Neuromuscular and Metabolic Responses during Repeated Bouts of Loaded Downhill Walking.

INTRODUCTION: The aim of this study was to compare vastus lateralis (VL) and rectus femoris (RF) muscles for their nervous and mechanical adaptations during two bouts of downhill walking (DW) with load carriage performed 2 wk apart. Moreover, we investigated cardiometabolic and perceived exertion responses during both DW bouts. METHODS: Seventeen participants performed two 45-min sessions of loaded DW (30% of body mass; slope, -25%; speed, 4.5 km·h -1 ) separated by 2 wk. Rating of perceived exertion, cost of walking, heart rate, and EMG activity of thigh muscles were assessed during the DW. Muscle shear elastic modulus ( µ ) of RF and VL were assessed before each exercise bout. Maximal voluntary contraction torque was assessed before (PRE), immediately after (POST), and 24 and 48 h after the two exercise bouts. RESULTS: Maximal voluntary contraction torque decreased from POST (-23.7% ± 9.2%) to 48 h (-19.2% ± 11.9%) after the first exercise (Ex1), whereas it was significantly reduced only at POST (-14.6% ± 11.0%) after the second exercise (Ex2; P < 0.001). Rating of perceived exertion (Ex1: 12.3 ± 1.9; Ex2: 10.8 ± 2.0), heart rate (Ex1: 156 ± 23 bpm; Ex2: 145 ± 25 bpm), cost of walking (Ex1: 4.5 ± 0.9 J·m -1 ·kg -1 ; Ex2: 4.1 ± 0.7 J·m -1 ·kg -1 ), and RF EMG activity (Ex1: 0.071 ± 0.028 mV; Ex2: 0.041 ± 0.014 mV) were significantly decreased during Ex2 compared with Ex1 ( P < 0.01). RF µ was significantly greater in Ex2 (0.44 ± 0.18) compared with Ex1 (0.56 ± 0.27; P < 0.001). CONCLUSIONS: The RF muscle displayed specific mechanical and nervous adaptations to repeated DW bouts as compared with VL. Moreover, the muscle adaptations conferred by the first bout of DW could have induced greater exercise efficiency, inducing lesser perceived exertion and cardiometabolic demand when the same exercise was repeated 2 wk later.

Contractile properties are less affected at long than short muscle length after eccentric exercise.

PURPOSE: The aim of the present study was to investigate whether the electrically evoked muscle responses are differently affected over time by the knee joint angle after an exercise-induced muscle damage (EIMD). We hypothesized that low-frequency-evoked responses would be less affected at long than short muscle length, and that mechanisms located within the muscle and tendinous tissues would be involved. METHODS: Fifteen males performed 45 min loaded downhill walking (DW) exercise. Maximal voluntary contraction torque (MVC), optimal angle for torque production, voluntary activation level (VAL), twitch, doublet at 10 and 100 Hz (Db10 and Db100, respectively), rate of torque development (RTD), post-activation potentiation (PAP), muscle shear elastic modulus (µ) and aponeurosis stiffness were assessed before, after, and 4, 24, 48, 72 and 168 h after the exercise at a knee angle of 40°, 90° and 120° (0°: full extension). RESULTS: MVC, VAL and Db100 were similarly decreased across joint angles after the DW and optimal angle was not affected. Twitch, Db10, Db10/Db100, PAP and RTD were less affected and muscle µ more increased at long than short muscle lengths (p < 0.05), especially during the first 24 h after the DW exercise. CONCLUSION: Low-frequency-evoked responses were more preserved at long than short muscle length the first 24 h after the DW exercise, suggesting that joint angle should be taken into account to assess muscular alterations after EIMD. This length-dependence could be associated to the higher sensitivity to Ca2+ and the higher increase in muscle stiffness at long than short muscle length.

Circulating microRNA levels after exercise-induced muscle damage and the repeated bout effect.

