Glioblastoma Cell-Secreted Interleukin-8 Induces Brain Endothelial Cell Permeability via CXCR2

Glioblastoma constitutes the most aggressive and deadly of brain tumors. As yet, both conventional and molecular-based therapies have met with limited success in treatment of this cancer. Among other explanations, the heterogeneity of glioblastoma and the associated microenvironment contribute to its development, as well as resistance and recurrence in response to treatments. Increased vascularity suggests that tumor angiogenesis plays an important role in glioblastoma progression. However, the molecular crosstalk between endothelial and glioblastoma cells requires further investigation. To examine the effects of glioblastoma-derived signals on endothelial homeostasis, glioblastoma cell secretions were collected and used to treat brain endothelial cells. Here, we present evidence that the glioblastoma secretome provides pro-angiogenic signals sufficient to disrupt VE-cadherin-mediated cell-cell junctions and promote endothelial permeability in brain microvascular endothelial cells. An unbiased angiogenesis-specific antibody array screen identified the chemokine, interleukin-8, which was further demonstrated to function as a key factor involved in glioblastoma-induced permeability, mediated through its receptor CXCR2 on brain endothelia. This underappreciated interface between glioblastoma cells and associated endothelium may inspire the development of novel therapeutic strategies to induce tumor regression by preventing vascular permeability and inhibiting angiogenesis.     

Substituting dietary polyunsaturated fat with monounsaturated fat increases insulin sensitivity in cultured rat hepatocytes

Increased dietary fat intake generally, and saturated fat specifically, will lead to impairment of insulin action and to development of metabolic syndrome. The aim of this study was to find out changing of hepatic glucose output in dependence of high monounsaturated and high polyunsaturated fat diet and possible direct action of insulin in hepatocytes. Hepatocytes were isolated by a collagenase perfusion technique and cultured for 24 h in M 199 serum-free medium. The glucose production in hepatocytes isolated from rats on high polyunsaturated fat diet, as well as those isolated from rats on high monounsaturated fat diet was significantly higher than in standard controls. Insulin significantly decreased glucose production but only in hepatocytes obtained from rats on high monounsaturated fat diet. On the other side energy expenditure was significantly higher in rats on high monounsaturated fat diet and significantly lower in rats on high polyunsaturated fat diet comparable with animals on standard diet. Monounsaturated fat in Mediterranean diet could have beneficial effect on the development of the metabolic syndrome by increasing insulin sensitivity and energy expenditure.     

Characterization of the three selected probiotic strains for the application in food industry

Previously selected bacterial probiotic strains Enterococcus faecium L3, Lactobacillus plantarum L4 and Lactobacillus acidophilus M92 have shown their potential as functional starter cultures in silage, white cabbage and milk fermentation. Therefore, the phenotypic and genotypic characteristics important for their application in food industry were investigated. Pulsed-field gel electrophoresis (PFGE) of NotI digested genomic DNA, in combination with physiological traits determined by API tests, made a useful tool for identification of these probiotic strains and differentiation among them. Lyophilized probiotic cells remained viable during 75 days of storage at −20, +4 and +15°C, while fresh concentrated cells remained viable only at −20°C with addition of glycerol as cryoprotectant. After the lyophilization with addition of skim milk as lyoprotectant, the viability of L. acidophilus M92, L. plantarum L4 and E. faecium L3 was reduced by only 0.37, 0.44 and 0.50 log, respectively. Furthermore, probiotic strains L. acidophilus M92, L. plantarum L4, and E. faecium L3, demonstrated anti-Salmonella activity, and L. acidophilus M92 having also antilisterial activity demonstrated by in vitro competition test. Overnight cultures and cell-free supernatants of the three probiotic strains exerted also an antagonistic effect against the Gram-positive and Gram-negative test microorganisms examined, demonstrated by the agar-well diffusion test. The inhibition of Listeria monocytogenes, Salmonella typhimurium, Yersinia enterocolitica, and Acinetobacter calcoaceticus obtained, achieved by the neutralized, 5-fold concentrated supernatant of L. plantarum L4, may be the result of its bacteriocinogenic activity. On the basis of these results, the application of the three examined probiotic strains may become a point of great importance in respect of food safety.     

