Homocysteine and vitamin therapy in stroke prevention and treatment: a review.

Homocysteine (Hcy), a sulfur amino acid, is the only direct precursor for L-methionine synthesis through a reaction that requires vitamin B12, representing a connection with "one-carbon" units metabolism. Hcy catabolism requires vitamin B6 and as a consequence, alteration in folic acid and B vitamins status impairs Hcy biotransformation. Numerous studies have indicated that Hcy is an independent risk factor for cardio- and cerebrovascular diseases. In the last decade, several clinical trials have investigated the possible correlation between the use of folic acid and vitamins B6 and B12 for lowering Hcy plasma concentration and the reduced risk of stroke or its recurrence. This review is aimed to present some aspects of Hcy biochemistry, as well as the mechanisms through which it exerts the toxic effects on the vascular endothelium. We also discuss the results of some of the clinical trials developed to investigate the beneficial effects of vitamin therapy in the prevention and management of stroke.

Natural compounds and the hypoxia-inducible factor (HIF) signalling pathway.

A decline in the tissue oxygen level below normal leads to cellular hypoxia. This situation is very frequently encountered in solid tumors as existing blood vessels cannot satisfy the requirements in oxygen of the rapidly growing tumor. Like hyperoxia, hypoxia is a stress factor for cells and tissues. Adapting to this stressful situation leads to activation of the dimeric transcription factor hypoxia-inducible factor-1 (HIF-1) that induces gene expression in promoting tumor cell survival. In addition, hypoxia acts as a selection factor for radio- and chemotherapy resistant tumor cells with a high potential of malignancy. Consequently, over expression of the HIF-1alpha subunit is associated with an advanced disease stage and poor prognosis of cancer patients. During the last few years intense effort has been made in investigating natural compounds that can be used as HIF-1 inhibitors. These compounds aim to suppress tumor hypoxia and to increase the susceptibility of tumor cells to radio- and chemo-therapy. In this review we summarize recent findings concerning HIF-1 regulation and present a survey of HIF-1 inhibiting natural compounds that have been discovered in the last few years.