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Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders

ABSTRACT: Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders

PROVIDER: PRJNA875926 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21389966_1.fastq.gz	Fastqsanger.gz
	SRR21389966_2.fastq.gz	Fastqsanger.gz
	SRR21389967_1.fastq.gz	Fastqsanger.gz
	SRR21389967_2.fastq.gz	Fastqsanger.gz
	SRR21389968_1.fastq.gz	Fastqsanger.gz

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Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders

Project description:Therapeutic aryl hydrocarbon receptor (AHR) modulating agents (TAMAs) gained attention in dermatology as non-steroidal anti-inflammatory drugs that improve skin barrier properties. By exploiting AHR’s known ligand promiscuity, we generated novel TAMAs by lead optimization of a selective AHR modulator (SAhRM; SGA360). Twenty-two newly synthesized compounds were screened yielding two novel derivatives, SGA360f and SGA388, in which agonist activity led to enhanced keratinocyte terminal differentiation. We questioned whether SGA derivatives can restore the disturbed epidermal differentiation processes that are known for the key AD-associated T helper-2 cytokine, interleukin-4 (IL-4). We performed genome-wide transcriptomic analysis by bulk RNA-sequencing after co-stimulation of human epidermal equivalents with interleukin-4 (IL-4; AD-HEE) and SGA360 (SAhRM activity), SGA360f or SGA388 (coupling of SAhRM to agonist activity), or TCDD (full AHR agonist).

2023-02-01 | GSE212539 | GEO

Zebrafish larvae aryl hydrocarbon receptor ligands and inhibitor

Project description:Zebrafish larvae aryl hydrocarbon receptor ligands and inhibitor

| PRJNA495640 | ENA

Zebrafish larvae aryl hydrocarbon receptor ligands and inhibitor

Project description:Wild type zebrafish (AB strain, https://zfin.org/action/genotype/view/ZDB-GENO-960809-7) were set up for mating overnight, in 3:2 ratios, females and males, respectively. Fertilized embryos from wildtype zebrafish AB strain were used for all experiments and kept in Embryo medium (E3, 5 mM NaCl, 0.17 mM KCl, 0.33 mM CaCl2, 0.33 mM MgSO4) in an incubator at 28ºC. At 1dpf, larvae were manually dechorionated under a stereomicroscope. At 2dpf, zebrafish larvae were divided randomly into the different experimental groups, at a density of 12 larvae per well of a 12 well plate (Corning) in 1.5mL of E3. Three biological replicates of 12 larvae per condition were exposed to different conditions for 4 hours at 28 ºC: DMSO; DMSO + CH223191 (5mM); 3-o-C12-L-HSL (50mM); 3-o-C12-L-HSL (50mM) + CH223191 (5 mM ); 1-hydroxyphenazine (1-HP, 5mM); 1-HP (5mM) + CH223191(5mM) and 1-HP (5mM) + 3-o-C12-L-HSL (50mM).To mention, in experiments using the Aryl hydrocarbon Receptor inhibitor CH223191, larvae were pre-exposed to 5uM of the inhibitor for 2h prior to the start of the experiment and the inhibitor was kept during the experiment. After the desired exposure to diverse ligands, larvae were euthanized with Tricaine (MS-222, 300 µg/mL) and placed in Trizol for RNA isolation. The same experimental layout was performed 5 times, and samples were subjected to microarray hybridization and analysis.

2019-10-01 | GSE121101 | GEO

Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development

Project description:Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development

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Ancestralization of the modern human aryl hydrocarbon receptor by genome editing

Project description:The aryl hydrocarbon receptor (AHR) is a transcription factor that upon binding ligands induces the expression of cytochrome P450 genes, which encode enzymes that metabolize aromatic hydrocarbons. The AHR carries an amino acid substitution at position 381 in all present-day humans that occurred after the divergence of modern humans from Neandertals and Denisovans. Here, we use genome editing to revert position 381 back to the ancestral state in human cells. Cells were treated with ligands for 4 h followed by RNA extraction and RNA-Seq.

2024-06-26 | GSE210514 | GEO

Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development [STEM]

Project description:Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development [STEM]

| PRJNA1033553 | ENA

Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development [EVT]

Project description:Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development [EVT]

| PRJNA1033543 | ENA

Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development [ST3D]

Project description:Aryl Hydrocarbon Receptor Ligands Present In The Environment Impact Human Trophoblast Cell Development [ST3D]

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The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries

Project description:This SuperSeries is composed of the following subset Series: GSE15857: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Kidney GSE15858: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Liver Refer to individual Series

2010-05-05 | E-GEOD-15859 | biostudies-arrayexpress

Characterization of glyceollins as novel aryl hydrocarbon receptor ligands and their role in cell migration

Project description:Characterization of glyceollins as novel aryl hydrocarbon receptor ligands and their role in cell migration

| PRJNA594408 | ENA