Hybrid/Chimera Drugs - Part 1 - Drug Hybrids Affecting Diseases of the Central Nervous System.

This review, focused on hybrid drugs, is the third in a series of reviews, where the first two reviews dealt with a) dimeric drugs, b) mutual prodrugs - codrugs. The compounds designated as hybrids are comprised of two (and sometimes three) biologically active entities, linked by metabolically stable bridges. In some cases, one of the two components of the hybrids serves as a carrier for the second component, and most frequently, the components elicit their individual biological properties, which are commonly synergistic or complementary.

Proteolytic Vesicles Derived from Serovar Typhimurium-Infected Macrophages: Enhancing MMP-9-Mediated Invasion and EV Accumulation.

Proteolysis of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) plays a crucial role in the immune response to bacterial infections. Here we report the secretion of MMPs associated with proteolytic extracellular vesicles (EVs) released by macrophages in response to serovar Typhimurium infection. Specifically, we used global proteomics, in vitro, and in vivo approaches to investigate the composition and function of these proteolytic EVs.

Mutual Prodrugs - Codrugs.

This review encapsulates an extensive variety of substances identified as mutual prodrugs or codrugs, wherein two, or sometimes three, biologically active moieties are linked using an assortment of metabolically unstable bridging entities. Following the administration of the mutual prodrugs, these undergo a bridge cleavage releasing the active molecules, which then elicit their respective biological effects. In some cases, the released drugs act synergistically, other times the biological activity of only one of the drugs is elicited, and in such cases, the accompanying drug serves only as a carrier, which may have an affinity to the desired receptor.

Validation and real-world clinical application of an artificial intelligence algorithm for breast cancer detection in biopsies.

Breast cancer is the most common malignant disease worldwide, with over 2.26 million new cases in 2020. Its diagnosis is determined by a histological review of breast biopsy specimens, which can be labor-intensive, subjective, and error-prone.

Synthesis and preliminary biological evaluation of gabactyzine, a benactyzine-GABA mutual prodrug, as an organophosphate antidote.

Organophosphates (OPs) are inhibitors of acetylcholinesterase and have deleterious effects on the central nervous system. Clinical manifestations of OP poisoning include convulsions, which represent an underlying toxic neuro-pathological process, leading to permanent neuronal damage. This neurotoxicity is mediated through the cholinergic, GABAergic and glutamatergic (NMDA) systems.