Expression data from primary human skin fibroblasts treated with vehicle (DMSO) and the antioxidant Trolox (0.5 mM, 96 hrs)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32502 | GEO | 2012/07/15
SECONDARY ACCESSION(S): PRJNA147755
REPOSITORIES: GEO
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Project description:Three (3) independent cell cultures for each condition (DMSO and Trolox) were analyzed. The effect of Trolox was checked on the protein level (being an increased protein level of fully assembled mitochondrial complex I) using blue-native PAGE analysis (as described in Koopman et al., Biochim. Biophys. Acta 1777:853-859, 2008, prior to mRNA extraction. We used the control cell line #5120 at similar passage number for all six experiments. We generated the following pairwise comparisons Vehicle > Trolox and Vehicle < Trolox. Changes ≥2 and Benjamini Hochberg corrected p-values <0.05 were considered significant.
2012-07-14 | E-GEOD-32502 | biostudies-arrayexpress
Project description:Atopic dermatitis (AD), a chronic, pruritic skin disease, affects 10%-30% of children and up to 14% of adults in developed countries. Since current AD treatments may lead to systemic drug exposure and AD pathophysiology is partially mediated by JAK1/3 signaling, ATI-1777, a potent and selective JAK1/3 inhibitor, was designed with multiple sites of metabolism to deliver local efficacy in the skin and limit systemic exposure. In preclinical studies, ATI-1777 selectively inhibited JAK1/3 with limited systemic exposure and without any adverse effects. ATI-1777-AD-201 (NCT04598269), a Phase 2a, first-in-human, randomized, double-blind,vehicle-controlled, parallel-group study, evaluated the efficacy, safety, tolerability, and pharmacokinetics of ATI-1777 topical solution in 48participants with AD over 4 weeks. The primary outcome was reduction of a modified EASI score from baseline; reduction was significantly greater in the ATI-1777 group at Day28 compared to vehicle (percent reduction from baseline 74.45% [SE6.455] and 41.43% [SE6.189], respectively [p<0.001]). Average plasma concentrations of ATI-1777 were <5% of the IC50 of ATI-1777 for inhibiting JAK1/3. No deaths or serious adverse events were reported. This demonstrates that topical ATI-1777 does not lead to pharmacologically relevant systemic drug exposure and may reduce clinical signs of AD.
2023-11-20 | GSE244201 | GEO
Project description:The antioxidant therapy to preserve residual hearing is relatively recent, and the search for effective antioxidants is still ongoing. Though nanoceria has shown promising radical-scavenging capability, improving its antioxidant ability and the dispersion stability of its nanofluid, which is critical to the desired site, i.e., cochlea, still remains a major challenge. The objective of the present work is to study the radical-scavenging capability of poly(ethylene glycol) (PEG)-coated CeO2 and Ce0.5Zr0.5O2 nanoparticles in water and the biologically relevant fluid (PBS buffer). Nanoparticles in the size range of 4.0-9.0 nm are synthesized using the coprecipitation method and characterized using suitable techniques. The scavenging and dispersion stability of the synthesized nanofluid are analyzed using a UV-vis spectrophotometer. It is found that the addition of PEG during the synthesis process promoted the generation of finer nanoparticles with a narrow size distribution and the doping of zirconium produced a large number of defects in the crystallite structure. The PEG coating over the nanoparticles improved the dispersion stability of nanofluids without affecting their surface reactivity, and it is found to be 94 and 80% in water and PBS, respectively, at 500 μM and 60 min, which is maintained till 90 min. The highest scavenging of hydroxyl radicals by PEG-coated Ce0.5Zr0.5O2 is found to be 60%, which is significantly superior to that of CeO2. The scavenging capability is found to be increased with the concentration of nanoparticles, showing the best scavenging activity at 190 and 150 μM for PEG-coated CeO2 and Ce0.5Zr0.5O2, respectively, and the scavenging in water is at par with that of PBS, indicating that these nanoparticles are suitable to be used in sites where a biologically relevant fluid is present, e.g., the cochlea. It is proposed that PEG-coated Ce0.5Zr0.5O2 having an average size of ∼ 4 nm can be a potential antioxidant in relevant biomedical applications.
| S-EPMC9260909 | biostudies-literature
Project description:Pulmonary arterial hypertension (PAH) is a progressive fatal disease that is characterized by pathological pulmonary artery remodeling, in which endothelial cell (EC) dysfunction is critically involved. We herein describe a previously unknown role of endothelial angiocrine in pulmonary hypertension. By searching for genes highly expressed in lung microvascular ECs, we identified inhibin--A (INHBA) as an angiocrine factor produced by pulmonary capillaries. We found that excess production of INHBA by ECs impairs the endothelial function in an autocrine manner by functioning as activin A (ActA). Mechanistically, ActA induces bone morphogenetic protein receptor type 2 (BMPRII) internalization and targeting to lysosomes for degradation, resulting in BMPRII signal deficiency in ECs. When endothelial ActA-BMPRII link is overdriven in mice, hypoxia-induced pulmonary hypertension was exacerbated, whereas conditional knockout of INHBA in ECs prevents the progression of pulmonary hypertension. These data collectively indicate a critical role for the dysregulated endothelial ActA-BMPRII link in the progression of pulmonary hypertension, and thus endothelial INHBA/ActA is an attractive pharmacotherapeutic target for the treatment of PAH.
