Vibration Rather than Microgravity Affects Bone Metabolism in Adult Zebrafish Scale Model.

Gravity and mechanical forces cause important alterations in the human skeletal system, as demonstrated by space flights. Innovative animal models like zebrafish embryos and medaka have been introduced to study bone response in ground-based microgravity simulators. We used, for the first time, adult zebrafish in simulated microgravity, with a random positioning machine (RPM) to study bone remodeling in the scales.

The Critical Impact of Sphingolipid Metabolism in Breast Cancer Progression and Drug Response.

Breast cancer is the second leading cause of cancer-related death in women in the world, and its management includes a combination of surgery, radiation therapy, chemotherapy, and immunotherapy, whose effectiveness depends largely, but not exclusively, on the molecular subtype (Luminal A, Luminal B, HER2+ and Triple Negative). All breast cancer subtypes are accompanied by peculiar and substantial changes in sphingolipid metabolism. Alterations in sphingolipid metabolite levels, such as ceramides, dihydroceramide, sphingosine, sphingosine-1-phosphate, and sphingomyelin, as well as in their biosynthetic and catabolic enzymatic pathways, have emerged as molecular mechanisms by which breast cancer cells grow, respond to or escape therapeutic interventions and could take on diagnostic and prognostic value.

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells.

(1) Background: Lipid metabolism is a fundamental hallmark of all tumors, especially of breast cancer. Few studies describe the different lipid metabolisms and sensitivities to the microenvironment of breast cancer cell subtypes that influence the proliferation, aggressiveness, and success of therapy. This study describes the impact of lipid microenvironment on endoplasmic reticulum (ER) membrane and metabolic activity in two breast cancer cell lines with Luminal A and triple-negative breast cancer (TNBC) features.

Characterization of Antioxidant Potential of Seaweed Extracts for Enrichment of Convenience Food.

In recent years, there has been a growing interest in natural antioxidants as replacements of synthetic compounds because of increased safety concerns and worldwide trend toward the usage of natural additives in foods. One of the richest sources of natural antioxidants, nowadays largely studied for their potential to decrease the risk of diseases and to improve oxidative stability of food products, are edible brown seaweeds. Nevertheless, their antioxidant mechanisms are slightly evaluated and discussed.

Effect of Unloading Condition on the Healing Process and Effectiveness of Platelet Rich Plasma as a Countermeasure: Study on In Vivo and In Vitro Wound Healing Models.

Wound healing is a very complex process that allows organisms to survive injuries. It is strictly regulated by a number of biochemical and physical factors, mechanical forces included. Studying wound healing in space is interesting for two main reasons: (i) defining tools, procedures, and protocols to manage serious wounds and burns eventually occurring in future long-lasting space exploration missions, without the possibility of timely medical evacuation to Earth; (ii) understanding the role of gravity and mechanical factors in the healing process and scarring, thus contributing to unravelling the mechanisms underlying the switching between perfect regeneration and imperfect repair with scarring.

Lipid Reshaping and Lipophagy Are Induced in a Modeled Ischemia-Reperfusion Injury of Blood Brain Barrier.

Ischemic-reperfusion (I/R) injury induced a remodeling of protein and lipid homeostasis, under oxidative stress and inflammatory status. Starvation occurring during I/R is a condition leading to autophagy activation, which allows abnormal material clearance or amino acid, or both, and fatty acid (FA) recycling essential for survival. This study investigated the lipid reshaping, peroxidation, and related-signaling pathways, in rat brain endothelial cells (RBE4) subjected to 3 h of oxygen and glucose deprivation (OGD) and restoration of standard condition (I/R in vitro model).

Interplay between Plasmodium falciparum haemozoin and L-arginine: implication for nitric oxide production.

Background: Plasmodium falciparum haemozoin, a detoxification product of digested haemoglobin from infected erythrocytes, is released into the bloodstream upon schizont rupture and accumulates in leukocytes. High levels of haemozoin correlate with disease severity. Some studies have shown that concentrations of the substrate of inducible nitric oxide synthase (iNOS), L-arginine, as well as nitric oxide are low in patients infected with P.

HaCaT Cells as a Reliable In Vitro Differentiation Model to Dissect the Inflammatory/Repair Response of Human Keratinocytes.

Cultured primary human keratinocytes are frequently employed for studies of immunological and inflammatory responses; however, interpretation of experimental data may be complicated by donor to donor variability, the relatively short culture lifetime, and variations between passages. To standardize the studies on keratinocytes, we investigated the use of HaCaT cells, a long-lived, spontaneously immortalized human keratinocyte line which is able to differentiate , as a suitable model to follow the release of inflammatory and repair mediators in response to TNF or IL-1. Different treatment conditions (presence or absence of serum) and differentiation stimuli (increase in cell density as a function of time in culture and elevation of extracellular calcium) were considered.

Effects of long-term space flight on erythrocytes and oxidative stress of rodents.

