Direct ingestion method for enhancing production and bioavailability of resveratrol and other phytoalexins in Vitis vinifera.

Phytoalexins such as resveratrol and pterostilbene, produced de novo by many plant species, including grapevine (Vitis vinifera), play a role in plant defense against injury and pathogens. In human cell lines and in animal studies, phytoalexins have been shown to be highly beneficial, with protective effects against cancer, cardiovascular disease, neurodegenerative diseases, diabetes, hyperglycemia, as well as potential effects on longevity. However, in clinical studies, there are multiple factors that restrict this plethora of health benefits attributed to phytoalexins. One of these barriers is rapid metabolism in the intestines and liver. As a means to overcome this barrier, there is evidence that retaining resveratrol in the mouth for extended periods allows for higher plasma levels of resveratrol. Processing, transport or storage may cause degradation due to light and air exposure. When the berries have been picked, they may not be at their peak phytoalexin production due to lack of elicitor induction. To overcome these barriers inherent in phytoalexin production and uptake, it is proposed that berries and possibly the edible leaves be directly ingested off of a grapevine, without harvesting. In addition to the benefit of removing these barriers to potential health benefits, this method introduces a variety of known phytoalexin elicitors, in the form of plant wounding and human saliva, which may enhance the levels of phytoalexins dramatically. The combined effect of multiple phytoalexins may also play a role in enhanced health benefits. To test this hypothesis, experiments with direct ingestion would be performed, followed by testing the participants' plasma levels of resveratrol and potentially other phytoalexins. Proposed variables to be tested include: different subjects, elicitors, cultivars of grapevine, ripeness of fruit, and a range of time for the ingestion process. The potential implications include a direct means of obtaining, in clinically beneficial doses, the tremendous health benefits that have been documented for phytoalexins in vitro and in animal studies, but that have so far remained elusive in clinical studies. This study on direct ingestion may lead to alternative methods for obtaining these clinically beneficial doses.

New insights into ADPKD molecular pathways using combination of SAGE and microarray technologies.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 or PKD2 gene, but cellular mechanisms of cystogenesis remain unclear. In an attempt to display the array of cyst-specific molecules and to elucidate the disease pathway, we have performed comprehensive high-throughput expression analysis of normal and ADPKD epithelia in a two-step fashion. First, we generated expression profiles of normal and cystic epithelia derived from kidney and liver using serial analysis of gene expression (SAGE). We found 472 and 499 differentially expressed genes with fivefold difference in liver and kidney libraries, respectively. These genes encode growth factors, transcription factors, proteases, apoptotic factors, molecules involved in cell-extracellular matrix interactions, and ion channels. As a second step, we constructed a custom cDNA microarray using a subset of the differentially regulated genes identified by SAGE and interrogated ADPKD patient samples. Subsequently, a set of differentially expressed genes was refined to 26 up-regulated and 48 down-regulated genes with ap value of <0.01. This study may provide valuable insights into the pathophysiology of ADPKD and suggest potential therapeutic targets.

Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism.

Oncogenic osteomalacia (OOM) is associated with primitive mesenchymal tumors that secrete phosphaturic factors resulting in low serum concentrations of phosphate and calcitriol, phosphaturia, and defective bone mineralization. To identify overexpressed genes in these tumors, we compared gene expression profiles of tumors resected from patients with OOM and histologically similar control tumors using serial analysis of gene expression (SAGE). Three hundred and sixty-four genes were expressed at least twofold greater in OOM tumors compared with control tumors. A subset of 67 highly expressed genes underwent validation with an extended set of OOM and control tumors using array analysis or reverse-transcription polymerase chain reaction (RT-PCR). Ten of these validated genes were consistently overexpressed in all OOM tumors relative to control tumors. Strikingly, genes with roles in bone matrix formation, mineral ion transport, and bone mineralization were highly expressed in the OOM tumors.