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SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. It is involved in the regulation of various pathophysiological processes, including cell proliferation, survival, differentiation, autophagy, and oxidative stress. Therapeutic activation of SIRT1 protects the heart and cardiomyocytes from pathology-related stress, particularly myocardial ischemia/reperfusion (I/R). Autophagy is an important metabolic pathway for cell survival during energy or nutrient deficiency, hypoxia, or oxidative stress. Autophagy is a double-edged sword in myocardial I/R injury. The activation of autophagy during the ischemic phase removes excess metabolic waste and helps ensure cardiomyocyte survival, whereas excessive autophagy during reperfusion depletes the cellular components and leads to autophagic cell death. Increasing research on I/R injury has indicated that SIRT1 is involved in the process of autophagy and regulates myocardial I/R. SIRT1 regulates autophagy through various pathways, such as the deacetylation of FOXOs, ATGs, and LC3. Recent studies have confirmed that SIRT1-mediated autophagy plays different roles at different stages of myocardial I/R injury. By targeting the mechanism of SIRT1-mediated autophagy at different stages of I/R injury, new small-molecule drugs, miRNA activators, or blockers can be developed. For example, resveratrol, sevoflurane, quercetin, and melatonin in the ischemic stage, coptisine, curcumin, berberine, and some miRNAs during reperfusion, were involved in regulating the SIRT1-autophagy axis, exerting a cardioprotective effect. Here, we summarize the possible mechanisms of autophagy regulation by SIRT1 in myocardial I/R injury and the related molecular drug applications to identify strategies for treating myocardial I/R injury.
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Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Daño por Reperfusión Miocárdica , Humanos , Daño por Reperfusión Miocárdica/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Isquemia Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Reperfusión , Autofagia , ApoptosisRESUMEN
Resistance training activates mammalian target of rapamycin (mTOR) pathway of hypertrophy for strength gain, while endurance training increases peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) pathway of mitochondrial biogenesis benefiting oxidative phosphorylation. The conventional view suggests that resistance training-induced hypertrophy signaling interferes with endurance training-induced mitochondrial remodeling. However, this idea has been challenged because acute leg press and knee extension in humans enhance both muscle hypertrophy and mitochondrial remodeling signals. Thus, we first examined the muscle mitochondrial remodeling and hypertrophy signals with endurance training and resistance training, respectively. In addition, we discussed the influence of resistance training on muscle mitochondria, demonstrating that the PGC-1α-mediated muscle mitochondrial adaptation and hypertrophy occur simultaneously. The second aim was to discuss the integrative effects of concurrent training, which consists of endurance and resistance training sessions on mitochondrial remodeling. The study found that the resistance training component does not reduce muscle mitochondrial remodeling signals in concurrent training. On the contrary, concurrent training has the potential to amplify skeletal muscle mitochondrial biogenesis compared to a single exercise model. Concurrent training involving differential sequences of resistance and endurance training may result in varied mitochondrial biogenesis signals, which should be linked to the pre-activation of mTOR or PGC-1α signaling. Our review proposed a mechanism for mTOR signaling that promotes PGC-1α signaling through unidentified pathways. This mechanism may be account for the superior muscle mitochondrial remodeling change following the concurrent training. Our review suggested an interaction between resistance training and endurance training in skeletal muscle mitochondrial adaptation.
