Triclosan (TCS), an antimicrobial agent extensively incorporated into pharmaceuticals and personal care products, poses significant environmental risks because of its persistence and ecotoxicity. So far, a few microorganisms were suggested to degrade TCS, but the microbial degradation mechanism remains elusive. Here, a two-component angular dioxygenase (TcsAaAb) responsible for the initial TCS degradation was characterized in Sphingomonas sp.
View Article and Find Full Text PDFOral administration of harmless antigens can induce suppression of reactive immune responses, a process that capitalises on the ability of the gastrointestinal tract to tolerate exposure to food and commensal microbiome without triggering inflammatory responses. Repeating exposure to type II collagen induces oral tolerance and inhibits induction of arthritis, a chronic inflammatory joint condition. Although some mechanisms underlying oral tolerance are described, how dysregulation of gut immune networks impacts on inflammation of distant tissues like the joints is unclear.
View Article and Find Full Text PDFThe parasitic worm-derived immunomodulator, ES-62 rescues defective levels of IL-10-producing regulatory B cells (Bregs) and suppresses chronic Th1/Th17-driven inflammation to protect against joint destruction in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis. Such autoimmune arthritis is also associated with dysbiosis of the gut microbiota and disruption of intestinal barrier integrity. We recently further exploited the CIA model to show that ES-62's prevention of joint destruction is associated with protection of intestinal barrier integrity and normalization of the gut microbiota, thereby suppressing the gut pathology that precedes the onset of autoimmunity and joint damage in CIA-mice.
View Article and Find Full Text PDFPetroleum-source and black carbon-source aromatic compounds are present in the cold seep environments, where ANaerobic MEthanotrophic (ANME) archaea as the dominant microbial community mediates the anaerobic oxidation of methane to produce inorganic and organic carbon. Here, by predicting the aromatics catabolic pathways in ANME metagenome-assembled genomes, we provide genomic and biochemical evidences that ANME have the potential of metabolizing aromatics via the strategy of CoA activation of the benzene ring using phenylacetic acid and benzoate as the substrates. Two ring-activating enzymes phenylacetate-CoA ligase (PaaK) and benzoate-CoA ligase (BadA) are able to convert phenylacetate to phenylacetyl-CoA and benzoate to benzoyl-CoA respectively.
View Article and Find Full Text PDFCD20 T cells comprise a highly inflammatory subset implicated in autoimmunity, including rheumatoid arthritis (RA). We sought to characterize the CD20 T cell subset in the murine collagen-induced arthritis (CIA) model of RA and investigate the phenotype and functional relevance of CD3CD20 T cells in the lymph nodes and arthritic joints using flow cytometry and immunohistochemistry. We demonstrate that CD3CD4CD20 and CD3CD8CD20 T cells are expanded in the draining lymph nodes of CIA mice, produce increased levels of pro-inflammatory cytokines and are less susceptible to regulation by regulatory T cells.
View Article and Find Full Text PDFSupercritical anti-solvent fluidized bed (SAS-FB) technology can be applied to reduce particle size, prevent particle aggregation, and improve the dissolution and bioavailability of poorly soluble drugs. In this work, drug-loaded microparticles of three similar structures, the flavonoids luteolin (LUT), naringenin (NGR), and dihydromyricetin (DMY) were prepared using SAS-FB technology, to explore its effect on the coating of flavonoid particles. Operating temperature, pressure, carrier, solvent, and concentration of drug solution were investigated for their effects on the yield and dissolution of flavonoid particles.
View Article and Find Full Text PDFSynovial fibroblasts have emerged as critical underlying factors to perpetuate chronic joint inflammation in Rheumatoid Arthritis. Like any other cell, synovial fibroblasts are covered with a complex layer of glycans that can change in response to extracellular signals, such as inflammation. We have previously shown that inflammatory synovial fibroblasts show decreased levels of sialic acid, but our understanding of sialic acid-dependent pathophysiological pathways in these stromal cells is still very limited.
View Article and Find Full Text PDFUsing tadalafil (TD) as a representative of heat-sensitive drug with high melting point and strong crystallization tendency, we observed that recrystallization of the prepared amorphous materials during extrusion can result in failure of amorphous solid dispersion (ASD) extrusion. Such recrystallization process of amorphous TD during reheating process was investigated systematically. Our results show that spray-dried amorphous TD sample is more prone to recrystallize (occurs from 150 °C) in comparison to the melt-quenched amorphous TD sample (recrystallizes from 190 °C).
View Article and Find Full Text PDFThe ability to increase the bioavailability and dissolution of poorly soluble hydrophobic drugs has been a major challenge for pharmaceutical development. This study shows that the dissolution rate, apparent solubility and oral bioavailability of tadalafil (Td) can be improved by nano-sized amorphous particles prepared by using antisolvent precipitation. Acetone and an acetone-water solution (v:v, 9:1) were selected as solvents, with deionized water as the antisolvent.
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