The Calcineurin Antagonist, RCAN1-4 is Induced by Exhaustive Exercise in Rat Skeletal Muscle

International audienceThe aim of this work was to study the regulation of the calcineurin antagonist regulator of calcineurin 1 (RCAN1) in rat skeletal muscles after exhaustive physical exercise, which is a physiological modulator of oxidative stress. Three skeletal muscles, namely extensor digitorum longus (EDL), gastrocnemius, and soleus, were investigated. Exhaustive exercise increased RCAN1-4 protein levels in EDL and gastrocnemius, but not in soleus. Protein oxidation as an index of oxidative stress was increased in EDL and gastrocnemius, but remained unchanged in soleus. However, lipid peroxidation was increased in all three muscles. CuZnSOD and catalase protein levels were increased at 3 h postexercise in soleus, whereas they remained unchanged in EDL and gastrocnemius. Calcineurin enzymatic activity declined in EDL and gastrocnemius but not in soleus, and its protein expression was decreased in all three muscles. The level of PGC1-α protein remained unchanged, whereas the protein expression of the transcription factor NFATc4 was decreased in all three muscles. Adiponectin expression was increased in all three muscles. RCAN1-4 expression in EDL and gastrocnemius muscles was augmented by the oxidative stress generated from exhaustive exercise. We propose that increased RCAN1-4 expression and the signal transduction pathways it regulates represent important components of the physiological adaptation to exercise-induced oxidative stress

The Oxygen Paradox, the French Paradox, and age-related diseases

open46openDavies, Joanna M. S.; Cillard, Josiane; Friguet, Bertrand; Cadenas, Enrique; Cadet, Jean; Cayce, Rachael; Fishmann, Andrew; Liao, David; Bulteau, Anne-Laure; Derbré, Frédéric; Rébillard, Amélie; Burstein, Steven; Hirsch, Etienne; Kloner, Robert A.; Jakowec, Michael; Petzinger, Giselle; Sauce, Delphine; Sennlaub, Florian; Limon, Isabelle; Ursini, Fulvio; Maiorino, Matilde; Economides, Christina; Pike, Christian J.; Cohen, Pinchas; Salvayre, Anne Negre; Halliday, Matthew R.; Lundquist, Adam J.; Jakowec, Nicolaus A.; Mechta-Grigoriou, Fatima; Mericskay, Mathias; Mariani, Jean; Li, Zhenlin; Huang, David; Grant, Ellsworth; Forman, Henry J.; Finch, Caleb E.; Sun, Patrick Y.; Pomatto, Laura C. D.; Agbulut, Onnik; Warburton, David; Neri, Christian; Rouis, Mustapha; Cillard, Pierre; Capeau, Jacqueline; Rosenbaum, Jean; Davies, Kelvin J. A.Davies, Joanna M. S.; Cillard, Josiane; Friguet, Bertrand; Cadenas, Enrique; Cadet, Jean; Cayce, Rachael; Fishmann, Andrew; Liao, David; Bulteau, Anne-Laure; Derbré, Frédéric; Rébillard, Amélie; Burstein, Steven; Hirsch, Etienne; Kloner, Robert A.; Jakowec, Michael; Petzinger, Giselle; Sauce, Delphine; Sennlaub, Florian; Limon, Isabelle; Ursini, Fulvio; Maiorino, Matilde; Economides, Christina; Pike, Christian J.; Cohen, Pinchas; Salvayre, Anne Negre; Halliday, Matthew R.; Lundquist, Adam J.; Jakowec, Nicolaus A.; Mechta-Grigoriou, Fatima; Mericskay, Mathias; Mariani, Jean; Li, Zhenlin; Huang, David; Grant, Ellsworth; Forman, HENRY J.; Finch, Caleb E.; Sun, Patrick Y.; Pomatto, Laura C. D.; Agbulut, Onnik; Warburton, David; Neri, Christian; Rouis, Mustapha; Cillard, Pierre; Capeau, Jacqueline; Rosenbaum, Jean; Davies, Kelvin J. A

Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality.

peer reviewedDespite advances in COVID-19 management, identifying patients evolving toward death remains challenging. To identify early predictors of mortality within 60 days of symptom onset (DSO), we performed immunovirological assessments on plasma from 279 individuals. On samples collected at DSO11 in a discovery cohort, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA), low receptor binding domain–specific immunoglobulin G and antibody-dependent cellular cytotoxicity, and elevated cytokines and tissue injury markers were strongly associated with mortality, including in patients on mechanical ventilation. A three-variable model of vRNA, with predefined adjustment by age and sex, robustly identified patients with fatal outcome (adjusted hazard ratio for log-transformed vRNA = 3.5). This model remained robust in independent validation and confirmation cohorts. Since plasma vRNA’s predictive accuracy was maintained at earlier time points, its quantitation can help us understand disease heterogeneity and identify patients who may benefit from new therapies

Effect of physical activity on human prostate cancer cells proliferation: involvement of oxidative stress?

International audienceProstate cancer constitutes a growing health concern which affects men in the Western world and it represents the first cause of death by cancer in France. Among the various origins of prostate cancer, sedentarity represents an important risk factor and a decrease of prostate cancer prevalence is associated with exercise. Physical activity is known to slow down and to prevent some cancers, preferentially breast and colon cancers (Kesaniemi et al., 2001; Leitzmann et al., 2007). However, studies concerning its effects in prostate cancer progression are today conflicting and conclusions are difficult to reach since there remains a lack of clarity on activity parameters (in terms of type, intensity, frequency and time). Recently, Farahmand and coll., have suggested that golf enhances the life expectancy about 5 years (adjusted by age, sex and socioeconomic status of subjects). This physical activity which numbered more than 410 377 members in France today corresponds mainly to a walking sport but it attracts more players. Golf could be suitable for men with low risk early stage prostate cancer during active surveillance. The objectives of this study are (1) to determine if physical activity (golf) has an effect on the in vitro proliferation of human prostate cancer cells and (2) to identify the involved molecular mechanisms. Oxidative stress (OS) phenotypes leading to an imbalance of pro/anti-oxidant in favor of pro-oxidant could play a role in the prostate tumorigenesis (reviewed by Khandrika and al., on 2009). The regular physical activity known to increase antioxidant defenses could reduce the evolution of the prostate cancer through OS-dependent signaling pathways. Serum of sedentary or golfers subjects (3 golf courses 18 holes/week, ? 9 MET-h/week) is incubated with LNCaP androgen-dependent human prostate cancer cells. Proliferation, cell death (necrosis and apoptosis) as well as molecular mechanisms are studied, mainly those dependent of OS. We demonstrate that golfers' serum inhibits the LNCaP cells proliferation without inducing cell death. This inhibition of proliferation doesnt depend on oxidative stress since no difference between the antioxidant status of sedentary serum and golfer serum appears. Golf could reduce the proliferation of prostate cancer cells in vitro but the preliminary results require further investigations

