Dark Chocolate Intake Positively Modulates Redox Status and Markers of Muscular Damage in Elite Football Athletes: A Randomized Controlled Study

Intensive physical exercise may cause increase oxidative stress and muscular injury in elite football athletes. The aim of this study was to exploit the effect of cocoa polyphenols on oxidative stress and muscular injuries induced by intensive physical exercise in elite football players. Oxidant/antioxidant status and markers of muscle damage were evaluated in 24 elite football players and 15 controls. Furthermore, the 24 elite football players were randomly assigned to either a dark chocolate (>85% cocoa) intake (n = 12) or a control group (n = 12) for 30 days in a randomized controlled trial. Oxidative stress, antioxidant status, and muscle damage were assessed at baseline and after 30 days of chocolate intake. Compared to controls, elite football players showed lower antioxidant power and higher oxidative stress paralleled by an increase in muscle damage markers. After 30 days of dark chocolate intake, an increased antioxidant power was found in elite athletes assuming dark chocolate. Moreover, a significant reduction in muscle damage markers (CK and LDH, p < 0.001) was observed. In the control group, no changes were observed with the exception of an increase of sNox2-dp, H2O2, and myoglobin. A simple linear regression analysis showed that sNox2-dp was associated with a significant increase in muscle damage biomarker release (p = 0.001). An in vitro study also confirmed that polyphenol extracts significantly decreased oxidative stress in murine myoblast cell line C2C12-derived. These results indicate that polyphenol-rich nutrient supplementation by means of dark chocolate positively modulates redox status and reduced exercise-induced muscular injury biomarkers in elite football athletes. This trial is registered with NCT03288623

Games for query inseparability of description logic knowledge bases

We consider conjunctive query inseparability of description logic knowledge bases with respect to a given signature---a fundamental problem in knowledge base versioning, module extraction, forgetting and knowledge exchange. We give a uniform game-theoretic characterisation of knowledge base conjunctive query inseparability and develop worst-case optimal decision algorithms for fragments of Horn-ALCHI, including the description logics underpinning OWL 2 QL and OWL 2 EL. We also determine the data and combined complexity of deciding query inseparability. While query inseparability for all of these logics is P-complete for data complexity, the combined complexity ranges from P- to ExpTime- to 2ExpTime-completeness. We use these results to resolve two major open problems for OWL 2 QL by showing that TBox query inseparability and the membership problem for universal conjunctive query solutions in knowledge exchange are both ExpTime-complete for combined complexity. Finally, we introduce a more flexible notion of inseparability which compares answers to conjunctive queries in a given signature over a given set of individuals. In this case, checking query inseparability becomes NP-complete for data complexity, but the ExpTime- and 2ExpTime-completeness combined complexity results are preserved

Natural experience acquired in adulthood enhances holistic processing of other-age faces

Adults have been shown to perform better when recognizing adult faces in comparison to their performance when recognizing faces of different ages, resulting in an other-age effect (OAE) that resembles the well-known other-race effect (ORE). Both the OAE and ORE have been proposed to be experience dependent. In the current study, we used the composite-face paradigm with adult- and child-face stimuli to test holistic processing abilities of two groups of participants, a group of child novices and a group of preschool teachers. Our results demonstrate that novices do engage in holistic processing with both child and adult faces. However, the data also show that, for child faces, teachers used holistic processing to a greater extent than do novices. Moreover, teachers also engaged in holistic processing to a greater extent with child faces than with adult faces. These data suggest that experience likely plays a critical role in tuning holistic processing strategies towards specific types of faces. © 2008 Psychology Press

Skeletal muscle myofibrillar protein oxidation in heart failure and the protective effect of Carvedilol

