effect of the daily ingestion of a purified anthocyanin extract from grape skin on rat serum antioxidant capacity

The aim of this work was to study the effect of the daily ingestion of a purified anthocyanin extract from red grape skin on rat serum antioxidant capacity (ORAC) and its safety for the intestinal epithelium. The study was carried out in rats orally administered with the extract for 10 days in either normal physiological conditions or exposed to a pro-oxidant chemical (CCl4). The oral administration of the extract significantly (P<0.05) enhanced the ORAC value of the deproteinised serum of about 50 % after 10 days of ingestion. Anthocyanin administration was also able to reverse completely the decrease in the serum ORAC activity induced by the CCl4 treatment. Experiments with Ussing chamber mounted intestine allowed to exclude any toxicity of the extract for the intestinal epithelium. In conclusion, our results demonstrate that the purified anthocyanin extract from red grape skin enhances the total antioxidant capacity of the serum in either normal physiological condition or during oxidative stress induction, revealing a protective role against the decrease in the serum antioxidant capacity induced by a pro-oxidant compound

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression

Tumour-associated angiogenesis is partly regulated by the hypoxia-inducible factor (HIF) pathway. Endocrine tumours are highly vascularised and the molecular mechanisms of their angiogenesis are not fully delineated. The aim of this study is to evaluate angiogenesis and expression of HIF-related molecules in a series of patients with pancreatic endocrine tumours (PETs). The expression of vascular endothelial growth factor (VEGF), HIF-1α, HIF-2α and carbonic anhydrase 9 (CA9) was examined by immunohistochemistry in 45 patients with PETs and compared to microvascular density (MVD), endothelial proliferation, tumour stage and survival. Microvascular density was very high in PETs and associated with a low endothelial index of proliferation. Microvascular density was significantly higher in benign PETs than in PETs of uncertain prognosis, well-differentiated and poorly differentiated carcinomas (mean values: 535, 436, 252 and 45 vessels mm−2, respectively, P<0.0001). Well-differentiated tumours had high cytoplasmic VEGF and HIF-1α expression. Poorly differentiated carcinomas were associated with nuclear HIF-1α and membranous CA9 expression. Low MVD (P=0.0001) and membranous CA9 expression (P=0.0004) were associated with a poorer survival. Contrary to other types of cancer, PETs are highly vascularised, but poorly angiogenic tumours. As they progress, VEGF expression is lost and MVD significantly decreases. The regulation of HIF signalling appears to be specific in pancreatic endocrine tumours

Effectiveness of alpha-fetoprotein for hepatocellular carcinoma surveillance: the return of the living-dead?

The evaluated article assesses the effectiveness in clinical practice of surveillance with ultrasound (US) and \u3b1-fetoprotein (AFP) in patients at risk of developing hepatocellular carcinoma. After a median follow-up of 3.5 years, among the 442 enrolled patients with cirrhosis, 41 developed tumor (annual incidence, 2.8%). Twenty-three hepatocellular carcinomas were diagnosed at Barcelona Clinic Liver Cancer early stage (single tumor 20\u2009ng/ml. Specificity was 91.5% for US and 90.5% for AFP. The combination of the tests increased the sensitivity to 90.2%, with a small decrease in specificity (83.3%). In a real-world setting, the combination of US and AFP would be the most effective for hepatocellular carcinoma surveillance

Chromosome 5 allele loss in human gastric, ampullary and pancreatic carcinomas

Chromosome 5 allele loss is a genetic alteration occurring during the multistep progression of colon carcinogenesis. To determine whether a similar genetic alteration occurs in other gastrointestinal malignancies, the authors have analyzed DNA extracted from freshly frozen normal and neoplastic tissue from nineteen patients who underwent radical resections for gastric, ampullary and pancreatic adenocarcinomas at the University of Chicago. Loss of heterozygosity for alleles on the long arm of chromosome 5 was detected in tumor DNA compared to normal tissue DNA from the same patient using restriction fragment length polymorphisms (RFLPs). Eleven patients were informative using the restriction endonuclease TaqI to generate RFLPs for chromosome 5 probes C11 P11 and pTP5E. Loss of heterozygosity was found in one of eight informative gastric carcinomas (12.5%) and in one of two informative ampullary carcinomas. The only informative pancreatic adenocarcinoma was heterozygous. It is concluded that chromosome 5 allele loss occurs in a variety of gastrointestinal malignancies and suggest that common genetic origins may underlie these different tumors