Effect of different types of supervised exercise programs on cardiorespiratory and muscular fitness, pain, fatigue, mental health and inflammatory and oxidative stress biomarkers in older patients with post-COVID-19 sequelae "EJerSA-COVID-19": a randomized controlled trial.

BACKGROUND: Many patients with COVID-19 present the so-called post-acute sequelae of COVID-19 such as fatigue, post-stress discomfort, dyspnea, headache, pain mental impairment, incapacity to perform daily physical tasks ant exercise intolerance. This study aims to investigate the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. METHODS: The sample will be made up of 120 eligible participants, over the age of 60 years who have had COVID-19 disease and are survivors and present persistent COVID-19 symptomatology diagnosed by the corresponding physician. The participants will be randomly assigned to the experimental groups: supervised endurance group (SEG, n = 30), supervised strength group (SSG, n = 30), supervised concurrent group (SCG, n = 30), which will perform the corresponding exercise program 3 days a week compared to the control group (CG, n = 30), which will not carry out a supervised exercise program. The design of this project will include measurements of four relevant dimensions; 1) Cardiorespiratory fitness; 2) Muscle fitness; 3) Pain and mental health; and 4) Biomarkers of inflammation and oxidative stress. CONCLUSIONS: The results of this study will provide insights into the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. These findings may be the basis for the formulation of health plans and rehabilitation programs that allow healthy aging and a reduction in the associated morbidity in patients with post-COVID-19 sequelae. TRIAL REGISTRATION: NCT05848518. Registered on May 8, 2023.

Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle.

Type 2 diabetes mellitus (T2D) affects millions of people worldwide and is one of the leading causes of morbidity and mortality. The skeletal muscle (SKM) is one of the most important tissues involved in maintaining glucose homeostasis and substrate oxidation, and it undergoes insulin resistance in T2D. In this study, we identify the existence of alterations in the expression of mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in skeletal muscle from two different forms of T2D: early-onset type 2 diabetes (YT2) (onset of the disease before 30 years of age) and the classical form of the disease (OT2). GSEA analysis from microarray studies revealed the repression of mitochondrial mt-aaRSs independently of age, which was validated by real-time PCR assays. In agreement with this, a reduced expression of several encoding mt-aaRSs was also detected in skeletal muscle from diabetic (db/db) mice but not in obese ob/ob mice. In addition, the expression of the mt-aaRSs proteins most relevant in the synthesis of mitochondrial proteins, threonyl-tRNA, and leucyl-tRNA synthetases (TARS2 and LARS2) were also repressed in muscle from db/db mice. It is likely that these alterations participate in the reduced expression of proteins synthesized in the mitochondria detected in db/db mice. We also document an increased iNOS abundance in mitochondrial-enriched muscle fractions from diabetic mice that may inhibit aminoacylation of TARS2 and LARS2 by nitrosative stress. Our results indicate a reduced expression of mt-aaRSs in skeletal muscle from T2D patients, which may participate in the reduced expression of proteins synthesized in mitochondria. An enhanced mitochondrial iNOS could play a regulatory role in diabetes.

Similar Slow Component of Oxygen Uptake and Ventilatory Efficiency between an Aerobic Dance Session on an Air Dissipation Platform and a Constant-Load Treadmill Test in Healthy Women.

There is a lack of evidence about the slow component of oxygen consumption (V.O2sc) and ventilatory efficiency (slope VE·VCO2−1) during an aerobic dance (AD) session on an air dissipation platform (ADP) despite the key role played in endurance exercises. This research was designed to assess V.O2sc, ventilatory efficiency, and blood lactate concentration by comparing two exercise modes: AD session on an ADP versus treadmill test at a constant-load intensity of the first ventilatory threshold (VT1). In the first session, an incremental treadmill test was completed. In sessions 2 and 3, the participants were randomly assigned to the AD session on an ADP or to a treadmill constant-load test at VT1 intensity to determine their cardioventilatory responses. In addition, their blood lactate levels and ratings of perceived exertion (RPE, CR-10) were evaluated. No significant differences were found between the constant-load treadmill test and AD session on an ADP with respect to V.O2sc, VE VCO2−1 slope, and RPE (p > 0.05). Higher blood lactate concentrations were observed in an AD session on an ADP than in a constant-load treadmill test at 10 min (p = 0.003) and 20 min (p < 0.001). The two different exercise modalities showed similar V.O2sc and VE·VCO2−1 slope, even though the blood lactate concentrations were different.