The neuromuscular system can quickly adapt to exercise-induced muscle damage (EIMD), such that it is less affected by subsequent damaging exercise, a phenomenon known as the repeated bout effect (RBE). Circulating muscle-specific microRNAs (myomiRs) may be able to potentially predict the long-lasting maximal voluntary contraction (MVC) torque deficit (>24 h), an indicator of EIMD. We aimed to investigate: 1) how plasma myomiR levels are modified by the RBE and 2) whether plasma myomiRs can predict the long-lasting MVC torque deficit. Nineteen participants performed two identical bouts of loaded downhill walking separated by 2 wk. MVC torque, creatine kinase (CK) activity, myoglobin (Mb) concentration, and myomiR levels were measured before and up to 48 h after exercise. Correlation and multiple regression analyses were performed to assess the ability of these markers to predict the largest MVC torque loss beyond 24 h postexercise. Similar to MVC torque, CK activity, and the Mb concentration, the relative abundance of certain myomiRs (hsa-miR-1-3p, and hsa-miR-133a-3p) was less affected after the second bout of exercise relative to the first bout. The CK activity, Mb concentration, and level of several myomiRs (hsa-miR-1-3p, hsa-miR-133a-3p, and hsa-miR-206) correlated with long-lasting MVC torque loss. Multiple regression showed that the best combination of markers to predict the long-lasting deficit of MVC torque included several myomiRs, Mb, and CK. Certain myomiR levels increased less after exercise bout 2 than after exercise bout 1, indicating the presence of the RBE. The measurement of myomiR levels in combination with Mb concentrations and CK activity could improve the prediction of the long-lasting MVC torque deficit.NEW & NOTEWORTHY The present study is the first to show that plasma muscle-specific microRNA (myomiR) levels can be modified by the repeated bout effect, as their levels increased less after the second exercise bout relative to the first. This study is also the first to suggest that myomiR levels could be used to partially predict maximal voluntary contraction torque loss at 24 h postexercise (i.e., the magnitude of exercise-induced muscle damage). Interestingly, the combined measurement of certain myomiR levels with those of myoglobin and creatine kinase improved the predictive value.

Appropriateness of indirect markers of muscle damage following lower limbs eccentric-biased exercises: A systematic review with meta-analysis.

PURPOSE: The aim of this review was to (1) characterize the time-course of markers of exercise-induced muscle damage (EIMD) based on the level of maximal voluntary contraction torque loss at 24-48h post-exercise (MVCloss24-48h), (2) identify factors (e.g., exercise and population characteristics) affecting the level of MVCloss24-48h, and (3) evaluate the appropriateness of EIMD markers as indicators of MVCloss24-48h. METHODS: Magnitude of change of each EIMD markers was normalized using the standardized mean differences method to compare the results from different studies. Time-course of EIMD markers were characterized according to three levels of MVCloss24-48h based on a clustering analysis of the 141 studies included. Association between MVCloss24-48h levels and participant´s characteristics or exercise type/modalities were assessed. Meta-regressions were performed to investigate the associations between MVCloss24-48h and EIMD markers changes at <6h, 24h, 48h, 72h and >96h after exercise. RESULTS: Time-course of EIMD markers recovery differs between levels of MVCloss24-48h. Training status and exercise type/modality were associated with MVCloss24-48h level (p<0.05). MVCloss24-48h was correlated to changes in myoglobin concentration (<6h), jump height (24h) and range of motion (48h) (p<0.001). CONCLUSION: As the exercise could differently affect markers as function of the EIMD severity (i.e., MVCloss24-48h levels), different markers should be used as function of the timing of measurement. Mb concentration should be used during the first hours after the exercise (<6h), whereas jump height (24h) and range of motion (48h) could be used as surrogate for maximal voluntary contraction later. Moreover, training status and exercise type/modality could influence the magnitude of MVCloss24-48h.

Muscle Shear Elastic Modulus Provides an Indication of the Protection Conferred by the Repeated Bout Effect.

