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BackgroundIn this study, a hydrogel comprising poly (vinyl alcohol)/pectin (PVA/PET) was prepared by the addition of Melia azedarach extract for epithelial restoration. M. azedarach extract (MAE) contains volatile organic plant-derived compounds with antimicrobial properties. MAE has a variety of physiological properties, including antimicrobial, insecticidal, and anti-inflammatory activity. This study aimed to investigate whether MAE-loaded PVA/PET hydrogels have protective effects against burn wound healing.Methods and findingsTo mix M. azedarach with the gel, nanoparticles containing M. azedarach were prepared using chitosan/maltodextrin as the wall material. A PVA/PET hydrogel containing M. azedarach was developed and its applicability as a wound dressing was evaluated. In the in vitro scratch assay, MAE treatment showed a scratch recovery-promoting effect comparable to that of the positive control TGF-β1. The MAE-PVA/PET hydrogel was found to be non-toxic, and the antibacterial activity of the hydrogel was excellent against both gram-positive and gram-negative bacteria. Furthermore, as the formulated hydrogel demonstrated strong antimicrobial activity, its wound-healing efficacy was investigated in vivo using a rat model.ConclusionMAE was found to be effective against burn wounds and to have antimicrobial activity in vitro and in vivo.

The mechanisms by which mutations of the purinergic housekeeping gene hypoxanthine guanine phosphoribosyltransferase (HPRT) cause the severe neurodevelopmental Lesch Nyhan Disease (LND) are poorly understood. The best recognized neural consequences of HPRT deficiency are defective basal ganglia expression of the neurotransmitter dopamine (DA) and aberrant DA neuronal function. We have reported that HPRT deficiency leads to dysregulated expression of multiple DA-related developmental functions and cellular signaling defects in a variety of HPRT-deficient cells, including human induced pluripotent stem (iPS) cells. We now describe results of gene expression studies during neuronal differentiation of HPRT-deficient murine ESD3 embryonic stem cells and report that HPRT knockdown causes a marked switch from neuronal to glial gene expression and dysregulates expression of Sox2 and its regulator, genes vital for stem cell pluripotency and for the neuronal/glial cell fate decision. In addition, HPRT deficiency dysregulates many cellular functions controlling cell cycle and proliferation mechanisms, RNA metabolism, DNA replication and repair, replication stress, lysosome function, membrane trafficking, signaling pathway for platelet activation (SPPA) multiple neurotransmission systems and sphingolipid, sulfur and glycan metabolism. We propose that the neural aberrations of HPRT deficiency result from combinatorial effects of these multi-system metabolic errors. Since some of these aberrations are also found in forms of Alzheimer's and Huntington's disease, we predict that some of these systems defects play similar neuropathogenic roles in diverse neurodevelopmental and neurodegenerative diseases in common and may therefore provide new experimental opportunities for clarifying pathogenesis and for devising new potential therapeutic targets in developmental and genetic disease.

Pseudomonas aeruginosa, a gram-negative bacterium of clinical importance, forms more robust biofilm during anaerobic respiration, a mode of growth presumed to occur in abnormally thickened mucus layer lining the cystic fibrosis (CF) patient airway. However, molecular basis behind this anaerobiosis-triggered robust biofilm formation is not clearly defined yet. Here, we identified a morphological change naturally accompanied by anaerobic respiration in P. aeruginosa and investigated its effect on the biofilm formation in vitro. A standard laboratory strain, PAO1 was highly elongated during anaerobic respiration compared with bacteria grown aerobically. Microscopic analysis demonstrated that cell elongation likely occurred as a consequence of defective cell division. Cell elongation was dependent on the presence of nitrite reductase (NIR) that reduces nitrite (NO(2) (-)) to nitric oxide (NO) and was repressed in PAO1 in the presence of carboxy-PTIO, a NO antagonist, demonstrating that cell elongation involves a process to respond to NO, a spontaneous byproduct of the anaerobic respiration. Importantly, the non-elongated NIR-deficient mutant failed to form biofilm, while a mutant of nitrate reductase (NAR) and wild type PAO1, both of which were highly elongated, formed robust biofilm. Taken together, our data reveal a role of previously undescribed cell biological event in P. aeruginosa biofilm formation and suggest NIR as a key player involved in such process.

Biological networks change dynamically as protein components are synthesized and degraded. Understanding the time-dependence and, in a multicellular organism, tissue-dependence of a network leads to insight beyond a view that collapses time-varying interactions into a single static map. Conventional algorithms are limited to analyzing evolving networks by reducing them to a series of unrelated snapshots.Here we introduce an approach that groups proteins according to shared interaction patterns through a dynamical hierarchical stochastic block model. Protein membership in a block is permitted to evolve as interaction patterns shift over time and space, representing the spatial organization of cell types in a multicellular organism. The spatiotemporal evolution of the protein components are inferred from transcript profiles, using Arabidopsis root development (5 tissues, 3 temporal stages) as an example.The new model requires essentially no parameter tuning, out-performs existing snapshot-based methods, identifies protein modules recruited to specific cell types and developmental stages, and could have broad application to social networks and other similar dynamic systems.