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This study aimed to investigate the association between biomarkers and overuse injuries in well-trained wrestlers. Seventy-six well-trained wrestlers on a national team completed two blood sample collections, two clinical overuse injuries diagnoses, and a questionnaire survey at a 2-week interval. Multivariate logistic regression analysis and receiver operating characteristic curve were used to screen for related factors and construct the prediction probability model of overuse injuries. Using a restricted cubic spline further clarifies the relationship between biomarker levels and the risk of overuse injuries. Creatine kinase (CK), cortisol, rheumatoid factor, testosterone in men, and C-reactive protein (CRP) levels in the overuse injuries group were significantly different compared to those in the non-overuse injuries group. The diagnostic efficiency of the prediction probability model was more valuable than any single variable (area under the curve=0.96, Specificity=0.91, Sensitivity=0.89, high accuracy). A J-shaped relationship was noted between biomarkers (cortisol, CRP, and CK) and the risk of overuse injuries (cutoff point: 17.95 µg·dL-1, 4.72 mg·L-1, and 344 U·L-1; p for nonlinearity:<0.001, 0.025, and 0.043, respectively). In conclusion, a predictive model based on biomarkers (cortisol, CRP, and CK) predicted the overuse injuries risk of well-trained wrestlers. High levels of these three biomarkers were associated with a higher risk of overuse injuries, and a J-shaped relationship was observed between them.
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Trastornos de Traumas Acumulados , Hidrocortisona , Masculino , Humanos , Factores de Riesgo , Trastornos de Traumas Acumulados/diagnóstico , Biomarcadores , Curva ROC , Proteína C-ReactivaRESUMEN
We aimed to explore the role of Sirt3 in the regulation of skeletal muscle mitophagy with hypoxic training. C57BL/6J mice were randomly divided into four groups: C group (control), HT group (mice performed a hypoxic training of living in an environment with an oxygen concentration of 13.8% and treadmill exercise under normoxia for 6 weeks), T group (mice were subjected to an intraperitoneal (i.p.) injection of the Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) 50 mg/kg three times per week for 6 weeks) and THT group (the hypoxic training of HT group with i.p. injection of 3-TYP in T group). The results showed that 6 weeks of hypoxic training could improve ATP synthesis in skeletal muscle. After the combined intervention of 3-TYP injection and hypoxic training, Sirt3, FOXO3a, and SOD2 protein contents were still lower than those in hypoxic training group. Hypoxic training cannot improve the negative effect of Sirt3 inhibition on muscle PINK1/Parkin signal. This study demonstrated that Sirt3 plays a key role in mediating skeletal muscle mitophagy by hypoxic training. The results of our study also provided the first evidence that mitophagy caused by hypoxic training might be transduced through the Sirt3-FOXO3a signaling pathway.
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Mitofagia , Sirtuina 3 , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Animales , Hipoxia/metabolismo , Ratones , Ratones Endogámicos C57BL , Mitofagia/fisiología , Músculo Esquelético/metabolismo , Oxígeno/metabolismo , Oxígeno/farmacología , Proteínas Quinasas/metabolismo , Proteínas Quinasas/farmacología , Piridinas/farmacología , Sirtuina 3/metabolismo , Sirtuina 3/farmacología , Ubiquitina-Proteína LigasasRESUMEN
Lipophagy is a kind of selective autophagy, which can selectively identify and degrade lipid droplets and plays an important role in regulating cellular lipid metabolism and maintaining intracellular lipid homeostasis. Exercise can induce lipophagy and it is also an effective means of reducing body fat. In this review, we summarized the relationship between exercise and lipophagy in the liver, pancreas, adipose tissue, and the possible molecular mechanisms to provide a new clue for the prevention and treatment of fatty liver, obesity and other related metabolic diseases by exercise.
