Low-Volume Squat Jump Training Improves Functional Performance Independent of Myofibre Changes in Inactive Young Male Individuals.

An investigation into the histological changes in skeletal muscle fibres and jump performance indicators after 8 weeks of plyometric squat jump training was conducted. Healthy inactive participants (n = 13; age: 21.5 ± 1.7 year.; height: 173.6 ± 10.7 cm; weight: 68.5 ± 18.4 kg; BMI 22.4 ± 3.8 kg/m2) were recruited, where eight participants completed plyometric squat jump training and five control participants refrained from performing any jumping activities. Blood samples, vastus lateralis muscle biopsies and functional testing (peak and average power, peak and average velocity, maximal jump height) were collected/recorded 10 days prior to and 3 days after the training/rest period. Participants completed 1644 squat jumps over an 8-week training period of 24 sessions with a progressive increase in the number of squat jumps. The trained group significantly increased their jumping average and peak power (mean increases in average power: 16.7 ± 1.2% and peak power: 8.2% ± 0.1) and velocity (mean increases in average velocity: 13.7 ± 0.1% and peak velocity: 5.2% ± 0.03), resulting in a 25% improvement in vertical jump height. No muscle morphological changes in terms of the cross-sectional area (CSA) or muscle-fibre-type transition were observed after the plyometric training. Improvements in the functional performance indicators following training may more likely be explained by sarcomere ultrastructural adaptation, which did not directly affect myosin heavy chain or CSA.

The c-Myc/AKT1/TBX3 Axis Is Important to Target in the Treatment of Embryonal Rhabdomyosarcoma.

Rhabdomyosarcoma is a highly aggressive malignant cancer that arises from skeletal muscle progenitor cells and is the third most common solid tumour in children. Despite significant advances, rhabdomyosarcoma still presents a therapeutic challenge, and while targeted therapy has shown promise, there are limited options because the molecular drivers of rhabdomyosarcoma are poorly understood. We previously reported that the T-box transcription factor 3 (TBX3), which has been identified as a druggable target in many cancers, is overexpressed in rhabdomyosarcoma patient samples and cell lines. To identify new molecular therapeutic targets to treat rhabdomyosarcoma, this study investigates the potential oncogenic role(s) for TBX3 and the factors responsible for upregulating it in this cancer. To this end, rhabdomyosarcoma cell culture models in which TBX3 was either stably knocked down or overexpressed were established and the impact on key hallmarks of cancer were examined using growth curves, soft agar and scratch motility assays, as well as tumour-forming ability in nude mice. Our data show that TBX3 promotes substrate-dependent and -independent proliferation, migration and tumour formation. We further reveal that TBX3 is upregulated by c-Myc transcriptionally and AKT1 post-translationally. This study identifies c-Myc/AKT1/TBX3 as an important axis that could be targeted for the treatment of rhabdomyosarcoma.

Mechanisms of doxorubicin-induced drug resistance and drug resistant tumour growth in a murine breast tumour model.

BACKGROUND: Doxorubicin is currently the most effective chemotherapeutic drug used to treat breast cancer. It has, however, been shown that doxorubicin can induce drug resistance resulting in poor patient prognosis and survival. Studies reported that the interaction between signalling pathways can promote drug resistance through the induction of proliferation, cell cycle progression and prevention of apoptosis. The aim of this study was therefore to determine the effects of doxorubicin on apoptosis signalling, autophagy, the mitogen-activated protein kinase (MAPK)- and phosphoinositide 3-kinase (PI3K)/Akt signalling pathway, cell cycle control, and regulators of the epithelial-mesenchymal transition (EMT) process in murine breast cancer tumours. METHODS: A tumour-bearing mouse model was established by injecting murine E0771 breast cancer cells, suspended in Hank's Balances Salt Solution and Corning® Matrigel® Basement Membrane Matrix, into female C57BL/6 mice. Fourty-seven mice were randomly divided into three groups, namely tumour control (received Hank's Balances Salt Solution), low dose doxorubicin (received total of 6 mg/ml doxorubicin) and high dose doxorubicin (received total of 15 mg/ml doxorubicin) groups. A higher tumour growth rate was, however, observed in doxorubicin-treated mice compared to the untreated controls. We therefore compared the expression levels of markers involved in cell death and survival signalling pathways, by means of western blotting and fluorescence-based immunohistochemistry. RESULTS: Doxorubicin failed to induce cell death, by means of apoptosis or autophagy, and cell cycle arrest, indicating the occurrence of drug resistance and uncontrolled proliferation. Activation of the MAPK/ extracellular-signal-regulated kinase (ERK) pathway contributed to the resistance observed in treated mice, while no significant changes were found with the PI3K/Akt pathway and other MAPK pathways. Significant changes were also observed in cell cycle p21 and DNA replication minichromosome maintenance 2 proteins. No significant changes in EMT markers were observed after doxorubicin treatment. CONCLUSIONS: Our results suggest that doxorubicin-induced drug resistance and tumour growth can occur through the adaptive role of the MAPK/ERK pathway in an effort to protect tumour cells. Previous studies have shown that the efficacy of doxorubicin can be improved by inhibition of the ERK signalling pathway and thereby treatment failure can be overcome.

