Taurine: a potential marker of apoptosis in gliomas

New cancer therapies are being developed that trigger tumour apoptosis and an in vivo method of apoptotic detection and early treatment response would be of great value. Magnetic resonance spectroscopy (MRS) can determine the tumour biochemical profile in vivo, and we have investigated whether a specific spectroscopic signature exists for apoptosis in human astrocytomas. High-resolution magic angle spinning (HRMAS) 1H MRS provided detailed 1H spectra of brain tumour biopsies for direct correlation with histopathology. Metabolites, mobile lipids and macromolecules were quantified from presaturation HRMAS 1H spectra acquired from 41 biopsies of grades II (n=8), III (n=3) and IV (n=30) astrocytomas. Subsequently, TUNEL and H&E staining provided quantification of apoptosis, cell density and necrosis. Taurine was found to significantly correlate with apoptotic cell density (TUNEL) in both non-necrotic (R=0.727, P=0.003) and necrotic (R=0.626, P=0.0005) biopsies. However, the ca 2.8 p.p.m. polyunsaturated fatty acid peak, observed in other studies as a marker of apoptosis, correlated only in non-necrotic biopsies (R=0.705, P<0.005). We suggest that the taurine 1H MRS signal in astrocytomas may be a robust apoptotic biomarker that is independent of tumour necrotic status

Adventurous Physical Activity Environments: A Mainstream Intervention for Mental Health

Adventurous physical activity has traditionally been considered the pastime of a small minority of people with deviant personalities or characteristics that compel them to voluntarily take great risks purely for the sake of thrills and excitement. An unintended consequence of these traditional narratives is the relative absence of adventure activities in mainstream health and well-being discourses and in large-scale governmental health initiatives. However, recent research has demonstrated that even the most extreme adventurous physical activities are linked to enhanced psychological health and well-being outcomes. These benefits go beyond traditional ‘character building’ concepts and emphasize more positive frameworks that rely on the development of effective environmental design. Based on emerging research, this paper demonstrates why adventurous physical activity should be considered a mainstream intervention for positive mental health. Furthermore, the authors argue that understanding how to design environments that effectively encourage appropriate adventure should be considered a serious addition to mainstream health and well-being discourse

Identification of Reference Genes across Physiological States for qRT-PCR through Microarray Meta-Analysis

The accuracy of quantitative real-time PCR (qRT-PCR) is highly dependent on reliable reference gene(s). Some housekeeping genes which are commonly used for normalization are widely recognized as inappropriate in many experimental conditions. This study aimed to identify reference genes for clinical studies through microarray meta-analysis of human clinical samples.After uniform data preprocessing and data quality control, 4,804 Affymetrix HU-133A arrays performed by clinical samples were classified into four physiological states with 13 organ/tissue types. We identified a list of reference genes for each organ/tissue types which exhibited stable expression across physiological states. Furthermore, 102 genes identified as reference gene candidates in multiple organ/tissue types were selected for further analysis. These genes have been frequently identified as housekeeping genes in previous studies, and approximately 71% of them fall into Gene Expression (GO:0010467) category in Gene Ontology.Based on microarray meta-analysis of human clinical sample arrays, we identified sets of reference gene candidates for various organ/tissue types and then examined the functions of these genes. Additionally, we found that many of the reference genes are functionally related to transcription, RNA processing and translation. According to our results, researchers could select single or multiple reference gene(s) for normalization of qRT-PCR in clinical studies

Radiotherapy Suppresses Angiogenesis in Mice through TGF-βRI/ALK5-Dependent Inhibition of Endothelial Cell Sprouting

BACKGROUND: Radiotherapy is widely used to treat cancer. While rapidly dividing cancer cells are naturally considered the main target of radiotherapy, emerging evidence indicates that radiotherapy also affects endothelial cell functions, and possibly also their angiogenic capacity. In spite of its clinical relevance, such putative anti-angiogenic effect of radiotherapy has not been thoroughly characterized. We have investigated the effect of ionizing radiation on angiogenesis using in vivo, ex vivo and in vitro experimental models in combination with genetic and pharmacological interventions. PRINCIPAL FINDINGS: Here we show that high doses ionizing radiation locally suppressed VEGF- and FGF-2-induced Matrigel plug angiogenesis in mice in vivo and prevented endothelial cell sprouting from mouse aortic rings following in vivo or ex vivo irradiation. Quiescent human endothelial cells exposed to ionizing radiation in vitro resisted apoptosis, demonstrated reduced sprouting, migration and proliferation capacities, showed enhanced adhesion to matrix proteins, and underwent premature senescence. Irradiation induced the expression of P53 and P21 proteins in endothelial cells, but p53 or p21 deficiency and P21 silencing did not prevent radiation-induced inhibition of sprouting or proliferation. Radiation induced Smad-2 phosphorylation in skin in vivo and in endothelial cells in vitro. Inhibition of the TGF-beta type I receptor ALK5 rescued deficient endothelial cell sprouting and migration but not proliferation in vitro and restored defective Matrigel plug angiogenesis in irradiated mice in vivo. ALK5 inhibition, however, did not rescue deficient proliferation. Notch signaling, known to hinder angiogenesis, was activated by radiation but its inhibition, alone or in combination with ALK5 inhibition, did not rescue suppressed proliferation. CONCLUSIONS: These results demonstrate that irradiation of quiescent endothelial cells suppresses subsequent angiogenesis and that ALK5 is a critical mediator of this suppression. These results extend our understanding of radiotherapy-induced endothelial dysfunctions, relevant to both therapeutic and unwanted effects of radiotherapy