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Metabolismo de los Lípidos , Enfermedades Metabólicas , Autofagia/fisiología , Humanos , Gotas Lipídicas/metabolismo , Metabolismo de los Lípidos/fisiología , Hígado , Enfermedades Metabólicas/metabolismoRESUMEN
Objectives: The purpose was to investigate the effects of hot and humid environments on thermoregulation and aerobic endurance capacity and whether high skin temperature serves as a more important thermoregulatory factor affecting aerobic exercise capacity. Methods: A randomized cross-over design was applied to this study, in which nine Laser sailors performed the 6 km rowing test (6 km test) in both a warm (ambient temperature: 23 ± 1.4 °C; relative humidity: 60.5 ± 0.7%; wind speed: 0 km/h; WARM) and hot environment (ambient temperature: 31.8 ± 1.1 °C; relative humidity: 63.5 ± 4.9%; wind speed: 3.5 ± 0.7 km/h; HOT). Results: The time for completing 6 km test of HOT group was significantly longer than that of WARM group (P = 0.0014). Mean power of 3-4 km, 4-5 km and 5-6 km were significant lower in HOT group (P = 0.014, P = 0.02, P = 0.003). Gastrointestinal temperature and skin temperature were significantly higher in HOT group during the 6 km test (P = 0.016, P = 0.04). Heat storage at 5 min and 15 min of HOT group were significantly higher than that of WARM group (P = 0.0036; P = 0.0018). Heart rate and physiological strain index of HOT group were significantly higher than that of WARM group during the 6 km test (P = 0.01, P < 0.01). Conclusion: When skin temperature and core temperature both increased, high skin temperature may be the more important thermoregulatory factor that affected the aerobic endurance performance in hot and humid environments. The high skin temperature narrowed the core to skin temperature gradient and skin to ambient temperature gradient, which may result in greater accumulation of heat storage. The greater heat storage led to the lower muscle power output, which contributed to the reduction of the heat production.
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The mitochondrial unfolded protein response is an important component of the mitochondrial protein quality control program. It can effectively remove unfolded or misfolded proteins under stress, and maintain a stable and healthy mitochondrial pool. The mitochondrial unfolded protein response is coordinated by multiple signaling pathways. The classical ATF4/ATF5-CHOP pathway is induced by accumulation of unfolded or misfolded proteins in the mitochondrial matrix, which reduces stress toxicity by regulating molecular chaperones and proteases. Sirt3-FOXO3a-SOD2 pathway, located in the mitochondrial matrix, plays an important role in anti-oxidative damage. The ERα-NRF1-HTRA2 pathway mainly removes unfolded proteins in the mitochondrial membrane space and improves the quality control of mitochondrial proteins. These three signaling pathways work both independently and cooperatively to enhance mitochondrial capacity and maintain health under stress.
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Mitocondrias , Respuesta de Proteína Desplegada , Proteínas Mitocondriales/metabolismo , Estrés Oxidativo , Transducción de SeñalRESUMEN
Magnetic solid-phase extraction (MSPE) employing a metal-organic framework (Fe3 O4 @UiO-66-OH) combined with high-performance liquid chromatography was developed for the determination of trace diuretics in urine. The structure and properties of Fe3 O4 @UiO-66-OH were investigated using X-ray diffraction, infrared spectroscopy, scanning electron microscopy and vibrating sample magnetometry. Magnetic solid-phase extraction conditions, such as adsorbent amount and solution pH, were optimized using response surface methodology. Under the optimal conditions, the method resulted in excellent linearity with a high correlation coefficient (r > 0.99), satisfactory intraday repeatability (1.78-2.99%), low limits of detection (0.08-0.23 ng/ml), and good recoveries in urine samples (between 93.5 and 103%). Fe3 O4 @UiO-66-OH based on MSPE is a novel pretreatment technique for the detection of trace diuretics in urine.
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Cromatografía Líquida de Alta Presión/métodos , Diuréticos/orina , Estructuras Metalorgánicas/química , Extracción en Fase Sólida/métodos , Compuestos Férricos/química , Humanos , Límite de Detección , Modelos Lineales , Compuestos Organometálicos/química , Ácidos Ftálicos/química , Reproducibilidad de los ResultadosRESUMEN
Mitochondrial dynamics, involving mitochondrial fusion, fission and autophagy, plays an important role in maintaining cellular physiological function and homeostasis. Mitochondria are the "energy plant" of human body, so the changes of mitochondrial fusion, division and autophagy are important for cell respiration and energy production. On the other hand, energy metabolism influences mitochondrial dynamics in turn. This paper reviewed the recent advances in studies on the relationship between energy metabolism and the proteins regulating mitochondrial fusion, fission and autophagy. The association of mitochondrial dynamics with electron chain complex expression, oxidative phosphorylation and ATP synthesis upon exercise intervention will provide theoretical references for the further studies in sports training and disease intervention.
