題目：
High-glucose environment enhanced oxidative stress and increased interleukin-8 secretion from keratinocytes: new insights into impaired diabetic wound healing
作者：Lan CC, Wu CS, Huang SM, Wu IH, Chen GS. Diabetes. 2013 Jul;62(7):2530-8. doi: 10.2337/db12-1714. Epub 2013 Feb 19.
摘要：
Impaired wound healing frequently occurs in patients with diabetes. Interleukin (IL)-8 production by keratinocyte is responsible for recruiting neutrophils during healing. Intense inflammation is associated with diabetic wounds, while reduction of neutrophil infiltration is associated with enhanced healing. We hypothesized that increased neutrophil recruitment by keratinocytes may contribute to the delayed healing of diabetic wounds. Using cultured human keratinocytes and a diabetic rat model, the current study shows that a high-glucose environment enhanced IL-8 production via epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) pathway in a reactive oxygen species (ROS)-dependent manner in keratinocytes. In addition, diabetic rat skin showed enhanced EGFR, ERK, and IL-8 expression compared with control rats. The dermal neutrophil infiltration of the wound, as represented by expression of myeloperoxidase level, was also significantly higher in diabetic rats. Treating diabetic rats with dapsone, an agent known to inhibit neutrophil function, was associated with improved healing. In conclusion, IL-8 production and neutrophil infiltration are increased in a high-glucose environment due to elevated ROS level and contributed to impaired wound healing in diabetic skin. Targeting these dysfunctions may present novel therapeutic approaches.
題目：
The copolymer of Poly(2-dimethylaminoethyl methacrylate) and methacrylated chondroitin sulfate with low cytotoxicity for gene delivery
作者：Lo YL, Wang YS, Wang LF. Adv Healthc Mater. 2013 Nov;2(11):1458-68. doi: 10.1002/adhm.201200373. Epub 2013 Apr 25.
摘要：
Poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) is one of the most potent synthetic nonviral gene-delivery vectors because of its high transfection efficiency. However, the cytotoxicity of PDMAEMA is a major concern for its clinical applications. An anionic crosslinker is synthesized based on a natural polysaccharide, chondroitin sulfate (CS), by introducing methacrylate groups (CSMA). By systematically adjusting the substitution degree of methacrylation on CS and the weight percent of CSMA and PDMAEMA, sol-type copolymers are obtained as a gene-delivery vector. The combination of CS and PDMAEMA is expected not only to reduce the cytotoxicity of PDMAEMA, but also to facilitate better transfection efficiency than PDMAEMA because of the recognition of CS by CD44 receptors on cell surfaces. Two CSMA-modified PDMAEMA copolymers with different CSMA constituents are selected and their polyplexes prepared with plasmid DNA. The cytotoxicity and gene transfection efficiency of the polyplexes are tested and compared with those of PDMAEMA/pDNA. The copolymers of CSMA and PDMAEMA show significantly improved cell viability as compared with PDMAEMA. Their formed polyplexes with pDNA also show lower cytotoxicity than does PDMAEMA/pDNA. The transfection efficiency remarkably increases as the CSMA-modified PDMAEMA/pDNA polyplex is prepared at a weight ratio of 2.4. The internalization mechanism of CSMA-modified PDMAEMA/pDNA in HEK 293T cells is mainly based on caveolae-mediated endocytosis. However, both caveolae-mediated and CD44-mediated endocytosis mechanisms are involved in U87 cells.