C-Reactive Protein Is Elevated Only in High Creatine Kinase Responders to Muscle Damaging Exercise.

The purpose of this study was to investigate if exertional rhabdomyolysis induced by an acute bout of plyometric exercise in untrained individuals was associated with histological characteristics of skeletal muscle, creatine kinase (CK) polymorphism or secondary damage. Twenty-six healthy male untrained individuals completed a bout of plyometric exercise (10 sets of 10 maximal squat jumps, with each standardized to achieve at least 95% of individual maximal jump height). Blood samples were taken, and perceived pain was scored immediately before the exercise intervention and 6 h, 1, 2, and 3 days post-intervention. Muscle biopsies were collected 9 or 4 days before (baseline) and 3 days after plyometric jumps. Subjects were divided into two groups, high (n = 10) and low responders (n = 16), based on a cut-off limit for exertional rhabdomyolysis of peak CK activity ≥ 1000 U/L in any post-exercise blood sample. Perceived pain was more severe assessed in squat than standing position. Low responders perceived more pain at 6 h and 1 day, while high responders perceived more pain than low responders on days three and four after exercise; structural (dystrophin staining) and ultra-structural (transmission electron microscopy) analysis of muscle fibers revealed no baseline pathology; damage was evident in all individuals in both groups, with no difference between high and low responders in either damage or fiber type proportion. High responders had significantly higher total white blood cell and neutrophil counts 6 h and significantly higher C-reactive protein (CRP) 6 h and days one and two after exercise compared to low responders. High responders had significantly greater muscle myeloperoxidase (MPO) levels in baseline and 3 day post-exercise biopsies compared to baseline of low responders. MLCK C49T single polymorphism was present in 26% of volunteers, whose CK responses were not higher than those with MLCK CC or CT genotype. In conclusion, perceived pain is more effectively assessed with potentially affected muscle under eccentric strain, even if static. High CK responders also have pronounced CRP responses to unaccustomed plyometric exercise intervention. Exertional rhabdomyolysis after unaccustomed eccentric exercise may be related to underlying inability to resolve intramuscular MPO.

Sickness-Associated Anorexia: Mother Nature's Idea of Immunonutrition?

During an infection, expansion of immune cells, assembly of antibodies, and the induction of a febrile response collectively place continual metabolic strain on the host. These considerations also provide a rationale for nutritional support in critically ill patients. Yet, results from clinical and preclinical studies indicate that aggressive nutritional support does not always benefit patients and may occasionally be detrimental. Moreover, both vertebrates and invertebrates exhibit a decrease in appetite during an infection, indicating that such sickness-associated anorexia (SAA) is evolutionarily conserved. It also suggests that SAA performs a vital function during an infection. We review evidence signifying that SAA may present a mechanism by which autophagic flux is upregulated systemically. A decrease in serum amino acids during an infection promotes autophagy not only in immune cells, but also in nonimmune cells. Similarly, bile acids reabsorbed postprandially inhibit hepatic autophagy by binding to farnesoid X receptors, indicating that SAA may be an attempt to conserve autophagy. In addition, augmented autophagic responses may play a critical role in clearing pathogens (xenophagy), in the presentation of epitopes in nonprovisional antigen presenting cells and the removal of damaged proteins and organelles. Collectively, these observations suggest that some patients might benefit from permissive underfeeding.