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Autofagia , Metabolismo Energético , Ejercicio Físico , Mitocondrias/fisiología , Dinámicas Mitocondriales , Adenosina Trifosfato/biosíntesis , Humanos , Proteínas Mitocondriales/metabolismoRESUMEN
The aim of this study was to investigate the effects of exercise training and dietary restriction on cardiac PINK1/Parkin and Bnip3/Nix pathways involved in mitophagy. C57BL/6 mice were assigned to control (C), exercise training (T), dietary restriction (D) and exercise training + dietary restriction (TD) groups. T group undertook 10 weeks of swimming training. D group was subjected to 40% food reduction. TD group undertook the combination of exercise training and food reduction. Suspectable mitophagy autophagosomes can be observed in T and D groups and more autophagosomes appeared in TD group. In T group, both PINK1 mRNA and protein levels increased significantly (p < 0.01) but Bnip3 and Nix expressions decreased significantly (p < 0.05). Dietary restriction resulted in elevation of Drp1 (p < 0.01) and reduction and Nix (p < 0.05) in D group. The load in TD group resulted in serious mitochondrial abnormalities and myofibrillar damages accompanied by increases in PINK1 and Drp1 levels (p < 0.01) and decreases in Bnip3 and Nix levels (p < 0.05). The increase in PINK1 expression (exercise protocol) or Drp1 expression (diet protocol) contributes to cardiac activation of mitophagy, whereas Bnip3 and Nix are not implicated in this activation.
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Mitocondrias , Mitofagia , Animales , Proteínas de la Membrana , Ratones , Ratones Endogámicos C57BL , Proteínas Mitocondriales , Condicionamiento Físico Animal , Proteínas Quinasas , Ubiquitina-Proteína LigasasRESUMEN
Background: Hypoxic and cold environments have been shown to improve the function and performance of athletes. However, it is unclear whether the combination of subalpine conditions and cold temperatures may have a greater effect. The present study aims to investigate the effects of 6 weeks of training in a sub-plateau cold environment on the physical function and athletic ability of elite parallel giant slalom snowboard athletes. Methods: Nine elite athletes (four males and five females) participated in the study. The athletes underwent 6 weeks of high intensity ski-specific technical training (150 min/session, six times/week) and medium-intensity physical training (120 min/session, six times/week) prior to the Beijing 2021 Winter Olympic Games test competition. The physiological and biochemical parameters were collected from elbow venous blood samples after each 2-week session to assess the athletes' physical functional status. The athletes' athletic ability was evaluated by measuring their maximal oxygen uptake, Wingate 30 s anaerobic capacity, 30 m sprint run, and race performance. Measurements were taken before and after participating in the training program for six weeks. The repeated measure ANOVA was used to test the overall differences of blood physiological and biochemical indicators. For indicators with significant time main effects, post-hoc tests were conducted using the least significant difference (LSD) method. The paired-samples t-test was used to analyze changes in athletic ability indicators before and after training. Results: (1) There was a significant overall time effect for red blood cells (RBC) and white blood cells (WBC) in males; there was also a significant effect on the percentage of lymphocytes (LY%), serum testosterone (T), and testosterone to cortisol ratio (T/C) in females (p < 0.001 - 0.015, η p 2 = 0 . 81 - 0 . 99 ). In addition, a significant time effect was also found for blood urea(BU), serum creatine kinase (CK), and serum cortisol levels in both male and female athletes (p = 0.001 - 0.029, η p 2 = 0 . 52 - 0 . 95 ). (2) BU and CK levels in males and LY% in females were all significantly higher at week 6 (p = 0.001 - 0.038), while WBC in males was significantly lower (p = 0.030). T and T/C were significantly lower in females at week 2 compared to pre-training (p = 0.007, 0.008, respectively), while cortisol (C) was significantly higher in males and females at weeks 2 and 4 (p (male) = 0.015, 0.004, respectively; p (female) = 0.024, 0.030, respectively). (3) There was a noticeable increase in relative maximal oxygen uptake, Wingate 30 s relative average anaerobic power, 30 m sprint run performance, and race performance in comparison to the pre-training measurements (p < 0.001 - 0.027). Conclusions: Six weeks of sub-plateau cold environment training may improve physical functioning and promote aerobic and anaerobic capacity for parallel giant slalom snowboard athletes. Furthermore, male athletes had a greater improvement of physical functioning and athletic ability when trained in sub-plateau cold environments.
