Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1–4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial–mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.
Bacterial infections are the key cause of death in patients suffering from burns and diabetic wounds while the use of traditional antibiotics has been growing steadily. Thus, in the present study, we are trying to introduce a paradigm shift strategy to improve chronic wound healing of bacterial infection. To that end, we have biologically synthesized silver nanoparticles (AgNPs) using Arthrospira sp polysaccharides, and evaluated their antibacterial efficacy with their safety pattern. Scanning electron micrographs showed spherical AgNPs coated with algal polysaccharides with an approximate size of 9.7 nm. Treatment of Pseudomonas aeruginosa with the AgNPs (0.5–1 μg/mL) resulted in a significant disruption in P. aeruginosa outer membrane, reduction in biofilm formation, and a significant decrease of production of alginate and pyocyanin along with a concentration-dependent reduction in β-lactamase activity. In addition, at the in vivo level, AgNPs displayed substantial activity to control P. aeruginosa infections in rat skin wounds with significant reduction in in COX-2 enzyme in both rat skin homogenate and serum samples. Furthermore, AgNPs facilitated wound curative in the P. aeruginosa infected model by reducing the hemorrhagic areas number and the infiltrated inflammatory cells. Taken all together, these biogenic nanoparticles showed unique properties in controlling bacterial wound infections and improving the healing process of damaged tissues via its direct and indirect effects.
1 March 2020 in International Journal of Biological Macromolecules