Erythrocyte and hemoglobin losses have been frequently observed in humans during space missions; these observations have been designated as "space anemia". Erythrocytes exposed to microgravity have a modified rheology and undergo hemolysis to a greater extent. Cell membrane composition plays an important role in determining erythrocyte resistance to mechanical stress and it is well known that membrane composition might be influenced by external events, such as hypothermia, hypoxia or gravitational strength variations.

Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane.

Background: PUFAs are important molecules for membrane order and function; they can modify inflammation-inducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. N-3 PUFAs could alter cancer growth influencing cell replication, cell cycle, and cell death.

A mint purified extract protects human keratinocytes from short-term, chemically induced oxidative stress.

Oxidative stress is strictly correlated to the pathogenesis of many diseases, and a diet rich in fruits and vegetables, or adequately integrated, is currently considered to be a protective and preventive factor. This study aimed to analyze the efficacy of a 1 h preincubation with the highest nontoxic dose of a characterized Mentha longifolia extract (80 μg/mL) in protecting human keratinocytes (NCTC2544) from chemically induced oxidative stress (500 μM H2O2 for 2, 16, and 24 h). As reference synthetic pure compounds rosmarinic acid (360.

Two active and differently N-glycosylated isoforms of human ST3Gal-V are produced from the placental mRNA variant by a leaky scanning mechanism.

Previously, we identified a human ST3Gal-V mRNA variant peculiarly characterized by the presence of a translational start codon localized up-stream and in-frame with the one that is usually considered as unique translation initiation site in the human gene. In this study we demonstrate, by cDNA transfection experiments, mutational analyses, enzyme activity assays, and endoglycosidase-H treatments, that the in vivo expression of this transcript gives rise to two human ST3Gal-V isoforms with distinct characteristics. Produced by a leaky scanning mechanism, they carry different N-glycan structures and exhibit differences in their GM(3) synthase activity that might be relevant for the modulation of GM(3) cellular content.

Gangliosides influence EGFR/ErbB2 heterodimer stability but they do not modify EGF-dependent ErbB2 phosphorylation.

Gangliosides are well-known regulators of cell differentiation through specific interactions with growth factor receptors. Previously, our group provided the first evidence about stable association of ganglioside GM(3) to EGFR/ErbB2 heterodimers in mammary epithelial cells. Goals of the present study were to better define the role of gangliosides in EGFR/ErbB2 heterodimerization and receptor phosphorylation events and to analyze their involvement in mammary cell differentiation.

Endogenous antioxidants and radical scavengers.

All living organisms are constantly exposed to oxidant agents deriving from both endogenous and exogenous sources capable to modify biomolecules and induce damages. Free radicals generated by oxidative stress exert an important role in the development of tissue damage and aging. Reactive species (RS) derived from oxygen (ROS) and nitrogen (RNS) pertain to free radicals family and are constituted by various forms of activated oxygen or nitrogen.

Simulated microgravity induce glutathione antioxidant pathway in Xenopus laevis embryos.

Space flights cause a number of patho-physiological changes. Oxidative damage has been demonstrated in astronauts after space flights. Oxidative stress is due to an imbalance between production of oxidant and antioxidative defence.

Analysis of major proteins and fat fractions associated with mare's milk fat globules.

Although several studies have aimed to identify mare's milk proteins, only the major whey proteins and some caseins have yet been characterized. Incomplete sequencing of the equine genome and the difficulty of recovering highly hydrophobic proteins mean that little is known to date about the proteins associated with milk fat globules, which have been shown to play an important role in newborns' defense mechanisms. The fat fraction, in particular the distribution of unsaturated fatty acids, has been more extensively studied, but complex lipids are only partially elucidated.

Ganglioside GM(3) is stably associated to tyrosine-phosphorylated ErbB2/EGFR receptor complexes and EGFR monomers, but not to ErbB2.

Gangliosides are known to modulate the activation of receptor tyrosine-kinases (RTKs). Recently, we demonstrated the functional relationship between ErbB2 and ganglioside GM(3) in HC11 epithelial cell line. In the present study we investigated, in the same cells, the ErbB2 activation state and its tendency to form stable molecular complexes with the epidermal growth factor receptor (EGFR) and with ganglioside GM(3) upon EGF stimulation.

Antioxidant metabolism in Xenopus laevis embryos is affected by stratospheric balloon flight.

To test the effects of low levels of radiation from space on living organisms, we flew Xenopus laevis embryos at different stages of development on a stratospheric balloon (BI.R.BA mission).

Human GM3 synthase: a new mRNA variant encodes an NH2-terminal extended form of the protein.

All human GM3 synthase mRNA variants until now identified predict a protein of 362 amino acids having substrate activity highly restricted to lactosylceramide. In this report we describe the identification of a new GM3 synthase transcript containing an additional translation start codon, located upstream and in-frame with that up to now considered unique translation initiation site in the human GM3 synthase gene. In vitro expression studies showed that the new transcript produces a longer form of human GM3 synthase, that is efficiently translocated into the microsomal lumen and glycosylated.