Circulating nitrate-nitrite reduces oxygen uptake for improving resistance exercise performance after rest time in well-trained CrossFit athletes.

This study aimed to determine the effects of circulating nitrate plus nitrite (NOx) concentrations on resistance exercise performance, VO2 and biomarkers of muscle damage. Eleven well-trained male CrossFit athletes (29.2 ± 3.7 years, 78.9 ± 5.4 kg, 175.1 ± 6.3 cm) carried out a resistance exercise test after drinking 140 mL of beetroot juice (BJ) or placebo. The test consisted of repeating the same resistance exercise routine twice: wall ball shots plus full back squat with 3-min rest (1st routine) or without rest (2nd routine) between the two exercises. Higher NOx plasma levels were verified after BJ than placebo in the pretest and post-test (p < 0.001). A higher number of repetitions was observed after BJ intake compared to placebo in the full back squat exercise during the first routine (p = 0.004). A significantly reduced VO2 was detected after BJ intake compared to placebo during rest and full back squat execution in the first routine (p < 0.05). Plasma myoglobin concentrations were significantly increased with BJ compared to placebo (p = 0.036). These results showed that plasma NOx levels reduced VO2 after BJ intake during rest time. These reduced VO2 was a key factor for improving full back squat performance during the first routine.

Liver Graft Hypothermic Static and Oxygenated Perfusion (HOPE) Strategies: A Mitochondrial Crossroads.

Marginal liver grafts, such as steatotic livers and those from cardiac death donors, are highly vulnerable to ischemia-reperfusion injury that occurs in the complex route of the graft from "harvest to revascularization". Recently, several preservation methods have been developed to preserve liver grafts based on hypothermic static preservation and hypothermic oxygenated perfusion (HOPE) strategies, either combined or alone. However, their effects on mitochondrial functions and their relevance have not yet been fully investigated, especially if different preservation solutions/effluents are used. Ischemic liver graft damage is caused by oxygen deprivation conditions during cold storage that provoke alterations in mitochondrial integrity and function and energy metabolism breakdown. This review deals with the relevance of mitochondrial machinery in cold static preservation and how the mitochondrial respiration function through the accumulation of succinate at the end of cold ischemia is modulated by different preservation solutions such as IGL-2, HTK, and UW (gold-standard reference). IGL-2 increases mitochondrial integrity and function (ALDH2) when compared to UW and HTK. This mitochondrial protection by IGL-2 also extends to protective HOPE strategies when used as an effluent instead of Belzer MP. The transient oxygenation in HOPE sustains the mitochondrial machinery at basal levels and prevents, in part, the accumulation of energy metabolites such as succinate in contrast to those that occur in cold static preservation conditions. Additionally, several additives for combating oxygen deprivation and graft energy metabolism breakdown during hypothermic static preservation such as oxygen carriers, ozone, AMPK inducers, and mitochondrial UCP2 inhibitors, and whether they are or not to be combined with HOPE, are presented and discussed. Finally, we affirm that IGL-2 solution is suitable for protecting graft mitochondrial machinery and simplifying the complex logistics in clinical transplantation where traditional (static preservation) and innovative (HOPE) strategies may be combined. New mitochondrial markers are presented and discussed. The final goal is to take advantage of marginal livers to increase the pool of suitable organs and thereby shorten patient waiting lists at transplantation clinics.

