PC-3 prostate carcinoma cells release signal substances that influence the migratory activity of cells in the tumor's microenvironment

<p>Abstract</p> <p>Background</p> <p>Tumor cells interact with the cells of the microenvironment not only by cell-cell-contacts but also by the release of signal substances. These substances are known to induce tumor vascularization, especially under hypoxic conditions, but are also supposed to provoke other processes such as tumor innervation and inflammatory conditions. Inflammation is mediated by two organ systems, the neuroendocrine system and the immune system. Therefore, we investigated the influence of substances released by PC-3 human prostate carcinoma cells on SH-SY5Y neuroblastoma cells as well as neutrophil granulocytes and cytotoxic T lymphocytes, especially with regard to their migratory activity.</p> <p>Results</p> <p>PC-3 cells express several cytokines and growth factors including vascular endothelial growth factors, fibroblast growth factors, interleukins and neurotrophic factors. SH-SY5Y cells are impaired in their migratory activity by PC-3 cell culture supernatant, but orientate chemotactically towards the source. Neutrophil granulocytes increase their locomotory activity only in response to cell culture supernantant of hypoxic but not of normoxic PC-3 cells. In contrast, cytotoxic T lymphocytes do not change their migratory activity in response to either culture supernatant, but increase their cytotoxicity, whereas supernatant of normoxic PC-3 cells leads to a stronger increase than that of hypoxic PC-3 cells.</p> <p>Conclusions</p> <p>PC-3 cells release several signal substances that influence the behavior of the cells in the tumor's microenvironment, whereas no clear pattern towards proinflammatory or immunosuppressive conditions can be seen.</p

GEM-TPC pre-design technical report

This document contains the pre-design of the beam diagnostics components Tracking Detectors for the Super-FRS. A GEM-TPC detector has been suggested as suitable tracking detector for the ion/fragment beams produced at the in-flight separator Super-FRS under construction at the FAIR facility. The detector concept combines two widely used approaches in gas filled detectors, the Time Projection Chamber (TPC) and the Gas Electron Multiplication (GEM). Three detector generations (prototypes) have been tested in 2011, 2012 and 2014 with relativistic ion beams at GSI. Due to the high-resolution achromatic mode of the Super-FRS, highly homogeneous transmission tracking detectors are crucial to tag the momentum of the ion/fragment beam. They must be able to provide precise information on the (horizontal and vertical) deviation from nominal beam optics, while operated with slow-extracted beam on event-by event basis, in order to provide unambiguous identification of the fragments. The main requirements are a maximum active area horizontally and vertically of (380x80) mm2, a position resolution of < 1 mm, a maximum rate capability of 1 MHz, a dynamic range of about 600 fC. About 32 tracking detectors operating in vacuum are needed along the Super-FRS beam line

Occurrence and distribution of Amphidomataceae (Dinophyceae) in Danish coastal waters of the North Sea, the Limfjord and the Kattegat/Belt area

Some species of the dinophytes Azadinium and Amphidoma (Amphidomataceae) produce azaspiracids (AZA), lipophilic polyether compounds responsible for Azaspiracid Shellfish Poisoning (AZP) in humans after consumption of contaminated seafood. Toxigenic Amphidomataceae are known to occur in the North Atlantic and the North Sea area, but little is known about their importance in Danish coastal waters. In 2016, 44 Stations were sampled on a survey along the Danish coastline, covering the German Bight, Limfjord, the Kattegat area, Great Belt and Kiel Bight. Samples were analysed by live microscopy, liquid chromatography-tandem mass spectrometry (LC–MS/MS) and quantitative polymerase-chain-reaction (qPCR) on the presence of Amphidomataceae and AZA. Amphidomataceae were widely distributed in the area, but were below detection limit on most of the inner Limfjord stations. Cell abundances of the three toxigenic species, determined with species-specific qPCR assays on Azadinium spinosum, Az. poporum and Amphidoma languida, were generally low and restricted to the North Sea and the northern Kattegat, which was in agreement with the distribution of the generally low AZA abundances in plankton samples. Among the toxigenic species, Amphidoma languida was dominant with highest cell densities up to 3×103 cells L−1 on North Sea stations and at the western entrance of the Limfjord. Azaspiracids detected in plankton samples include low levels of AZA-1 at one station of the North Sea, and higher levels of AZA-38 and -39 (up to 1.5 ng L−1) in the North Sea and the Limfjord entrance. Furthermore, one new AZA (named AZA-63) was discovered in plankton of two North Sea stations. Morphological, molecular, and toxinological characterisation of 26 newly established strains from the area confirmed the presence of four amphidomatacean species (Az. obesum, Az. dalianense, Az. poporum and Am. languida). The single new strain of Az. poporum turned out as a member of Ribotype A2, which was previously only known from the Mediterranean. Consistent with some of these Mediterranean A2 strains, but different to the previously established AZA-37 producing Az. poporum Ribotype A1 strains from Denmark, the new strain did not contain any AZA. Azaspiracids were also absent in all Az. obesum and Az. dalianense strains, but AZA-38 and -39 were found in all Am. languida strains with total AZA cell quotas ranging from 0.08 up to 94 fg cell−1. In conclusion, AZA-producing microalgae and their respective toxins were low in abundance but widely present in the area, and thus might be considered in local monitoring programs to preserve seafood safety in Danish coastal waters

Mindfulness-Based Student Training Improves Vascular Variability Associated With Sustained Reductions in Physiological Stress Response

