Suppression of the Epithelial-Mesenchymal Transition and Maintenance of the Liver Functions in Primary Hepatocytes through Dispersion Culture within a Dome-Shaped Collagen Matrix.

Primary hepatocytes are valuable for studying liver diseases, drug-induced liver injury, and drug metabolism. However, when cultured in a two-dimensional (2D) environment, primary hepatocytes undergo rapid dedifferentiation via an epithelial-mesenchymal transition (EMT) and lose their liver-specific functions. On the other hand, a three-dimensional (3D) culture of primary hepatocyte organoids presents challenges for analyzing cellular functions and molecular behaviors due to strong cell-cell adhesion among heterogeneous cells.

Enhanced sensitivity of chimeric insect olfactory co-receptors for detecting odorant molecules.

Insect olfactory receptors (ORs) are seven-transmembrane domain ion channels that function by forming heteromeric complexes with olfactory receptor co-receptors (Orcos). In this study, we investigated the potential for enhancing sensitivity of odor detection and responsivity through genetic modification of Orcos, considering its wider application in odor sensing. First, we measured the intensity of response to 1-octen-3-ol for the mosquito Aedes aegypti OR (AaOR8) when complexed individually with an Orco from the same mosquito (AaOrco), the honeybee Apis mellifera (AmOrco), the silkworm Bombyx mori (BmOrco), or the fruit fly Drosophila melanogaster (DmOrco).

Designing a novel photoinduced electron transfer-based small-molecule fluorescent probe specific for CYP3A isozymes.

Cytochrome P450 (CYPs) are oxidoreductases distributed in various tissues in plants and animals. Among the CYP families, CYP3A is the most abundant in vivo, particularly in humans, and it is involved in the metabolism of many drugs. It is crucial to measure CYP3A activity for both pharmaceuticals and agrochemicals because inhibition or induction of this enzyme can seriously affect the occurrence of toxicity or efficacy.

Construction of a Biohybrid Odorant Sensor Using Biological Olfactory Receptors Embedded into Bilayer Lipid Membrane on a Chip.

This paper describes an odorant sensor based on mosquito olfactory receptors (ORs) that is sensitive to the volatile organic compound octenol. The ORs and OR coreceptors were reconstructed in the lipid bilayer membrane in a chamber device equipped with electrodes. Using this odorant sensor, we obtained ion current changes caused by specific OR responses to octenol.

Quantitative structure-activity relationship model for the fetal-maternal blood concentration ratio of chemicals in humans.

A quantitative structure-activity relationship (QSAR) model of the fetal-maternal blood concentration ratio (F/M ratio) of chemicals was developed to predict the placental transfer in humans. Data on F/M ratio of 55 compounds found in the literature were separated into training (75%, 41 compounds) and testing sets (25%, 14 compounds). The training sets were then subjected to multiple linear regression analysis using the descriptors of molecular weight (MW), topological polar surface area (TopoPSA), and maximum E-state of hydrogen atom (Hmax).

Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals.

A physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of flumioxazin, in the blood and fetus of pregnant humans during a theoretical accidental intake (1000mg/kg). The data on flumioxazin concentration in pregnant rats (30mg/kg po) was used to develop the PBPK model in pregnant rats using physiological parameters and chemical specific parameters. The rat PBPK model developed was extrapolated to a human model.

Metabolism of propyrisulfuron: 14C excretion, 14C concentration in plasma and tissues, and amount of metabolites in rats.

1. Metabolism of a novel sulfonylurea herbicide, propyrisulfuron [1-(2-chloro-6-propylimidazo[1,2-b]pyridazin-3-ylsulfonyl)-3-(4,6-dimethoxypyrimidin-2-yl)urea] labeled at the C-1 position of the propyl group and C-5 position of the pyrimidine ring with (14)C was investigated after a single oral administration in male and female rats. 2.

Identification of metabolites of propyrisulfuron in rats.

The metabolites found in the urine, feces and bile of male and female rats administered with (14)C-labeled herbicide, propyrisulfuron [1-(2-chloro-6-propylimidazo[1,2-b]pyridazin-3-ylsulfonyl)-3- (4,6-dimethoxypyrimidin-2-yl)urea] were identified by high-performance liquid chromatography (HPLC) with the ultraviolet (UV) and radioisotope (RI) detectors, tandem mass spectrometry and nuclear magnetic resonance (NMR). Administered (14)C was excreted into the urine (5.7-29.

In vitro metabolism of trans-permethrin and its major metabolites, PBalc and PBacid, in humans.

To estimate the metabolic profile of trans-permethrin in humans, a comparison of the in vitro metabolism of trans-permethrin in humans and rats was conducted using hepatic microsomes, and cytochrome P450 and UDP-glucuronyltransferase isoforms, which catalyze the metabolism of 3-phenoxybenzyl alcohol (PBalc) and 3-phenoxybenzoic acid (PBacid), respectively. In humans and rats, the major metabolic reaction of trans-permethrin in microsomal incubations was the cleavage of ester linkage to give PBalc, followed by oxidation to 4'-OH-PBalc, 4'-OH-PBacid, and PBacid. As to 4'-hydroxylation of PBalc, several CYPs were able to catalyze the reaction, and CYP2E1 was identified as a predominant isoform.

Solution structure of a novel Cdc42 binding module of Bem1 and its interaction with Ste20 and Cdc42.

Bem1 is a scaffold protein essential for the establishment of cell polarity in Saccharomyces cerevisiae. This work reports the solution structure of a Cdc42 binding module of Bem1 comprising the second SH3 domain (SH3b) and its C-terminal flanking region termed Cdc42 interacting (CI). First, the structure of Bem1 SH3b-CI was determined by NMR spectroscopy, which shows that Bem1 SH3b-CI is a structurally and functionally related domain that binds Cdc42.