scholarly journals Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects

BMC Genomics ◽  
2012 ◽  
Vol 13 (1) ◽  
pp. 636 ◽  
Author(s):  
Kristel R van Eijk ◽  
Simone de Jong ◽  
Marco PM Boks ◽  
Terry Langeveld ◽  
Fabrice Colas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Genetic Analysis ◽  
Whole Blood ◽  
Human Subjects ◽  
Healthy Human ◽  
Expression Levels ◽  
Healthy Human Subjects ◽  
Gene Expression Levels

scholarly journals A Sparse and Low-Rank Regression Model for Identifying the Relationships Between DNA Methylation and Gene Expression Levels in Gastric Cancer and the Prediction of Prognosis

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 854
Author(s):  
Yishu Wang ◽  
Lingyun Xu ◽  
Dongmei Ai
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Regression Model ◽  
The Cancer Genome Atlas ◽  
Low Rank ◽  
Expression Levels ◽  
Rank Regression ◽  
Prediction Of Prognosis ◽  
Gene Expression Levels

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.

Thixotropic properties of whole blood from healthy human subjects

Biorheology ◽  
1987 ◽  
Vol 24 (6) ◽  
pp. 795-801 ◽  
Author(s):  
C.R. Huang ◽  
W.D. Pan ◽  
H.Q. Chen ◽  
A.L. Copley
Keyword(s):  
Whole Blood ◽  
Human Subjects ◽  
Healthy Human ◽  
Healthy Human Subjects

scholarly journals Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

2019 ◽  
Vol 28 (15) ◽  
pp. 2477-2485 ◽  
Author(s):  
Diana A van der Plaat ◽  
Judith M Vonk ◽  
Natalie Terzikhan ◽  
Kim de Jong ◽  
Maaike de Vries ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Occupational Exposure ◽  
Health Effects ◽  
Mineral Dust ◽  
Occupational Exposures ◽  
Expression Levels ◽  
Adverse Health Effects ◽  
Never Smokers ◽  
Gene Expression Levels

Abstract Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2×)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted.

scholarly journals A Genome-Wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues

PLoS Genetics ◽  
2011 ◽  
Vol 7 (2) ◽  
pp. e1001316 ◽  
Author(s):  
Athma A. Pai ◽  
Jordana T. Bell ◽  
John C. Marioni ◽  
Jonathan K. Pritchard ◽  
Yoav Gilad
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Expression Levels ◽  
Genome Wide ◽  
A Genome ◽  
Methylation Patterns ◽  
Genome Wide Study ◽  
Gene Expression Levels

scholarly journals Gene expression levels of DNA methyltransferase enzymes in Shank3-deficient mouse model of autism during early development

2021 ◽  
Vol 55 (4) ◽  
pp. 234-237
Author(s):  
Annamaria Srancikova ◽  
Alexandra Reichova ◽  
Zuzana Bacova ◽  
Jan Bakos
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Brain Development ◽  
Early Development ◽  
Molecular Mechanisms ◽  
Altered Expression ◽  
Expression Levels ◽  
The Brain ◽  
Deficient Mice ◽  
Gene Expression Levels

Abstract Objectives. The balance between DNA methylation and demethylation is crucial for the brain development. Therefore, alterations in the expression of enzymes controlling DNA methylation patterns may contribute to the etiology of neurodevelopmental disorders, including autism. SH3 and multiple ankyrin repeat domains 3 (Shank3)-deficient mice are commonly used as a well-characterized transgenic model to investigate the molecular mechanisms of autistic symptoms. DNA methyltransferases (DNMTs), which modulate several cellular processes in neurodevelopment, are implicated in the pathophysiology of autism. In this study, we aimed to describe the gene expression changes of major Dnmts in the brain of Shank3-deficient mice during early development. Methods and Results. The Dnmts gene expression was analyzed by qPCR in 5-day-old homo-zygous Shank3-deficient mice. We found significantly lower Dnmt1 and Dnmt3b gene expression levels in the frontal cortex. However, no such changes were observed in the hippocampus. However, significant increase was observed in the expression of Dnmt3a and Dnmt3b genes in the hypothalamus of Shank3-deficient mice. Conclusions. The present data indicate that abnormalities in the Shank3 gene are accompanied by an altered expression of DNA methylation enzymes in the early brain development stages, therefore, specific epigenetic control mechanisms in autism-relevant models should be more extensively investigated.

scholarly journals Sodium valproate and 5-aza-2′-deoxycytidine differentially modulate DNA demethylation in G1 phase-arrested and proliferative HeLa cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Marina Amorim Rocha ◽  
Giovana Maria Breda Veronezi ◽  
Marina Barreto Felisbino ◽  
Maria Silvia Viccari Gatti ◽  
Wirla M. S. C. Tamashiro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Sodium Valproate ◽  
Hela Cells ◽  
Dna Methyltransferase ◽  
Dna Demethylation ◽  
G1 Phase ◽  
Expression Levels ◽  
Demethylation Pathway ◽  
Gene Expression Levels