In today's fast-paced society, chronic stress has become an increasing problem, as it can lead to psycho-physiological health problems. University students are also faced with stress due to the demands of many courses and exams. The positive effects of mindfulness-based stress reduction (MBSR) on stress management and self-regulation have already been studied. We have developed a new mindfulness intervention tailored for students—the Mindfulness-Based Student Training (MBST). In this study, we present longitudinal results of the MBST evaluation. Biosignal analysis methods, including pulse wave variability (PWV), heart rate variability, and respiratory activity, were used to assess participants' state of autonomic regulation during the 12-week intervention and at follow-up. The progress of the intervention group (IGR, N = 31) up to 3 months after the end of MBST was compared with that of a control group (CON , N = 34). In addition, the long-term effect for IGR up to 1 year after intervention was examined. The analysis showed significant positive changes in PWV exclusively for IGR. This positive effect, particularly on vascular function, persists 1 year after the end of MBST. These results suggest a physiologically reduced stress level in MBST participants and a beneficial preventive health care program for University students

Short Hypoxia Does not Affect Plasma Leptin in Healthy Men under Euglycemic Clamp Conditions

Leptin is involved in the endocrine control of energy expenditure and body weight regulation. Previous studies emphasize a relationship between hypoxic states and leptin concentrations. The aim of this study was to investigate the effects of acute hypoxia on leptin concentrations in healthy subjects. We examined 14 healthy men. Hypoxic conditions were induced by decreasing oxygen saturation to 75% for 30 minutes. Plasma leptin concentrations were determined at baseline, after 3 hours of euglycemic clamping, during hypoxia, and repeatedly the following 2.5 hours thereafter. Our results show an increase of plasma leptin concentrations in the course of 6 hours of hyperinsulinemic-euglycemic clamping which may reflect diurnal rhythmicity. Notwithstanding, there was no difference between levels of leptin in the hypoxic and the normoxic condition (P = .2). Since we did not find any significant changes in leptin responses upon hypoxia, plasma leptin levels do not seem to be affected by short hypoxic episodes of moderate degree

Yoga in school sports improves functioning of autonomic nervous system in young adults: A non-randomized controlled pilot study

Background Yoga in school is a beneficial tool to promote the good health and well-being of students by changing the way they react to stress. The positive effects of yoga—taught in schools—on children, youth and young adults have been demonstrated in former studies using mostly subjective psychometric data. Aim The present trial aims to evaluate the potential effects of yoga on autonomic regulation in young adults by analyzing heart rate variability (HRV). Methods This study is a non-randomized, explorative, two-arm-pilot study with an active control group. Fourteen healthy young adults took part in a 10-week yoga program (90 min once a week) in school and were compared to a control group of 11 students who participated in conventional school sports (90 min once a week over 10 weeks). 24-hour electrocardiograms (ECGs) were recorded at baseline and following the 10-week intervention. From 20-minute of nocturnal sleep phases, HRV parameters were calculated from linear (time and frequency domain) and nonlinear dynamics (such as symbolic dynamics and Poincaré plot analysis). Analyses of variance (ANOVA) followed by t-tests as post-hoc tests estimating both statistical significance and effect size were used to compare pre-post-intervention for the two groups. Results The statistical analysis of the interaction effects did not reveal a significant group and time interaction for the individual nocturnal HRV indices. Almost all indices revealed medium and large effects regarding the time main effects. The changes in the HRV indices following the intervention were more dramatic for the yoga group than for the control group which is reflected in predominantly higher significances and stronger effect sizes in the yoga group. Conclusion In this explorative pilot trial, an increase of HRV (more parasympathetic dominance and overall higher HRV) after ten weeks of yoga in school in comparison to regular school sports was demonstrated, showing an improved self-regulation of the autonomic nervous system

Evaluation of high-sensitivity C-reactive protein and uric acid in vericiguat-treated patients with heart failure with reduced ejection fraction

Aims: The effects of vericiguat vs. placebo on high-sensitivity C-reactive protein (hsCRP) and serum uric acid (SUA) were assessed in patients with heart failure with reduced ejection fraction (HFrEF) in the Phase 2 SOCRATES-REDUCED study (NCT01951625). Methods and results: Changes from baseline hsCRP and SUA values at 12 weeks with placebo and vericiguat (1.25 mg, 2.5 mg, 5.0 mg and 10.0 mg, respectively) were assessed. The probability of achieving an hsCRP value of ≤3.0 mg/L or SUA value of <7.0 mg/dL at week 12 was tested. Median baseline hsCRP and SUA levels were 3.68 mg/L [interquartile range (IQR) 1.41–8.41; n = 335] and 7.80 mg/dL (IQR 6.40–9.33; n = 348), respectively. Baseline-adjusted mean percentage changes in hsCRP were 0.2%, −19.5%, −24.3%, −25.7% and −31.9% in the placebo and vericiguat 1.25 mg, 2.5 mg, 5.0 mg and 10.0 mg groups, respectively; significance vs. placebo was observed in the vericiguat 10.0 mg group (P = 0.035). Baseline-adjusted mean percentage changes in SUA were 5.0%, −1.3%, −1.1%, −3.5% and −5.3% in the placebo, and vericiguat 1.25 mg, 2.5 mg, 5.0 mg and 10.0 mg groups, respectively; significance vs. placebo was observed in the 5.0 mg and 10.0 mg groups (P = 0.0202 and P = 0.004, respectively). Estimated probability for an end-of-treatment hsCRP value of ≤3.0 mg/L and SUA value of <7.0 mg/dL was higher with vericiguat compared with placebo. The effect was dose-dependent, with the greatest effect observed in the 10.0 mg group. Conclusions: Vericiguat treatment for 12 weeks was associated with reductions in hsCRP and SUA, and a higher likelihood of achieving an hsCRP value of ≤3.0 mg/L and SUA value of <7.0 mg/dL