Women in space: A review of known physiological adaptations and health perspectives.

Exposure to the spaceflight environment causes adaptations in most human physiological systems, many of which are thought to affect women differently from men. Since only 11.5% of astronauts worldwide have been female, these issues are largely understudied.

Identification of non-Hodgkin lymphoma patients at risk for treatment-related vertebral density loss and fractures.

Unlabelled: Information on bone loss in treated non-Hodgkin's lymphoma patients is limited. In this study, we used CT to analyze bone loss as well as prevalent and incident fractures. We found severe bone loss, a high rate of fractures, and a novel association between bone loss and the international prognostic index.

Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial).

Background: Patients with peripheral artery disease (PAD) experience significant morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded, placebo-controlled trial, addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function and inflammation in PAD.

Methods And Results: Eighty patients with stable claudication received 4.

Spaceflight alters expression of microRNA during T-cell activation.

Altered immune function has been demonstrated in astronauts during spaceflights dating back to Apollo and Skylab; this could be a major barrier to long-term space exploration. We tested the hypothesis that spaceflight causes changes in microRNA (miRNA) expression. Human leukocytes were stimulated with mitogens on board the International Space Station using an onboard normal gravity control.

Spaceflight impairs antigen-specific tolerance induction in vivo and increases inflammatory cytokines.

The health risks of a dysregulated immune response during spaceflight are important to understand as plans emerge for humans to embark on long-term space travel to Mars. In this first-of-its-kind study, we used adoptive transfer of T-cell receptor transgenic OT-II CD4 T cells to track an in vivo antigen-specific immune response that was induced during the course of spaceflight. Experimental mice destined for spaceflight and mice that remained on the ground received transferred OT-II cells and cognate peptide stimulation with ovalbumin (OVA) 323-339 plus the inflammatory adjuvant, monophosphoryl lipid A.

Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation.

Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS).

Molecular mechanisms underlying the enhanced functions of three-dimensional hepatocyte aggregates.

Three-dimensional (3D) culture of hepatocytes leads to improved and prolonged synthetic and metabolic functions, but the underlying molecular mechanisms are unknown. In order to investigate the role of 3D cell-cell interactions in maintaining hepatocyte differentiated functions ex vivo, primary mouse hepatocytes were cultured either as monolayers on tissue culture dishes (TCD) or as 3D aggregates in rotating wall vessel (RWV) bioreactors. Global gene expression analyses revealed that genes upregulated in 3D culture were distinct from those upregulated during liver development and liver regeneration.

n-3 Polyunsaturated fatty acids supplementation in peripheral artery disease: the OMEGA-PAD trial.

Despite current consensus guidelines recommending intensive cardiovascular risk factor management for peripheral artery disease (PAD), patients suffering from PAD continue to experience significant morbidity and mortality. This excess morbid burden is at least partially related to impaired vascular function and systemic inflammation. Interventions bridging this gap are critical.

Effects of gravitational mechanical unloading in endothelial cells: association between caveolins, inflammation and adhesion molecules.

Mechanical forces including gravity affect endothelial cell (ECs) function, and have been implicated in vascular disease as well as physiologic changes associated with low gravity environments. The goal of this study was to investigate the impact of gravitational mechanical unloading on ECs phenotype as determined by patterns of gene expression. Human umbilical vascular endothelial cells were exposed to 1-gravity environment or mechanical unloading (MU) for 24 hours, with or without periods of mechanical loading (ML).

Can I take a space flight? Considerations for doctors.

Commercial investment is bringing space tourism closer to reality. Marlene Grenon and colleagues: outline what doctors will need to know.

The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity.

This study tested the hypothesis that transcription of immediate early genes is inhibited in T cells activated in μg. Immunosuppression during spaceflight is a major barrier to safe, long-term human space habitation and travel. The goals of these experiments were to prove that μg was the cause of impaired T cell activation during spaceflight, as well as understand the mechanisms controlling early T cell activation.

Effects of fatty acids on endothelial cells: inflammation and monocyte adhesion.

Background: Diet is known to have an important impact on cardiovascular health. n-3 Fatty acids (FAs), found in high quantity in fish oil, have demonstrated beneficial effects in patients with coronary artery disease. The role of n-6 FAs remains more controversial.

Polyunsaturated fatty acids and peripheral artery disease.

There is substantial evidence that polyunsaturated fatty acids (PUFAs) such as n-3 and n-6 fatty acids (FAs) play an important role in prevention of atherosclerosis. In vitro and in vivo studies focusing on the interactions between monocytes and endothelial cells have explored the molecular effects of FAs on these interactions. Epidemiological surveys, followed by large, randomized, control trials have demonstrated a reduction in major cardiovascular events with supplementation of n-3 FAs in secondary prevention settings.

Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation.

Background: Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial.

Methods: Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n = 29) or fish oil (n = 27) supplementation or placebo (n = 28).

The role of FGF-2 and BMP-2 in regulation of gene induction, cell proliferation and mineralization.

Introduction: The difficulty in re-growing and mineralizing new bone after severe fracture can result in loss of ambulation or limb. Here we describe the sequential roles of FGF-2 in inducing gene expression, cell growth and BMP-2 in gene expression and mineralization of bone.

