Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 inflammasome.

The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3.

Intrathecal IgG and IgM synthesis correlates with neurodegeneration markers and corresponds to meningeal B cell presence in MS.

Intrathecal synthesis of immunoglobulins (Igs) is a key hallmark of multiple sclerosis (MS). B cells are known to accumulate in the leptomeninges of MS patients and associate with pathology in the underlying cortex and a more severe disease course. However, the role of locally produced antibodies in MS brain pathology is poorly understood.

Bridging the gap: Insights in the immunopathology of Lyme borreliosis.

Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) genospecies transmitted by Ixodes spp. ticks, is a significant public health concern in the Northern Hemisphere. This review highlights the complex interplay between Bbsl infection and host-immune responses, impacting clinical manifestations and long-term immunity.

Discovery of 6,7-Dihydropyrazolo[1,5-]pyrazin-4(5)-one Derivatives as mGluR Negative Allosteric Modulators with Activity in a Rodent's Model of Cognition.

Allosteric modulators of the metabotropic group II receptors, mGluR and mGluR, have been widely explored due to their ability to modulate cognitive and neurological functions in mood disorders, although none have been approved yet. In our search for new and selective mGluR negative allosteric modulators (NAMs), series of 6,7-dihydropyrazolo[1,5-]pyrazin-4(5)-one derivatives were identified from our published series of 1,3,5-trisubstituted pyrazoles. SAR evolution of the initial hit resulted in 100-fold improvement in the mGluR NAM potency and subsequent selection of compound based on its overall profile, including selectivity and ADMET properties.

Determination of Taurine in Infant Formula and Adult/Pediatric Nutritionals by Ultra High-Performance Liquid Chromatography with Multiple Reaction Monitoring-Mass Spectrometry: Single-Laboratory Validation, First Action 2022.08.

Background: Taurine (2-aminoethanesulfonic acid) is an essential β-amino acid, which is one of the most abundant intracellular amino acid component in humans. The level of free taurine in human milk is higher than in bovine milk. Since taurine is considered important for the development of a newborn, fortification of infant nutrition with taurine is common.