GSE63024 | GEO
Project description:Heavy metals residue in the natural ecosystem had become one global environmental problem that was eager to solve. Due to the non-biodegradability, organism could deposit excessive heavy metals elements into tissues. Existing literature proposed that prolonged heavy metals enrichment had comprehensive toxicity to multi-organs of vertebrates. However, little research focus on the molecular mechanism for the hepatotoxicity of heavy metal enrichment to Chiroptera. In the present study, ten Hipposideros armiger individuals from Yingde City (YD, relatively pollution-free) and Chunwan City (CW, excessive heavy metals emission) were dissected while environment samples were also obtained. To corroborate the toxicity mechanism of heavy metals to bats liver, multi-omics, pathology and molecular biology methods were performed. Our results showed that more Cd and Pb elements were significantly enriched in bats liver and food sources in the CW group. In addition, prolonged heavy metals accumulation disturbed the hepatic transcription profiling associated with solute carriers family, ribosome pathway, ATP usage and heat shock proteins. Excessive heavy metals enrichment also altered the relative abundance of typical gut microbe taxa to inhibit the tight-junction protein expression. We also found that the levels of superoxide dismutase, glutathione peroxidase and glutathione were decreased while ROS density and malondialdehyde content were elevated after excessive heavy metals enrichment. Besides, hepatic fat accumulation and inflammation injury were also observed under the excessive heavy metals enrichment while the metabolism biomarkers contents were decreased. Therefore, prolonged heavy metals enrichment would induce a series of hepatotoxicity by disturbing the microbes-gut-liver axis and hepatic transcription modes, which could decrease the overall metabolism level in bats. Our study provided protection strategy for biodiversity conservation and raised public attention to environment pollution.
2024-01-28 | GSE254017 | GEO
Project description:We hypothesize that microarray-based analysis of Lycopersicon esculentum is a sensitive tool for the early detection of potential toxicity of heavy metals, as well as an effective tool for identifying the heavy metal-specific genes. To test the hypothesis, the Agilent whole-genome cDNA microarrays were used to assess the effects of heavy metal on L. esculentum at relatively low concentrations (1/10 LC50 of heavy metals). Results showed that the characteristic gene expression profiles induced by Cd, Cr, Hg and Pb were not only distinct from the control but also distinct from one another, demonstrating the feasibility of discriminating between the effects of these four heavy metals present at relatively low concentrations. Moreover, heavy metal-specific genes were identified by microarray analysis. These findings support the above hypothesis. A total of fifteen microarrays (4*44K tomato gene expression microarray; G2519F-022270) were used to hybridize with RNA extracted from Cd-, Cr-, Hg-, Pb-treated and the untreated roots (control) of Lycopersicon esculentum. Each treatment was carried out for three replicates. A total of thirty seedlings were used for each treatment. Root samples from ten seedlings randomly selected from each Petri dish were pooled together to obtain three biological replicates.
2014-11-06 | E-GEOD-63024 | biostudies-arrayexpress
Project description:Environmental contamination from heavy metals poses a global concern for the marine environment, as heavy metals are passed up the food chain and persist in the environment long after the pollution source is contained. Cnidarians, dating back to 700 million years ago, play an important role in shaping marine ecosystems, but environmental pollution profoundly affects their vitality. Among the cnidarians, the sea anemone Nematostella vectensis is an advantageous model for addressing questions in molecular ecology and toxicology as it tolerates extreme environments and its genome has been published. Here we employed a transcriptome-wide RNA-Seq approach to analyze N.vectensis molecular defense mechanisms against four heavy metals: Hg, Cu, Cd and Zn. Altogether, more than 5000 transcripts showed significant changes in gene expression, with Hg having the greatest impact on up-regulating transcripts, followed by Cu, Cd and Zn. We identified, for the first time, co-up-regulation of immediate-early transcription factors such as Egr1, AP1 and NF-κB. Time-course analysis of these genes revealed their early expression as rapidly as one hour after exposure to heavy metals, suggesting that they may complement or substitute for the roles of the metal mediating Mtf1 transcripton factor. We further characterized regulation of a large array of stress-response gene families including Hsp, ABC, CYP members and phytochelatin synthase that may regulate synthesis of the metal-binding phytochelatins instead of the methallothioneins that are absent from Cnidaria genome. This study provides mechanistic insight into heavy-metal toxicity in N.vectensis and sheds light on ancestral stress adaptations. 4 metals were tested in triplicates in comparison to control (4 replicates)
2015-12-22 | E-GEOD-58769 | biostudies-arrayexpress