Pharmacogenomic screening identifies and repurposes leucovorin and dyclonine as pro-oligodendrogenic compounds in brain repair.

Oligodendrocytes are critical for CNS myelin formation and are involved in preterm-birth brain injury (PBI) and multiple sclerosis (MS), both of which lack effective treatments. We present a pharmacogenomic approach that identifies compounds with potent pro-oligodendrogenic activity, selected through a scoring strategy (OligoScore) based on their modulation of oligodendrogenic and (re)myelination-related transcriptional programs. Through in vitro neural and oligodendrocyte progenitor cell (OPC) cultures, ex vivo cerebellar explants, and in vivo mouse models of PBI and MS, we identify FDA-approved leucovorin and dyclonine as promising candidates.

Bioinspired Design and Oriented Synthesis of Immunogenic Site-Specifically Penicilloylated Peptides.

β-Lactam antibiotics allergy is recognized as a public health concern. By covalently binding to serum proteins, penicillins are known to form immunogenic complexes. The latter are recognized and digested by antigen-presenting cells into drug-hapten peptides leading to the immunization of treated persons and IgE-mediated hypersensitivity reactions encompassing anaphylaxis.

Interhelical loops within the bHLH domain are determinant in maintaining TWIST1-DNA complexes.

The basic helix-loop-helix (bHLH) transcription factor TWIST1 is essential to embryonic development, and hijacking of its function contributes to the development of numerous cancer types. It forms either a homodimer or a heterodimeric complex with an E2A or HAND partner. These functionally distinct complexes display sometimes antagonistic functions during development, so that alterations in the balance between them lead to pronounced morphological alterations, as observed in mice and in Saethre-Chotzen syndrome patients.

C(16)-methyl corticosteroids are far less allergenic than the non-methylated molecules.

Background: It has been confirmed that binding to amino acids in skin proteins takes place at C(21) after oxidation of the corticosteroid molecule, which gives to the constituents of the D-ring an essential role in cross-reactivity patterns. In 2000, Matura et al. subdivided the corticosteroid esters of the D-group into two subgroups: D1, the 'stable' esters; and D2, the 'labile' esters.

Delayed hypersensitivity to corticosteroids in a series of 315 patients: clinical data and patch test results.

Background: Corticosteroids may cause immediate or delayed hypersensitivity. In 1989, based on structural and clinical characteristics, we put forward a classification of corticosteroids into four cross-reacting groups, namely group A, B, C, and D, the latter later subdivided into two subgroups, i.e.