In vitro hepatic steatosis model based on gut-liver-on-a-chip.

Hepatic steatosis, also known as fatty liver disease, occurs due to abnormal lipid accumulation in the liver. It has been known that gut absorption also plays an important role in the mechanism underlying hepatic steatosis. Conventional in vitro cell culture models have limitations in recapitulating the mechanisms of hepatic steatosis because it does not include the gut absorption process.

Three-tissue microphysiological system for studying inflammatory responses in gut-liver Axis.

The interaction between the gut and the liver, often known as the gut-liver axis, play crucial roles in modulating the body's responses to the xenobiotics as well as progression of diseases. Dysfunction of the axis can cause metabolic disorders as well as obesity, diabetes, and fatty liver disease. During the progression of such diseases, inflammatory responses involving the immune system also play an important part.

Angiotensin-cleaving catalysts: conversion of N-terminal aspartate to pyruvate through oxidative decarboxylation catalyzed by Co(III)cyclen.

To provide a firm basis for the new paradigm of drug discovery based on peptide-cleaving catalysts, oligopeptide-cleaving catalysts were searched for by using human angiotensin I (Ang-I) and angiotensin II (Ang-II) as the substrates. Catalyst candidates containing the Co(III) complex of cyclen as the catalytic center were prepared by multicomponent condensation reactions. From two types of chemical libraries containing about 3,600 catalyst candidates, two compounds [SS-Co(III)X and S-Co(III)Y] were selected as the most active catalysts.

Toward protein-cleaving catalytic drugs: artificial protease selective for myoglobin.

A protein-cleaving catalyst highly selective for a disease-related protein can be used as a catalytic drug. As the first protein-cleaving catalyst selective for a protein substrate, a catalyst for myoglobin (Mb) was designed by attaching the Cu(II) or Co(III) complex of cyclen to a binding site searched by a combinatorial method using peptide nucleic acid monomers as building units. Various linkers were inserted between the catalytic Co(III) center and the binding site of the Mb-cleaving catalyst.

Protein-cleaving catalyst selective for protein substrate.

A protein-cleaving catalyst specific for a disease-related protein can be used as a catalytic drug. As the first protein-cleaving catalyst selective for a protein substrate, a catalyst for myoglobin was designed by attaching Cu(II) or Co(III) complex of cyclen to a binding site searched by a combinatorial method using peptide nucleic acid monomers as building units. [reaction: see text]