Aerobic Dance on an Air Dissipation Platform Improves Cardiorespiratory, Muscular and Cellular Fitness in the Overweight and Obese Elderly.

Background: Obesity is a global health problem associated with a high number of comorbidities that decrease functional capacity, especially in elderly people. Aerobic dance is considered a viable strategy to prevent the effects of aging, mainly in obese and overweight elderly people. This study aimed to evaluate the effects of aerobic dance on an air dissipation platform (ADP) on body composition, oxidative stress and muscular and cardiorespiratory fitness in elderly people. Methods: In total, 32 elderly adults (67.1 ± 3.6) were divided into 3 groups based on body mass index: healthy (HG), overweight (OWG) and obese (OG). Training program of aerobic dance on an ADP was carried out twice a week for 12 weeks. Results: OWG (p = 0.016) and OG decreased their weight (p < 0.001). There was a significant decrease in malondialdehyde concentrations in all experimental groups (p < 0.05). OWG and OG significantly improved their peak oxygen uptake (p < 0.01). HG increased the vertical jump height (p < 0.05), and HG and OG improved the power output of the lower extremities (p < 0.05). Conclusions: The aerobic dance on an ADP may be an effective alternative to lose weight, prevent oxidative stress and improve cardiorespiratory fitness in obese and overweight elderly people.

PEG35 and Glutathione Improve Mitochondrial Function and Reduce Oxidative Stress in Cold Fatty Liver Graft Preservation.

The need to meet the demand for transplants entails the use of steatotic livers, more vulnerable to ischemia-reperfusion (IR) injury. Therefore, finding the optimal composition of static cold storage (SCS) preservation solutions is crucial. Given that ROS regulation is a therapeutic strategy for liver IR injury, we have added increasing concentrations of PEG35 and glutathione (GSH) to the preservation solutions (IGL-1 and IGL-2) and evaluated the possible protection against energy depletion and oxidative stress. Fatty livers from obese Zücker rats were isolated and randomly distributed in the control (Sham) preserved (24 h at 4 °C) in IGL-0 (without PEG35 and 3 mmol/L GSH), IGL-1 (1 g/L PEG35, and 3 mmol/L GSH), and IGL-2 (5 g/L PEG35 and 9 mmol/L GSH). Energy metabolites (ATP and succinate) and the expression of mitochondrial oxidative phosphorylation complexes (OXPHOS) were determined. Mitochondrial carrier uncoupling protein 2 (UCP2), PTEN-induced kinase 1 (PINK1), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the inflammasome (NLRP3) expressions were analyzed. As biomarkers of oxidative stress, protein oxidation (AOPP) and carbonylation (DNP derivatives), and lipid peroxidation (malondialdehyde (MDA)-thiobarbituric acid (TBA) adducts) were measured. In addition, the reduced and oxidized glutathione (GSH and GSSG) and enzymatic (Cu-Zn superoxide dismutase (SOD), CAT, GSH S-T, GSH-Px, and GSH-R) antioxidant capacities were determined. Our results showed that the cold preservation of fatty liver graft depleted ATP, accumulated succinate and increased oxidative stress. In contrast, the preservation with IGL-2 solution maintained ATP production, decreased succinate levels and increased OXPHOS complexes I and II, UCP2, and PINK-1 expression, therefore maintaining mitochondrial integrity. IGL-2 also protected against oxidative stress by increasing Nrf2 and HO-1 expression and GSH levels. Therefore, the presence of PEG35 in storage solutions may be a valuable option as an antioxidant agent for organ preservation in clinical transplantation.

Nrf2 and oxidative stress in liver ischemia/reperfusion injury.

