Discovery of Novel NLRP3 Inflammasome Inhibitors Composed of an Oxazole Scaffold Bearing an Acylsulfamide.

The NLRP3 inflammasome plays an important role in the defense mechanism of the innate immune system and has recently attracted much attention as a drug target for various inflammatory disorders. Among the strategies for generating the novel chemotype in current drug discovery, scaffold hopping and bioisosteric replacement are known to be attractive approaches. As the results of our medicinal chemistry campaign, which involved exploration of core motifs using a ring closing approach, a five-membered oxazole-based scaffold was identified, and subsequent implementation of bioisosteric replacement led to discovery of a novel chemical class of NLRP3 inflammasome inhibitor bearing the acylsulfamide group.

Role for Neutrophil Extracellular Traps (NETs) and Platelet Aggregation in Early Sepsis-induced Hepatic Dysfunction.

Background/aim: Severe sepsis is associated with high morbidity and mortality rates. Inflammation and coagulation play pivotal roles in the pathogenesis of sepsis leading to multiple organ failure, especially in the liver. The aim of the present study was to assess the mechanism from sepsis to liver damage in a mouse model.

Relation between muscle fiber conduction velocity and exerted dynamic characteristics of muscular tension in patients with hemiplegia caused by stroke.

[Purpose] The aim of this study was to clarify the relationships among muscle fiber conduction velocity, time-force characteristics of muscle force production, and voluntary movement in patients with hemiplegia. [Subjects and Methods] The participants in the present study were 13 patients with hemiplegia. Muscle fiber conduction velocity, deep temperature of muscles and muscle thickness were measured for the tibialis anterior, and a time force curve was obtained from dorsiflexion of the ankle and lower thigh girth (maximum, minimum) for both sides.

Detection of relative and uniform motion.

We measured the lowest velocity (velocity threshold) for discriminating motion direction in relative and uniform motion stimuli, varying the contrast and the spatial frequency of the stimulus gratings. The results showed significant differences in the effects of contrast and spatial frequency on the threshold, as well as on the absolute threshold level between the two motion conditions, except when the contrast was 1% or lower. Little effect of spatial frequency was found for uniform motion, whereas a bandpass property with a peak at approximately 5 cycles per degree was found for relative motion.