Effect of hyperoxia on the immune status of oxygen divers and endurance athletes.

Physical activity, particularly that, exerted by endurance athletes, impacts the immune status of the human body. Prolonged duration and high-intensity endurance training lead to increased production of reactive oxygen species (ROS) and thereby to oxidative stress. Military combat swimmers (O2-divers) are regularly exposed to hyperbaric hyperoxia (HBO) in addition to intensive endurance training intervals. They are, therefore, exposed to extreme levels of oxidative stress. Several studies support that the intensity of oxidative stress essentially determines the effect on immune status. The aim of this study was to comparatively characterise peripheral blood mononuclear cells (PBMCs) of O2-divers (military combat swimmers), endurance athletes (amateur triathletes), and healthy control volunteers with respect to DNA fragmentation, immune status and signs of inflammation. Furthermore, it was investigated how PBMCs from these groups responded acutely to exposure to HBO. We showed that DNA fragmentation was comparable in PBMCs of all three groups under basal conditions directly after HBO exposure. However, significantly higher DNA fragmentation was observed in O2-divers 18 hours after HBO, possibly indicating a slower recovery. O2-divers also exhibited a proinflammatory immune status exemplified by an elevated number of CD4+CD25+ T cells, elevated expression of proinflammatory cytokine IL-12, and diminished expression of anti-inflammatory TGF-ß1 compared to controls. Supported by a decreased basal gene expression and prolonged upregulation of anti-oxidative HO-1, these data suggest that higher oxidative stress levels, as present under intermitted hyperbaric hyperoxia, e.g. through oxygen diving, promote a higher inflammatory immune status than oxidative stress through endurance training alone.

Structure-Based Design of Potent Tumor-Associated Antigens: Modulation of Peptide Presentation by Single-Atom O/S or O/Se Substitutions at the Glycosidic Linkage.

GalNAc-glycopeptides derived from mucin MUC1 are an important class of tumor-associated antigens. α- O-glycosylation forces the peptide to adopt an extended conformation in solution, which is far from the structure observed in complexes with a model anti-MUC1 antibody. Herein, we propose a new strategy for designing potent antigen mimics based on modulating peptide/carbohydrate interactions by means of O → S/Se replacement at the glycosidic linkage. These minimal chemical modifications bring about two key structural changes to the glycopeptide. They increase the carbohydrate-peptide distance and change the orientation and dynamics of the glycosidic linkage. As a result, the peptide acquires a preorganized and optimal structure suited for antibody binding. Accordingly, these new glycopeptides display improved binding toward a representative anti-MUC1 antibody relative to the native antigens. To prove the potential of these glycopeptides as tumor-associated MUC1 antigen mimics, the derivative bearing the S-glycosidic linkage was conjugated to gold nanoparticles and tested as an immunogenic formulation in mice without any adjuvant, which resulted in a significant humoral immune response. Importantly, the mice antisera recognize cancer cells in biopsies of breast cancer patients with high selectivity. This finding demonstrates that the antibodies elicited against the mimetic antigen indeed recognize the naturally occurring antigen in its physiological context. Clinically, the exploitation of tumor-associated antigen mimics may contribute to the development of cancer vaccines and to the improvement of cancer diagnosis based on anti-MUC1 antibodies. The methodology presented here is of general interest for applications because it may be extended to modulate the affinity of biologically relevant glycopeptides toward their receptors.

Neuroprotective Effects of Pycnogenol Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Primary Rat Astrocytes via NF-κB and ERK1/2 MAPK Pathways.

BACKGROUNDS/AIMS: Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. In this study, we investigated the effects of PYC on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in primary rat astrocytes. METHODS: The primary rat astrocytes were randomly divided into 6 groups, blank control, OGD/R, OGD/R+PYC (10, 20, 40, and 60 µg/mL). The cell activity were detected by MTT and LDH assays, then the levels of oxidant products [malondialdehyde (MDA) and reactive oxygen species (ROS)] , antioxidants [superoxide dismutase (SOD)], mitochondrial membrane potential (MMP) and inflammatory cytokines were detected. In addition, the expression levels of apoptosis-related proteins (Bax, Bcl-2 and Cleaved caspase 3), proinflammatory factors (NF-κB p65), and p-ERK1/2 were measured by Western blot analysis. RESULTS: The results showed that PYC incubation dose-dependently attenuated cell viability loss, LDH leakage, oxidative stress, inflammatory cytokines accumulation and cell apoptosis caused by OGD/R. Furthermore, PYC pretreatment dose-dependently suppressed OGD/R-induced NF-κB p65 nuclear translocation, NF-κB activity and ERK1/2 phosphorylation. Similarly to PYC, NF-κB inhibitor PDTC and ERK1/2 inhibitor PD098059 dramatically inhibited OGD/R-induced NF-κB activation, ERK1/2 phosphorylation, and ROS production, as well as TNF-α secretion. CONCLUSIONS: These findings revealed that PYC has neuroprotective effects against OGD/R-induced injury via NF-κB and ERK1/2 pathways in primary rat astrocytes.

