Anthocyanin management in fruits by fertilization

Anthocyanins are water-soluble vacuolar plant pigments that are mainly synthesized in epidermal layers and the flesh of fruits such as apples, cherries, grapes, and other berries. Because of their attractive red to purple coloration and their health-promoting potential, anthocyanins are significant determinants for the quality and market value of fruits and fruit-derived products. In crops, anthocyanin accumulation in leaves can be caused by nutrient deficiency which is usually ascribed to insufficient nitrogen or phosphorus fertilization. However, it is a little-known fact that the plant’s nutrient status also impacts anthocyanin synthesis in fruits. Hence, strategic nutrient supply can be a powerful tool to modify the anthocyanin content and consequently the quality and market value of important agricultural commodities. Here we summarize the current knowledge of the influence of plant nutrients on anthocyanin synthesis in fruits of major global market value and discuss the underlying cellular processes that integrate nutrient signaling with fruit anthocyanin formation. It is highlighted that fertilization that is finely tuned in amount and timing has the potential to positively influence the fruit quality by regulating anthocyanin levels. We outline new approaches to enrich plant based foods with health-promoting anthocyanins

Locally applied Simvastatin improves fracture healing in mice

<p>Abstract</p> <p>Background</p> <p>HMG-CoA reductase inhibitors, statins, are widely prescribed to lower cholesterol. High doses of orally administered simvastatin has previously been shown to improve fracture healing in a mouse femur fracture model. In this study, simvastatin was administered either subcutaneously or directly to the fracture area, with the goal of stimulating fracture repair at acceptable doses.</p> <p>Methods</p> <p>Femur fractures were produced in 70 mature male Balb-C mice and stabilized with marrow-nailing. Three experiments were performed. Firstly, 20 mice received subcutaneous injections of either simvastatin (20 mg) or vehicle. Secondly, 30 mice were divided into three groups of 10 mice receiving continuous subcutaneous delivery of the vehicle substance, the vehicle with 5 mg or with 10 mg of simvastatin per kg bodyweight per day. Finally, in 20 mice, a silicone tube was led from an osmotic mini-pump to the fracture area. In this way, 10 mice received an approximate local dose of simvastatin of 0.1 mg per kg per day for the duration of the experiment and 10 mice received the vehicle compound. All treatments lasted until the end of the experiment. Bilateral femurs were harvested 14 days post-operative. Biomechanical tests were performed by way of three-point bending. Data was analysed with ANOVA, Scheffé's post-hoc test and Student's unpaired t-test.</p> <p>Results</p> <p>With daily simvastatin injections, no effects could be demonstrated for any of the parameters examined. Continuous systemic delivery resulted in a 160% larger force at failure. Continuous local delivery of simvastatin resulted in a 170% larger force at failure as well as a twofold larger energy uptake.</p> <p>Conclusion</p> <p>This study found a dramatic positive effect on biomechanical parameters of fracture healing by simvastatin treatment directly applied to the fracture area.</p

Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer

Circulating endothelial cells (CECs) as well as bone-marrow-derived endothelial precursor cells (EPC) play an important role in neovascularisation and tumour growth. To study the impact of neoadjuvant chemotherapy on the amounts of CEC and their precursor cells, mature CEC and their progenitors were quantified by flow cytometry in peripheral blood of breast cancer patients during anthracycline and/or taxane based neoadjuvant chemotherapy and subsequent surgery in comparison to age-matched healthy controls. Cell numbers were tested for correlation with serum levels of angiopoietin-2, erythropoietin, endostatin, endoglin, VEGF and sVCAM-1 as well as clinical and pathological features of breast cancer disease. Circulating endothelial cells were significantly elevated in breast cancer patients and decreased during chemotherapy, whereas EPC (CD34+/VEGFR-2+) as well as their progenitor cell population CD133+/CD34+ and the population of CD34+ stem cells increased. Concomitantly with the increase of progenitor cells an increase of VEGF, erythropoietin and angiopoietin-2 was observed. These data suggest that chemotherapy can only reduce the amounts of mature CEC, probably reflecting detached cells from tumour vessels, whereas the EPC and their progenitors are mobilised by chemotherapy. Since this mobilisation of EPC may contribute to tumour neovascularisation an early antiangiogenic therapy in combination with chemotherapy could be beneficial for the success of cancer therapy

Differential Effects of Pravastatin and Simvastatin on the Growth of Tumor Cells from Different Organ Sites

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, commonly known as statins, may possess cancer preventive and therapeutic properties. Statins are effective suppressors of cholesterol synthesis with a well-established risk-benefit ratio in cardiovascular disease prevention. Mechanistically, targeting HMGCR activity primarily influences cholesterol biosynthesis and prenylation of signaling proteins. Pravastatin is a hydrophilic statin that is selectively taken up by a sodium-independent organic anion transporter protein-1B1 (OATP1B1) exclusively expressed in liver. Simvastatin is a hydrophobic statin that enters cells by other mechanisms. Poorly-differentiated and well-differentiated cancer cell lines were selected from various tissues and examined for their response to these two statins. Simvastatin inhibited the growth of most tumor cell lines more effectively than pravastatin in a dose dependent manner. Poorly-differentiated cancer cells were generally more responsive to simvastatin than well-differentiated cancer cells, and the levels of HMGCR expression did not consistently correlate with response to statin treatment. Pravastatin had a significant effect on normal hepatocytes due to facilitated uptake and a lesser effect on prostate PC3 and colon Caco-2 cancer cells since the OATP1B1 mRNA and protein were only found in the normal liver and hepatocytes. The inhibition of cell growth was accompanied by distinct alterations in mitochondrial networks and dramatic changes in cellular morphology related to cofilin regulation and loss of p-caveolin. Both statins, hydrophilic pravastatin and hypdrophobic simvastatin caused redistribution of OATP1B1 and HMGCR to perinuclear sites. In conclusion, the specific chemical properties of different classes of statins dictate mechanistic properties which may be relevant when evaluating biological responses to statins

Effects of IL-2 on MMP Expression in Freshly Isolated Human NK Cells and the IL-2-independent NK Cell Line YT

Interleukin-2 is an important activation factor for natural killer (NK) cells but its effect on NK cell matrix metalloproteinases (MMP) production and matrix degradation is less well investigated. We have used freshly isolated human NK cells and the IL-2-independent NK cell line, YT, to investigate the effects of IL-2 stimulation on NK cell invasion of Matrigel and on MMP expression and production. In YT cells, we found opposing early and late effects of IL-2 stimulation with an early (2 h) increase in MMP-9 protein level and enhanced migration in the Matrigel invasion assay and by 30 hours a decreased mRNA expression of MMP-2, MMP-9, MMP-13, MT3-MMP, and MT6-MMP. We also found a preculture period of 48 hours with IL-2 to negatively affect YT cell migration. We furthermore found that freshly isolated human NK cells Matrigel invasion was MMP-dependent and it increased in response to IL-2. Importantly, in freshly isolated human NK cells we did not see a downregulation of MMPs after 24 hours IL-2 stimulation, but instead a significant upregulation of MT6-MMP mRNA. Because of the cellular localisation of MT6-MMP, which ensures a focalized proteolytic activity, and its high expression compared with the other MMPs in freshly isolated human NK cells makes it of interest to study further.Surgical oncolog