Glycine-functionalized copper(ii) hydroxide nanoparticles with high intrinsic superoxide dismutase activity.

Superoxide dismutases (SOD) are a group of enzymes that catalyze the dismutation of superoxide (O2-) radicals into molecular oxygen (O2) and H2O2 as a first line of defense against oxidative stress. Here, we show that glycine-functionalized copper(ii) hydroxide nanoparticles (Gly-Cu(OH)2 NPs) are functional SOD mimics, whereas bulk Cu(OH)2 is insoluble in water and catalytically inactive. In contrast, Gly-Cu(OH)2 NPs form water-dispersible mesocrystals with a SOD-like activity that is larger than that of their natural CuZn enzyme counterpart. Based on this finding, we devised an application where Gly-Cu(OH)2 NPs were incorporated into cigarette filters. Cigarette smoke contains high concentrations of toxic reactive oxygen species (ROS, >1016 molecules per puff) including superoxide and reactive nitrogen species which lead to the development of chronic and degenerative diseases via oxidative damage and subsequent cell death. Embedded in cigarette filters Gly-Cu(OH)2 NPs efficiently removed ROS from smoke, thereby protecting lung cancer cell lines from cytotoxic effects. Their stability, ease of production and versatility make them a powerful tool for a wide range of applications in environmental chemistry, biotechnology and medicine.

Transcriptional regulation of the VEGF gene in dependence of individual genomic variations.

Overexpression of the vascular endothelial growth factor (VEGF) gene has been associated with advanced stage and poor survival in several cancers. The majority of disease-associated VEGF-single nucleotide polymorphisms (SNPs) locate within regulatory regions. Therefore, an influence of SNPs located in the promoter/5'-untranslated region (5'UTR) on transcription factor binding (TFB) and gene expression seems feasible. We reviewed the literature investigating a potential connection of VEGF-SNPs and transcriptional regulation of the VEGF gene. In addition, we employed transcription factor databases to search for VEGF-SNPs which have already been associated with diseases. The objective of this review is to gain an overview about an association of VEGF-SNPs and the transcription factor dependent regulation of the VEGF gene. A decreasing binding specificity of the transcription factor MZF1 in presence of the VEGF-SNP +405 C-allele has been reported. TF databases indicated a potential HIF binding site for the -2578 C-allele representing an important potential inducer of VEGF expression. Additionally, linkage disequilibrium of the -2578 A-allele and an 18 bp insertion increases the number of potential TFB sites. For the VEGF promoter SNP -1154 A/G an interaction with the HRE under participation of the SNP +405 C/G was supposed. The comprehension of the association of specific SNPs and TFB could be an essential part in our understanding of individual differences of VEGF regulation and course of diseases.

Vascular endothelial growth factor polymorphisms as effect modifiers of oral squamous cell carcinoma risk: A systematic review and meta-analysis.

Smoking is one of the main risk factors for the development of oral squamous cell carcinoma (OSCC). Smoking may affect single-nucleotide polymorphism (SNP)-dependent vascular endothelial growth factor (VEGF)-induced angiogenic activity. Therefore, we systematically reviewed the published VEGF-SNP genotype data of OSCC patients and healthy individuals and performed a meta-analysis comparing the VEGF-SNP genotypes of smoking and non-smoking patients in association with OSCC incidence. Prospective and retrospective studies on the clinical comparison of OSCC patients with different VEGF-SNP genotypes were reviewed. The meta-analysis re-pooled studies of smoking and non-smoking OSCC patients with different VEGF-SNPs between 2006 and 2014. The identified articles were reviewed and those reporting pertinent information, assignment to smoking and non-smoking patient groups and sufficient data for estimation of an odds ratio (OR) with a 95% confidence interval (CI) were selected for the meta-analysis. Pooled ORs and CIs for the comparison of SNP distribution in the smoking and non-smoking subgroups were calculated and compared using the random-effects model. A total of 7 studies were included in the systematic review, which was followed by a meta-analysis using 3 pertinent studies. The reviewed studies reported discrepant findings, with differences between Asian and European patients. The meta-analysis demonstrated marginal but not statistically significant differences, suggesting that specific VEGF-SNPs may be OSCC risk modifiers for smokers, depending on the ethnic background. The performed meta-analysis suggested an increased OSCC risk for smokers carrying specific VEGF-genotypes, although the calculated data did not reach the level of significance. However, data have to be interpreted with caution due to the limited sample size. Therefore, further studies, including larger patient samples, are mandatory.