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Rendimiento Atlético , Frío , Acondicionamiento Físico Humano , Femenino , Humanos , Masculino , Atletas , Hidrocortisona , Oxígeno , Deportes , Testosterona , Deportes de NieveRESUMEN
OBJECTIVE: The impact of high-nitrate beetroot juice (BRJ) supplementation has seen a recent explosion of interest in sports science. This study examined the potential influence of 7-day BRJ supplementation on the endurance performance of winter triathletes. METHODS: Eighty young active winter triathletes (44 males, age = 21.50 ± 1.15 yrs; 36 females, age = 20.66 ± 1.45 yrs) participated in this study and were provided with either BRJ (6.5 mmol NO3-/70 mL) or a placebo (PL, 0.065 mmol NO3-/70 mL) for 7 days (a dose of ×3 per day) in a randomized, double-blind design. The athletes then completed a submaximal treadmill run, intraday cycling exhaustion testing, and a 10-km cross country (XC) skiing competition on the second day. RESULTS: There was a significant decrease in the oxygen uptake, respiratory exchange ratio, and blood lactic acid level (p < 0.05) between the BRJ and PL treatment groups during V3 speed running (males: 13.3 km·h-1, females: 11.6 km·h-1). BRJ treatment also remarkably increased the time to exhaustion (TTE) during cycling exhaustion testing (males: p = 0.02, females: p = 0.04). No significant differences were observed in medium- or low-speed submaximal treadmill runs and 10-km XC skiing performance. CONCLUSIONS: One week of daily nitrate-rich BRJ supplementation improved running economy at high speed during the submaximal treadmill running test and extended the TTE of athletes during cycling exhaustion testing. However, BRJ supplementation did not improve the performance in 10-km on-snow time trials in XC skiing. Regarding nutritional strategies to improve endurance performance in exercise training and competition, these results should be carefully considered owing to the different motor skill levels and competitive abilities of participants.
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Beta vulgaris , Nitratos , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Suplementos Dietéticos , Jugos de Frutas y Vegetales , AntioxidantesRESUMEN
In this study, disulfide bonds between the interfacial protein film formed on the lipid particles and the protein in ovalbumin emulsion gels were blocked with 0, 1, 3, 5 and 10 mM of the N-ethylmaleimide (NEM) to explore the influence and effect mechanism of disulfide bonds between the interfacial proteins on the physicochemical properties, microstructure, and protein structure of sunflower oil-ovalbumin emulsion gels. Ovalbumin emulsion gels with NEM-treated ovalbumin emulsion (N-OE) had lower hardness, free sulfhydryl content, water holding capacity (WHC), and surface hydrophobicity, but higher spin-spin relaxation time (T2) than ovalbumin emulsion gels with NEM-treated ovalbumin substrate solution (N-OSS). In addition, N-OE and N-OSS had lower hardness, free sulfhydryl content, WHC and surface hydrophobicity, as well as a more coarse and disordered microstructure than non-NEM treated ovalbumin emulsion gel (control group). The free sulfhydryl content, hardness, WHC, and surface hydrophobicity of the ovalbumin emulsion gels all decreased as the NEM concentration rose (p < 0.05), whereas the amide A band changed to higher wave numbers. These results collectively indicated that the reduction of disulfide between the interfacial layer and the proteins inhibited the hydrophobic effect, the formation of hydrogen bonds, and prevented the formation of larger aggregates. Thus the disulfide bonds between the interfacial proteins contribute to the hardness enhancement and water stabilization of the ovalbumin gel.