In response to stress signal, nuclear factor-erythroid 2-related factor 2 (Nrf2) induces the expression of target genes involved in antioxidant defense and detoxification. Nrf2 activity is strictly regulated through a variety of mechanisms, including regulation of Keap1-Nrf2 stability, transcriptional regulation (NF-ĸB, ATF3, ATF4), and post-transcriptional regulation (miRNA), evidencing that transcriptional responses of Nrf2 are critical for the maintenance of homeostasis. Ischemia-reperfusion (IR) injury is a major cause of graft loss and dysfunction in clinical transplantation and organ resection. During the IR process, the generation of reactive oxygen species (ROS) leads to damage from oxidative stress, oxidation of biomolecules, and mitochondrial dysfunction. Oxidative stress can trigger apoptotic and necrotic cell death. Stress factors also result in the assembly of the inflammasome protein complex and the subsequent activation and secretion of proinflammatory cytokines. After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense against the cytotoxic effects of oxidative stress and help to promote hepatic recovery during IR. The complex crosstalk between Nrf2 and cellular pathways in liver IR injury and the potential therapeutic target of the Nrf2 inducers will be discussed in the present review.

IGL-2 as a Unique Solution for Cold Static Preservation and Machine Perfusion in Liver and Mitochondrial Protection.

Hypothermic static cold storage and machine perfusion strategies remain the clinical standard of care for liver graft preservation. Recently, the protection of the mitochondrial function and the energetic levels derived from it has emerged as one of the key points for organ preservation. However, the complex interactions between liver mitochondrial protection and its relation with the use of solutions/perfusates has been poorly investigated. The use of an alternative IGL-2 solution to Belzer MPS one for hypothermic oxygenated perfusion (HOPE), as well as in static cold storage, introduce a new kind of perfusate to be used for liver grafts subjected to HOPE strategies, either alone or in combination with hypothermic static preservation strategies. IGL-2 not only protected mitochondrial integrity, but also avoided the mixture of different solutions/perfusates reducing. Thus, the operational logistics and times prior to transplantation, a critical factor when suboptimal organs such as donation after circulatory death or steatotic ones, are used for transplantation. The future challenges in graft preservation will go through (1) the improvement of the mitochondrial status and its energetic status during the ischemia and (2) the development of strategies to reduce ischemic times at low temperatures, which should translate in a better transplantation outcome.

Intermittent Hypobaric Hypoxic Preconditioning Provides Neuroprotection by Increasing Antioxidant Activity, Erythropoietin Expression and Preventing Apoptosis and Astrogliosis in the Brain of Adult Rats Exposed to Acute Severe Hypoxia.

BACKGROUND: Exposure to intermittent hypoxia has been demonstrated to be an efficient tool for hypoxic preconditioning, preventing damage to cells and demonstrating therapeutic benefits. We aimed to evaluate the effects of respiratory intermittent hypobaric hypoxia (IHH) to avoid brain injury caused by exposure to acute severe hypoxia (ASH). METHODS: biomarkers of oxidative damage, mitochondrial apoptosis, and transcriptional factors in response to hypoxia were assessed by Western blot and immunohistochemistry in brain tissue. Four groups of rats were used: (1) normoxic (NOR), (2) exposed to ASH (FiO2 7% for 6 h), (3) exposed to IHH for 3 h per day over 8 days at 460 mmHg, and (4) ASH preconditioned after IHH. RESULTS: ASH animals underwent increased oxidative-stress-related parameters, an upregulation in apoptotic proteins and had astrocytes with phenotype forms compatible with severe diffuse reactive astrogliosis. These effects were attenuated and even prevented when the animals were preconditioned with IHH. These changes paralleled the inhibition of NF-κB expression and the increase of erythropoietin (EPO) levels in the brain. CONCLUSIONS: IHH exerted neuroprotection against ASH-induced oxidative injury by preventing oxidative stress and inhibiting the apoptotic cascade, which was associated with NF-κB downregulation and EPO upregulation.

Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach.