2020-12-15 | GSE156225 | GEO
Project description:Pulmonary arterial hypertension (PAH) is a progressive fatal disease that is characterized by pathological pulmonary artery remodeling, in which endothelial cell (EC) dysfunction is critically involved. We herein describe a previously unknown role of endothelial angiocrine in pulmonary hypertension. By searching for genes highly expressed in lung microvascular ECs, we identified inhibin--A (INHBA) as an angiocrine factor produced by pulmonary capillaries. We found that excess production of INHBA by ECs impairs the endothelial function in an autocrine manner by functioning as activin A (ActA). Mechanistically, ActA induces bone morphogenetic protein receptor type 2 (BMPRII) internalization and targeting to lysosomes for degradation, resulting in BMPRII signal deficiency in ECs. When endothelial ActA-BMPRII link is overdriven in mice, hypoxia-induced pulmonary hypertension was exacerbated, whereas conditional knockout of INHBA in ECs prevents the progression of pulmonary hypertension. These data collectively indicate a critical role for the dysregulated endothelial ActA-BMPRII link in the progression of pulmonary hypertension, and thus endothelial INHBA/ActA is an attractive pharmacotherapeutic target for the treatment of PAH.
2020-12-15 | GSE156233 | GEO
Project description:Myeloma bone disease is characterized by tremendous bone destruction with suppressed bone formation. IL-3 is a multifunctional cytokine that increases myeloma cell growth and osteoclast proliferation while inhibiting osteoblast differentiation. While IL-3 appears to be an attractive therapeutic target for myeloma, attempts at targeting IL-3 have been unsuccessful due to IL-3’s effects on normal hematopoiesis. Thus identification of IL-3’s downstream effects in MMBD is important for effective targeting of this cytokine in MM. Here we demonstrated that treatment of myeloma patient CD14+ bone marrow monocyte / macrophages with IL-3 induces high levels of Activin A (ActA), a pluripotent TGF-β superfamily member that, like IL-3, modulates MMBD by enhancing osteoclastogenesis and inhibiting osteoblasts. We show that IL-3 induced osteoclastogenesis is mediated by ActA and is RANKL independent. Additionally, IL-3 induced ActA secretion is greatest early in osteoclastogenesis and ActA acts early in osteoclastogenesis. Therefore we suggest that therapies targeting ActA production should block IL-3’s effects in myeloma bone disease.
2014-11-01 | GSE41992 | GEO
Project description:The goal of the investigators study is to investigate the role of a hormone named Activin A (ActA) in the development of the skeletal muscle atrophy caused by cancer. According to the investigators hypothesis, ActA could be released by the tumor and activate a muscle atrophy gene program. To answer this question, the investigators plan first to compare circulating levels of ActA in cancer patients with and without cachexia. In a second step, the investigators would like to assess whether ActA circulating levels are predictive for the development of cachexia and short survival.
| 2125819 | ecrin-mdr-crc
Project description:EGR4 (early growth response 4), a transcription factor, was previously shown to be up-regulated in lung cancer bone metastasis, compared with its expression in metastasis in other organs, using a multiorgan metastasis model of human small-cell lung cancer cells (SBC-5) in NK cell-depleted SCID mice (Kakiuchi S et al. Mol Cancer Res 2003). Here we show that EGR4 was essential for survival cancer cells, and migration ability. Next, in searching of downstream genes regulated by EGR4, we analyzed the changes in transcriptomes of SBC-5 cells at different time-points (24, 48 and 72 hr) when knockdown of EGR4 by siRNA. Lots of genes were identified either up-regulated or down-regulated in siEGR4 samples compared with control siRNA. Among these genes, there were genes with roles in metastasis or bone biology. The fact that EGR4 knockdown led to up-regulation or suppression of these genes also indicated dual roles of EGR4 in transcriptional regulation, which is consistent with previous reports: EGR4 may repress its own promoter (Zipfel PF et al. Biochim Biophys Acta. 1997) or activate certain inflammatory genes (Decker EL et al. Nucleic Acids Res. 2003; Wieland GD et al. J Cell Sci. 2005).
2013-04-01 | GSE40558 | GEO
Project description:Genome-wide analysis of H3K9ac in the liver of mice fed a control or a high-fat diet, and asked whether this histone mark associates with changes in gene expression. We found that over 70% of RNAPII peaks in promoter-proximal regions overlapped with H3K9ac, consistent with a role of H3K9ac in the regulation of transcription. When comparing high-fat with control diet, approximately 17% of the differentially expressed genes were associated with changes in H3K9ac in their promoters, showing a strong correlation between changes in H3K9ac signal and gene expression. Overall, our data indicate that in response to a high-fat diet, dysregulated gene expression of a subset of genes may be attributable to changes in transcription elongation driven by H3K9ac. Our results point at an added mechanism of gene regulation that may be important in the development of metabolic diseases. Citation: Morral N, Liu S, Conteh AM, Chu X, Wang Y, Dong XC, Liu Y, Linnemann AK, Wan J. Aberrant gene expression induced by a high fat diet is linked to H3K9 acetylation in the promoter-proximal region. Biochim Biophys Acta Gene Regul Mech. 2021 Mar;1864(3):194691. doi: 10.1016/j.bbagrm.2021.194691. Epub 2021 Feb 6. PMID: 33556624; PMCID: PMC7933127.
2022-03-08 | GSE197649 | GEO