Materials And Methods: The regulation of gene expression was determined using real-time RTPCR (qRTPCR) and cell proliferation was measured by thymidine incorporation or fluorescent analysis of DNA content in MC3T3E1 osteoblast-like cells.

Nutritional supplements, COX-2 and IGF-1 expression in men on active surveillance for prostate cancer.

Background: Nutritional factors are associated with reduced risk of prostate cancer progression, yet mechanisms remain unclear. We examined the effects of lycopene and fish oil supplements versus placebo on the normal prostate microenvironment, among men pursuing active surveillance for low-burden prostate cancer. We hypothesized that lycopene or fish oil supplements would down-regulate insulin-like growth factor-1 (IGF-1) and cyclooxygenase 2 (COX-2) gene expression, respectively, reflecting putative proliferation (IGF-1) and inflammatory (COX-2) pathways relevant to carcinogenesis.

Monolayer and spheroid culture of human liver hepatocellular carcinoma cell line cells demonstrate distinct global gene expression patterns and functional phenotypes.

Understanding cell biology of three-dimensional (3D) biological structures is important for more complete appreciation of in vivo tissue function and advancing ex vivo organ engineering efforts. To elucidate how 3D structure may affect hepatocyte cellular responses, we compared global gene expression of human liver hepatocellular carcinoma cell line (HepG2) cells cultured as monolayers on tissue culture dishes (TCDs) or as spheroids within rotating wall vessel (RWV) bioreactors. HepG2 cells grown in RWVs form spheroids up to 100 mum in diameter within 72 h and up to 1 mm with long-term culture.

Glycosylation regulates turnover of cyclooxygenase-2.

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the prostanoid biosynthesis pathway, converting arachidonic acid into prostaglandin H(2). COX-2 exists as 72 and 74kDa glycoforms, the latter resulting from an additional oligosaccharide chain at residue Asn(580). In this study, Asn(580) was mutated to determine the biological significance of this variable glycosylation.

Fibroblast growth factor-2 is an immediate-early gene induced by mechanical stress in osteogenic cells.

Unlabelled: Fifteen minutes of physiological MS induces FGF-2 in osteogenic cells. Here, we show that MS induced proliferation in both MC3T3-E1 and BMOp cells isolated from Fgf2(+/+) mice; Fgf2(-/-) BMOp cells required exogenous FGF-2 for a normal proliferation response. The induction of fgf-2 is mediated by PKA and ERK pathways.

Reduction of anabolic signals and alteration of osteoblast nuclear morphology in microgravity.

Bone loss has been repeatedly documented in astronauts after flight, yet little is known about the mechanism of bone loss in space flight. Osteoblasts were activated during space flight in microgravity (microg) with and without a 1 gravity (1 g) field and 24 genes were analyzed for early induction. Induction of proliferating cell nuclear antigen (PCNA), transforming growth factor beta (TGFbeta), cyclo-oxygenase-2 (cox-2), cpla2, osteocalcin (OC), c-myc, fibroblast growth factor-2 (fgf-2), bcl2, bax, and fgf-2 message as well as FGF-2 protein were significantly depressed in microg when compared to ground (gr).

Arachidonic acid activates phosphatidylinositol 3-kinase signaling and induces gene expression in prostate cancer.

Essential fatty acids are not only energy-rich molecules; they are also an important component of the membrane bilayer and recently have been implicated in induction of fatty acid synthase and other genes. Using gene chip analysis, we have found that arachidonic acid, an omega-6 fatty acid, induced 11 genes that are regulated by nuclear factor-kappaB (NF-kappaB). We verified gene induction by omega-6 fatty acid, including COX-2, IkappaBalpha, NF-kappaB, GM-CSF, IL-1beta, CXCL-1, TNF-alpha, IL-6, LTA, IL-8, PPARgamma, and ICAM-1, using quantitative reverse transcription-PCR.

Key gravity-sensitive signaling pathways drive T cell activation.

Returning astronauts have experienced altered immune function and increased vulnerability to infection during spaceflights dating back to Apollo and Skylab. Lack of immune response in microgravity occurs at the cellular level. We analyzed differential gene expression to find gravity-dependent genes and pathways.

Lessons learned about spaceflight and cell biology experiments.

Conducting cell biology experiments in microgravity can be among the most technically challenging events in a biologist's life. Conflicting events of spaceflight include waiting to get manifested, delays in manifest schedules, training astronauts to not shake your cultures and to add reagents slowly, as shaking or quick injection can activate signaling cascades and give you erroneous results. It is important to select good hardware that is reliable.

Early immune response and regulation of IL-2 receptor subunits.

Affymetrix oligonucleotide arrays were used to monitor expression of 8796 genes and probe sets in activated T-cells; analysis revealed that 217 genes were significantly upregulated within 4 h. Induced genes included transcription factors, cytokines and their receptor genes. Analysis by semi-quantitative RT-PCR confirmed the significant induction of IL-2, IL-2R(gamma) and IL-2R(alpha).