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Disulfuros , Gotas Lipídicas , Emulsiones/química , Ovalbúmina/química , Etilmaleimida , Geles/química , Disulfuros/química , Agua/químicaRESUMEN
This study was designed to investigate the influence and effect mechanism of the filler type on the physicochemical properties, microbial numbers, and digestibility of ovalbumin emulsion gels (OEGs) during storage. Sunflower oil was emulsified with ovalbumin (20 mg mL-1) and Tween 80 (20 mg mL-1) separately to prepare ovalbumin emulsion gels (OEGs) that contained active and inactive fillers, respectively. The formed OEGs were stored at 4 °C for 0, 5, 10, 15, and 20 days. The active filler enhanced the gel hardness, water holding capacity, fat holding capacity, and surface hydrophobicity and decreased the digestibility and free sulfhydryl content during storage compared to control (unfilled) ovalbumin gel, whereas the inactive filler had the opposite effects. Protein aggregation diminished, lipid particle aggregation increased, and the amide A band shifted to a higher wavenumber for all three types of gel during storage, suggesting that the compact network structure of the OEG became rough and disordered with storage. The OEG with the active filler did not inhibit microbial growth, and the OEG with the inactive filler did not significantly promote the development of bacteria. In addition, the active filler delayed the in vitro digestion of the protein in the OEG throughout storage. Emulsion gels containing active filler facilitated the retention of the gel properties during storage, whereas emulsion gels containing inactive filler exacerbated the loss of the gel properties during storage.
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Polisorbatos , Proteínas , Emulsiones/química , Ovalbúmina , Geles/químicaRESUMEN
Objective: This work aimed to explore the application and optimization of the electrophysiological monitoring system to real-time monitor the exercise-induced fatigue (EIF) animals and investigate the intervention mechanism of hyperbaric oxygen (HBO) combined with natural astaxanthin (NAX) on EIF. Methods: First, a system was constructed for acquisition, processing, and feature extraction of electrocardiograph (ECG) signal and surface electromyography (EMG) signal for EIF monitoring. The mice were randomly divided into a control group (CG), EIF group (EG), HBO treatment (HBO) group, and HBO combined with NAX treatment (HBO + NAX) group. The effect of the constructed system on classification recognition of EIF was analyzed. The levels of serum antioxidative stress indicators of mice in each group were detected, including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione-peroxidation (GSH-Px), and total antioxidant capacity (T-AOC). In addition, the mRNA and protein levels of Keap1/Nrf2/HO-1 pathway related genes in liver tissue were detected. Results: The results showed that the normalized least mean squares algorithm effectively removed the motion artifact interference of ECG signal and can clearly display the signal peak, and high-pass filtering and power frequency filtering effectively removed the motion and baseline drift interference of surface EMG signal. The recognition sensitivity, specificity, and accuracy of the EIF recognition model based on the long- and short-term memory network were 90.0%, 93.3%, and 92.5%, respectively. Compared with the CG, the characteristics of ECG signal and surface EMG signal of the mice in the EIF group changed greatly (P < 0.05); the serum MDA level was increased obviously; the CAT, SOD, GSH, GSH-Px, and T-AOC levels were observably reduced (P < 0.05); the expressions of Keap1 and HO-1 in the liver were reduced remarkably, while the expression of Nrf2 was increased notably (P < 0.05). Compared with the EIF group, the characteristics of ECG signal and surface EMG signal of the mice in the HBO and HBO + NAX groups were obviously improved (P < 0.05); the serum MDA level was significantly reduced; the CAT, SOD, GSH, GSH-Px, and T-AOC levels were greatly increased (P < 0.05); the expressions of Keap1 and HO-1 in the liver were greatly increased, while the expression of Nrf2 was decreased sharply (P < 0.05). Conclusion: Therefore, the feature extraction and classification system of ECG signal combined with surface EMG signal could realize real-time monitoring of EIF status. HBO intervention could improve the body's ability to resist oxidative stress through the Keap1/Nrf2/HO-1 pathway and then improve the EIF state. In addition, the improvement effect of HBO + NAX was more obvious.