AbstractSodium valproate/valproic acid (VPA), a histone deacetylase inhibitor, and 5-aza-2-deoxycytidine (5-aza-CdR), a DNA methyltransferase 1 (DNMT1) inhibitor, induce DNA demethylation in several cell types. In HeLa cells, although VPA leads to decreased DNA 5-methylcytosine (5mC) levels, the demethylation pathway involved in this effect is not fully understood. We investigated this process using flow cytometry, ELISA, immunocytochemistry, Western blotting and RT-qPCR in G1 phase-arrested and proliferative HeLa cells compared to the presumably passive demethylation promoted by 5-aza-CdR. The results revealed that VPA acts predominantly on active DNA demethylation because it induced TET2 gene and protein overexpression, decreased 5mC abundance, and increased 5-hydroxy-methylcytosine (5hmC) abundance, in both G1-arrested and proliferative cells. However, because VPA caused decreased DNMT1 gene expression levels, it may also act on the passive demethylation pathway. 5-aza-CdR attenuated DNMT1 gene expression levels but increased TET2 and 5hmC abundance in replicating cells, although it did not affect the gene expression of TETs at any stage of the cell cycle. Therefore, 5-aza-CdR may also function in the active pathway. Because VPA reduces DNA methylation levels in non-replicating HeLa cells, it could be tested as a candidate for the therapeutic reversal of DNA methylation in cells in which cell division is arrested.

Abstract 420: Exploring the Role of TNFα in TLR4-/NLPR3 Inflammasome-driven Inflammation in Humans

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Matthijs Moerland ◽  
Karen Malone ◽  
Marlous Dillingh ◽  
Wieke Grievink ◽  
Joannes Reijers ◽  
...  
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Human Subjects ◽  
Healthy Human ◽  
Mechanistic Investigation ◽  
Healthy Human Subjects ◽  
Key Factor ◽  
Culture Supernatants

The role of TNFα in the pathogenesis of atherosclerosis is incompletely understood. TNFα blockade reduces the severity of various autoimmune diseases and the often related atherosclerosis. However, excessively released TNFα is only one component of the hyperactive innate immune system in such diseases. To provide more insight into the role of TNFα in the induction of inflammation, we explored the effects of TNFα blockade in human whole blood. TLR4/NLPR3 inflammasome challenges were applied to induce an inflammatory response. For this purpose, whole blood was incubated 4 hours with LPS and aluminium hydroxide (Alhydrogel). TNFα blockade was evaluated in vitro (LPS/Alhydrogel challenge in whole blood of 4 healthy human subjects, +concentration range of adalimumab) and ex vivo (LPS/Alhydrogel challenge in whole blood of 13 healthy human subjects receiving a single subcutaneous (sc) dose of 40 mg adalimumab). Cytokine release was evaluated in culture supernatants. In vitro, TNFα blockade strongly reduced TNFα levels detected; -97±1% at the lowest adalimumab concentration (0.3125 μg/mL). TNFα blockade did not affect LPS/Alhydrogel-induced IL-6, IL-1β and IL-18 release, but reduced IFNγ release; maximally -93±4% at 5 μg/mL adalimumab. A single sc adalimumab dose in healthy subjects reduced LPS/Alhydrogel-induced TNFα levels (maximally -98±1% on day 4, and still -58±59% on day 64; versus baseline). IL-6, IL-1β and IL-8 release were not reduced after anti-TNFα treatment. The effect of TNFα blockade on IFNγ release could not be reliably estimated due to highly variable IFNγ levels, especially between genders (baseline IFNγ levels 1248±1771 and 140±283 pg/mL, males vs females). TNFα is a major inducer of NFκB-driven cytokine gene transcription, but TNFα blocking did not reduce LPS/Alhydrogel-induced release of IL-1β, IL-6, IL-8 or IL-18 by primary human cells. This suggests that primary TLR4- and inflammasome-mediated signalling is sufficient to drive secretion of these cytokines. However, in vitro TNFα blockade did impair IFNγ release. Since IFNγ is a key factor in atherogenesis, exerting both pro- and anti-atherogenic properties, our data warrant further mechanistic investigation of the role of TNFα and anti-TNFα therapies in atherosclerosis.

scholarly journals The impact of preserved Klotho gene expression on antioxidative stress activity in healthy kidney

2018 ◽  
Vol 315 (2) ◽  
pp. F345-F352 ◽  
Author(s):  
Takaaki Kimura ◽  
Kazuhiro Shiizaki ◽  
Tetsu Akimoto ◽  
Takahiro Shinzato ◽  
Toshihiro Shimizu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Function ◽  
Human Kidney ◽  
Wild Type ◽  
Healthy Human ◽  
Expression Levels ◽  
Klotho Gene ◽  
Antioxidative Stress ◽  
Deficient Mice ◽  
Gene Expression Levels

Klotho, which was originally identified as an antiaging gene, forms a complex with fibroblast growth factor 23 receptor in the kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho, including antiaging effects such as protection from various types of cellular stress, have been shown; however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and antioxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. The nitrotyrosine expression level in the kidney was evaluated in these animal models. Expression levels of Klotho gene were positively correlated with the p53 gene and antioxidant enzyme genes such as catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function or pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for catalase, PRDX3, and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The preservation of Klotho gene expression might induce the antioxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition, including age, renal function, and histological findings.

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