Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR12834694_1.fastq.gz | Fastqsanger.gz | |||
| ERR12834694_2.fastq.gz | Fastqsanger.gz | |||
| ERR12834695_1.fastq.gz | Fastqsanger.gz | |||
| ERR12834695_2.fastq.gz | Fastqsanger.gz |
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Project description:Nanostring gene expression analysis using tumors from mice treated with GLA, X-ray radiation or the combination of GLA and radiation showed that the combination of GLA and radiation has synergistic effect in modulating the tumor micronenvironment.
2021-12-22 | GSE178553 | GEO
Project description:The goal of this study was to investigate the effect of intratumoral injection of GLA-SE, a TLR4 agonist in stable emulsion (SE), in Balb/c mice with established A20 lymphoma.
2020-08-04 | GSE150457 | GEO
Project description:Bioactive compounds, including some fatty acids (FAs), can induce beneficial effects on body fat-content and metabolism. In this work, we have used C. elegans as a model to examine the effects of several FAs on body fat accumulation. Both omega-3 and omega-6 fatty acids induced a reduction of fat content in C. elegans, with linoleic, gamma-linolenic and dihomo-gamma-linolenic acids being the most effective ones. These three FAs are sequential metabolites in PUFA synthesis pathway and the effects seem to be primarily due to dihomo-gamma-linolenic acid, being independent of transformation into omega-3 or arachidonic acid. Gene expression analyses show that peroxisomal beta oxidation is the main mechanism involved in this fat-loss. All these results point out the importance of further analysis of the activity of these omega-6 FAs, due to their potential application in obesity and related diseases. In order to elucidate the mechanisms underlying the fat loss induced by the omega-6 FAs LNA, GLA and DGLA, we analyzed the whole-transcriptome expression profiling in response to LNA, GLA and DGLA treatments in wild-type worms using Affymetrix C. elegans expression arrays.
2017-08-19 | GSE102802 | GEO
Project description:Recent studies in non-human model systems have shown therapeutic potential of modified mRNA (modRNA) treatments for lysosomal storage diseases. Here, we assessed the efficacy of a modRNA treatment to restore the expression of the α-galactosidase (GLA) gene in a human cardiac model generated from induced-pluripotent stem cell-derived from two patients with Fabry disease. In line with the clinical phenotype, cardiomyocytes from Fabry patient’s induced pluripotent stem cells show accumulation of the glycosphinolipid Globotriaosylceramide (GB3), which is an α-galactosidase substrate. Further, the patient-specific cardiomyocytes have significant upregulation of lysosomal associated proteins. Upon modRNA treatment, a subset of lysosomal proteins were partially restored to wildtype levels, implying the rescue of the molecular phenotype associated with the Fabry genotype. Importantly, a significant reduction of GB3 levels was observed in GLA modRNA treated cardiomyocytes demonstrating that α-galactosidase enzymatic activity was restored. Together, our results validate the utility of patient IPSC-derived cardiomyocytes as a model to study disease processes in Fabry disease and the therapeutic potential of GLA modRNA treatment to reduce GB3 accumulation in the heart.
2023-07-20 | PXD038361 | Pride
Project description:Fabry disease (FD) is a hereditary lysosomal storage disorder caused by mutations in GLA gene resulting in reduction or lack of α-galactosidase A activity. In humans, enzymatic deficiency leads to accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in lysosomes. Current therapies focus on reversing Gb3 accumulation but fail to restore altered cellular signaling in the long run. Zebrafish (ZF) lacks Alpha 1,4-Galactosyltransferase (A4GALT) gene and cannot synthesize Gb3 or lysoGb3. We used previously generated GLA-mutant ZF model to investigate Gb3-accumulation-independent alterations by untargeted proteomics analysis of renal tissues. We observed lysosomal and mitochondrial-related pathways disfunction, higher oxidative stress, as indicated by GSH/GSSH and MDA levels, and higher antioxidant activity in mutant ZF. Moreover, mitochondrial morphological alterations also affecting cristae structure were evident. By immunohistochemistry, we also detected decreased lysosomal Tetraspanin (CD63), Superoxide dismutase 2 (SOD2), and Cadherin 1 (CDH1) protein expression. Thus, this ZF model Gb3-independently mirrors GLA mutation-related changes, and unravels novel FD pathogenic mechanisms, thereby representing a powerful tool for innovative drug screening, and the identification of markers of potential clinical relevance.
2023-10-24 | PXD035409 | Pride
Project description:The proteasome can regulate transcription through proteolytic processing of transcription factors and via gene locus binding, but few targets of proteasomal regulation have been identified. Using genome-wide location analysis and transcriptional profiling in Saccharomyces cerevisiae, we have established which genes are bound and regulated by the proteasome, and by Spt23 and Mga2, transcription factors activated by the proteasome. We observed proteasome association with gene sets that are highly transcribed, controlled by the mating-type loci, and involved in lipid metabolism. At ribosomal protein genes, proteasome and RNA polymerase II binding was enriched in a proteasome mutant, indicating a role for the proteasome in dissociating elongation complexes. The genomic occupancies of Spt23 and Mga2 overlapped significantly with the genes bound by the proteasome. Finally, the proteasome acts in two distinct ways, one dependent and one independent of Spt23/Mga2 cleavage, providing evidence for cooperative gene regulation by the proteasome and its substrates. Keywords: ChIP-chip; genetic modification transcriptional profiling Six genomic localization analysis (GLA, ChIP2) experiments are represented by 18 samples. Six transcriptional profiling experiments (prof) are also represented. Experiments were generally done in triplicate, with fluors swapped on the third replicate.
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Project description:Syngergistic Anti-tumor Effects between GLA and X-ray Radiation
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Project description:Intratumoral injection of TLR4 agonist GLA in A20 tumor model
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Project description:To determine the maximum tolerated dose (MTD), the recommended phase 2 dose (RP2D) and the toxicity profile (NCI CTCAE v5.0 and immune related adverse events) of i.t. administration of anti-CTLA4 antibody (ipilimumab) and TLR4 agonist (synthetic glucopyranosyl lipid A formulated in a stable emulsion [GLA-SE]) in colorectal LM (CRLM) in combination with intravenous (i.v.) administration of anti-PD-1 antibody (nivolumab) and chemotherapy (FOLFOX regimen).
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Project description:Matrix Gla Protein acts as a driver of stemness and tumor initiation in ovarian cancer
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