Test compound one, 5,6-benzoflavone (BNF), was known to act through both the Ah receptor and Nrf2 receptor pathways, while test compounds two and three, 3H-1,2-dithiole-3-thione (D3T) and 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (OLT), were known to act through the Nrf2 receptor pathway. Furthermore, D3T is known to be more potent and efficacious than OLT for Nrf2 activation. OLT has been shown to exhibit 20-50% of the efficacy of D3T for inhibition of alfatoxin-induced heptic foci. Nonetheless, because OLT is an approved drug, it is currently being evaluated in human phase II intervention trials of biomarkers of alfatoxin-related hepatocellular carcinoma. More recently, BNF was shown to be an effective chemopreventive agent in the rat mammary carcinogen model, inhibiting 7,12-dimethylbenz(a)anthracene DNA adduct formation in liver and mammary cells by 96 and 83% respectively.
Analyzing microarray data with transitive directed acyclic graphs.
No sample metadata fields
View SamplesAnalysis of gene expression in prostatic tissue from BPH patients with and without SRD5A2 gene methylation. The hypothesis is that BPH patients with DNA methylation of the SRD5A2 gene promoter have impaired conversion of testosterone to dihydrotestosterone, and therefore may use an alternative signaling pathway for prostatic tissue growth. Here, we compare gene expression profiles of SRD5A2-methylated vs. unmethylated prostatic tissue to nominate alternative biological pathways relevant in each molecular subtype of BPH.
Androgenic to oestrogenic switch in the human adult prostate gland is regulated by epigenetic silencing of steroid 5α-reductase 2.
Sex, Specimen part
View SamplesReprogramming intermediates (pre-iPSCs) were subjected to control DMSO, ascorbic acid (AA), 2i ( MAP kinase inhibitor + GSKinhibitor) or AA+2i conditions to assess conversion to the iinduced pluripotent stem cell state (iPSC) after 10days. Overall design: Pre-iPSC cells exposed to control DMSO, AA, 2i or AA+2i were harvested on day 2 for RNA sequencing after treatment, in biological triplicate.
Collaborative rewiring of the pluripotency network by chromatin and signalling modulating pathways.
No sample metadata fields
View SamplesTranscriptome profiling of radial glia, intermediate progenitors, and cortical neurons in WT and Prdm16 conditional knock-out (cKO) mouse (Emx1Ires-Cre; Prdm16flox/flox) at embryonic day 15.5. Overall design: Sorting of PAX6+ radial glia, TBR2+ intermediate progenitors and Pax6-TBR2- neurons from WT and Prdm16 cKO embryonic cerebral cortex was followed by library preparation and RNA-seq of 4 biological replicates per cell type and genotype.
The Epigenetic State of PRDM16-Regulated Enhancers in Radial Glia Controls Cortical Neuron Position.
Specimen part, Subject
View SamplesDM1 and DM2 biopsies from patients were compared to Normal adult individuals
Differences in aberrant expression and splicing of sarcomeric proteins in the myotonic dystrophies DM1 and DM2.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
Time
View SamplesThe immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs. The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs.
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
Time
View SamplesFetal spleens were collected at days 82 and 97 of gestation following maternal infection with BVDV on day 75 of gestation.
Attenuated lymphocyte activation leads to the development of immunotolerance in bovine fetuses persistently infected with bovine viral diarrhea virus†.
Sex, Specimen part
View SamplesEnvironmental enrichment (EE) replicates mind-body therapy by providing complex housing to laboratory animals to improve their activity levels, behavior and social interactions. Using a Tcf4Het/+ ApcMin/+-mediated model of colon tumorigenesis, we found that EE vastly improved the survival of tumor-bearing animals, with differential effect on tumor load in male compared to female animals. Analysis of Tcf4Het/+ ApcMin/+ males showed drastically reduced expression of circulating inflammatory cytokines and induced nuclear hormone receptor signaling, both of which are common in the wound repair process. Interestingly, EE provoked tumor wound repair resolution through revascularization, plasma cell recruitment and IgA secretion, replacement of glandular tumor structures with pericytes in a process reminiscent of scarring, and normalization of microbiota. These EE-dependent changes likely underlie the profound improvement in survival of colon-tumor-bearing Tcf4Het/+ ApcMin/+ males. Our studies highlight the exciting promise of EE in the design of future therapeutic strategies for colon cancer patients. Overall design: Four samples from EE and NE (non-enriched controls) were analyzed
Environmental Enrichment Induces Pericyte and IgA-Dependent Wound Repair and Lifespan Extension in a Colon Tumor Model.
Specimen part, Subject
View SamplesThese experiments were designed to detect transcript (mRNA) changes in whole circulating blood in animals exposed to D-amphetamine under neurotoxic and non-neurotoxic conditions, or subjected to elevated environmental temperatures that produced a hyperthermia very similar to heat stroke. The study objectives were: 1) to detect transcript changes in blood due to life-threatening hyperthermia produced by elevated environmental temperatures (39°C, produces no or minimal neurotoxicity); 2) detect transcripts that could serve as biomarkers specific for neurotoxic amphetamine exposures and not seen with environmentally-induced hyperthermia; and 3) determine the transcript changes related to the immune system in circulating blood produced by either non-neurotoxic or neurotoxic amphetamine exposures. Amphetamine effects on gene expression are dependent on body temperature and indicate that many significant changes in genes related to the immune system occur, some likely in response to damage, even when animals remain normothermic during amphetamine exposure. Also, hyperthermia alone produces many changes in immune related genes in blood Overall design: Five groups of animals were necessary to meet the study objectives. All groups were given 4 injections of either normal saline or amphetamine, and the injections were sequentially given with 2 h between each injection. Dosing started at 7:30 to 8:30 a.m. The groups are: 1) normothermic controls given normal saline in a 22.5°C environment; 2) controls given normal saline in a 16°C environment (also remained normothermic); 3) environmentally-induced hyperthermia given saline in a 39°C environment; 4) non-neurotoxic amphetamine given in a 16°C environment and 5) neurotoxic amphetamine group given amphetamine in a 22.5°C environment. Note the the saline controls (normothermic data) is contained in a separate but linked GEO file GSE62368
Evaluating the Stability of RNA-Seq Transcriptome Profiles and Drug-Induced Immune-Related Expression Changes in Whole Blood.
No sample metadata fields
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