Transplanted Mesoangioblasts Require Macrophage IL-10 for Survival in a Mouse Model of Muscle Injury

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Training Effects on ROS Production Determined by Electron Paramagnetic Resonance in Master Swimmers

Acute exercise induces an increase in Reactive Oxygen Species (ROS) production dependent on exercise intensity with highest ROS amount generated by strenuous exercise. However, chronic repetition of exercise, that is, exercise training, may reduce exercise-induced oxidative stress. Aim of this study was to evaluate the effects of 6-weeks high-intensity discontinuous training (HIDT), characterized by repeated variations of intensity and changes of redox potential, on ROS production and antioxidant capacity in sixteen master swimmers. Time course changes of ROS generation were assessed by Electron Paramagnetic Resonance in capillary blood by a microinvasive approach. An incremental arm-ergometer exercise (IE) until exhaustion was carried out at both before (PRE) and after (POST) training (Trg) period. A significant (P<0.01) increase of ROS production from REST to the END of IE in PRE Trg (2.82±0.66 versus 3.28±0.66 µmol·min−1) was observed. HIDT increased peak oxygen consumption (36.1±4.3 versus 40.6±5.7 mL·kg−1·min−1 PRE and POST Trg, resp.) and the antioxidant capacity (+13%) while it significantly decreased the ROS production both at REST (−20%) and after IE (−25%). The observed link between ROS production, adaptive antioxidant defense mechanisms, and peak oxygen consumption provides new insight into the correlation between ROS response pathways and muscle metabolic function

A twofold subjective measure of income inequality

Social scientists have been aiming to calculate a “subjective income Gini coefficient”of survey respondents that would describe their beliefs about income inequality in their country. Niehues (Subjective perceptions of inequality and redistributive preferences: an international comparison, Cologne Institute for Economic Research, IWTRENDS Discussion Paper, 2014) derives this estimate from respondents’ beliefs about the relative sizes of different social classes (answers to “shape of society” questions), while Kuhn (The individual perception of wage inequality: a measurement framework and some empirical evidence, Technical report, Institute of Labor Economics (IZA), 2015) estimates it using beliefs about the pay structure. We combine their efforts to calculate what we call a twofold subjective Gini coefficient, which incorporates both pieces of information independently from one another. We present the country-level distribution of perceived and desired twofold subjective Gini coefficients using the ISSP Social Inequality V survey (ISSP Research Group in International social survey programme: social inequalityv—issp 2019, 2019. https://doi.org/10.4225/13/511C71F8612C3 ). Accounting for both subjective class structure and pay structure yields much lower perceived and desired levels of inequality. At the country level the averages of the twofold subjective Gini coefficients are closer to actual income Gini coefficients than the previous measures. At the individual level the twofold subjective Gini coefficients are better predictors of the individual’s verbal assessment of inequality and their preferences towards redistribution

Hyperactive Akt1 Signaling Increases Tumor Progression and DNA Repair in Embryonal Rhabdomyosarcoma RD Line and Confers Susceptibility to Glycolysis and Mevalonate Pathway Inhibitors

In pediatric rhabdomyosarcoma (RMS), elevated Akt signaling is associated with increased malignancy. Here, we report that expression of a constitutively active, myristoylated form of Akt1 (myrAkt1) in human RMS RD cells led to hyperactivation of the mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway, resulting in the loss of both MyoD and myogenic capacity, and an increase of Ki67 expression due to high cell mitosis. MyrAkt1 signaling increased migratory and invasive cell traits, as detected by wound healing, zymography, and xenograft zebrafish assays, and promoted repair of DNA damage after radiotherapy and doxorubicin treatments, as revealed by nuclear detection of phosphorylated H2A histone family member X (γH2AX) through activation of DNA-dependent protein kinase (DNA-PK). Treatment with synthetic inhibitors of phosphatidylinositol-3-kinase (PI3K) and Akt was sufficient to completely revert the aggressive cell phenotype, while the mTOR inhibitor rapamycin failed to block cell dissemination. Furthermore, we found that pronounced Akt1 signaling increased the susceptibility to cell apoptosis after treatments with 2-deoxy-D-glucose (2-DG) and lovastatin, enzymatic inhibitors of hexokinase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), especially in combination with radiotherapy and doxorubicin. In conclusion, these data suggest that restriction of glucose metabolism and the mevalonate pathway, in combination with standard therapy, may increase therapy success in RMS tumors characterized by a dysregulated Akt signaling

FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration

Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue

An Integrated Approach for a Structural and Functional Evaluation of Biosimilars: Implications for Erythropoietin