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Oxigenoterapia Hiperbárica , Factor 2 Relacionado con NF-E2 , Animales , Antioxidantes/farmacología , Fatiga , Glutatión/metabolismo , Glutatión/farmacología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Transducción de Señal , Superóxido Dismutasa/metabolismo , XantófilasRESUMEN
Transient receptor potential vanilloid 1 (TRPV1) is a protein that is susceptible to cell environment temperature. High temperatures of 40-45°C can activate the TRPV1 channel. TRPV1 is highly expressed in skeletal muscle and located on the sarcoplasmic reticulum (SR). Therefore, TRPV1 activated by high-temperature stress releases Ca2+ from the SR to the cytoplasm. Cellular Ca2+ accumulation is a key event that enhances TRPV1 activity by directly binding to the N-terminus and C-terminus. Moreover, Ca2+ is the key messenger involved in regulating mitochondrial biogenesis in skeletal muscle. Long-term activation of TRPV1 may promote mitochondrial biogenesis in skeletal muscle through the Ca2+-CaMKII-p38 MAPK-PGC-1α signaling axis. The discovery of the TRPV1 channel highlights the potential mechanism for high-temperature stress improving muscle mitochondrial biogenesis. The appropriate hot stimulus in thermal environments might be beneficial to the muscular mitochondrial adaptation for aerobic capacity. However, the investigation of TRPV1 on mitochondrial biogenesis is at an early stage. Further investigations need to examine the role of TRPV1 in response to mitochondrial biogenesis in skeletal muscle induced by different thermal environments.
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Most of the primary hepatocellular carcinoma (HCC) develops from Viral Hepatitis including Hepatitis B virus, Hepatitis C Virus, and Nonalcoholic Steatohepatitis. Herein, T cells play crucial roles combined with chronic inflammation and chronic viral infection. However, T cells are gradually exhausted under chronic antigenic stimulation, which leads to T cell exhaustion in the tumor microenvironment, and the exhaustion is associated with mitochondrial dysfunction in T cells. Meanwhile, mitochondria play a crucial role in altering T cells' metabolism modes to achieve desirable immunological responses, wherein mitochondria maintain quality control (MQC) and promote metabolism regulation in the microenvironment. Although immune checkpoint inhibitors have been widely used in clinical practice, there are some limitations in the therapeutic effect, thus combining immune checkpoint inhibitors with targeting mitochondrial biogenesis may enhance cellular metabolic adaptation and reverse the exhausted state. At present, several studies on mitochondrial quality control in HCC have been reported, however, there are gaps in the regulation of immune cell function by mitochondrial metabolism, particularly the modulating of T cell immune function. Hence, this review summarizes and discusses existing studies on the effects of MQC on T cell populations in liver diseases induced by HCC, it would be clued by mitochondrial quality control events.
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Background: Pressure-strain loop (PSL) analysis provides a novel, less load-dependent non-invasive method to quantify myocardial work and demonstrates a significant correlation with the contractile reserve in adult athletes. We aim to validate PSL-derived markers in characterizing LV function in pre-adolescent basketball players by comparing results before and after the cardiopulmonary exercise test (CPX) and explore its association with CPX-derived aerobic capacity. Methods: Cardiac morphology and function in 20 pre-adolescent basketball players were assessed at 9.7 years old (9.7 ± 1.1 year) before and after cardiopulmonary exercise testing. Echocardiography was performed in all subjects, including two-dimensional speckle-tracking echocardiography (STE). Simultaneous brachial-cuff-measured blood pressure was recorded to perform PSL analysis. Results: Nineteen subjects were included in the final analysis. Exercise training in pre-adolescent males was associated with lower global work index (GWI) and global work efficiency (GWE) at rest. GWE at stress was significantly correlated with VO2max and peak O2 pulse (p = 0.0122, r = 0.56; p = 0.00122, r = 0.69, respectively). When indexed by body mass, GWI and GWE both significantly correlated with relative VO2max (p = 0.0086 and 0.0011 respectively, r = 0.58 and 0.69 respectively); GWI and GWE at baseline and stress were all significantly correlated with peak O2 pulse (GWI at baseline, p < 0.0001, r = -0.90; GWE at baseline, p < 0.0001, r = -0.89; GWI at stress, p = 0.0289, r = -0.50; GWE at stress, p < 0.0001, r = -0.83). Conclusion: PSL-analysis-derived GWI and GWE at rest indexed by body mass are associated with cardiopulmonary exercise test-derived peak oxygen consumption and oxygen pulse in pre-adolescent athletes.