Effect of post-exercise protein-leucine feeding on neutrophil function, immunomodulatory plasma metabolites and cortisol during a 6-day block of intense cycling.

Whey protein and leucine ingestion following exercise increases muscle protein synthesis and could influence neutrophil function during recovery from prolonged intense exercise. We examined the effects of whey protein and leucine ingestion post-exercise on neutrophil function and immunomodulators during a period of intense cycling. In a randomized double-blind crossover, 12 male cyclists ingested protein/leucine/carbohydrate/fat (LEUPRO 20/7.5/89/22 g h(-1), respectively) or isocaloric carbohydrate/fat control (CON 119/22 g h(-1)) beverages for 1-3 h post-exercise during 6 days of high-intensity training. Blood was taken pre- and post-exercise on days 1, 2, 4 and 6 for phorbol myristate acetate (PMA)-stimulated neutrophil superoxide (O2 (-)) production, immune cell counts, amino acid and lipid metabolism via metabolomics, hormones (cortisol, testosterone) and cytokines (interleukin-6, interleukin-10). During recovery on day 1, LEUPRO ingestion increased mean concentrations of plasma amino acids (glycine, arginine, glutamine, leucine) and myristic acid metabolites (acylcarnitines C14, myristoylcarnitine; and C14:1-OH, hydroxymyristoleylcarnitine) with neutrophil priming capacity, and reduced neutrophil O2 production (15-17 mmol O2 (-) cell(-1) ± 90 % confidence limits 20 mmol O2 (-) cell(-1)). On day 2, LEUPRO increased pre-exercise plasma volume (6.6 ± 3.8 %) but haematological effects were trivial. LEUPRO supplementation did not substantially alter neutrophil elastase, testosterone, or cytokine concentrations. By day 6, however, LEUPRO reduced pre-exercise cortisol 21 % (±15 %) and acylcarnitine C16 (palmitoylcarnitine) during exercise, and increased post-exercise neutrophil O2 (-) (33 ± 20 mmol O2 (-) cell(-1)), relative to control. Altered plasma amino acid and acylcarnitine concentrations with protein-leucine feeding might partly explain the acute post-exercise reduction in neutrophil function and increased exercise-stimulated neutrophil oxidative burst on day 6, which could impact neutrophil-dependent processes during recovery from intense training.

The use of hyperbaric oxygen therapy to treat chronic wounds: A review.

Chronic wounds, defined as those wounds which fail to proceed through an orderly process to produce anatomic and functional integrity, are a significant socioeconomic problem. A wound may fail to heal for a variety of reasons including the use of corticosteroids, formation of squamous cell carcinoma, persistent infection, unrelieved pressure, and underlying hypoxia within the wound bed. Hypoxia appears to inhibit the wound healing process by blocking fibroblast proliferation, collagen production, and capillary angiogenesis and to increase the risk of infection. Hyperbaric oxygen therapy (HBOT) has been shown to aid the healing of ulcerated wounds and demonstrated to reduce the risk of amputation in diabetic patients. However, the causal reasons for the response of the underlying biological processes of wound repair to HBOT, such as the up-regulation of angiogenesis and collagen synthesis are unclear and, consequently, current protocols remain empirical. Here we review chronic wound healing and the use of hyperbaric oxygen as an adjunctive treatment for nonhealing wounds. Databases including PubMed, ScienceDirect, Blackwell Synergy, and The Cochrane Library were searched for relevant phrases including HBOT, HBO/HBOT, wound healing, and chronic/nonhealing wounds/ulcers.