The total damage inflicted on the liver before transplantation is associated with several surgical manipulations, such as organ recovery, washout of the graft, cold conservation in organ preservation solutions (UW, Celsior, HTK, IGL-1), and rinsing of the organ before implantation. Polyethylene glycol 35 (PEG35) is the oncotic agent present in the IGL-1 solution, which is an alternative to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation in rats (4 °C; 24 h), we evaluated the effects induced by PEG35 on detoxifying enzymes and nitric oxide, comparing IGL-1 to IGL-0 (which is the same as IGL-1 without PEG). The benefits were also assessed in a new IGL-2 solution characterized by increased concentrations of PEG35 (from 1 g/L to 5 g/L) and glutathione (from 3 mmol/L to 9 mmol/L) compared to IGL-1. We demonstrated that PEG35 promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented the formation of toxic aldehyde adducts (measured as 4-hydroxynonenal) and oxidized proteins (AOPP). In addition, PEG35 promoted the vasodilator factor nitric oxide, which may improve the microcirculatory disturbances in steatotic grafts during preservation and revascularization. All of these results lead to a reduction in damage inflicted on the fatty liver graft during the cold storage preservation. In this communication, we report on the benefits of IGL-2 in hypothermic static preservation, which has already been proved to confer benefits in hypothermic oxygenated dynamic preservation. Hence, the data reported here reinforce the fact that IGL-2 is a suitable alternative to be used as a unique solution/perfusate when hypothermic static and preservation strategies are used, either separately or combined, easing the logistics and avoiding the mixture of different solutions/perfusates, especially when fatty liver grafts are used. Further research regarding new therapeutic and pharmacological insights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in static and dynamic graft preservation strategies for clinical liver transplantation purposes.

Justificación y diseño del estudio multicéntrico prospectivo de cohortes para evaluar los resultados del cierre percutáneo en procedimientos de reparación aórtica endovascular. Registro SPAIN / Justification and design of the prospective multicentre cohort study to evaluate the results of percutaneous closure in endovascular aortic repair procedures. SPAIN Registry

Introducción: el cierre percutáneo es una herramienta esencial en el tratamiento endovascular actual. Los procedimientos de patología aórtica precisan abordajes arteriales de gran calibre a nivel inguinal, lo que conlleva mayor posibilidad de complicaciones en el cierre. Es por esto que actualmente continúan conviviendo la técnica quirúrgica abierta y el abordaje percutáneo, siendo también así en el territorio nacional, con resultados a día de hoy no cuantificados. La literatura actual aporta buenos resultados para la técnica de presutura en patología aórtica, sin embargo aún existen dudas respecto a determinados factores de riesgo como la obesidad, calcificación severa o arterias de pequeño calibre. Tampoco existen suficientes datos que estudien cómo afecta este procedimiento a la calidad de vida, lo cual es un punto esencial, especialmente en pacientes mayores. Dado que un alto porcentaje de los pacientes que se someten a estas intervenciones son ancianos con patologías concomitantes (los llamados pacientes frágiles), minimizar la agresión quirúrgica y mejorar su calidad de vida inmediata post-procedimiento puede ser determinante. Objetivos: primarios: estimar la tasa de éxito técnico del procedimiento de cierre percutáneo en intervenciones aórticas, estimación del impacto en la calidad de vida así como encontrar posibles diferencias en la morbimortalidad a 30 días en relación a la puntuación de cada paciente en la escala de fragilidad modificada; secundarios: evaluar el tiempo de presutura, tiempo de hemostasia, complicaciones derivadas del cierre, estancia hospitalaria y el dolor posoperatorio. Material y métodos: el Registro SPAIN es un estudio multicéntrico prospectivo de pacientes sometidos a procedimientos percutáneos sobre la aorta y sus ramas con dispositivos ≥ 10 French (F), en el que serán recogidas variables relacionadas con el cierre de sus accesos inguinales. El periodo de seguimiento será de 30 días...(AU)

