Development of a Novel, Small-Molecule Brain-Penetrant Histone Deacetylase Inhibitor That Enhances Spatial Memory Formation in Mice.

Histone acetylation is a prominent epigenetic modification linked to the memory loss symptoms associated with neurodegenerative disease. The use of existing histone deacetylase inhibitor (HDACi) drugs for treatment is precluded by their weak blood-brain barrier (BBB) permeability and undesirable toxicity. Here, we address these shortcomings by developing a new class of disulfide-based compounds, inspired by the scaffold of the FDA-approved HDACi romidepsin (FK288).

Neutrophils Recirculate through Lymph Nodes to Survey Tissues for Pathogens.

The adaptive immune function of lymph nodes is dependent on constant recirculation of lymphocytes. In this article, we identify neutrophils present in the lymph node at steady state, exhibiting the same capacity for recirculation. In germ-free mice, neutrophils still recirculate through lymph nodes, and in mice cohoused with wild microbiome mice, the level of neutrophils in lymph nodes increases significantly.

Calcium-oligochitosan-pectin microcarrier for colonic drug delivery.

Pectin-based hydrogel microcarriers have shown promise for drug delivery to the colonic region. Microcarriers must remain stable throughout the upper gastrointestinal tract for effective colonic delivery, an issue that traditional pectin-based microcarriers have faced. The positively-charged natural biopolymer oligochitosan and divalent cation Ca were used to dually cross-link pectin-based hydrogel microcarriers to improve carrier stability through simulated gastric and intestinal environments.

MIDD0301 - A first-in-class anti-inflammatory asthma drug targets GABA receptors without causing systemic immune suppression.

We report a 28-day repeat dose immunotoxicity evaluation of investigational drug MIDD0301, a novel oral asthma drug candidate that targets gamma amino butyric acid type A receptors (GABA R) in the lung. The study design employed oral administration of mice twice daily throughout the study period with 100 mg/kg MIDD0301 mixed in peanut butter. Compound dosing did not reveal signs of general toxicity as determined by animal weight, organ weight or haematology.