Comparative Effects of Basic Fibroblast Growth Factor Delivery or Voluntary Exercise on Muscle Regeneration after Volumetric Muscle Loss

Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of spatially nanopatterned collagen scaffold implants with either bFGF delivery or in conjunction with voluntary exercise. Aligned nanofibrillar collagen scaffold bundles were adsorbed with bFGF, and the bioactivity of bFGF-laden scaffolds was examined by skeletal myoblast or endothelial cell proliferation. The therapeutic efficacy of scaffold implants with either bFGF release or exercise was examined in a murine VML model. Our results show an initial burst release of bFGF from the scaffolds, followed by a slower release over 21 days. The released bFGF induced myoblast and endothelial cell proliferation in vitro. After 3 weeks of implantation in a mouse VML model, twitch force generation was significantly higher in mice treated with bFGF-laden scaffolds compared to bFGF-laden scaffolds with exercise. However, myofiber density was not significantly improved with bFGF scaffolds or voluntary exercise. In contrast, the scaffold implant with exercise induced more re-innervation than all other groups. These results highlight the differential effects of bFGF and exercise on muscle regeneration.

Nutritional Approach to Cancer Cachexia: A Proposal for Dietitians

Cachexia is one of the most common, related factors of malnutrition in cancer patients. Cancer cachexia is a multifactorial syndrome characterized by persistent loss of skeletal muscle mass and fat mass, resulting in irreversible and progressive functional impairment. The skeletal muscle loss cannot be reversed by conventional nutritional support, and a combination of anti-inflammatory agents and other nutrients is recommended. In this review, we reviewed the effects of nutrients that are expected to combat muscle loss caused by cancer cachexia (eicosapentaenoic acid, β-hydroxy-β-methylbutyrate, creatine, and carnitine) to propose nutritional approaches that can be taken at present. Current evidence is based on the intake of nutrients as supplements; however, the long-term and continuous intake of nutrients as food has the potential to be useful for the body. Therefore, in addition to conventional nutritional support, we believe that it is important for the dietitian to work with the clinical team to first fully assess the patient’s condition and then to safely incorporate nutrients that are expected to have specific functions for cancer cachexia from foods and supplements.

Impact of Cancer Cachexia on Cardiac and Skeletal Muscle: Role of Exercise Training

Cachexia is a multifactorial syndrome that presents with, among other characteristics, progressive loss of muscle mass and anti-cardiac remodeling effect that may lead to heart failure. This condition affects about 80% of patients with advanced cancer and contributes to worsening patients’ tolerance to anticancer treatments and to their premature death. Its pathogenesis involves an imbalance in metabolic homeostasis, with increased catabolism and inflammatory cytokines levels, leading to proteolysis and lipolysis, with insufficient food intake. A multimodal approach is indicated for patients with cachexia, with the aim of reducing the speed of muscle wasting and improving their quality of life, which may include nutritional, physical, pharmacologic, and psychological support. This review aims to outline the mechanisms of muscle loss, as well as to evaluate the current clinical evidence of the use of physical exercise in patients with cachexia.

Sarcopenia of Cirrhosis and the Therapeutic Potential of Transjugular Intrahepatic Portosystemic Shunt Creation

Sarcopenia is a major sequela of cirrhosis, contributing to significant morbidity and mortality. Advances in body composition analysis using medical imaging have begun to identify changes in skeletal muscle and fat that are prognostic of the impact of sarcopenia on medical outcomes in cirrhosis and other pathologies. Recently, observational studies have shown a correlation between transjugular intrahepatic portosystemic shunt (TIPS) creation and a reversal of the progressive muscle loss in cirrhosis. This reversal is also associated with improved clinical outcomes and survival. This review summarizes current understanding of cirrhotic sarcopenia, and discusses the implications of TIPS creation in reversing this process.

Activating the Protein Synthesis Signaling by HIIT Concomitant with the Suppression of Protein Degradation in Wistar Rats’ Skeletal Muscle

Background: Muscle loss occurs in some conditions such as aging, sarcopenia, and cancer. The interaction between protein synthesis and degradation signaling components induced by high-intensity interval training (HIIT) is not well studied. Objectives: The purpose of the present study was to simultaneously examine the effect of eight-week HIIT on the gene expression of both signaling components. Methods: Sixteen male Wistar rats were randomly assigned to HIIT and non-exercise control groups. The HIIT group ran on a treadmill, five days/week for eight weeks, with 0º slope, including five interval sets of high and low intensity. Forty-eight hours after the last exercise session, dissected soleus muscles were stored at -80°C for later analyses. Results: The gene expression of Akt1, mTORC1, and S6K1 were increased in the HIIT group compared with the control group (All P ≤ 0.031) concomitant with the suppression of eIF4EBP1. The results of the S6K1 and eIF4EBP1 mRNA were also confirmed by the Western blotting. According to the inhibitory effect of Akt1, the gene expressions of FoxO3a and, consequently, MuRF1 and LC3A were significantly inhibited (All P ≤ 0.003). Western blot analysis did not confirm the LC3A protein expression, which may underline the role of LC3A in autophagy to promote cell survival. Conclusions: The intensities and durations of the exercise training protocol are sufficient to increase protein synthesis signaling components and especially inhibit the atrophy-related gene expression, which may lead to attenuating muscle loss and increasing muscle mass. Accordingly, it may be considered for rehabilitation and/or prevention of some conditions such as sarcopenia and cachexia.