BACKGROUND: Authorization to market a biosimilar product by the appropriate institutions is expected based on biosimilarity with its originator product. The analogy between the originator and its biosimilar(s) is assessed through safety, purity, and potency analyses. OBJECTIVE: In this study, we proposed a useful quality control system for rapid and economic primary screening of potential biosimilar drugs. For this purpose, chemical and functional characterization of the originator rhEPO alfa and two of its biosimilars was discussed. METHODS: Qualitative and quantitative analyses of the originator rhEPO alfa and its biosimilars were performed using reversed-phase high-performance liquid chromatography (RP-HPLC). The identification of proteins and the separation of isoforms were studied using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF–MS) and two-dimensional gel electrophoresis (2D-PAGE), respectively. Furthermore, the biological activity of these drugs was measured both in vitro, evaluating the TF-1 cell proliferation rate, and in vivo, using the innovative experimental animal model of the zebrafish embryos. RESULTS: Chemical analyses showed that the quantitative concentrations of rhEPO alfa were in agreement with the labeled claims by the corresponding manufacturers. The qualitative analyses performed demonstrated that the three drugs were pure and that they had the same amino acid sequence. Chemical differences were found only at the level of isoforms containing N-glycosylation; however, functional in vitro and in vivo studies did not show any significant differences from a biosimilar point of view. CONCLUSION: These rapid and economic structural and functional analyses were effective in the evaluation of the biosimilarity between the originator rhEPO alfa and the biosimilars analyzed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40259-015-0136-3) contains supplementary material, which is available to authorized users

Teleneuropsychology: normative data for the assessment of memory in online settings

The present study provides to create a reference for the clinical use of neuropsychological instruments to assess verbal memory performance in a remote settin

The impacts of COVID-19 on the relationship between perceived economic inequality and political action among socioeconomic classes

Economic inequality qualifies as a structural characteristic leading to political action, albeit this relationship manifests differently across socioeconomic classes. COVID-19 pandemic has amplified existing economic inequalities in ways that increased social tensions and political unrest around the world. This research investigates the effect of COVID-19 personal impacts on the relationship between perceived economic inequality and individuals’ political actions. An online survey was administered to a representative sample of 1446 Italians of which 51% were women with a mean age of 42.42 years (SD = 12.87). The questionnaire assessed the perceived economic inequality, the personal impacts of COVID-19 (i.e., on finance, mental health, and ability to procure resources), and individuals’ involvement in political actions. Moderation analyses were conducted separately for different socioeconomic classes (i.e., lower, middle, and upper classes). Results showed that individuals who perceive greater economic inequality are more likely to take action, but only if they belong to the higher class. For lower-class individuals, perceiving greater inequality erodes political action. Interaction effects occurred mainly in the middle class and with COVID-19 impacts on resources procurement, which inhibits political action

Assessment of a Standardized ROS Production Profile in Humans by Electron Paramagnetic Resonance

Despite the growing interest in the role of reactive oxygen species (ROS) in health and disease, reliable quantitative noninvasive methods for the assessment of oxidative stress in humans are still lacking. EPR technique, coupled to a specific spin probe (CMH: 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) is here presented as the method of choice to gain a direct measurement of ROS in biological fluids and tissues. The study aimed at demonstrating that, differently from currently available “a posteriori” assays of ROS-induced damage by means of biomolecules (e.g., proteins and lipids) spin-trapping EPR provides direct evidence of the “instantaneous” presence of radical species in the sample and, as signal areas are proportional to the number of excited electron spins, lead to absolute concentration levels. Using a recently developed bench top continuous wave system (e-scan EPR scanner, Bruker) dealing with very low ROS concentration levels in small (50 μL) samples, we successfully monitored rapid ROS production changes in peripheral blood of athletes after controlled exercise and sedentary subjects after antioxidant supplementation. The correlation between EPR results and data obtained by various enzymatic assays (e.g., protein carbonyls and thiobarbituric acid reactive substances) was determined too. Synthetically, our method allows reliable, quick, noninvasive quantitative determination of ROS in human peripheral blood

Parallelism of Chemicostructural Properties between Filgrastim Originator and Three of Its Biosimilar Drugs

The approval and granting of marketing authorization for a putative biosimilar is based on strong comparability studies with its biological reference product. This is due to the complexity of the structure and nature of the manufacturing process of biological drugs. Hence, a rigorous analytical workflow for chemical characterization and clinical trials to evaluate the efficacy and safety is required to demonstrate their high similarities to the reference drug. This work is focused on the comparison of the originator of filgrastim with three of its biosimilars by evaluating their structural similarity and biological activity. Qualiquantitative analyses were performed by MALDI-TOF/TOF-MS and RP-HPLC-UV. An innovative functional assay using zebrafish as the animal model was developed to evaluate the biological activities of the drugs. The different analyses performed in this study highlighted the structural similarity of biosimilar drugs and their originator. This result was further confirmed by a similar in vivo biological activity