Diabetic foot ulcers (DFUs) are a significant health problem. A single existing FDA-approved drug for this ailment, becaplermin, is not standard-of-care. We previously demonstrated that upregulation of active matrix metalloproteinase (MMP)-9 is the reason that the diabetic wound in mice is recalcitrant to healing and that MMP-8 participates in wound repair. In the present study, we validate the target MMP-9 by identifying and quantifying active MMP-8 and MMP-9 in human diabetic wounds using an affinity resin that binds exclusively to the active forms of MMPs coupled with proteomics. Furthermore, we synthesize and evaluate enantiomerically pure ( R)- and ( S)-ND-336, as inhibitors of the detrimental MMP-9, and show that the ( R)-enantiomer has superior efficacy in wound healing over becaplermin. Our results reveal that the mechanisms of pathology and repair are similar in diabetic mice and diabetic humans and that ( R)-ND-336 holds promise for the treatment of DFUs as a first-in-class therapeutic.

Impurity diffusion in -Ti and -Zr is characterized by fast interstitial diffusion of small atoms and slow substitutional diffusion of large atoms. The mechanism of the fast diffusion is discussed on the basis of the several features: the effect of -phase transformation, the diffusion anisotropy, the atomic size effect and the correlation between solubility and diffusivity. The temperature dependence of the diffusion coefficients of all the solutes and solvent Ti studied in -Ti follows the Arrhenius law, whereas in -Zr, all the elements studied with exception of Ti show downward curvatures that follow the self-diffusion behaviour in -Zr. The influence of ultra-fast diffusion impurities on the diffusion process in these matrices, as well as the possibility that different mechanism acts in each matrix is analyzed.

Mitochondria targeting nanoGUMBOS were successfully fabricated based on self-assembly of IR780 GUMBOS with different counter-anions that show promising anticancer effects.

The use of quartz crystal microbalance (QCM) sensor arrays for analyses of volatile organic compounds (VOC) has attracted significant interest in recent years. In this regard, a group of uniformed materials based on organic salts (GUMBOS) has proven to be promising recognition elements in QCM based sensor arrays due to diverse properties afforded by this class of tunable materials. Herein, we examine the application of four novel phthalocyanine based GUMBOS as recognition elements for VOC sensing using a QCM based multisensor array (MSA). These synthesized GUMBOS are composed of copper (II) phthalocyaninetetrasulfonate (CuPcS) anions coupled with ammonium or phosphonium cations respectively (tetrabutylammonium (TBA), tetrabutylphosphonium (P), 3-(dodecyldimethyl-ammonio)propanesulfonate (DDMA), and tributyl-n-octylphosphonium (P)). These materials were characterized using ESI-MS and FTIR, while thermal properties were investigated using TGA. Vapor sensing properties of these GUMBOS towards a set of common VOCs at three sample flow rate ratios were examined. Upon exposure to VOCs, each sensor generated analyte specific response patterns that were recorded and analyzed using principal component and discriminant analyses. Use of this MSA allowed discrimination of analytes into different functional group classes (alcohols, chlorohydrocarbons, aromatic hydrocarbons, and hydrocarbons) with 98.6% accuracy. Evaluation of these results provides further insight into the use of phthalocyanine GUMBOS as recognition elements for QCM-based MSAs for VOC discrimination.

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