Discovery of N-(5-amido-2-methylphenyl)-5-methylisoxazole-3-carboxamide as dual CSF-1R/c-Kit Inhibitors with improved stability and BBB permeability.

This study explores the potential of CSF-1R inhibitors as therapeutic agents for neurodegenerative diseases. CSF-1R, a receptor tyrosine kinase primarily expressed in macrophage lineages, plays a pivotal role in regulating various cellular processes. Recent research highlights the significance of CSF-1R inhibition in mitigating neuroinflammation, particularly in Alzheimer's disease, where microglial overactivation contributes to neurodegeneration.

Biomechanical comparative finite element analysis between a conventional proximal interphalangeal joint flexible hinge implant and a novel implant design using a rolling contact joint mechanism.

Background: The rolling contact joint (RCJ) mechanism is a system of constraint that allows two circular bodies connected with flexible straps to roll relative to one another without slipping. This study aims to compare the biomechanical characteristics between the conventional proximal interphalangeal joint (PIPJ) flexible hinge (FH) implant and the novel PIPJ implant adopting a RCJ mechanism during PIPJ range of motion using finite element (FE) analysis.

Methods: The three-dimensional (3D) surface shape of a conventional PIPJ FH implant was obtained using a 3D laser surface scanning system.

Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease.

Despite innumerable efforts to develop effective therapeutics, it is difficult to achieve breakthrough treatments for Alzheimer's disease (AD), and the main reason is probably the absence of a clear target. Here, we reveal c-Jun N-terminal kinase 3 (JNK3), a protein kinase explicitly expressed in the brain and involved in neuronal apoptosis, with a view toward providing effective treatment for AD. For many years, we have worked on JNK3 inhibitors and have discovered 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile-based JNK3 inhibitors with superb potency (IC < 1.

Design and Synthesis of Aminopyrimidinyl Pyrazole Analogs as PLK1 Inhibitors Using Hybrid 3D-QSAR and Molecular Docking.

Cancer continues to be one of the world's most severe public health issues. Polo-like kinase 1 (PLK1) is one of the most studied members of the polo-like kinase subfamily of serine/threonine protein kinases. PLK1 is a key mitotic regulator responsible for cell cycle processes, such as mitosis initiation, bipolar mitotic spindle formation, centrosome maturation, the metaphase to anaphase transition, and mitotic exit, whose overexpression is often associated with oncogenesis.

Rational design and synthesis of 2-(1-indazol-6-yl)-1-benzo[d]imidazole derivatives as inhibitors targeting FMS-like tyrosine kinase 3 (FLT3) and its mutants.

Fms-like tyrosine kinase 3 (FLT3) has been verified as a therapeutic target for acute myeloid leukaemia (AML). In this study, we report a series of 2-(1-indazol-6-yl)-1-benzo[d]imidazol-5-yl benzamide and phenyl urea derivatives as potent FLT3 inhibitors based on the structural optimisation of previous FLT3 inhibitors. Derivatives were synthesised as benzamide -, -, and phenyl urea -, with various substituents.

A survey of the perspectives of patients who are seriously ill regarding end-of-life decisions in some medical institutions of Korea, China and Japan.

Purpose: The debate about the end-of-life care decision is becoming a serious ethical and legal concern in the Far-Eastern countries of Korea, China and Japan. However, the issues regarding end-of-life care will reflect the cultural background, current medical practices and socioeconomic conditions of the countries, which are different from Western countries and between each other. Understanding the genuine thoughts of patients who are critically ill is the first step in confronting the issues, and a comparative descriptive study of these perspectives was conducted by collaboration between researchers in all three countries.

Biochemical characterisation of a glycogen branching enzyme from Streptococcus mutans: Enzymatic modification of starch.

A gene encoding a putative glycogen branching enzyme (SmGBE) in Streptococcus mutans was expressed in Escherichia coli and purified. The biochemical properties of the purified enzyme were examined relative to its branching specificity for amylose and starch. The activity of the approximately 75kDa enzyme was optimal at pH 5.