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Hypoxic training improves the microcirculation function of human skeletal muscle, but its mechanism is still unclear. Silent information regulator 2 homolog 3 (Sirt3) can improve mitochondrial function and oxidative status. We aimed to examine the role of Sirt3 in the process of hypoxic training, which affects skeletal muscle microcirculation. C57BL/6 mice were assigned to control (C), hypoxic training (HT), Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP), and 3-TYP + hypoxic training (3-TYP + HT) groups (n = 6/group). Sirt3 inhibition was induced by intraperitoneal injection of Sirt3 inhibitor 3-TYP. After 6 weeks of intervention, microcirculatory capillary formation and vasomotor capacity were evaluated using immunofluorescence, Western blot, biochemical tests, and transmission electron microscopy (TEM). Laser Doppler flowmetry was used to evaluate skeletal muscle microcirculation blood flow characteristics. Six weeks of hypoxic training enhanced skeletal muscle microcirculation function and increased microcirculatory vasodilation capacity and capillary formation. After the pharmacological inhibition of Sirt3, the reserve capacity of skeletal muscle microcirculation was reduced to varying degrees. After the inhibition of Sirt3, mice completed the same hypoxic training, and we failed to observe the microcirculation function adaptation like that observed in hypoxic training alone. The microcirculation vasodilation and the capillaries number did not improve. Hypoxic training improved skeletal muscle microcirculation vasodilation capacity and increased skeletal muscle microcirculation capillary density. Sirt3 is involved in the adaptation of skeletal muscle microcirculation induced by hypoxic training.
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AIMS: Hypoxic training promotes human cardiopulmonary function and exercise performance efficiently, but the myocellular mechanism has been less studied. We aimed to examine the effects of hypoxic trainings on mitochondrial turnover and vascular remodeling of skeletal muscle. MAIN METHODS: C57BL/6 J mice were divided into control, hypoxic exposure, exercise training, "live high-train low" (LHTL), and "live low-train high" (LLTH) groups (n = 8/group). Western blot and immunohistochemistry were used to evaluate mitochondrial turnover of gastrocnemius and angiogenesis of quadriceps after six weeks interventions. KEY FINDINGS: Compared with control group, both LHTL and LLTH increased phosphorylation levels of p38 MAPK markedly (p < 0.05). LLTH also elevated PGC-1α protein expression significantly (p < 0.05). All interventions did not influence Bnip3 and Drp-1 proteins levels (p > 0.05), while LLTH enhanced Parkin and Mff protein contents significantly (p < 0.05). Immunohistochemical analysis showed both LHTL and LLTH promoted CD31 and VEGF expressions (p < 0.05). ATP content, citrate synthase activities of gastrocnemius were robustly elevated in LHTL and LLTH groups (p < 0.01). The exercise training increased Mff protein and ATP content in gastrocnemius as well as VEGF expression in quadriceps (p < 0.05). The hypoxic exposure also increased ATP content, citrate synthase, and ATP synthase activities in gastrocnemius as well as VEGF expression in quadriceps (p < 0.01). SIGNIFICANCE: Our results suggested that hypoxic trainings, especially LLTH, promoted mitochondrial turnover and angiogenesis of skeletal muscle, which may be an underlying mechanism of hypoxic training-induced exercise capacity.