Background: The neuromuscular system is able to quickly adapt to exercise-induced muscle damage (EIMD), such that it is less affected by subsequent damaging exercise, a phenomenon known as the repeated bout effect (RBE). The objective was to determine whether the mechanical properties of the quadriceps, as evaluated by shear wave elastography (SWE), were less affected when a second bout of eccentric-biased exercise was performed 2 weeks later. It was hypothesized that the first bout would confer protection against extensive muscle damage through an adaptation of the muscle stiffness before the second bout (i.e., higher muscle stiffness). Methods: Sixteen males performed two identical bouts of downhill walking separated by 2 weeks (45 min at 4.5 km.h-1; gradient: 25%; load: 30% of the body mass). Rectus femoris (RF) and vastus lateralis (VL) resting shear elastic modulus (µ) and EIMD symptoms were measured before and up to 7 days following the exercise bouts. Changes in neuromuscular function was evaluated by maximal voluntary contraction torque, voluntary activation level, evoked mechanical response to single and double (10 and 100 Hz doublets) electrical stimulation. An index of protection (IP) was calculated for EIMD symptoms to assess magnitude the RBE. Results: EIMD symptoms were less affected after the second than the first exercise bout. RF and VL-µ increased (p < 0.001) only after the first exercise. RF µ was elevated up to 2 weeks after the end of the first exercise (p < 0.001) whereas VL µ was only increased up to 24 h. The increase in µ observed 2 weeks after the end of the first exercise was correlated with the IP; i.e., attenuation of alterations in muscle µ, 10 Hz-doublet amplitude and rate of torque development after the second exercise bout (p < 0.05). Conclusion: We showed that muscle µ assessed by SWE was sensitive to the RBE, with a differential effect between VL and RF. The persistent increase in µ was associated with the attenuation of neuromuscular impairments observed after the second bout, suggesting that the increased muscle stiffness could be a "protective" adaptation making muscles more resistant to the mechanical strain associated to eccentric contractions.

Fluctuations in food and fluid intake during a 24-h World Championship: analysis of the deviation from nutritional programs.

Background: A food and fluid intake program is essential for ultraendurance athletes to maximize performance and avoid possible gastrointestinal symptoms (GIS). However, the ability to follow such a program during a race has been under-assessed. We thus investigated the fluctuations of food and fluid intake during the 24-h run World Championship of 12 elite athletes (6 men and 6 women; age: 46 ± 7 years, height: 170 ± 9 cm, weight: 61.1 ± 9.6 kg, total distance run: 193-272 km) and assessed their ability to follow their nutritional program. Methods: Real-time overall intake (fluids, energy, and macronutrients) was recorded and compared to that of their program. The temporal difference in absolute values and the degree of divergence from their program were assessed, divided into four 6-h periods. GIS were recorded during the race. A questionnaire identifying the details of their nutritional program and the self-assessed causes of their inability to follow it was completed by the participants the day after the race. Results: Water, total fluid, carbohydrates (CHO), and energy intake decreased during the last quarter of the 24-h ultramarathon relative to the first half (p = 0.024, 0.022, 0.009, and 0.042). However, the differences were no longer significant after these values were normalized by the number of passages in front of the supply tent. The participants progressively failed to follow their nutritional program, with the intake of their planned items dropping to approximately 50% during the last quarter. However, this was adequately compensated by increases in unplanned foods allowing them to match their expected targets. GIS, lack of appeal of the planned items, and attractivity of unplanned items were the main explanations given for their deviation from the program (64, 27, and 27%, respectively). Conclusion: Despite evident difficulty in following their nutritional programs (mostly attributed to GIS), elite ultraendurance runners managed to maintain high rates of fluid and food intake during a 24-h ultramarathon and therefore still met their planned elevated nutritional objectives.Abbreviations: CHO: carbohydrates, GIS: gastrointestinal symptoms.

Effects of Acute Heat and Cold Exposures at Rest or during Exercise on Subsequent Energy Intake: A Systematic Review and Meta-Analysis.

The objective of this meta-analysis was to assess the effect of acute heat/cold exposure on subsequent energy intake (EI) in adults. We searched the following sources for publications on this topic: PubMed, Ovid Medline, Science Direct and SPORTDiscus. The eligibility criteria for study selection were: randomized controlled trials performed in adults (169 men and 30 women; 20-52 years old) comparing EI at one or more meals taken ad libitum, during and/or after exposure to heat/cold and thermoneutral conditions. One of several exercise sessions could be realized before or during thermal exposures. Two of the thirteen studies included examined the effect of heat (one during exercise and one during exercise and at rest), eight investigated the effect of cold (six during exercise and two at rest), and three the effect of both heat and cold (two during exercise and one at rest). The meta-analysis revealed a small increase in EI in cold conditions (g = 0.44; p = 0.019) and a small decrease in hot conditions (g = -0.39, p = 0.022) for exposure during both rest and exercise. Exposures to heat and cold altered EI in opposite ways, with heat decreasing EI and cold increasing it. The effect of exercise remains unclear.

