Oxygen uptake, heart rate and activities of locomotor muscles during a critical swimming speed protocol in the gilthead sea bream Sparus aurata

Oxygen uptake, heart rate, and contraction frequencies of slow oxidative (SO) and fast glycolytic (FG) muscle, were measured simultaneously in gilthead seabream Sparus aurata submitted to stepwise increases in current speed in a swimming respirometer. Variation in oxygen uptake was closely related to variation in heart rate, over initial steps these rose in concert with an increase in contraction frequency of SO muscle. There was an asymptote in oxygen uptake and heart rate at high speeds, that reflected a transition from exclusive use of aerobic SO muscle to a combination of SO and anaerobic FG muscle, and which preceded fatigue

Programmed cell death ligand 2 regulates TH9 differentiation and induction of chronic airway hyperreactivity.

Our findings suggest that PD-L2 plays a pivotal role in the regulation of TH9 cell development in chronic AHR, providing novel strategies for modulating adaptive immunity during chronic allergic responses

A TLR4 Agonist Induces Osteosarcoma Regression by Inducing an Antitumor Immune Response and Reprogramming M2 Macrophages to M1 Macrophages

Osteosarcoma (OsA) has limited treatment options and stagnant 5-year survival rates. Its immune microenvironment is characterized by a predominance of tumor-associated macrophages (TAMs), whose role in OsA progression remain unclear. Nevertheless, immunotherapies aiming to modulate macrophages activation and polarization could be of interest for OsA treatment. In this study, the antitumor effect of a liposome-encapsulated chemically detoxified lipopolysaccharide (Lipo-MP-LPS) was evaluated as a therapeutic approach for OsA. Lipo-MP-LPS is a toll-like receptor 4 (TLR4) agonist sufficiently safe and soluble to be IV administered at effective doses. Lipo-MP-LPS exhibited a significant antitumor response, with tumor regression in 50% of treated animals and delayed tumor progression in the remaining 50%. The agent inhibited tumor growth by 75%, surpassing the efficacy of other immunotherapies tested in OsA. Lipo-MP-LPS modulated OsA’s immune microenvironment by favoring the transition of M2 macrophages to M1 phenotype, creating a proinflammatory milieu and facilitating T-cell recruitment and antitumor immune response. Overall, the study demonstrates the potent antitumor effect of Lipo-MP-LPS as monotherapy in an OsA immunocompetent model. Reprogramming macrophages and altering the immune microenvironment likely contribute to the observed tumor control. These findings support the concept of immunomodulatory approaches for the treatment of highly resistant tumors like OsA

Effects of extraction method and storage of dry tissue on marine lipids and fatty acids

Various protocols are currently used to study marine lipids, but there is a growing interest in working on dry samples that are easier to transport. However, reference protocols are still lacking for dry samples. In order to make recommendations on this use, lipid classes and fatty acids (FA) obtained from six analytical protocols using two different tissue states (dry vs wet) and three extraction methods (automat vs manual potter vs leaving the solvent to work on tissue) were compared. Three dry storage modes of tissue (freezer vs gas nitrogen vs dry room) during one and three months were also compared. These comparisons were made on seven marine species with different lipid profiles, including fishes, crustaceans and mollusks. Lipid classes and FA obtained from wet and dry tissues were similar, but they were affected by the extraction methods. Regardless of tissue state, “Leave to work” methods obtained the highest lipid quantities, followed by manual potter and automat methods (ca. 90% and 80% of “Leave to work” methods, respectively). Linear relationships allowed correction for lipid classes and FA concentrations obtained from different protocols. The repeatability of all protocols still needs to be improved, especially for fish species. Increasing the replicate number for each sample might be an indirect way to improve lipid quantification. Our results show that storing dry tissues in the freezer for more than one month was associated with a decrease in lipids, which is also observed for other storage methods. For qualitative studies of FA (expressed in %), a three-month storage of dry tissue in freezer did not affect the relative composition of species/tissues with a lipid content below 20% of dry weight

A CD1d-Dependent Antagonist Inhibits the Activation of Invariant NKT Cells and Prevents Development of Allergen-Induced Airway Hyperreactivity

The prevalence of asthma continues to increase in westernized countries, and optimal treatment remains a significant therapeutic challenge. Recently, CD1d-restricted invariant NKT (iNKT) cells were found to play a critical role in the induction of airway hyperreactivity (AHR) in animal models and are associated with asthma in humans. To test whether iNKT cell-targeted therapy could be used to treat allergen-induced airway disease, mice were sensitized with OVA and treated with di-palmitoyl-phosphatidyl-ethanolamine polyethylene glycol (DPPE-PEG), a CD1d-binding lipid antagonist. A single dose of DPPE-PEG prevented the development of AHR and pulmonary infiltration of lymphocytes upon OVA challenge, but had no effect on the development of OVA-specific Th2 responses. In addition, DPPE-PEG completely prevented the development of AHR after administration of α-galactosylceramide (α-GalCer) intranasally. Furthermore, we demonstrate that DPPE-PEG acts as antagonist to α-GalCer and competes with α-GalCer for binding to CD1d. Finally, we show that DPPE-PEG completely inhibits the α-GalCer–induced phosphorylation of ERK tyrosine kinase in iNKT cells, suggesting that DPPE-PEG specifically blocks TCR signaling and thus activation of iNKT cells. Because iNKT cells play a critical role in the development of AHR, the inhibition of iNKT activation by DPPE-PEG suggests a novel approach to treat iNKT cell-mediated diseases such as asthma