Effects of Active Video Games in Patients With Cancer: Systematic Review

BackgroundPhysical activity (PA) is now considered an adjuvant therapy in cancer treatment; nevertheless, multiple barriers could reduce PA engagement during treatment. Active video games (AVGs) lead to the achievement of mild- to moderate-intensity PA and represent a promising tool for regular movement and exercise. ObjectiveThis paper aims to review the current literature and provide updated content on the physiological and psychological effects of AVG-based interventions in patients with cancer undergoing treatment. MethodsFour electronic databases were investigated. Studies reporting on AVG interventions delivered to patients undergoing treatment were included. A total of 21 articles (17 interventions) were identified for data extraction and quality assessment. ResultsA total of 362 patients with cancer participated in the studies (number of participants 3-70). The majority underwent treatment for breast, lung, prostate, hematologic, or oral or laryngeal cancer. The types and stages of cancer varied in all studies. Participants ranged in age from 3 to 93 years. Four studies included patients with pediatric cancer. The duration of interventions ranged from 2 to 16 weeks, with a minimum of 2 sessions per week and a maximum of 1 daily session. Sessions were supervised in 10 studies, and 7 included home-based interventions. AVG interventions improved endurance, quality of life, cancer-related fatigue, and self-efficacy. Effects were mixed on strength, physical function, and depression. AVGs did not affect activity level, body composition, or anxiety. Compared with standard physiotherapy, physiological effects were lower or similar, and psychological effects were higher or similar. ConclusionsOverall, our results suggest that AVGs can be recommended to patients undergoing cancer treatment, given the physiological and psychological benefits. When AVGs are proposed, supervision of the sessions should be considered as it can limit dropouts. In the future, it is important to develop AVGs that combine endurance and muscle strengthening, with the possibility of achieving moderate to high exercise intensity, depending on the physical abilities of the patients, as indicated in the World Health Organization’s recommendations

The Janus-Faced Role of Antioxidants in Cancer Cachexia: New Insights on the Established Concepts

Chronic inflammation and excessive loss of skeletal muscle usually occur during cancer cachexia, leading to functional impairment and delaying the cure of cancer. The release of cytokines by tumor promotes the formation of reactive oxygen species (ROS), which in turn regulate catabolic pathways involved in muscle atrophy. ROS also exert a dual role within tumor itself, as they can either promote proliferation and vascularization or induce senescence and apoptosis. Accordingly, previous studies that used antioxidants to modulate these ROS-dependent mechanisms, in cancer and cancer cachexia, have obtained contradictory results, hence the need to gather the main findings of these studies and draw global conclusions in order to stimulate more oriented research in this field. Based on the literature reviewed in this paper, it appears that antioxidant supplementation is (1) beneficial in cancer cachectic patients with antioxidant deficiencies, (2) most likely harmful in cancer patients with adequate antioxidant status (i.e., lung, gastrointestinal, head and neck, and esophageal), and (3) not recommended when undergoing radiotherapy. At the moment, measuring the blood levels of antioxidants may help to identify patients with systemic deficiencies. This approach is simple to realize but could not be a gold standard method for cachexia, as it does not necessarily reflect the redox state in other organs, like muscle

Effect of physical activity on human prostate cancer cells proliferation: involvement of oxidative stress?

International audienceKey words: physical activity, oxidative stress, prostate cancer. Prostate cancer (PC) constitutes a growing health concern. It represents the second cause of death by cancer in France. Among the various origins of PC, sedentary behaviour is an important risk factor and a decrease of PC prevalence is associated with exercise. Physical activity could prevent some cancers, especially breast and colon cancers. However, studies concerning its effects in PC progression are today conflicting and conclusions are difficult to reach. A recent study has suggested that golf enhances the life expectancy about 5 years (adjusted by age, sex and socioeconomic status of subjects). This physical activity which registered 410377 members in France mainly corresponds to a walking sport but it attracts more players. Golf could be suitable for men with low grade PC. The objectives of this study are (1) to determine if golfers’ serum has an effect on the in vitro proliferation of human PC cells and (2) to identify the involved molecular mechanisms. Oxidative stress (OS) phenotypes leading to an imbalance of redox status in favor of oxidant could play a role in the prostate tumorigenesis. The regular physical activity known to increase antioxidant defenses could reduce the evolution of the PC through OS-dependent signaling pathways. Sedentary or golfer subjects’ serum is incubated with androgen-dependent LNCaP cells. Proliferation, cell death as well as molecular mechanisms are studied, mainly those dependent of OS. We demonstrate that golfers' serum inhibits the LNCaP cells proliferation without inducing cell death. This inhibition of proliferation doesn’t depend on oxidative stress since no difference appears between the redox status of sedentary’s and golfer’s serum. Golf could reduce the proliferation of PC cells in vitro but the preliminary results require further investigations

Effect of physical activity on human prostate cancer cells proliferation: involvement of oxidative stress?

