Discovery of a Phosphodiesterase 7A Inhibitor of High Isozyme Selectivity Exhibiting Anti-Osteoporotic Effects.

Phosphodiesterases (PDEs) have drawn attention due to their critical roles in physiological and pathological conditions. Many research groups have studied these hydrolytic enzymes to develop new drugs, including apremilast as a PDE4 inhibitor and sildenafil as a PDE5 inhibitor. Targeting PDE7 has also been deemed a rational strategy to ameliorate autoimmune conditions.

Macrophage polarization toward M1 phenotype in T cell transfer colitis model.

Background: T cell transfer colitis model is often used to study the CD4 T cell functions in the intestine. However, the specific roles of macrophages in colitis remain unclear. In this study, we aimed to evaluate the phenotype and functions of macrophages in the colonic lamina propria (LP) in a colitis model.

Small-molecule inhibitors of linear ubiquitin chain assembly complex (LUBAC), HOIPINs, suppress NF-κB signaling.

Nuclear factor-κB (NF-κB) is a crucial transcription factor family involved in the regulation of immune and inflammatory responses and cell survival. The linear ubiquitin chain assembly complex (LUBAC), composed of the HOIL-1L, HOIP, and SHARPIN subunits, specifically generates Met1-linked linear ubiquitin chains through the ubiquitin ligase activity in HOIP, and activates the NF-κB pathway. We recently identified a chemical inhibitor of LUBAC, which we named HOIPIN-1 (HOIP inhibitor-1).

High-Throughput Screening for Linear Ubiquitin Chain Assembly Complex (LUBAC) Selective Inhibitors Using Homogenous Time-Resolved Fluorescence (HTRF)-Based Assay System.

The nuclear factor κB (NF-κB) pathway is critical for regulating immune and inflammatory responses, and uncontrolled NF-κB activation is closely associated with various inflammatory diseases and malignant tumors. The Met1-linked linear ubiquitin chain, which is generated by linear ubiquitin chain assembly complex (LUBAC), is important for regulating NF-κB activation. This process occurs through the linear ubiquitination of NF-κB essential modulator, a regulatory subunit of the canonical inhibitor of the NF-κB kinase complex.

3D spheroid cultures improve the metabolic gene expression profiles of HepaRG cells.

3D (three-dimensional) cultures are considered to be an effective method for toxicological studies; however, little evidence has been reported whether 3D cultures have an impact on hepatocellular physiology regarding lipid or glucose metabolism. In the present study, we conducted physiological characterization of hepatoma cell lines HepG2 and HepaRG cells cultured in 3D conditions using a hanging drop method to verify the effect of culture environment on cellular responses. Apo (Apolipoprotein)B as well as albumin secretion was augmented by 3D cultures.

Charade of the SR K+-channel: two ion-channels, TRIC-A and TRIC-B, masquerade as a single K+-channel.

The presence of a sarcoplasmic reticulum (SR) K+-selective ion-channel has been known for >30 years yet the molecular identity of this channel has remained a mystery. Recently, an SR trimeric intracellular cation channel (TRIC-A) was identified but it did not exhibit all expected characteristics of the SR K+-channel. We show that a related SR protein, TRIC-B, also behaves as a cation-selective ion-channel.