Edited by Varda RotterKeywords: p53 p73 Protoporphyrin IX Photodynamic therapy Fluorescent band shift Fluorescence polarization a b s t r a c tThe p53 tumor suppressor is recognized as a promising target for anti-cancer therapies. We previously reported that protoporphyrin IX (PpIX) disrupts the p53/murine double minute 2 (MDM2) complex and leads to p53 accumulation and activation of apoptosis in HCT 116 cells. Here we show the direct binding of PpIX to the N-terminal domain of p53. Furthermore, we addressed the induction of apoptosis in HCT 116 p53-null cells by PpIX and revealed interactions between PpIX and p73. We propose that PpIX disrupts the p53/MDM2 or MDMX and p73/MDM2 complexes and thereby activates the p53-or p73-dependent cancer cell death.

BackgroundScopoletin and its glucoside scopolin are important secondary metabolites synthesized in plants as a defense mechanism against various environmental stresses. They belong to coumarins, a class of phytochemicals with significant biological activities that is widely used in medical application and cosmetics industry. Although numerous studies showed that a variety of coumarins occurs naturally in several plant species, the details of coumarins biosynthesis and its regulation is not well understood. It was shown previously that coumarins (predominantly scopolin and scopoletin) occur in Arabidopsis thaliana (Arabidopsis) roots, but until now nothing is known about natural variation of their accumulation in this model plant. Therefore, the genetic architecture of coumarins biosynthesis in Arabidopsis has not been studied before.ResultsHere, the variation in scopolin and scopoletin content was assessed by comparing seven Arabidopsis accessions. Subsequently, a quantitative trait locus (QTL) mapping was performed with an Advanced Intercross Recombinant Inbred Lines (AI-RILs) mapping population EstC (Est-1 × Col). In order to reveal the genetic basis of both scopolin and scopoletin biosynthesis, two sets of methanol extracts were made from Arabidopsis roots and one set was additionally subjected to enzymatic hydrolysis prior to quantification done by high-performance liquid chromatography (HPLC). We identified one QTL for scopolin and five QTLs for scopoletin accumulation. The identified QTLs explained 13.86% and 37.60% of the observed phenotypic variation in scopolin and scopoletin content, respectively. In silico analysis of genes located in the associated QTL intervals identified a number of possible candidate genes involved in coumarins biosynthesis.ConclusionsTogether, our results demonstrate for the first time that Arabidopsis is an excellent model for studying the genetic and molecular basis of natural variation in coumarins biosynthesis in plants. It additionally provides a basis for fine mapping and cloning of the genes involved in scopolin and scopoletin biosynthesis. Importantly, we have identified new loci for this biosynthetic process.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-014-0280-9) contains supplementary material, which is available to authorized users.

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Stroke is one of the most devastating neurological conditions, with an approximate worldwide mortality of 5.5 million annually and loss of 44 million disability-adjusted life-years. The etiology of stroke is often unknown; it has been estimated that the etiology and pathophysiology remains unexplained in more than 40% of stroke cases. The conventional stroke risk factors, including hypertension, diabetes mellitus, smoking, and cardiac diseases, do not fully account for the risk of stroke, and stroke victims, especially young subjects, often do not have any of these factors. It is very likely that inflammation, specific genetic predispositions and traditional risk factors interact with each other and may together increase the risk of stroke. Inflammatory and immune responses play important roles in the course of ischemic stroke. Hyperhomocysteinemia (hcy) is considered a modifiable risk factor for stroke, possibly through an atherogenic and prothrombotic mechanism. Both genetic and environmental factors (e.g., dietary intake of folic acid and B vitamins) affect homocysteine level. Identification of the role of hcy as a modifiable risk factor for stroke and of HSPs as regulators of the immune response may lead to more effective prevention and treatment of stroke through dietary and pharmacological intervention. Dietary modification may also include supplementation with novel preventive compounds, such as the antioxidative isoflavones -genistein or daidzein.

Ischemic stroke is the second leading cause of death worldwide. One of the main risk factors of the ischemic stroke is atherosclerosis which is a chronic inflammatory and immune-mediated disease. Bacterial infections generate specific human antibodies against various antigens, including Hsps. It has been demonstrated that Hsps are selectively overexpressed in the atherosclerotic lesions. The amino acid sequence homology between human and bacterial Hsps may lead to an autoimmune response by immunological cross-reaction. Such immune response against Hsps overexpressed in the blood vessels under stressful conditions may contribute to inflammatory processes and subsequent development of atherosclerosis. In this study we determined the antibody levels against bacterial and human Hsp by ELISA in blood plasma obtained from stroke patients. Using ANOVA we analyzed levels of Hsp-antibodies in control and patient groups and correlate them with several stroke risk factors. The group of stroke patients had elevated levels of anti-Hsp antibodies compared to the control group. We also discovered an antibody level increase in patients that previously underwent another stroke. Our data provide evidence that autoimmunity could underlie formation of atherosclerosis plaque leading to stroke. Abbreviations: ANOVA, analysis of variance statistical test; ELISA, enzyme-linked immunosorbent assay; Hsp, heat shock protein; JDP, J-domain protein

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Recent clinical research has pointed at hyperhomocysteinemia as an independent risk factor in a number of cardiovascular and neurological diseases. We have improved a chromatographic method of total plasma homocysteine measurements in order to obtain higher sensitivity, reliability and reproducibility. The method demonstrates excellent linearity (R=0.999), range (

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