Selective degradation of histone deacetylase 8 mediated by a proteolysis targeting chimera (PROTAC).

We developed a first-in-class proteolysis targeting chimera (PROTAC) for selective degradation of histone deacetylase 8 (HDAC8). The PROTAC induced degradation of HDAC8 without affecting the levels of other HDACs in cellular assays, and inhibited the growth of T-cell leukemia Jurkat cells more potently than a conventional HDAC8 inhibitor.

Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors.

Fe(II)/α-ketoglutarate-dependent lysine demethylases (KDMs) are attractive drug targets for several diseases including cancer. In this study, we designed and screened ortho-substituted anilides that are expected to function as Fe(II) chelators, and identified ortho-hydroxy anilide as a novel scaffold for KDM5A inhibitors. Treatment of human lung cancer A549 cells with a prodrug form of 4-carboxy-2-hydroxy-formanilide (9c) increased trimethylated lysine 4 on histone H3 level, suggesting KDM5 inhibition in the cells.

In vitro evaluation of local antibiotic delivery via fibrin hydrogel.

BACKGROUND/PURPOSE: Fibrin hydrogel is commonly used as hemostatic agent and scaffold but it is questionable for carrying antibiotics. Thus, this study aimed to investigate whether the fibrin hydrogel can be used to deliver the optimal concentration of ciprofloxacin against oral pathogen. MATERIALS AND METHODS: The optimal concentration of ciprofloxacin was investigated from broth microdilution technique against three common oral bacteria. Ten times the bactericidal concentration of ciprofloxacin loaded to 0.4% fibrin hydrogel was observed by using a confocal laser scanning microscope and then was left in tris-buffer saline solution (TBS) for 0, 1, 12, 24, 72 and 168 h in parallel with the control group of ciprofloxacin loaded to 0.5% alginate hydrogel and ciprofloxacin solution. Spectrophotometer was used to analyze the accumulated drug release from the collected TBS, of which the measurement method was calibrated. The efficacy of the released ciprofloxacin was tested using an agar well diffusion assay. The inhibition zone of the released ciprofloxacin from fibrin hydrogel was statistically compared with 150 and 1500 µg/ml ciprofloxacin solution, while non-loaded fibrin hydrogel served as the control. RESULTS: The results revealed that minimum inhibitory concentration was 1-2 µg/ml and minimum bactericidal concentration was 4-15 µg/ml. The fibrin hydrogel gradually released ciprofloxacin until 168 h while the alginate hydrogel immediately liberated all the loaded ciprofloxacin within an hour. The agar well diffusion significantly showed greater clear zone in fibrin hydrogel loaded ciprofloxacin compared to non-loaded fibrin hydrogel but not with ciprofloxacin in TBS. CONCLUSION: The results suggested that fibrin hydrogel can be used for local ciprofloxacin delivery without interfering the efficacy of ciprofloxacin.

Eucalyptus ash alters secondary protein conformation of human grey hair and facilitates anthocyanin dyeing.

Wood ashes infused with water have been traditionally used as hair cosmetics, but little or no research has examined the effects of ash on human hair. This study investigated the effect of eucalyptus ash on the structure and morphology of excised human grey hair and its potential use as a pretreatment in natural hair dyeing using anthocyanins extracted from purple cops of Zea mays. Tensile characteristics and surface morphology of ash-pretreated hair was monitored by texture analysis, scanning electron microscopy and atomic force microscopy. The biochemical characteristics of ash-treated hair were analyzed by synchrotron radiation-FTIR and sulfur K-edge X-ray absorption near edge. Dyeing with anthocyanins was analyzed by Lab color scale and adsorption of anthocyanins. Ash-treated hair was elastically and plastically deformed with microscopic alterations to the ridges of the cuticle cells, similar to ammonia-treated hair. The ash extract significantly changed the relative proportion of alpha-helices in the cuticle and cortex layers (p < 0.05), but did not affect the interaction of S-bonds with neighboring atoms (p > 0.05). Ash-treated hair showed significantly enhanced adsorption of anthocyanins (p < 0.05) which changed the color of the grey hair. The alteration of secondary proteins in the cuticle and cortex layers of the grey hair by ash extract pre-treatment, enhanced anthocyanin adsorption. The eucalyptus ash could potentially be useful as a natural hair dyeing pre-treatment.