Introduction: percutaneous closure is an essential tool in current endovascular treatment. Aortic pathology procedures require large-caliber arterial approaches, leading to a greater possibility of closure complications. For this reason, nowadays, both open surgical and the preclose technique coexist in almost every center worldwide, as it does in Spain with no contrasted results. The current literature provides good results for the pre-closing technique in aortic pathology, however there are still doubts regarding certain risk factors such as obesity, severe calcification or small-caliber arteries. There is not enough data to study how this procedure affects quality of life, an essential point, especially in older patients. Minimizing surgical aggression and improving their immediate post-procedure quality of life can be decisive because most of the patients are elderly with concomitant pathologies (fragile patients). Objetives: primary objectives: to estimate the technical success rate of the percutaneous closure procedure in aortic interventions, estimate the impact on quality of life and find possible differences in morbidity and mortality at 30 days in relation to the score of each patient on the frailty scale; secondary objectives: To evaluate the pre-suture time, hemostasis time, complications derived from closure, hospital stay and post-operative pain. Material and methods: the SPAIN Registry is a prospective multicenter study of patients undergoing percutaneous procedures on the aorta and its branches with ≥ 10 French (F) devices. Variables related to the closure of their inguinal access will be collected. The follow-up period will be 30 days. The duration of the recruitment period will be one year initially. Participants must certify that they have performed the closure of at least 10 large caliber percutaneous approaches (≥ 10 F) in national units of the specialties of Angiology and Vascular Surgery and Cardiology...(AU)

Extracellular ferritin contributes to neuronal injury in an in vitro model of ischemic stroke.

Previous clinical and experimental studies have shown that neurological decline and poor functional outcome after acute ischemic stroke in humans are associated with high ferritin levels in serum and cerebrospinal fluid (CSF) within 24 h of ischemic stroke onset. The aim of the present study was to find out if and how high extracellular ferritin concentrations can increase the excitotoxicity effect in a neuronal cortical culture model of stroke. Extracellular ferritin (100 ng/ml) significantly increased the excitotoxic effect caused by excessive exogenous glutamate (50 µM and 100 µM) by leading to an increase in lipid peroxidation, a reduction in mitochondrial membrane potential, and a decrease in neuron viability. Extracellular apoferritin (100 ng/ml), the iron-free form of the protein, does not increase the excitotoxicity of glutamate, which proves that iron was responsible for the neurotoxic effect of the exogenous ferritin. We present evidence that extracellular ferritin iron exacerbates the neurotoxic effect induced by glutamate excitotoxicity and that the effect of ferritin iron is dependent of glutamate excitotoxicity. Our results support the idea that body iron overload is involved in the severity of the brain damage caused by stroke and reveal the need to control systemic iron homeostasis.

Oxygen Uptake Slow Component and the Efficiency of Resistance Exercises.

ABSTRACT: Garnacho-Castaño, MV, Albesa-Albiol, L, Serra-Payá, N, Gomis Bataller, M, Pleguezuelos Cobo, E, Guirao Cano, L, Guodemar-Pérez, J, Carbonell, T, Domínguez, R, and Maté-Muñoz, JL. Oxygen uptake slow component and the efficiency of resistance exercises. J Strength Cond Res 35(4): 1014-1022, 2021-This study aimed to evaluate oxygen uptake slow component (V̇o2sc) and mechanical economy/efficiency in half squat (HS) exercise during constant-load tests conducted at lactate threshold (LT) intensity. Nineteen healthy young men completed 3 HS exercise tests separated by 48-hour rest periods: 1 repetition maximum (1RM), incremental-load HS test to establish the %1RM corresponding to the LT, and constant-load HS test at the LT. During the last test, cardiorespiratory, lactate, and mechanical responses were monitored. Fatigue in the lower limbs was assessed before and after the constant-load test using a countermovement jump test. A slight and sustained increase of the V̇o2sc and energy expended (EE) was observed (p < 0.001). In blood lactate, no differences were observed between set 3 to set 21 (p > 0.05). A slight and sustained decrease of half squat efficiency and gross mechanical efficiency (GME) was detected (p < 0.001). Significant inverse correlations were observed between V̇o2 and GME (r = -0.93, p < 0.001). Inverse correlations were detected between EE and GME (r = -0.94, p < 0.001). Significant losses were observed in jump height ability and in mean power output (p < 0.001) in response to the constant-load HS test. In conclusion, V̇o2sc and EE tended to rise slowly during constant-load HS exercise testing. This slight increase was associated with lowered efficiency throughout constant-load test and a decrease in jump capacity after testing. These findings would allow to elucidate the underlying fatigue mechanisms produced by resistance exercises in a constant-load test at LT intensity.

