Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats

Background: Metabolic syndrome (coexisting visceral obesity, dyslipidemia, hyperglycemia, and hypertension) is a prominent risk factor for cardiovascular morbidity and mortality, however, its effect on cardiac gene expression pattern is unclear. Therefore, we examined the possible alterations in cardiac gene expression pattern in male Zucker Diabetic Fatty (ZDF) rats, a model of metabolic syndrome. Methods: Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were measured at 6, 16, and 25 wk of age in male ZDF and lean control rats. Oral glucose tolerance test was performed at 16 and 25 wk of age. At week 25, total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 14921 genes. Expression of selected genes was confirmed by qRT-PCR. Results: Fasting blood glucose, serum insulin, cholesterol and triglyceride levels were significantly increased, glucose tolerance and insulin sensitivity were impaired in ZDF rats compared to leans. In hearts of ZDF rats, 36 genes showed significant up-regulation and 49 genes showed down-regulation as compared to lean controls. Genes with significantly altered expression in the heart due to metabolic syndrome includes functional clusters of metabolism (e.g. 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2; argininosuccinate synthetase; 2-amino-3ketobutyrate-coenzyme A ligase), structural proteins (e.g. myosin IXA; aggrecan1), signal transduction (e. g. activating transcription factor 3; phospholipase A2; insulin responsive sequence DNA binding protein-1) stress response (e.g. heat shock 70kD protein 1A; heat shock protein 60; glutathione S-transferase Yc2 subunit), ion channels and receptors (e.g. ATPase, (Na+)/K+ transporting, beta 4 polypeptide; ATPase, H+/K+ transporting, nongastric, alpha polypeptide). Moreover some other genes with no definite functional clusters were also changed such as e. g. S100 calcium binding protein A3; ubiquitin carboxy-terminal hydrolase L1; interleukin 18. Gene ontology analysis revealed several significantly enriched functional inter-relationships between genes influenced by metabolic syndrome. Conclusions: Metabolic syndrome significantly alters cardiac gene expression profile which may be involved in development of cardiac pathologies in the presence of metabolic syndrome

Bacterial Models for Tumor Development

The tumor-inducing effects of Agrobacterium, Bartonella and Helicobacter bacterial species are compared step by step. An analogy for the existence of these individual steps is considered in connection with the development of cancer. The transformations of eukaryotic cells occur in particular in the type IV secretion system, i.e. involving the simultaneous transmission of DNA and protein from bacterial cells to eukaryotic cells. Thus, transfected cells facilitate the indefinite growth of tissue cells and additionally produce growth factors, triggering further bacterial multiplication. The higher numbers of bacteria then produce more transfection and the cycle repeats as long as the host lives. The main limiting factor is the frequency of bacterial infection, while the secondary rate-limiting factors are the levels of transforming growth factors and factors triggering bacteria growth. Conclusions: Analogous processes are probably responsible for the tumor induction by the three different bacterial species; however, the critical points for eradication are different. The early eradication or limitation of B. henselae or H. pylori can prevent hemangiomas, stomach cancer and malignant cell proliferation. The crown gall formation by A. tumefaciens can only be avoided by prevention of the transforming activity of a single bacterial infection. Questions arise as to what is common in the three processes, and the nature of the rate-limiting step in the three different models. The frequency of transformation is the rate-limiting step, but the co-transmission of the DNA-protein complex is common in the three systems

In vitro search for synergy between flavonoids and epirubicin on multidrug-resistant cancer cells

The drug accumulation of a human multidrug resistance 1 (mdr1) gene-transfected mouse lymphoma cell line and a multidrug resistance protein (MRP)-expressing human breast cancer cell line MDA-MB-231 was compared in the presence of sixteen flavonoids and five isoflavonoids. The expression of the 170-kDa P-glycoprotein (P-gp) (MDR1) and 190-kDa multidrug resistance protein (MRP) in both cell lines was confirmed by immunocytochemistry. The rhodamine 123 accumulation of the P-glycoprotein (P-gp) -expressing cells increased up to 46.4, while 2,' 7 '-bis(2-carboxyethyl)-5(6)carboxy-fluorescein acetoxymethyl ester (BCECF-AM) accumulation of the MRP-expressing cells increased up to 1.6, in fluorescence activity ratio (FAR). Major P-gp-mediated efflux pump modifiers are formononetin, amorphigenin, rotenone and chrysin, while MRP-mediated efflux pump modifiers are formononetin, afrormosin, robinin, kaempferol and epigallocatechin. In antiproliferative assay, afrormosin, amorphigenin, chrysin and rotenone exhibited the strongest antiproliferative effects in L5178 (max. ID50: 19.70) and MDA-MB-231 cell lines (max. ID50: 55.47). In a checkerboard microplate method in vitro, furthermore, the most effective multidrug resistance (MDR) resistance modifiers, amorphigenin, formononetin, rotenone and chrysin, were assayed for their antiproliferative effects in combination with epirubicin. Rotenone and afrormosin showed additive effects. Chrysin and amorphigenin on the mouse lymphoma cell line and formononetin on the MDA-MB-231 cell line synergistically enhanced the effect of epirubicin

Carotenoid composition and in vitro pharmacological activity of rose hips

The aim of the present study was to compare carotenoid extracts of Rose hips (Rosa canina L.) with regard to their phytochemical profiles and their in vitro anti-Helicobacter pylori (H. pylori), cytotoxic, multidrug resistance (MDR) reversal and radical scavenging activity. Carotenoid composition was investigated in the different fractionation of rose hips, using extraction methods. Six main carotenoids - epimers of neochrome, lutein, zeaxanthin, rubixanthin, lycopene, β,β-carotene - were identified from Rose hips by their chromatographic behavior and UV-visible spectra, which is in accordance with other studies on carotenoids in this plant material. The active principles in the carotenoid extract might differ, depending upon the extraction procedures