16 research outputs found
TGF-β 1-induced IL-6 expression via MEK pathway in mesenchymal stem cells enhances NGF-dependent neurite extension in PC12 cells.
Influence of Hydroxyapatite Coating for the Prevention of Bone Mineral Density Loss and Bone Metabolism after Total Hip Arthroplasty: Assessment Using 18F-Fluoride Positron Emission Tomography and Dual-Energy X-Ray Absorptiometry by Randomized Controlled Trial
Background. Hydroxyapatite- (HA-) coated implants tend to achieve good osteoinductivity and stable clinical results; however, the influence of the coating on the prevention of bone mineral density (BMD) loss around the implant is unclear. The purpose of this randomized controlled trial was to evaluate the effectiveness of HA-coated implants for preventing BMD loss and to determine the status of bone remodeling after total hip arthroplasty (THA), making comparisons with non-HA-coated implants. Methods. A total of 52 patients who underwent primary THA were randomly allocated to HA and non-HA groups. BMD was measured by dual-energy X-ray absorptiometry (DEXA) at 1 week postoperation to form a baseline measurement, and then 24 weeks and 48 weeks after surgery. The relative change in BMD was evaluated for regions of interest (ROIs) based on the Gruen zone classifications. 18F-fluoride positron emission tomography (PET) was performed at 24 weeks postsurgery, and the maximum standardized uptake values (SUVmax) were evaluated in the proximal (HA-coated) and distal (non-HA-coated) areas in both groups. Results. There were significant differences in BMD loss in ROIs 3 and 6 (p=0.03), while no significant difference was observed in ROI 7 at either 24 or 48 weeks postsurgery. There was no significant correlation between PET uptake and BMD (24 or 48 weeks) in either group. Conclusion. The influence of a HA coating in terms of BMD preservation is limited. No significant correlation was found between BMD and SUVmax measured by PET, either with or without the use of a HA coating
Novel Photodegradation of the Antifungal Antibiotic Pyrrolnitrin in Anhydrous and Aqueous Aprotic Solvents
Self-healing and shape-memory properties of polymeric materials cross-linked by hydrogen bonding and metal–ligand interactions
Identification of a New Type of Covalent PPARγ Agonist using a Ligand-Linking Strategy
Peroxisome proliferator-activated
receptor γ (PPARγ)
is a ligand-activated transcription factor that plays an important
role in adipogenesis and glucose metabolism. The ligand-binding pocket
(LBP) of PPARγ has a large Y-shaped cavity with multiple subpockets
where multiple ligands can simultaneously bind and cooperatively activate
PPARγ. Focusing on this unique property of the PPARγ LBP,
we describe a novel two-step cell-based strategy to develop PPARγ
ligands. First, a combination of ligands that cooperatively activates
PPARγ was identified using a luciferase reporter assay. Second,
hybrid ligands were designed and synthesized. For proof of concept,
we focused on covalent agonists, which activate PPARγ through
a unique activation mechanism regulated by a covalent linkage with
the Cys285 residue in the PPARγ LBP. Despite their biological
significance and pharmacological potential, few covalent PPARγ
agonists are known except for endogenous fatty acid metabolites. With
our strategy, we determined that plant-derived cinnamic acid derivatives
cooperatively activated PPARγ by combining with GW9662, an irreversible
antagonist. GW9662 covalently reacts with the Cys285 residue. A docking
study predicted that a cinnamic acid derivative can bind to the open
cavity in GW9662-bound PPARγ LBP. On the basis of the putative
binding mode, structures of both ligands were linked successfully
to create a potent PPARγ agonist, which enhanced the transactivation
potential of PPARγ at submicromolar levels through covalent
modification of Cys285. Our approach could lead to the discovery of
novel high-potency PPARγ agonists