Pharmacological Properties of JTE-151; A Novel Orally Available RORγ Antagonist That Suppresses Th17 Cell-Related Responses and .

Retinoid-related orphan receptor-γ (RORγ) is a nuclear receptor that plays important roles in the development and activation of T helper type-17 (Th17) cells. In this study, we characterized the pharmacological profile of JTE-151 ((4S)-6-[(2-chloro-4-methylphenyl)amino]-4-{4-cyclopropyl-5-[cis-3-(2,2-dimethylpropyl)cyclobutyl]isoxazol-3yl}-6-oxohexanoic acid), which is a novel RORγ antagonist identified by our group. JTE-151 dissociated co-activator peptide from the human RORγ-ligand binding domain (LBD) and recruited co-repressor peptide into human RORγ-LBD, and potently inhibited the transcriptional activity of RORγ of human, mouse and rat.

Dynamic variation of tibiofemoral compression force during total knee arthroplasty: Implications for soft tissue balance and functional outcomes.

Background: Achieving precise alignment and soft tissue balance is crucial for optimal total knee arthroplasty (TKA) outcomes. We aimed to explore how tibiofemoral compression force (TFCF) varies with knee flexion and its correlation with functional outcomes.

Methods: This prospective study included 60 patients undergoing cruciate-retaining TKA (FINE Total Knee System).

Neuronal substance P-driven MRGPRX2-dependent mast cell degranulation products differentially promote vascular permeability.

Mas-related G protein-coupled receptor b2 (Mrgprb2) binding to its cationic endogenous and exogenous ligands induces mast cell degranulation and promotes inflammation in mice. However, the physiological roles of its human homologue MRGPRX2 remain unclear. Here we aimed to elucidate the mechanisms by which MRGPRX2 regulates vascular permeability, and generated MRGPRX2 knock-in (MRGPRX2-KI) and Mrgprb2 knockout (Mrgprb2-KO) mice.

Perspectives in newborn screening for SCID in Japan. Case report: newborn screening identified X-linked severe combined immunodeficiency with a novel variant.

Background: Newborn screening (NBS) for severe combined immunodeficiency (SCID) has improved the prognosis of SCID. In Japan, NBS testing (measurement of the T-cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC)) was launched in 2017 and has expanded nationwide in recent years. In this study, we report a Japanese patient with X-linked SCID with a novel variant identified through NBS.