Chronic Prosopis glandulosa treatment blunts neutrophil infiltration and enhances muscle repair after contusion injury.

The current treatment options for soft tissue injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscle. The current study aimed to evaluate the effects of oral Prosopis glandulosa treatment on inflammation and regeneration in skeletal muscle after contusion injury, in comparison to a conventional treatment. The gastrocnemius muscle of rats was subjected to mass-drop injury and muscle samples collected after 1-, 3 h, 1- and 7 days post-injury. Rats were treated with P. glandulosa (100 mg/kg/day) either for 8 weeks prior to injury (up until day 7 post-injury), only post-injury, or with topically applied diclofenac post-injury (0.57 mg/kg). Neutrophil (His48-positive) and macrophage (F4/80-positive) infiltration was assessed by means of immunohistochemistry. Indicators of muscle satellite cell proliferation (ADAM12) and regeneration (desmin) were used to evaluate muscle repair. Chronic P. glandulosa and diclofenac treatment (p<0.0001) was associated with suppression of the neutrophil response to contusion injury, however only chronic P. glandulosa treatment facilitated more effective muscle recovery (increased ADAM12 (p<0.05) and desmin (p<0.001) expression), while diclofenac treatment had inhibitory effects on repair, despite effective inhibition of neutrophil response. Data indicates that P. glandulosa treatment results in more effective muscle repair after contusion.

Heat stroke risk for open-water swimmers during long-distance events.

Open-water swimming is a rapidly growing sport discipline worldwide, and clinical problems associated with long-distance swimming are now better recognized and managed more effectively. The most prevalent medical risk associated with an open-water swimming event is hypothermia; therefore, the Federation Internationale De Natation (FINA) has instituted 2 rules to reduce this occurrence related to the minimum water temperature and the time taken to complete the race. Another medical risk that is relevant to open-water swimmers is heat stroke, a condition that can easily go unnoticed. The purpose of this review is to shed light on this physiological phenomenon by examining the physiological response of swimmers during long-distance events, to define a maximum water temperature limit for competitions. We conclude that competing in water temperatures exceeding 33°C should be avoided.

Preferential type II muscle fiber damage from plyometric exercise.

CONTEXT: Plyometric training has been successfully used in different sporting contexts. Studies that investigated the effect of plyometric training on muscle morphology are limited, and results are controversial with regard to which muscle fiber type is mainly affected. OBJECTIVE: To analyze the skeletal muscle structural and ultrastructural change induced by an acute bout of plyometric exercise to determine which type of muscle fibers is predominantly damaged. DESIGN: Descriptive laboratory study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Eight healthy, untrained individuals (age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg). INTERVENTION(S): Participants completed an acute bout of plyometric exercise (10 sets of 10 squat-jumps with a 1-minute rest between sets). MAIN OUTCOME MEASURE(S): Blood samples were collected 9 days and immediately before and 6 hours and 1, 2, and 3 days after the acute intervention. Muscle samples were collected 9 days before and 3 days after the exercise intervention. Blood samples were analyzed for creatine kinase activity. Muscle biopsies were analyzed for damage using fluorescent and electron transmission microscopy. RESULTS: Creatine kinase activity peaked 1 day after the exercise bout (529.0 ± 317.8 U/L). Immunofluorescence revealed sarcolemmal damage in 155 of 1616 fibers analyzed. Mainly fast-twitch fibers were damaged. Within subgroups, 7.6% of type I fibers, 10.3% of type IIa fibers, and 14.3% of type IIx fibers were damaged as assessed by losses in dystrophin staining. Similar damage was prevalent in IIx and IIa fibers. Electron microscopy revealed clearly distinguishable moderate and severe sarcomere damage, with damage quantifiably predominant in type II muscle fibers of both the glycolytic and oxidative subtypes (86% and 84%, respectively, versus only 27% of slow-twitch fibers). CONCLUSIONS: We provide direct evidence that a single bout of plyometric exercise affected mainly type II muscle fibers.