We report the discovery and optimization of aryl piperidinone urea formyl peptide receptor 2 (FPR2) agonists from a weakly active high-throughput screening (HTS) hit to potent and selective agonists with favorable efficacy in acute models. A basis for the selectivity for FPR2 over FPR1 is proposed based on docking molecules into recently reported FPR2 and FPR1 cryoEM structures. Compounds from the new scaffold reported in this study exhibited superior potency and selectivity and favorable ADME profiles.
View Article and Find Full Text PDF: Chronic kidney disease and as a consequence end-stage kidney disease (EKSD) is increasing globally. More and more people across the world are requiring hemodialysis (HD). The HD procedure produces a large quantity of biomedical waste.
View Article and Find Full Text PDFPlant-derived saponins are bioactive surfactant compounds that can solubilize organic pollutants in environmental matrices, thereby facilitating pollutant remediation. Externally applied saponin has potential to enhance total petroleum hydrocarbon (TPH) biodegradation in the root zone (rhizosphere) of wild plants, but the associated mechanisms are not well understood. For the first time, this study evaluated a triterpenoid saponin (from red ash leaves, Alphitonia excelsa) in comparison to a synthetic surfactant (Triton X-100) for their effects on plant growth and biodegradation of TPH in the rhizosphere of two native wild species (a grass, Chloris truncata, and a shrub, Hakea prostrata).
View Article and Find Full Text PDFSpecific microorganisms in the human gut (i.e., gut microbes) provide mutually beneficial outcomes such as microbial balance by inhibiting the growth of pathogenic organisms, immune system modulation, fermentation of ingested products, and vitamin production.
View Article and Find Full Text PDFThis study assessed the ability of phosphorus (P) fertilizer to remediate the rhizosphere of three wild plant species (Banksia seminuda, a tree; Chloris truncata, a grass; and Hakea prostrata, a shrub) growing in a soil contaminated with total (aliphatic) petroleum hydrocarbon (TPH). Plant growth, photosynthesis (via chlorophyll fluorescence), soil microbial activity, alkane hydroxylase AlkB (aliphatic hydrocarbon-degrading) gene abundance, and TPH removal were evaluated 120 days after planting. Overall, although TPH served as an additional carbon source for soil microorganisms, the presence of TPH in soil resulted in decreased plant growth and photosynthesis.
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