Chronic intestinal inflammation significantly contributes to the development of colorectal cancer (CRC) and remains a pertinent clinical challenge, necessitating novel therapeutic approaches. Indole-based microbial metabolite mimics FKK6, which is a ligand and agonist of the pregnane X receptor (PXR), was recently demonstrated to have PXR-dependent anti-inflammatory and protective effects in a mouse model of dextran sodium sulfate (DSS)-induced acute colitis. Here, we examined the therapeutic potential of FKK6 in a mouse model (C57BL/6 FVB humanized PXR mice) of colitis-associated colon cancer (CAC) induced by azoxymethane (AOM) and dextran sodium sulfate (DSS).
View Article and Find Full Text PDFMicrobial indoles have been demonstrated as selective or dual agonists and ligands of the pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR). However, structural determinants of microbial indoles selectivity towards both receptors remain elusive. Here, we studied the effects of existing and newly synthesized derivatives of indole microbial metabolite tryptamine on the activity of AhR and PXR receptors.
View Article and Find Full Text PDFBiochem Pharmacol
July 2023
The aryl hydrocarbon receptor (AhR) belongs to the essential helix-loop-helix transcription factors family. This receptor has a central role in determining host physiology and a variety of pathophysiologies ranging from inflammation and metabolism to cancer. AhR is a ligand-driven receptor with intricate pharmacology of activation depending on the type and quantity of ligand present.
View Article and Find Full Text PDFTargeting the aryl hydrocarbon receptor (AhR) is an emerging therapeutic strategy for multiple diseases (e.g., inflammatory bowel disease).
View Article and Find Full Text PDFChickpea ( L.) is one of the main sources of plant proteins in the Indian subcontinent and West Asia, where two different morphotypes, desi and kabuli, are grown. Despite the progress in genome mapping and sequencing, the knowledge of the chickpea genome at the chromosomal level, including the long-range molecular chromosome organization, is limited.
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