Heart failure is characterized by limited exercise tolerance and by a skeletal muscle myopathy with atrophy and shift toward fast fibres. An inflammatory status with elevated pro-inflammatory cytokines and exaggerated free radicals production, can worsen muscle damage. In a well established model of heart failure, the monocrotaline treated rat, we show that CHF is accompanied by oxidation of the skeletal muscle actin, tropomyosin and myosin, which further depresses muscle function and exercise capacity. We have also tested the efficacy of Carvedilol, a non-selective beta(1)-beta(2)-blocker, which has been widely used in clinical trials to improve exercise tolerance and reduce mortality in moderate and severe CHF, in preventing contractile protein oxidation in CHF rats. As comparison we used Bisoprolol a beta(1) selective agent, without known anti-oxidative properties. Carvedilol at the dose of 2 mg/kg per day was able to prevent the myofibrillar protein oxidation, while Bisoprolol (0.1 mg/kg) did it only partially, as demonstrated by the oxyblot analysis. While Carvedilol improved force production on isolated muscles, Bisoprolol did not. After the COMET trial, the anti-oxidative capacity of Carvedilol has been invoked as one of the mechanism that makes this drug superior to other selective beta-blockers in the treatment of CHF. One of the reason of Carvedilol superiority could be the effect on skeletal muscle with reduction of contractile protein peroxidation, amelioration of muscle function and improvement of exercise tolerance. Inhibition of reactive oxygen species (ROS) production, and of pro-inflammatory cytokines may also lead to a decreased muscle wastage, another factor contributing to worsening of exercise tolerance

Skeletal muscle proteins oxidation in chronic right heart failure in rats: can different beta-blockers prevent it to the same degree?

BACKGROUND: Skeletal muscle atrophy and decreased expression of slow fibers contribute to exercise capacity limitation in Chronic Heart Failure (CHF). Pro-inflammatory cytokines and free radicals worsen muscle damage. In CHF sarcomeric proteins are oxidized with reduction of muscle twitch efficiency, and VO(2)-max. Beta-blockers with anti-oxidative capacity such as carvedilol have been shown to prevent contractile protein oxidation in CHF rats. Recently a new class of beta-blockers with NO donor activity has been introduced and approved for the treatment of CHF. Since a clinical clear superiority of a beta-blocker has never been shown, we compared nebivolol, that possesses NO donor activity, with bisoprolol, looking at possible differences in skeletal muscle that may have an impact on muscle function and exercise capacity in humans. We therefore studied skeletal muscle apoptosis and wastage, sarcomeric protein composition and oxidation, and muscle efficiency. METHODS AND RESULTS: In the monocrotaline rat model of CHF we compared nebivolol a beta-blocker with vasodilative properties mediated by NO production, with bisoprolol. Nebivolol prevented protein oxidation, while bisoprolol did it only partially, as demonstrated by the oxyblot analysis (Oxy/RP values) (0.90+/-0.14 Controls.; 1.7+/-0.14 CHF; 1.1+/-0.05 bisoprolol; 0.82+/-0.17 nebivolol low; 0.62+/-0.10 nebivolol high). Only nebivolol improved twitch force production and relaxation. Nebivolol prevented fibers shift towards fast isoforms, atrophy, decreased apoptosis and sphingosine levels. CONCLUSIONS: Nebivolol seems better than bisoprolol in CHF by decreasing apoptosis and cytokines induced muscle wastage, preventing fibers shift and protein oxidation. Nebivolol by stimulating NO generation may have prevented protein oxidation. It could be speculated that ROS release, pro-inflammatory cytokines production and NF-kappa-B activation may play a key role. These positive changes could produce a favorable impact on exercise capacity in man

A transient antioxidant stress response accompanies the onset of disuse atrophy in human skeletal muscle

It is presently unknown whether oxidative stress increases in disused skeletal muscle in humans. Markers of oxidative stress were investigated in biopsies from the vastus lateralis muscle, collected from healthy subjects before [time 0 (T0)], after 1 wk (T8), and after 5 wk (T35) of bed rest. An 18% decrease in fiber cross-sectional area was detected in T35 biopsies (P < 0.05). Carbonylation of muscle proteins significantly increased about twofold at T35 (P < 0.02) and correlated positively with the decrease in fiber cross-sectional area (P = 0.04). Conversely, T8 biopsies showed a significant increase in protein levels of heme oxygenase-1 and glucose-regulated protein-75 (Grp75)/mitochondrial heat shock protein-70, two stress proteins involved in the antioxidant defense (P < 0.05). Heme oxygenase-1 increase, which involved a larger proportion of slow fibers compared with T0, appeared blunted in T35 biopsies. Grp75 protein level increased threefold in T8 biopsies and localized especially in slow fibers (P < 0.025), to decrease significantly in T35 biopsies (P < 0.05). Percent change in Grp75 levels positively correlated with fiber cross-sectional area (P = 0.01). Parallel investigations on rat soleus muscles, performed after 1-15 days of hindlimb suspension, showed that Grp75 protein levels significantly increased after 24 h of unloading (P = 0.02), i.e., before statistically significant evidence of muscle atrophy, to decrease thereafter in relation to the degree of muscle atrophy (P = 0.03). Therefore, in humans as in rodents, disuse muscle atrophy is characterized by increased protein carbonylation and by the blunting of the antioxidant stress response evoked by disuse

Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure

Muscle atrophy is a determinant of exercise capacity in heart failure (CHF). Myocyte apoptosis, triggered by tumor necrosis factor-alpha (TNF-alpha) or its second messenger sphingosine (SPH), is one of the causes of atrophy. Growth hormone (GH) improves hemodynamic and cardiac trophism in several experimental models of CHF, but its effect on skeletal muscle in CHF is not yet clear. We tested the hypothesis that GH can prevent skeletal muscle apoptosis in rats with CHF. CHF was induced by injecting monocrotaline. After 2 wk, 2 groups of rats were treated with GH (0.2 mg.kg(-1).day(-1) and 1.0 mg.kg(-1).day(-1)) subcutaneously. A third group of controls had saline. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, myosin heavy chain (MHC) composition, and a study on myocyte apoptosis and serum levels of TNF-alpha and SPH were carried out. The number of apoptotic nuclei, muscle atrophy, and serum levels of TNF-alpha and SPH were decreased with GH at high but not at low doses compared with CHF rats. Bcl-2 was increased, whereas activated caspases and bax were decreased. The MHC pattern in GH-treated animals was similar to that of controls. Monocrotaline slowed down both contraction and relaxation but did not affect specific tetanic force, whereas absolute force was decreased. GH treatment restored contraction and relaxation to control values and brought muscle mass and absolute twitch and tetanic tension to normal levels. These findings may provide an insight into the therapeutic strategy of GH given to patients with CHF to improve exercise capacity

UHRF1-miRNAs modulate Dnmt3a expression in prostate transformed cells

UHRF1 is overexpressed in many tumours and is an epigenetic regulator required for DNA methylation (DNAm) by recruiting all DNMTs to methylation sites. UHRF1 is also crucial for histone modifications, epigenetic gene silencing and has an important impact on prostate cancer pathogenesis and progression. Here we studied whether UHRF1 could exert its role in the epigenetic of cancer by changes in microRNA (miRNA) levels in prostate transformed cells. MiRNAs are small non-coding RNAs that negatively control gene expression and play crucial functions in all cellular processes. Growing evidences indicate their deregulated expression in human cancer, proposing miRNAs as oncogenes or tumour suppressors. Besides, miRNAs can induce gene silencing via epigenetic mechanisms e.g. by targeting a specific gene region for DNAm and histone modifications or by regulating expression of epigenetic enzymes. MiRNAs expression profile of siRNA-UHRF1 PC3 cells showed both increased and decreased miRNA levels. Using different target predictive software, Dnmt3a appeared as a target of two new miRNAs (miRNA-a and miRNA-b) overexpressed in siRNA-UHRF1 PC3 cells. Levels of miRNA-a and -b were confirmed by RT-QPCR in siRNA-UHRF1 PC3 and in LNCaP cells (with UHRF1 and Dnmt3a lower levels than PC3) and the binding of the two new miRNAs to the Dnmt3a3\u2019UTR and its inhibitory effect were validated by reporter luciferase system. We studied the effect of the overexpression of miRNA-a and -b in PC3 finding a decrease of Dnmt3a mRNA and protein, and a decrease in PC3 proliferation. We studied the effects of miRNA silencing in LNCaP finding an increase of Dnmt3a mRNA and protein, and an increase in LNCaP proliferation. These data show the role of miRNA-a and -b in the modulation of Dnmt3a and propose their involvement in prostate cancer progression. Next goal is to study their promoters evaluating the role of UHRF1 in miRNAs transcription