Effect of heat acclimation on metabolic adaptations induced by endurance training in soleus rat muscle.

Aerobic training leads to well-known systemic metabolic and muscular alterations. Heat acclimation may also increase mitochondrial muscle mass. We studied the effects of heat acclimation combined with endurance training on metabolic adaptations of skeletal muscle. Thirty-two rats were divided into four groups: control (C), trained (T), heat-acclimated (H), and trained with heat acclimation (H+T) for 6 weeks. Soleus muscle metabolism was studied, notably by the in situ measurement of mitochondrial respiration with pyruvate (Pyr) or palmitoyl-coenzyme A (PCoA), under phosphorylating conditions ( V˙max ) or not ( V˙0 ). Aerobic performance increased, and retroperitoneal fat mass decreased with training, independently of heat exposure (p < 0.001 and p < 0.001, respectively). Citrate synthase and hydroxyl-acyl-dehydrogenase activity increased with endurance training (p < 0.001 and p < 0.01, respectively), without any effect of heat acclimation. Training induced an increase of the V˙0 and V˙max for PCoA (p < .001 and p < .01, respectively), without interference with heat acclimation. The training-induced increase of V˙0 (p < 0.01) for pyruvate oxidation was limited when combined with heat acclimation (-23%, p < 0.01). Training and heat acclimation independently increased the V˙max for pyruvate (+60% p < 0.001 and +50% p = 0.01, respectively), without an additive effect of the combination. Heat acclimation doubled the training effect on muscle glycogen storage (p < 0.001). Heat acclimation did not improve mitochondrial adaptations induced by endurance training in the soleus muscle, possibly limiting the alteration of carbohydrate oxidation while not facilitating fatty-acid utilization. Furthermore, the increase in glycogen storage observed after HA combined with endurance training, without the improvement of pyruvate oxidation, appears to be a hypoxic metabolic phenotype.

An augmented food strategy leads to complete energy compensation during a 15-day military training expedition in the cold.

Soldiers on military expeditions usually fail to compensate for the increase in energy expenditure, with potential deleterious consequences. We therefore analyzed the characteristics of energy compensation in 12 male soldiers, during a 15-day expedition in the cold, while alleviating some of the contextual limitations of food intake (~20-MJ daily bags of easy-to-use, highly palatable and familiar foods with multiple and long breaks allowed during the day). Body and fat mass losses were low and moderate, respectively (-1.13 ± 1.42% and -19.5 ± 15.6%, respectively, p < .021). Mean energy intake (EI) was high (~16.3 MJ) and increased at each third of the expedition (15.3 ± 2.1, 16.1 ± 2.1, and 17.6 ± 2.0 for D1-5, D6-10 and D11-15, respectively, p < .012). This resulted in reaching a neutral energy balance as soon as the D6 to 10 period and reaching normal energy availability during D11 to 15. Participants only increased their EI during the mid-day (10:00-14:00) period (p = .002) whereas hunger and thirst only increased in the morning, with higher scores during D11-15 than D1-5 (p < .009). Last, the reward value of sweet foods was also higher during D11-15 than during D1-5 (p = .026). The changes in body mass were positively associated with EI (r = 0.598, p = .040) and carbohydrate intake (r = 0.622, p = .031). This study indicates that complete energy compensation can be reached in challenging field conditions when food intake is facilitated, offering some guidelines to limit energy deficit during operational missions.

Circulating microRNAs after a 24-h ultramarathon run in relation to muscle damage markers in elite athletes.

