Small-molecule inhibitor of OGG1 suppresses pro-inflammatory gene expression and inflammation

The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor κB and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo

Optical Characterization of SERS Substrates Based on Porous Au Films Prepared by Pulsed Laser Deposition

The SERS (surface enhanced Raman spectroscopy) substrates based on nanocomposite porous films with gold nanoparticles (Au NPs) arrays were formed using the method of the pulsed laser deposition from the back low-energy flux of erosion torch particles on the glass substrate fixed at the target plain. The dependencies of porosity, and morphology of the surface of the film regions located near and far from the torch axis on the laser ablation regime, laser pulses energy density, their number, and argon pressure in the vacuum chamber, were ascertained. The Au NPs arrays with the controllable extinction spectra caused by the local surface plasmon resonance were prepared. The possibility of the formation of SERS substrates for the detection of the Rhodamine 6G molecules with the concentration 10−10 Mol/L with the enhancement factor 4·107 was shown