Cardiorespiratory, Metabolic and Muscular Responses during a Video-Recorded Aerobic Dance Session on an Air Dissipation Platform.

BACKGROUND: Aerobic dance (AD) is an appropriate physical activity for improving cardiorespiratory fitness. This study aimed to compare cardiorespiratory and metabolic responses, and muscle fatigue between an air dissipation platform (ADP) and a hard surface during a video-recorded AD session. METHODS: 25 healthy young women (23.3 ± 2.5 years) completed three sessions. In session 1, participants performed an incremental test to exhaustion on a treadmill. One week after session 1, participants were randomly assigned in a crossover design to perform video-recorded AD sessions on an ADP and on a hard surface (sessions 2 and 3). Cardiorespiratory and metabolic responses were assessed during AD sessions. Muscular fatigue was measured before and after AD sessions by a countermovement jump test. RESULTS: Significantly higher heart rate, respiratory exchange ratio, pulmonary ventilation, ventilatory oxygen equivalent, and ventilatory carbon dioxide equivalent were observed on an ADP than on a hard surface (p < 0.05). Despite a significant increase in lactate levels on an ADP (p ≤ 0.01), muscular fatigue and perceived exertion rating were similar on both surfaces (p > 0.05). CONCLUSIONS: Video-recorded AD on an ADP increased the cardioventilatory and metabolic responses compared to a hard surface, preventing further muscle fatigue.

Understanding the effects of beetroot juice intake on CrossFit performance by assessing hormonal, metabolic and mechanical response: a randomized, double-blind, crossover design.

BACKGROUND: Acute beetroot juice (BJ) intake has shown to enhance aerobic and anaerobic performance. However, no studies have evaluated the effects of BJ intake on CrossFit (CF) performance by linking hormonal, metabolic, and mechanical responses. The purpose of this study was to determine the causal physiological association between hormonal, metabolic and mechanical responses, and CF workouts performance after acute BJ intake. METHODS: Twelve well-trained male practitioners undertook a CF workout after drinking 140 mL of BJ (~ 12.8 mmol NO3-) or placebo. The two experimental conditions (BJ or placebo) were administered using a randomized, double-blind, crossover design. The CF workout consisted of repeating the same exercise routine twice: Wall ball (WB) shots plus full back squat (FBS) with 3-min rest (1st routine) or without rest (2nd routine) between the two exercises. A 3-min rest was established between the two exercise routines. RESULTS: An interaction effect was observed in the number of repetitions performed (p = 0.04). The Bonferroni test determined a higher number of repetitions after BJ than placebo intake when a 3-min rest between WB and FBS (1st routine) was established (p = 0.007). An interaction effect was detected in cortisol response (p = 0.04). Cortisol showed a higher increase after BJ compared to placebo intake (76% vs. 36%, respectively). No interaction effect was observed in the testosterone and testosterone/cortisol ratio (p > 0.05). A significant interaction effect was found in oxygen saturation (p = 0.01). A greater oxygen saturation drop was observed in BJ compared to placebo (p <  0.05). An interaction effect was verified in muscular fatigue (p = 0.03) with a higher muscular fatigue being observed with BJ than placebo (p = 0.02). CONCLUSIONS: BJ intake improved anaerobic performance only after the recovery time between exercises. This increase in performance in the first routine probably generated greater hypoxia in the muscle mass involved, possibly conditioning post-exercise performance. This was observed with a fall in oxygen saturation and in muscle fatigue measured at the end of the CF workout. The greatest perceived changes in cortisol levels after BJ intake could be attributed to the nitrate-nitrite-nitric oxide pathway.