Ultra-endurance sports are growing in popularity but can be associated with adverse health effects, such as exercise-induced muscle damage (EIMD), which can lead to exertional rhabdomyolysis. Circulating microRNAs (miRNAs) may be useful to approach the degree of EIMD. We aimed to (1) investigate the relevance of circulating miRNAs as biomarkers of muscle damage and (2) examine the acute response of skeletal/cardiac muscle and kidney biomarkers to a 24-h run in elite athletes. Eleven elite athletes participated in the 24-h run World Championships. Counter-movement jump (CMJ), creatine kinase (CK), myoglobin (Mb), creatinine (Cr), high-sensitive cardiac troponin T (hs-cTnT), and muscle-specific miRNA (myomiR) levels were measured before, immediately after, and 24 and 48h after the race. CMJ height was reduced immediately after the race (-84.0 ± 25.2%, p < 0.001) and remained low at 24 h (-43.6 ± 20.4%, p = 0.002). We observed high CK activity (53 239 ± 63 608 U/L, p < 0.001) immediately after the race, and it remained elevated 24h after (p < 0.01). Circulating myomiR levels (miR-1-3p, miR-133a-3p, miR-133b, miR-208a-3p, miR-208b-3p, and miR-499a-5p) were elevated immediately after the 24-h run (fold changes: 18-124,723, p<0.001) and significantly (p < 0.05) correlated or tended to significantly (p < 0.07) correlate with the reduction in CMJ height at 24 h. We found no significant correlation between CMJ height loss at 24 h and CK (p = 0.23) or Mb (p = 0.41) values. All elite ultramarathon runners included in our study were diagnosed with exertional rhabdomyolysis after the 24-h ultramarathon race. MyomiR levels may be useful to approach the degree of muscle damage.

Four-month operational heat acclimatization positively affects the level of heat tolerance 6 months later.

Benefits obtained after heat acclimation/acclimatization should be completely lost after an estimated period of 6 weeks. However, this estimate is still hypothetical. We evaluate the long-term effects of heat acclimatization on the level of heat tolerance. Physiological and subjective markers of heat tolerance were assessed during a heat stress test (HST: 3 × 8-min runs outdoors [~ 40 °C and 20% RH] at 50% of their estimated speed at VO2max) performed on the 2nd day upon arrival to the desert military base in the United Arab Emirates after a first day of mostly passive exposure to heat. Among the 50 male French soldiers, 25 partook in a 4-month military mission in countries characterized by a hot environment ~ 6 months prior to the study (HA). The other 25 participants were never heat acclimatized (CT). Rectal temperature (p = 0.023), heart rate (p = 0.033), and perceived exertion (p = 0.043) were lower in the HA than CT group at the end of HST. Soldiers who experienced a former 4-month period of natural heat acclimatization very likely had a higher level of heat tolerance during exercise in the heat, even 6 months after returning from the previous desert mission, than that of their non-acclimatized counterparts.

A basal heat stress test to detect military operational readiness after a 14-day operational heat acclimatization period.

A basal heat stress test (HST) to predict the magnitude of adaptive responses during heat acclimatization (HA) would be highly useful for the armed forces. The aim was to identify physiological markers assessed during a HST (three 8-min running sets at 50% of the speed at VO2max) performed just before a 14-day HA period that would identify participants still at "risk" at the end of HA. Individuals that responded poorly (large increases in rectal temperature [Trec] and heart rate [HR]) during the initial HST were more likely to respond favorably to HA (large reductions in Trec and HR). However, they were also more likely to exhibit lower tolerance to HST at D15. Basal Trec was found to efficiently discriminate participants showing a Trec > 38.5°C after HA, who are considered to be "at risk". Finally, participants were classified by quartiles based on basal Trec and HR at the end of the HST and physiological strain index (PSI). Most of the participants "at risk" were among the upper quartile (i.e. the least tolerant) of Trec and PSI (p = 0.011 for both). Overall, these results show that the individuals who are less tolerant to a basal HST are very likely to benefit the most from HA but they also remain less tolerant to heat at the end of HA than those who better tolerated the basal HST. A basal HST could therefore theoretically help the command to select the most-ready personnel in hot conditions while retaining those who are less tolerant 6.

Analysis of food and fluid intake in elite ultra-endurance runners during a 24-h world championship.

