Functional Analysis of Modified Caco-2 Cells Carrying CES2A1 as a Model for Intestinal Absorption of Prodrugs.

Carboxylesterase (CES) plays an important role in the metabolism of ester-containing drugs such as prodrugs and is highly expressed in the human intestine and liver. The ideal prodrug is barely hydrolyzed by human intestinal CES (CES2A1) but is extensively converted to an active drug by human hepatic CES (CES1A). It is, therefore, important to evaluate CES2A1-mediated hydrolysis during intestinal absorption.

The Association of the Cholesterol Efflux Capacity with the Paraoxonase 1 Q192R Genotype and the Paraoxonase Activity.

Aims: Paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and protects against atherosclerosis. However, the relationship between functional PON1 Q192R polymorphism, which is associated with the hydrolysis of paraoxon (POXase activity) and atherosclerotic cardiovascular disease (ASCVD), remains controversial. As the effect of PON1 Q192R polymorphism on the HDL function is unclear, we investigated the relationship between this polymorphism and the cholesterol efflux capacity (CEC), one of the biological functions of HDL, in association with the PON1 activity.

Gene-Transferred Skeletal Muscles with Needle-Type Electrodes as Efficient and Reliable Biomaterials for Bone Regeneration.

Background: Bone morphogenetic protein-2 () has a high potential to induce bone tissue formation in skeletal muscles. We developed a bone induction system in skeletal muscles using the gene through in vivo electroporation. Natural bone tissues with skeletal muscles can be considered potential candidates for biomaterials.

The Mc4r gene is responsible for the development of experimentally induced testicular teratomas.

Teratomas in mice, composed of different tissue types, are derived from primordial germ cells in the fetal gonads. Previously, we identified a locus responsible for experimental testicular teratoma (ETT) formation on chromosome 18, referred to as ett1. The strongest candidate sequence in the ett1 locus was found to be a missense mutation in the melanocortin 4 receptor (Mc4r), Mc4r.

Bioconversion and P-gp-Mediated Transport of Depot Fluphenazine Prodrugs after Intramuscular Injection.

Fluphenazine (FPZ) decanoate, an ester-type prodrug formulated as a long-acting injection (LAI), is used in the treatment of schizophrenia. FPZ enanthate was also developed as an LAI formulation, but is no longer in use clinically because of the short elimination half-life of FPZ, the parent drug, after intramuscular injection. In the present study, the hydrolysis of FPZ prodrugs was evaluated in human plasma and liver to clarify the reason for this difference in elimination half-lives.