Gut Microbiota Influence the Development of Abdominal Aortic Aneurysm by Suppressing Macrophage Accumulation in Mice.

Background: Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease characterized by dilated abdominal aorta. Immune cells have been shown to contribute to the development of AAA, and that the gut microbiota is associated with numerous diseases, including cardiovascular diseases, by regulating immune systems or metabolic pathways of the host. However, the interaction between the gut microbiota and AAA remains unknown.

CDP-ribitol prodrug treatment ameliorates ISPD-deficient muscular dystrophy mouse model.

Ribitol-phosphate modification is crucial for the functional maturation of α-dystroglycan. Its dysfunction is associated with muscular dystrophy, cardiomyopathy, and central nervous system abnormalities; however, no effective treatments are currently available for diseases caused by ribitol-phosphate defects. In this study, we demonstrate that prodrug treatments can ameliorate muscular dystrophy caused by defects in isoprenoid synthase domain containing (ISPD), which encodes an enzyme that synthesizes CDP-ribitol, a donor substrate for ribitol-phosphate modification.

Metabolic alterations in plasma after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG) is an important therapeutic option for morbidly obese patients. Although LSG promotes sufficient weight loss, how LSG changes plasma metabolites remains unclear. We assessed changes in plasma metabolite levels after LSG.

Bioconversion of 5-deoxystrigol stereoisomers to monohydroxylated strigolactones by plants.

The bioconversion of 5-deoxystrigol (5DS) and 4-deoxyorobanchol (4DO), the simplest canonical strigolactones (SLs), into monohydroxylated SLs such as strigol, sorgomol and orobanchol was confirmed by administering of stable isotope-labeled substrates to hydroponically grown plants. Liquid chromatography-mass spectrometry analyses established that 5DS was stereoselectively converted into strigol and sorgomol by cotton () and Chinese milk vetch (), respectively. 4DO was converted into orobanchol by rice ().

Regioselective and stereospecific hydroxylation of GR24 by Sorghum bicolor and evaluation of germination inducing activities of hydroxylated GR24 stereoisomers toward seeds of Striga species.

Bioconversion of GR24, the most widely used synthetic strigolactone (SL), by hydroponically grown sorghum (Sorghum bicolor) and biological activities of hydroxylated GR24 stereoisomers were studied. Analysis of extracts and exudates of sorghum roots previously fed with a racemic and diastereomeric mixture of GR24, using liquid chromatography-tandem mass spectrometry with multiple reaction monitoring (MRM), confirmed uptake of GR24 and suggested its conversion to mono-hydroxylated products. Two major GR24 metabolites, 7-hydroxy-GR24 and 8-hydroxy-GR24, were identified in the root extracts and exudates by direct comparison of chromatographic behavior with a series of synthetic mono-hydroxylated GR24 analogues.

The molecular dynamics of crawling migration in microtubule-disrupted keratocytes.

Cell-crawling migration plays an essential role in complex biological phenomena. It is now generally believed that many processes essential to such migration are regulated by microtubules in many cells, including fibroblasts and neurons. However, keratocytes treated with nocodazole, which is an inhibitor of microtubule polymerization - and even keratocyte fragments that contain no microtubules - migrate at the same velocity and with the same directionality as normal keratocytes.

The bioconversion of 5-deoxystrigol to sorgomol by the sorghum, Sorghum bicolor (L.) Moench.

Strigolactones, important rhizosphere signalling molecules and a class of phytohormones that control shoot architecture, are apocarotenoids of plant origin. They have a structural core consisting of a tricyclic lactone connected to a butyrolactone group via an enol ether bridge. Deuterium-labelled 5-deoxystrigol stereoisomers were administered to aquacultures of a high sorgomol-producing sorghum cultivar, Sorghum bicolor (L.

Structural requirements of strigolactones for germination induction and inhibition of Striga gesnerioides seeds.

Structure-activity relationship studies of strigolactones and Striga gesnerioides seed germination revealed strict structural requirements for germination induction and a new function of the plant hormones as germination inhibitors. Stereoisomers of the naturally occurring strigolactones, strigol, sorgolactone, orobanchol, sorgomol and 5-deoxystrigol, 36 in total, were prepared and screened for the ability to induce and/or inhibit the germination of Striga hermonthica and Striga gesnerioides seeds collected from mature plants that parasitized on sorghum and cowpea, respectively. All of the compounds induced S.

Design of novel hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-TRP as an IDO affinity moiety.

We presented here design, syntheses and inhibitory activities of novel hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety without inhibitor 1MT, such as L-Trp-TPZ hybrids 1 (TX-2274), 2 (UTX-3), 3 (UTX-4), and 4 (UTX-2). TPZ-monoxide hybrids 1 and 3 were good competitive IDO inhibitors, while TPZ hybrids 2 and 4 were uncompetitive IDO inhibitors. Among them TPZ-monoxide hybrid 1 have the strongest IDO inhibitory activity.

Synthesis and biological activity of 1-methyl-tryptophan-tirapazamine hybrids as hypoxia-targeting indoleamine 2,3-dioxygenase inhibitors.

We have designed and synthesized new hypoxic-neoplastic cells-targeted indoleamine 2,3-dioxygenase (IDO) inhibitors. 1-Methyl-tryptophan (1MT)-tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-dioxide) hybrid inhibitors including 1 (TX-2236), 2 (TX-2235), 3 (TX-2228), and 4 (TX-2234) were prepared. All of these compounds were uncompetitive IDO inhibitors.

Design of antiangiogenic hypoxic cell radiosensitizers: 2-nitroimidazoles containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety.

We designed chiral 2-nitroimidazole derivatives containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety as antiangiogenic hypoxic cell radiosensitizers. Based on results of molecular orbital calculations, the 2-aminomethylene-4-cyclopentene-1,3-dione moiety is expected to show high electrophilicity comparable to that of the 2-methylene-4-cyclopentene-1,3-dione moiety included in TX-1123 and tyrphostin AG17. We evaluated the antiangiogenic and radiosensitizing effects of the new compounds, along with other biological properties including their activities as hypoxic cytotoxicities and protein tyrosine kinase (PTK) inhibitory activities.