The influenza virus NS1A binding protein gene modulates macrophages response to cytokines and phagocytic potential in inflammation.

Macrophages show remarkable phenotypic plasticity in response to environmental signals. Although it is generally less considered, cytoskeletal changes in macrophages influence their phenotype, including phagocytosis and secretion of soluble cytokines. Influenza virus NS1A-binding protein (Ivns1abp) belongs to the Kelch family of proteins that play a central role in actin cytoskeleton dynamics by directly associating with F-actin and by protecting against actin derangement. Due to its role in cytoskeleton preservation, the Ivns1abp gene might be a critical regulator of the macrophage phenotype and function under inflammatory conditions. In this study, we determine that the modulation of the Ivns1abp gene in macrophages could modify resistance to macrophages against inflammation and maintain functional phagocytosis. Our results indicate that inflammatory insults inhibit the Ivns1abp gene, whereby phagocytosis is inhibited and the ability of macrophages to induce proliferation and repair of damaged cells is compromised. Furthermore, our results show that inflammatory insults alter the activity of the transcription factor c-myc, a factor which directly modulates the expression of the Ivns1abp gene. In conclusion, this study demonstrates a central role of lvns1abp in promoting and preserving a reparative macrophage phenotype and resistance to this inflammatory environment.

Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation.

Organ transplantation is a multifactorial process in which proper graft preservation is a mandatory step for the success of the transplantation. Hypothermic preservation of abdominal organs is mostly based on the use of several commercial solutions, including UW, Celsior, HTK and IGL-1. The presence of the oncotic agents HES (in UW) and PEG35 (in IGL-1) characterize both solution compositions, while HTK and Celsior do not contain any type of oncotic agent. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic and water-soluble polymers, which present a combination of properties of particular interest in the clinical context of ischemia-reperfusion injury (IRI): they limit edema and nitric oxide induction and modulate immunogenicity. Besides static cold storage (SCS), there are other strategies to preserve the organ, such as the use of machine perfusion (MP) in dynamic preservation strategies, which increase graft function and survival as compared to the conventional static hypothermic preservation. Here we report some considerations about using PEG35 as a component of perfusates for MP strategies (such as hypothermic oxygenated perfusion, HOPE) and its benefits for liver graft preservation. Improved liver preservation is closely related to mitochondria integrity, making this organelle a good target to increase graft viability, especially in marginal organs (e.g., steatotic livers). The final goal is to increase the pool of suitable organs, and thereby shorten patient waiting lists, a crucial problem in liver transplantation.

MicroRNAs in the regulation of cellular redox status and its implications in myocardial ischemia-reperfusion injury.

MicroRNAs (miRNAs) are small RNAs that do not encode for proteins and play key roles in the regulation of gene expression. miRNAs are involved in a comprehensive range of biological processes such as cell cycle control, apoptosis, and several developmental and physiological processes. Oxidative stress can affect the expression levels of multiple miRNAs and, conversely, miRNAs may regulate the expression of redox sensors, alter critical components of the cellular antioxidants, interact with the proteasome, and affect DNA repair systems. The number of publications identifying redox-sensitive miRNAs has increased significantly over the last few years, and some miRNA targets such as Nrf2, SIRT1 and NF-κB have been identified. The complex interplay between miRNAs and ROS is discussed together with their role in myocardial ischemia-reperfusion injury and the potential use of circulating miRNAs as biomarkers of myocardial infarction. Detailed knowledge of redox-sensitive miRNAs is needed to be able to effectively use individual compounds or sets of miRNA-modulating compounds to improve the health-related outcomes associated with different diseases.