Color changing bioadhesive barrier for peripherally inserted central catheters.

Bacteria migration at catheter insertion sites presents a serious complication (bacteraemia) with high mortality rates. One strategy to mediate bacteraemia is a physical barrier at the skin-catheter interface. Herein a colorimetric biosensor adhesive (CathoGlu) is designed and evaluated for both colorimetric detection of bacterial infection and application as a bacteria barrier. The design intent combines viscous, hydrophobic bioadhesive with an organic pH indicator (bromothymol blue). Visual observation can then distinguish healthy skin at pH = ∼5 from an infected catheter insertion site at pH = ∼8. The liquid-to-biorubber transition of CathoGlu formulation occurs via a brief exposure to UVA penlight, providing an elastic barrier to the skin flora. Leachates from CathoGlu demonstrate no genotoxic and skin sensitization effect, assessed by OECD-recommended in vitro and in chemico assays. The CathoGlu formulation was found non-inferior against clinically approved 2-octyl-cyanoacrylate (Dermabond™), and adhesive tape (Micropore™) within an in vivo porcine model. CathoGlu skin adhesive provides new opportunities to prevent sepsis in challenging clinical situations.

H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions.

The mechanisms underlying gene repression and silencers are poorly understood. Here we investigate the hypothesis that H3K27me3-rich regions of the genome, defined from clusters of H3K27me3 peaks, may be used to identify silencers that can regulate gene expression via proximity or looping. We find that H3K27me3-rich regions are associated with chromatin interactions and interact preferentially with each other. H3K27me3-rich regions component removal at interaction anchors by CRISPR leads to upregulation of interacting target genes, altered H3K27me3 and H3K27ac levels at interacting regions, and altered chromatin interactions. Chromatin interactions did not change at regions with high H3K27me3, but regions with low H3K27me3 and high H3K27ac levels showed changes in chromatin interactions. Cells with H3K27me3-rich regions knockout also show changes in phenotype associated with cell identity, and altered xenograft tumor growth. Finally, we observe that H3K27me3-rich regions-associated genes and long-range chromatin interactions are susceptible to H3K27me3 depletion. Our results characterize H3K27me3-rich regions and their mechanisms of functioning via looping.

Synthesis and anticancer activity of certain mononuclear Ru (II) complexes.

Bis(1,10-phenanthroline/2,2'-bipyridine) ruthenium(II)complexes containing TCP, TTZ OPBI, and BTSC ligands (where, TCP = 1-thiocarbamoyl-3,5-diphenyl-2-pyrazoline, TTZ = 2-(3,5-diphenyl-4,5-dihydropyrazol-1-yl)-4-phenylthiazole, OPBI = 2-hydroxyphenyl benzimidazole and BTSC = benzoin thiosemicarbazone) have been prepared and characterized. The spectral data suggested that the ligands were coordinated with the metal through nitrogen, sulfur and oxygen atoms. The target complexes were tested in vivo for anticancer activity against transplantable murine tumor cell line, Ehrlich's Ascitic Carcinoma (EAC). All these complexes increased the life span of the EAC-bearing mice, decreased their tumor volume and viable ascitic cell count as well as improved Hb, RBC and WBC counts. These results suggest that the Ru(II) complexes exhibit significant antitumor activity in EAC-bearing mice. It was also observed that the ruthenium complexes protected red blood cells from 2,2'-azo-bis(2-methylpropionamidine) dihydrochloride (AAPH)- induced hemolysis. The inhibitory effect was dose-dependent at a concentration of 20-120 microg/ml.