BACKGROUND: Properly replacing energy and fluids is a challenge for 24-h ultramarathoners because such unusually high intake may induce adverse effects (gastrointestinal symptoms [GIS] and exercise-associated hyponatremia [EAH]). We analyzed such intake for 12 twelve elite athletes (6 males and 6 females; age: 46 ± 7 years, height: 170 ± 9 cm, weight: 61.1 ± 9.6 kg, total distance run: 193-272 km) during the 2019 24-h World Championships and compared it to the latest nutritional recommendations described by the International Society of Sports Nutrition in 2019. We hypothesized that these elite athletes would easily comply these recommendations without exhibiting detrimental adverse symptoms. METHODS: Ad libitum food and fluid intake was recorded in real-time and energy, macronutrient, sodium, and caffeine intake then calculated using a spreadsheet in which the nutritional composition of each item was previously recorded. GIS, markers of dehydration (body mass modifications, plasma and urine osmolality, and plasma volume; samples obtained 26 h before and just after the race) and EAH (plasma and urine sodium concentrations) were also assessed. RESULTS: Fluid, energy, and carbohydrate intake of the 11 finishers was 16.4 ± 6.9 L, 35.1 ± 15.7 MJ, and 1.49 ± 0.71 kg, respectively. Individual analyses showed that all but one (for fluid intake) or two (for energy and carbohydrate intake) consumed more than the minimum recommendations. The calculated energy balance remained, however, largely negative (- 29.5 ± 16.1 MJ). Such unusually high intake was not accompanied by detrimental GIS (recorded in 75%, but only transiently [3.0 ± 0.9 h]) or EAH (0%). The athletes were not dehydrated, shown by the absence of significant body mass loss (- 0.92 ± 2.13%) and modifications of plasma osmolality and an increase in plasma volume (+ 19.5 ± 15.8%). Performance (distance ran) positively correlated with energy intake (ρ = 0.674, p = 0.023) and negatively (ρ = - 0.776, p = 0.005) with fluid intake. CONCLUSIONS: Overall, almost all of these elite 24-h ultramarathoners surpassed the nutritional recommendations without encountering significant or the usual adverse effects.

Changes in the Viscoelastic Properties of the Vastus Lateralis Muscle With Fatigue.

We investigated the in vivo effects of voluntary fatiguing isometric contractions of the knee extensor muscles on the viscoelastic properties of the vastus lateralis (VL). Twelve young males (29.0 ± 4.5 years) performed an intermittent voluntary fatigue protocol consisting of 6 sets × 10 repetitions of 5-s voluntary maximal isometric contractions with 5-s passive recovery periods between repetitions. Voluntary and evoked torque were assessed before, immediately after, and 20 min after exercise. The shear modulus (µ) of the VL muscle was estimated at rest and during a ramped isometric contraction using a conventional elastography technique. An index of active muscle stiffness was then calculated (slope from the relationship between shear modulus and absolute torque). Resting muscle viscosity (η) was quantified using a shear-wave spectroscopy sequence to measure the shear-wave dispersion. Voluntary and evoked torque decreased by ∼37% (P < 0.01) immediately after exercise. The resting VL µ was lower at the end of the fatigue protocol (-57.9 ± 5.4%, P < 0.001), whereas the resting VL η increased (179.0 ± 123%, P < 0.01). The active muscle stiffness index also decreased with fatigue (P < 0.05). By 20 min post-fatigue, there were no significant differences from the pre-exercise values for VL η and the active muscle stiffness index, contrary to the resting VL µ. We show that the VL µ is greatly reduced and η greatly enhanced by fatigue, reflecting a more compliant and viscous muscle. The quantification of both shear µ and η moduli in vivo may contribute to a better understanding of the mechanical behavior of muscles during fatigue in sports medicine, as well as in clinical situations.

Resting Muscle Shear Modulus Measured With Ultrasound Shear-Wave Elastography as an Alternative Tool to Assess Muscle Fatigue in Humans.

The aim of this study was to investigate the time course of the resting vastus lateralis (VL) muscle shear elastic modulus (µ) measured with ultrasound shear-wave elastography during repetition of isometric maximal voluntary contractions (MVCs) of the knee extensors (KE). Fifteen well-trained young males repeated 60 5-s isometric MVCs. Evoked electrical stimulations and the VLµ were measured every ten MVCs at rest. The resting VLµ significantly decreased (-34.7 ± 6.7%; P < 0.001) by the end of the fatigue protocol. There was also a 38.4 ± 12.6 % decrease in MVC after exercise (P < 0.001). The potentiated doublet and single twitch torque amplitudes and properties were significantly modified by the end of exercise (P < 0.001). This study shows the time course of the resting VLµ during the repetition of maximal voluntary fatiguing exercise of the KE muscles. The decrease of the resting VLµ could directly affect the force transmission capabilities accounting for peripheral fatigue.

