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Induction of cytochrome P450 3A4 (CYP3A4) expression is often implicated in clinically relevant drug-drug interactions (DDI), as metabolism catalyzed by this enzyme is the dominant route of elimination for many drugs. Although several DDI models have been proposed, none have comprehensively considered the effects of enzyme transcription/translation dynamics(More)
Blood and/or breast milk have been used to assess human exposure to various environmental contaminants. Few studies have been available to compare the concentrations in one matrix with those in another. The goals of this study were to determine the current levels of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in Japanese(More)
Chitosan has potential as a biocompatible gene carrier. However, its gene transfection efficiency is low because of its slow endosomal escape rate. Histidine has buffering capacity in the pH range of endosomes/lysosomes. The structure of dendron consists of a central core with several chains radiating from it and many histidines could be conjugated on the(More)
In the present study, we developed an approach involving a combination of molecular orbital (MO) calculation and neural network to predict Caco-2 cell permeability (logP(app)) from the molecular structure of compounds. For a total of 87 compounds with logP(app) values obtained from the literature, three-dimensional molecular structures were determined by(More)
Caco-2 cell monolayers are widely used systems for predicting human intestinal absorption. This study was carried out to develop a quantitative structure-property relationship (QSPR) model of Caco-2 permeability using a novel genetic algorithm-based partial least squares (GA-PLS) method. The Caco-2 permeability data for 73 compounds were taken from the(More)
The nuclear factor kappa B (NFκB) signaling pathway is a key mechanism in the pathophysiology of lung inflammation. NFκB is critically responsible for the expression of pro-inflammatory mediators following activation. The specific inhibition of NFκB by a NFκB decoy via inhalation appears to improve therapeutic effects. However, administration of naked NFκB(More)
Caco-2 cell monolayers grown on a filter support are the most widely used systems for predicting intestinal absorption. However, inter- and intralaboratory variability in Caco-2 permeability makes it difficult to analyze any QSPR relationship for a large number of compounds. We proposed the "latent membrane permeability" concept, assuming that all Caco-2(More)
Nuclear factor kappa B (NFkappaB) is a transcriptional factor for the expression of many cytokines that are involved in the pathogenesis of inflammatory diseases. Unstimulated NFkappaB sequestered in the cytoplasm bound to inhibitory proteins is called IkappaBs. Many activators of NFkappaB cause degradation of IkappaB proteins and free NFkappaB can enter(More)
BACKGROUND Here we describe a novel DNA vaccine formulation that can enhance cytotoxic T lymphocyte (CTL) activity through efficient gene delivery to dendritic cells (DCs) by mannose receptor-mediated endocytosis. METHODS Ovalbumin (OVA) was selected as a model antigen for vaccination; accordingly, OVA-encoding pDNA (pCMV-OVA) was constructed to evaluate(More)