International audienceProstate cancer constitutes a growing health concern which affects men in the Western world and it represents the first cause of death by cancer in France. Among the various origins of prostate cancer, sedentarity represents an important risk factor and a decrease of prostate cancer prevalence is associated with exercise. Physical activity is known to slow down and to prevent some cancers, preferentially breast and colon cancers (Kesaniemi et al., 2001; Leitzmann et al., 2007). However, studies concerning its effects in prostate cancer progression are today conflicting and conclusions are difficult to reach since there remains a lack of clarity on activity parameters (in terms of type, intensity, frequency and time). Recently, Farahmand and coll., have suggested that golf enhances the life expectancy about 5 years (adjusted by age, sex and socioeconomic status of subjects). This physical activity which numbered more than 410 377 members in France today corresponds mainly to a walking sport but it attracts more players. Golf could be suitable for men with low risk early stage prostate cancer during active surveillance. The objectives of this study are (1) to determine if physical activity (golf) has an effect on the in vitro proliferation of human prostate cancer cells and (2) to identify the involved molecular mechanisms. Oxidative stress (OS) phenotypes leading to an imbalance of pro/anti-oxidant in favor of pro-oxidant could play a role in the prostate tumorigenesis (reviewed by Khandrika and al., on 2009). The regular physical activity known to increase antioxidant defenses could reduce the evolution of the prostate cancer through OS-dependent signaling pathways. Serum of sedentary or golfers subjects (3 golf courses 18 holes/week, ? 9 MET-h/week) is incubated with LNCaP androgen-dependent human prostate cancer cells. Proliferation, cell death (necrosis and apoptosis) as well as molecular mechanisms are studied, mainly those dependent of OS. We demonstrate that golfers' serum inhibits the LNCaP cells proliferation without inducing cell death. This inhibition of proliferation doesn’t depend on oxidative stress since no difference between the antioxidant status of sedentary serum and golfer serum appears. Golf could reduce the proliferation of prostate cancer cells in vitro but the preliminary results require further investigations

Exercise shapes redox signaling in cancer

International audienc

The Practice of Physical Activity in the Setting of Lower-Extremities Sarcomas: A First Step toward Clinical Optimization

International audienceLower-extremities sarcoma patients, with bone tumor and soft-tissue sarcoma, are a unique population at high risk of physical dysfunction and chronic heart diseases. Thus, providing an adequate physical activity (PA) program constitutes a primary part of the adjuvant treatment, aiming to improve patients' quality of life. The main goal of this paper is to offer clear suggestions for clinicians regarding PA around the time between diagnosis and offered treatments. These preliminary recommendations reflect our interpretation of the clinical and preclinical data published on this topic, after a systematic search on the PubMed database. Accordingly, patients could be advised to (1) start sessions of supportive rehabilitation and low-intensity PA after surgery and (2) increase PA intensities progressively during home stay. The usefulness of PA during the preoperative period remains largely unknown but emerging preclinical data on mice bearing intramuscular sarcoma are most likely discouraging. However, efforts are still needed to in-depth elucidate the impact of PA before surgery completion. PA should be age-, sex-, and treatment-adapted, as young/adolescent, women and patients receiving platinum-based chemotherapy are more susceptible to physical quality deterioration. Concerning PA intensity, the practice of moderate-intensity resistance and endurance exercises (30-60 min/day) are safe after surgery, even when receiving adjuvant chemo/radiotherapy. The general PA recommendations for cancer patients, 150 min/week of combined moderate-intensity endurance/resistance exercises, could be feasible after 18-24 months of rehabilitation. We believe that these suggestions will help clinicians to design a low-risk and useful PA program