Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis.

Bayer AG.

For future interplanetary manned spaceflight, mental issues, as well as physiological problems, must inevitably be considered and solved. Mars500 is a high-fidelity ground simulation experiment that involved 520 days of confined isolation for six multinational crewmembers. This experiment provided a good opportunity to perform psycho-physiological and psycho-social researches on such missions. To investigate emotional responses and psychological adaptation over long-term confinement, the International Affective Pictures System (IAPS) was selected as the visual emotional stimuli in this study. Additional data collected and analyzed included the Profile of Mood States (POMS) questionnaire and the levels of four types of plasma hormones: cortisol, 5-hydroxy tryptamine, dopamine, and norepinephrine. The results demonstrated an obvious bias on valence rating for unpleasant stimuli with time (p<0.05), and the correlation between psychological and biochemical data was identified (p<0.05). Overall, we concluded that the confined crew tended to assign positive ratings to negative pictures with time, which might be driven by a defensive system. There was a stage-changing pattern of psychological adaptation of the Mars500 crew, which is similar to the third-quarter phenomenon.

The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth’s environment, which is characterized by a 24-hour light–dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.

No abstract

SummaryBackground: Recent studies have reported that the presence of cancer stem cells (CSCs) has major implications in the treatment of cancer and is responsible for tumor relapse. In the current study, we identified and characterized colon CSC-like side population (SP) cells from colon cancer tissue. Materials and Methods: The colon cancer samples were subjected to fluorescence-activated cell sorting (FACS) based on Hoechst 33342 dye exclusion for the purification of SP cells. The sorted SP cells were subjected to further characterization by immunofluorescence, real-time polymerase chain reaction (RT-PCR), multidrug resistance, and sphere formation assays. Results: We identified a fraction of 3.3% of SP cells in the colon cancer cell samples, which was reduced to 0.6% upon treatment with verapamil. The sorted SP cells showed high positivity with regard to CD133, CD44, CD147, and EpCAM, by fluorescence microscopic analysis. Further, these SP cells were highly resistant to multidrug treatment due to overexpression of the multidrug resistance 1 (MDR1) transporter protein ABCG2. Conclusion: Our findings suggest that the overexpression of ABCG2 and the expression of stem cell surface markers are collectively responsible for chemotherapy failure, tumor recurrence, and invasion in colon cancer.

SOD2 (superoxide dismutase 2) is one of the endogenous antioxidant enzymes that protect against reactive oxygen species. While explorations of SOD2 expression regulation are mainly focused on transcriptional and post-translational activation, there are few reports about the post-transcriptional regulation of SOD2. MicroRNAs (miRNAs) are 21nt-25nt (nucleotide) small noncoding RNAs that have emerged as indispensable regulators of gene expression. Here we show that miR-146a, a widely expressed miRNA, is up-regulated by H2O2-induced stress. By sequence analysis we found a binding site for miR-146a in the sod2 mRNA 3′UTR, and a luciferase reporter assay confirmed that miR-146a can interact with this sod2 regulatory region. Our results further show that miR-146a could down-regulate the SOD2 protein expression, and antisense-miR-146a could reverse the decrease of both the SOD2 level and cell viability in H2O2 treated PC12 cells. In conclusion, here we have identified a novel function of miR-146a in the post-transcriptional regulation of SOD2 expression.

Tumor necrosis factor (TNF)-alpha plays a prominent role in inflammations and is a proinflammatory cytokine that has been implicated in the pathogenesis of autoimmune and infectious diseases. Recent association studies have found that the TNF-alpha-857T allele was associated with several disorders. Here we demonstrate, with reporter genes under the control of the two allelic TNF-alpha promoters, that the minor allele -857T is a much stronger transcriptional activator than the major allele -857C in RAW264.7 cell line in response to lipopolysaccharide stimulation. However, the result was not consistent in HeLa cell line. Furthermore, for the quantitative analysis of TNF-alpha synthesis between the -857C/C genotype from healthy subjects and the -857C/T genotype from AS patients, the quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed separately. There was no significant difference between the two groups at the level of mRNA and protein. These results show that this polymorphism may have a direct effect on TNF-alpha regulation in a tissue-specific manner, and apart from the polymorphism at -857 in the TNF-alpha promoter, there may be other factors affecting the expression of TNF-alpha.