Circulating microRNA profile in a mouse model of Crimean-Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is a severe disease leading to high mortality in humans. Early diagnosis and evaluation of the severity are necessary to improve patient survival. In a model of CCHF virus-infected interferon-receptor-deficient (IFNAR) KO mice, we found a specific circulating miRNA (c-miRNA) profile when compared to wild-type (wt), resistant mice. Among this response, 20 c-miRNA were shown to be specifically altered, including miR-122-5p, miR-216a-5p, 217-5p, miR-29a-3p and miR-511-5p. Using a logistic regression analysis, a combination of 8 miRNAs allowed a 100% discrimination of mice developing a severe illness (IFNAR-KO) from non-detectable clinical signs (wt).

Circulating levels of non-muscle-specific miRNAs in response to acute muscle damage in rat.

MicroRNA (miRNA) are found in numerous biofluids including blood and are considered a new class of biomarkers. In several animal models as well as in human diseases, they are interesting circulating markers of acute or chronic tissue injury. This article provides additional data related to a previous research article entitled "Circulating miRNAs as biomarkers of acute muscle damage in rats" by Siracusa et al. (2016) [1]. The data were obtained by RT-qPCR performed on plasma of rats exposed to acute muscle damage. The present set of data displays 45 non muscle-specific miRNA responses to acute, experimental muscle injury in healthy rats. They complement previous findings showing that circulating levels of miRNAs can be affected by muscle damage.

Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage.

Skeletal muscle is a heterogeneous tissue composed of a continuum of contracting fibers ranging from slow-type to fast-type fibers. Muscle damage is a frequent event and a susceptibility of fast-fibers to exercise-induced damage (EIMD) or statins toxicity has been reported. Biological markers of muscle damage such as creatine kinase (CK) are not fiber-type specific and new biomarkers are needed. Some microRNAs (miRNAs) are specific to the muscle tissue, can be found in the extracellular compartment and can rise in the plasma following muscle damage. Our aim was to identify whether a set of circulating miRNAs can be used as fiber-type specific biomarkers of muscle damage in a model of traumatic (crush) injuries induced either in the slow soleus (SOL) or in the fast extensor digitorum longus (EDL) muscles of rats. A subset of miRNAs composed of miR-1-3p, -133a-3p, -133b-3p, 206-3p, -208b-3p, 378a-3p, -434-3p, and -499-5p were measured by RT-PCR in non-injured SOL or EDL muscle and in the plasma of rats 12 h after damage induced to SOL or EDL. MiR-133b-3p, -378a-3p, and -434-3p were equally expressed both in SOL and EDL muscles. MiR-1-3-p and -133a-3p levels were higher in EDL compared to SOL (1.3- and 1.1-fold, respectively). Conversely, miR-206-3p, -208b-3p, and -499-5p were mainly expressed in SOL compared to EDL (7.4-, 35.4-, and 10.7-fold, respectively). In the plasma, miR-1-3p and -133a-3p were elevated following muscle damage compared to a control group, with no difference between SOL and EDL. MiR-133b-3p and -434-3p plasma levels were significantly higher in EDL compared to SOL (1.8- and 2.4-fold, respectively), while miR-378a-3p rose only in the EDL group. MiR-206-3p levels were elevated in SOL only (fourfold compared to EDL). Our results show that plasma miR-133b-3p and -434 are fast-fiber specific biomarkers, while miR-206-3p is a robust indicator of slow-fiber damage, opening new perspectives to monitor fiber-type selective muscle damage in research and clinic.

Circulating myomiRs: a new class of biomarkers to monitor skeletal muscle in physiology and medicine.

MicroRNAs (miRNA) are small non-coding RNAs that target mRNAs and are consequently involved in the post-transcriptional regulation of gene expression. Some miRNAs are ubiquitously expressed in tissue, while others are tissue-specific or tissue-enriched. miRNAs can be released by cells and are found in various biofluids, including serum and plasma. Thus, measuring miRNAs in the circulation may provide information on the originating tissue or cells. MyomiRs are described as striated muscle-specific or muscle-enriched miRNAs. Their circulating levels can be measured and have been proposed to be new biomarkers of physiological and pathological muscle processes. The aims of this review are to summarize the current knowledge of circulating myomiRs, to identify the types of information they can provide about skeletal muscle, and to determine how to apply that information in the fields of research and medicine.