Antimicrob Agents Chemother
July 2016
Broad-spectrum antibiotic therapy decimates the gut microbiome, resulting in a variety of negative health consequences. Debio 1452 is a staphylococcus-selective enoyl-acyl carrier protein reductase (FabI) inhibitor under clinical development and was used to determine whether treatment with pathogen-selective antibiotics would minimize disturbance to the microbiome. The effect of oral Debio 1452 on the microbiota of mice was compared to the effects of four commonly used broad-spectrum oral antibiotics.
View Article and Find Full Text PDFBackground: Previous studies identified the human nonmetastatic gene 23 (NME1, hereafter Nm23-H1) as the first metastasis suppressor gene. An inverse relationship between Nm23-H1 and expression of lysophosphatidic acid receptor 1 gene (LPAR1, also known as EDG2 or hereafter LPA1) has also been reported. However, the effects of LPA1 inhibition on primary tumor size, metastasis, and metastatic dormancy have not been investigated.
View Article and Find Full Text PDFMetastasis is the main cause of death for cancer patients. Targeting factors that control metastasis formation is a major challenge for clinicians. Lysophosphatidic acid (LPA) is a bioactive phospholipid involved in cancer.
View Article and Find Full Text PDFHuman 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) catalyzes the interconversion of cortisone into active cortisol. 11betaHSD1 inhibition is a tempting target for the treatment of a host of human disorders that might benefit from blockade of glucocorticoid action, such as obesity, metabolic syndrome, and diabetes type 2. Here, we report an in silico screening study aimed at identifying new selective inhibitors of human 11betaHSD1 enzyme.
View Article and Find Full Text PDFGastroenterol Clin Biol
November 2003
Background: Leptin, a protein with a cytokine-like structure, is produced predominantly by adipocytes. It appears to play a key role in immune responses by increasing the secretion of Th1 and pro-inflammatory cytokines. As fat-wrapping is a characteristic feature of Crohn's disease (CD), and as increased leptin levels have been reported in animal models of intestinal inflammation, this study investigated whether mesenteric adipose tissue could be a source of leptin in human inflammatory bowel disease (IBD).
View Article and Find Full Text PDFMast cells are key regulators in allergy and inflammation, and release histamine upon clustering of their IgE receptors. Here we demonstrate that murine mast cell responses are exacerbated in vitro and in vivo by autocrine signals through G protein-coupled receptors (GPCRs) and require functional phosphoinositide 3-kinase gamma (PI3Kgamma). Adenosine, acting through the A(3) adenosine receptor (A(3)AR) as well as other agonists of G(alphai)-coupled GPCRs, transiently increased PtdIns(3,4,5)P(3) exclusively via PI3Kgamma.
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