Environmental factors, health-related habits, and serum selenium levels in cancer patients and healthy controls

Previous studies conducted in Yugoslavia indicated that the concentration of selenium in soil, food items, and serum of the population is very low. The aim of the study was to investigate the possible relationship among environmental, health-related habits, nutrition, and selenium serum levels in cancer patients and the healthy population. The case-control study included a group of cancer patients and a matched group of healthy controls: 57 cancer patients and 41 healthy controls living in Stari Grad (an urban area of Belgrade), as well as 17 cancer patients and 13 healthy controls living in Barajevo (a rural community in the vicinity of Belgrade). The healthy controls were matched to cancer patients in sex and age; they were not blood related. The selenium serum levels were measured by atomic absorption spectrophotometry. Health-related habits and relevant dietary factors (“food frequency” method) that may influence the selenium serum levels were assessed by questionnaires. The differences in average values of selenium serum levels between the cancer patients and healthy controls were not significantly different, but both were below the lowest recorded in referential studies. A significant difference between the values obtained from urban and rural subgroups was noted. The most important factors that influenced the level of selenium included the residence place in the region with selenium deficiency (Barajevo), age, associated chronic diseases, and some dietary factors potentially related to the intake of selenium. The results obtained in this investigation pointed out that use of selenium supplementation in this area should be seriously considered. Deceased     

Using single photon emission tomography (SPECT) and positron emission tomography (PET) to trace the distribution of muscarinic acetylcholine receptor (MACHR) binding radioligands

Two [18F] labeled ligands for the mAChR were prepared and evaluated in rodents and nonhuman primates. The properties of both compounds, one an agonist and the other an antagonist, were consistent with M2 subtype specificity.     

Balance index score as a predictive factor for lower sports results or anterior cruciate ligament knee injuries in Croatian female athletes--preliminary study

Female athletes participating in high-risk sports suffer anterior cruciate ligament (ACL) knee injury at a 4- to 6-fold greater rate than do male athletes. ACL injuries result either from contact mechanisms or from certain unexplained non-contact mechanisms occurring during daily professional sports activities. The occurrence of non-contact injuries points to the existence of certain factors intrinsic to the knee that can lead to ACL rupture. When knee joint movement overcomes the static and the dynamic constraint systems, non-contact ACL injury may occur. Certain recent results suggest that balance and neuromuscular control play a central role in knee joint stability, protection and prevention of ACL injuries. The purpose of this study is to evaluate balance neuromuscular skills in healthy Croatian female athletes by measuring their balance index score, as well as to estimate a possible correlation between their balance index score and balance effectiveness. This study is conducted in an effort to reduce the risk of future injuries and thus prevent female athletes from withdrawing from sports prematurely. We analysed fifty-two female athletes in the high-risk sports of handball and volleyball, measuring for their static and dynamic balance index scores, using the Sport KAT 2000 testing system. This method may be used to monitor balance and coordination systems and may help to develop simpler measurements of neuromuscular control, which can be used to estimate risk predictors in athletes who withdraw from sports due to lower sports results or ruptured anterior cruciate ligament and to direct female athletes to more effective, targeted preventive interventions. The tested Croatian female athletes with lower sports results and ACL knee injury incurred after the testing were found to have a higher balance index score compared to healthy athletes. We therefore suggest that a higher balance index score can be used as an effective risk predictor for lower sports results and lesser sports motivation, anterior cruciate ligament injury and the ultimate decision to withdraw from active participation in sports. If the balance testing results prove to be effective in predicting the occurrence of ligament injuries during future sports activities, we suggest that prophylactic training programs be introduced during athlete training, since the prevention of an initial injury will be more effective than prevention of injury recurrence.     

Oxygen enhancement ratio of fractionated regimens in vitro

The oxygen enhancement ratio (OER) of proliferating and nonproliferating cells grown in vitro was measured using accelerated fractionated regimens. Irradiations were performed either twice daily or three times per day, with a minimum of 6 h between the consecutive fractions. The dose delivered was 2.3 Gy per fraction. Two significant observations were made: (i) the OER of accelerated fractionation regimens for proliferating cells is lower than that obtained from single-exposure experiments at 2.3 Gy (approximately 1.4 vs 2.4, respectively), while for nonproliferating cells it is approximately the same (2.3); (ii) the fractionated regimen does not spare proliferating cells irradiated under hypoxic conditions, and thus the fractionated survival curve lies below the single-exposure curve. For cells irradiated under aerobic conditions or for nonproliferating cells, irradiated under either hypoxic or aerobic conditions, the fractionated survival curve lies above the single-exposure curves as expected.