In non-alcoholic fatty liver disease (NAFLD) and insulin resistance, hepatic de novo lipogenesis is often elevated, but the underlying mechanisms remain poorly understood. Recently, we show that CDK8 functions to suppress de novo lipogenesis. Here, we identify the mammalian target of rapamycin complex 1 (mTORC1) as a critical regulator of CDK8 and its activating partner CycC.
View Article and Find Full Text PDFA nanohybrid vesicle was developed from cholesteryl succinyl silane(CSS) in combination of sol-gel process and self-assembly technique. The silicalike surface adds CSS vesicles remarkably high stability against destabilization in blood or leakage of drug cargos. It was found that CSS vesicles alone exhibited selective antiproliferative effects on leukemia cells without destroying normal blood cells.
View Article and Find Full Text PDFNanotoxicology
December 2011
Biomimetic cerasome has drawn much attention as a novel drug delivery system because its atomic layer of polyorganosiloxane surface imparts higher morphological stability than conventional liposomes and its liposomal bilayer structure reduces the overall rigidity and density greatly compared to silica nanoparticles. But, the issues about the interactions between cerasomes and biological systems have not been addressed as far as we could find. Herein, we reported cellular uptake of cerasomes and their biological effects toward human umbilical vein endothelial cells (HUVECs) compared with silica nanoparticles.
View Article and Find Full Text PDFThe adhesion of tumor cells with platelets is important in the process of tumor metastasis. A huge work has indicated that anti-adhesion is an effective strategy for metastasis inhibition. In this article, we assess the role of platelet integrin alpha(IIb)beta(3) in adhesion of melanoma cells to platelets and the effects of heparin and modified heparins on the adhesion in vitro and in vivo.
View Article and Find Full Text PDFP-selectin plays a crucial role during hematogenous metastasis, and the blockade of P-selectin binding to its ligand can attenuate metastasis in various tumor models. Heparin or chemically modified heparins with decreased anticoagulant activities exhibit marked inhibitory effects on P-selectin-mediated adhesion. Here, we prepared chemically modified heparins with reduced anticoagulant activities and investigated whether they effectively inhibited P-selectin binding to breast cancer cells under static and flow conditions.
View Article and Find Full Text PDFIron-polysaccharide complex have been extensively utilized in the treatment of iron deficiency anemia for parenteral administration. Herein, a novel iron-heparin complexed hollow capsules with nanoscaled wall thickness have been fabricated by means of alternating deposition of ferric ions (III) (Fe+) and heparin (Hep) onto the surface of submicroscaled (488 nm) and microscaled (10.55 microm) polystyrene latex particles via both electrostatic interaction and chemical complexation processes, followed by dissolution of the cores using tetrahydrofuran.
View Article and Find Full Text PDFAim: To investigate the anti-inflammatory mechanism of the polysaccharides of Ginkgo biloba leaves (PGBL) by inhibiting leucocyte adhesion.
Methods: The rough PGBL were isolated and purified. The anti-inflammatory effects of purified PGBL (p-PGBL) were assayed by ear edema induced by xylol and the acute peritonitis model in mice.
J Cancer Res Clin Oncol
April 2006
Purpose: Several independent studies have indicated that tumor metastasis can be inhibited by chemically modified heparin with low anticoagulant activity in the different tumor models. The mechanism of inhibition by the heparin derivatives in part accounts for the interference of tumor cell-platelet interaction mediated by P-selectin.
Methods: In the present study, we demonstrated that both heparin and chemically modified heparins inhibited the adhesion of nonsmall cell lung cancer (NSCLC) cells to P-selectin under static or flow conditions in vitro.
PSGL-1, the optimal selectin ligand demonstrated by in vivo studies to date, is an essential adhesive molecule mediating the rolling of leukocytes on the endothelial cells and the recruitment of leukocytes to the inflamed tissue. Recent studies demonstrated, in addition to its direct role in capture of leukocytes from the bloodstream, PSGL-1 also functions as a signal-transducing receptor and initiates a series of intracellular signal events during the activation of leukocytes. Our present work showed antibody engagement of PSGL-1 upregulated the transcriptional activity of CSF-1 promotor and increased the endogenous expression of CSF-1 mRNA in Jurkat cell.
View Article and Find Full Text PDFAccumulating evidence has suggested that one of the mechanisms by which heparin inhibits metastasis is by blocking the P-selectin-based interaction of platelets with tumor cells. Here we demonstrate that the sulfate groups at C6/N and especially C6, but not C2 and C3, of heparin play a critical role in P-selectin recognition and that 2-O,3-O-desulfated heparin can block P-selectin-mediated A375 human melanoma cell adhesion. Our findings show that chemical modification of heparin, especially 2-O,3-O-desulfation, may result in a therapeutic agent that is anti-metastatic because it blocks unwanted P-selectin-dependent adhesion but that lacks dose-limiting anticoagulant effects.
View Article and Find Full Text PDFSelectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Heparin can bind to P-selectin, and its anti-inflammatory property is mainly due to inhibition of P-selectin. However, the strong anticoagulant activity of heparin limits its clinical use.
View Article and Find Full Text PDFP-selectin glycoprotein ligand-1 (PSGL-1) is the best-characterized selectin ligand that has been demonstrated to mediate leukocytes rolling on endothelium and leukocytes recruitment into inflamed tissue in vivo. In addition to its direct role in leukocyte capturing, PSGL-1 also functions as a signal-transducing receptor. The present work showed that after cross-linking of PSGL-1 with KPL1, an anti-PSGL-1 monoclonal antibody, PSGL-1 linked to the cytoskeleton and became a detergent-insoluble component in activated neutrophils.
View Article and Find Full Text PDFAccumulating evidence indicates that the formation of tumor cell platelet emboli complexes in the blood stream is a very important step during metastases and that the anti-metastasis effects of heparin are partially due to a blockade of P-selectin on platelets. In this study, heparin and chemically modified heparins were tested as inhibitors of three human colon carcinoma cell lines (COLO320, LS174T, and CW-2) binding to P-selectin, adhering to CHO cells expressing a transfected human P-selectin cDNA, and adhering to surface-anchored platelets expressing P-selectin under static and flow conditions. The aim was to screen for heparin derivatives with high anti-adhesion activity but negligible anticoagulant activity.
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