Muscles, Volume 1, Issue 2 (September 2022) – 4 articles

Cancer cachexia is characterized by irreversible muscle loss which is a critical factor in the prognosis of cancer patients. Myoblasts are myogenic precursor cells that are required to maintain skeletal muscle tissue. Previous studies reported that cancer-released factors deteriorate myoblast differentiation, which is one of the causes of cachexia-associated muscle wasting. We recently identified the myogenetic oligodeoxynucleotide, iSN04, which serves as an anti-nucleolin aptamer and promotes myogenesis. The present study investigated the effects of iSN04 on human myoblasts exposed to a conditioned medium (CM) of cancer cells. CM of colon cancer cell lines LoVo and HCT-116 significantly impaired myogenic differentiation and the myotube formation of human myoblasts by inducing the expression of inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor-α (TNF-α); however, the CM of the colon fibroblast cell line CCD-18Co did not. Intriguingly, iSN04 completely reversed the deterioration of myoblast differentiation by LoVo-CM by upregulating MyoD and myogenin, and downregulating myostatin, IL-1β, and TNF-α. TNF-α, of which a high level was produced in LoVo, alone inhibited myogenic differentiation and induced IL-1β, IL-6, and IL-8 transcriptions of myoblasts; however, pre-treatment with iSN04 reversed TNF-α-induced cachectic phenotypic features. The results indicate that iSN04 protects myoblasts against the effects of cancer-released factors and maintains their myogenic activity. This study provides a novel therapeutic strategy to prevent muscle loss associated with cancer cachexia. Full article

Summary: It was repeatedly shown that the locomotion evoked by epidural-induced electrical stimulation can last for a certain amount of time after stimulation cessation in decerebrated and spinal animals. This so-called after-stepping reflects the maintenance level for the activation of locomotor neuronal circuitry, but only scarce information exists about after-stepping peculiarities. We provide a comparative investigation of after-stepping and stepping under epidural stimulation using electromyographic and kinematic signals as well as ground reaction forces in 16 decerebrated cats. Our principal findings are as follows: (1) the ground reaction forces decrease more after epidural stimulation cessation compared to anterior–posterior limb movements; (2) the step cycle duration is longer for after-steps; (3) the electromyographic signal of the extensor gastrocnemius lateralis muscle during after-stepping decreases faster compared to the signal from the flexors iliopsoas and tibialis anterior and to the extensor soleus muscle; and (4) electromyographic stability is reduced after epidural stimulation cessation. We suppose that different levels of the spinal central pattern generator can be differently attenuated after external trigger cessation. These data could be important for the elaboration of locomotor models and for rehabilitation techniques. New Findings: Our new findings come from comparative investigations of the so-called after-stepping (locomotion after electrical stimulation cessation) and locomotion observed during epidural-induced electrical stimulation. Our new findings are as follows: after epidural stimulation cessation, (1) the ground reaction forces decrease faster compared to anterior–posterior limb movements; (2) the electromyographic signal of the extensor gastrocnemius lateralis muscle decreases faster compared to the signals from the flexors iliopsoas and tibialis anterior and to the extensor soleus muscle; and (3) electromyographic stability is reduced. Full article

Researchers and health practitioners seek to understand the upper limit of muscle hypertrophy under different conditions. Although there are models to estimate the muscle-building threshold in drug-free resistance training practitioners, little is known about the population using anabolic–androgenic steroids (AASs) in this regard. Because of a plateau effect of muscle hypertrophy upon AAS regimens, there is a hypothesis among clinicians and enthusiasts that AASs downregulate skeletal muscle androgen receptors (ARs). Conversely, in this narrative review, we show that seminal and recent evidence—primarily using testosterone and oxandrolone administration as human experimental models—support that AASs upregulate ARs, eliciting greater anabolic effects on skeletal muscle receptors through a dose-dependent relationship. Thus, to date, there is no scientific basis for claiming that myocyte AR downregulation is the cause of the AAS-induced plateau in muscle gains. This phenomenon is likely driven by the neutral nitrogen balance, but further research is imperative to clarify the intrinsic mechanisms related to this landscape. Full article

Yohimbine hydrochloride (YHM) is an alpha-2-adrenergic receptor antagonist that possesses sympathomimetic properties, but few studies have investigated YHM in the context of exercise. The purpose of this study was to examine the effects of acute YHM ingestion on bench press exercise power, velocity, and strength-endurance levels. In a double-blinded crossover design, resistance-trained males (n = 16) participated in two separate bench press trials, each with a different single-dose treatment: placebo (PL; gluten-free corn starch) or yohimbine hydrochloride (YHM; 2.5 mg). In each trial, the participants consumed their respective treatment 20 min prior to exercise. Following a warm-up, the participants completed 1 set × 2 explosive repetitions while a linear position transducer monitored the barbell velocity. The participants then completed 3 sets × repetitions to failure (RTF) at 75% of 1-repetition maximum (1-RM) separated by 2 min of rest. The motivation to exercise and subjective measures of energy or fatigue were measured post-exercise. The total RTF, mean velocity, mean power, motivation, and subjective energy or fatigue values were compared and analyzed. The mean power (p = 0.472; d = 0.16) and mean velocity (p = 0.297; d = 0.25) values were unchanged by treatment. However, the RTF (p = 0.002; d = 0.82) value was higher with YHM treatment. The motivation to exercise (p = 0.011; d = 0.64) and energy levels (p < 0.001; d = 1.27) were significantly higher with YHM ingestion versus PL. The subjective fatigue was significantly lower with YHM ingestion (p < 0.001; d = 1.65). In conclusion, the current findings show that YHM consumption enhanced muscular strength-endurance while improving feelings of motivation, energy, and fatigue. YHM ingestion may, therefore, be useful for athletes or competitors seeking to improve their performance or combat subjective fatigue. Full article