Synthesis and Neurotropic Activity of Novel Quinoline Derivatives

Hydroxyalkyl and carboxyalkyl derivatives of silatetrahydroisoquinoline, tetrahydroisoquinoline and tetrahydroquinoline have been synthesized. Their neurotropic activity has been investigated

Iron Oxide Superparamagnetic Nanocarriers Bearing Amphiphilic N-Heterocyclic Choline Analogues as Potential Antimicrobial Agents

Magnetic nanoparticles represent an advanced tool in biomedicine because they can be simultaneously functionalized and guided using a magnetic field. Iron oxide magnetic nanoparticles precoated with oleic acid and bearing novel antimicrobial N-heterocyclic choline analogues, namely O-, N- and O,N-bis-undecyl-substituted N-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinolinium derivatives, have been obtained as potential biomedical agents for drug delivery and antimicrobial therapy. Structural and size determinations for the novel synthesized magnetic nanosystems were carried out based upon magnetogranulometry, dynamic light-scattering measurements and X-ray diffraction analysis. The most expected iron oxide core diameter was 6.2-10.5 nm. The magnetization analyses showed that the particles are superparamagnetic at room temperature. Aqueous magnetic fluids of the synthesized nanoparticles were examined in vitro concerning Gram-positive (Staphylococcus aureus MSCL 334, Bacillus cereus MSCL 330) and Gram-negative (Escherichia coli MSCL 332, Pseudomonas aeruginosa MSCL 331, Proteus mirabilis MSCL 590) bacterial strains and fungi (Candida albicans MSCL 378, Aspergillus niger MSCL 324). It was found that the samples have magnetic properties and possess antimicrobial activity. The minimum inhibitory concentration against S. aureus for the most active magnetic fluid was determined as 16 μg ml^-1

Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice

Hepatic stellate cells (HSCs) drive hepatic fibrosis. Therapies that inactivate HSCs have clinical potential as antifibrotic agents. We previously identified acid ceramidase (aCDase) as an antifibrotic target. We showed that tricyclic antidepressants (TCAs) reduce hepatic fibrosis by inhibiting aCDase and increasing the bioactive sphingolipid ceramide. We now demonstrate that targeting aCDase inhibits YAP/TAZ activity by potentiating its phosphorylation-mediated proteasomal degradation via the ubiquitin ligase adaptor protein β-TrCP. In mouse models of fibrosis, pharmacologic inhibition of aCDase or genetic knockout of aCDase in HSCs reduces fibrosis, stromal stiffness, and YAP/TAZ activity. In patients with advanced fibrosis, aCDase expression in HSCs is increased. Consistently, a signature of the genes most down-regulated by ceramide identifies patients with advanced fibrosis who could benefit from aCDase targeting. The findings implicate ceramide as a critical regulator of YAP/TAZ signaling and HSC activation and highlight aCDase as a therapeutic target for the treatment of fibrosis