Muscle atrophy leads to decreased muscle mass, weakness, inactivity, and increased mortality. E3 ubiquitin ligases, key regulators of protein degradation via the ubiquitin–proteasome system, play a critical role in atrophic mechanisms. This meta-analysis followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and its objective was to evaluate the association between E3 ligases Muscle Atrophy F-box (MAFbx)/Atrogin-1 (Fbxo32) and Muscle RING-finger protein 1 (MuRF-1) (TRIM63) E3 ligase mRNA levels, reductions in skeletal muscle CSA measures, and atrophy conditions. We examined papers published on PubMed®, Scopus, and Web of Science that studied E3 ligase gene expression signatures for Fbxo32 (MAFbx/Atrogin-1) and Trim63 (MuRF1) in different types of muscle atrophy and hypertrophy murine models. Twenty-nine studies selected by two independent raters were analyzed. Standardized mean differences (SMDs)/effect sizes (ESs) and 95% confidence intervals (CIs) were calculated for the outcomes using fixed-effects models. We found that 6- and 4.8-fold upregulation, respectively, of Fbxo32 and Trim63 was sufficient to reduce the ES to −3.89 (95% CI: −4.45 to −3.32) for the muscle fiber cross-sectional area and the development of skeletal muscle atrophy. I² and Q test statistics did not indicate heterogeneous data. There was a low probability of bias after both the funnel plot and Egger’s test analyses. These results were sustained independently of the atrophic model and muscle type. Therefore, the magnitude of the increase in muscle Fbxo32 and Trim63 mRNA is a feasible, reliable molecular marker for skeletal muscle atrophy in mice. The next step for the Ubiquitin-proteasome system (UPS) field involves elucidating the targets of E3 ligases, paving the way for diagnostic and treatment applications in humans.

INPLASY202520089 Biomarkers of Skeletal Muscle Atrophy Based on Atrogenes Evaluation: A Systematic Review and Meta-Analysis Study Keywords: musculoskeletal; atrophy; E3 ligases; molecular research;…

Gouvêa, AL, Martinez, CG, and Kurtenbach, E. Determining maximal muscle strength in mice: validity and reliability of an adapted swimming incremental overload test. J Strength Cond Res 34(8): 2360–2368, 2020—At present, there are no reliable methods to determine maximal muscle strength in small rodents. Here, we established an adapted swimming incremental overload test (SIOT) as an instrument for this purpose. First, to validate the test, BALB/c mice received 20 mg·kg⁻¹·d⁻¹ of dexamethasone (DEXA group) or water (control group). After 14 days, with a cumulative dose of 120 mg·kg⁻¹ of dexamethasone, the SIOT could detect a decrease of approximately 7% in muscle strength. In addition, this decrease was consistent with a significant reduction in body (above 13.5%) and muscle (approximately 15%) weight in DEXA atrophic animals. To establish the SIOT reliability, another group of animals was evaluated for 5 consecutive days. In this second protocol, the SIOT was executed with an initial load corresponding to 12% of the mouse body weight (BW) fixed to the tail. Increments between 1 and 5% of the BW were added during each attempt to obtain the highest load that was tolerated for a time interval of 5–7 seconds. On the last day, the SIOT reliability test was performed by 2 different raters to obtain the inter-rater reproducibility. The adapted SIOT was shown to be reliable when measured by the same rater (intraclass correlation coefficient [ICC] = 0.939) and by 2 different raters (ICC = 0.830). The Bland-Altman graphical representation did not demonstrate heteroscedastic errors. Therefore, the SIOT proved to be a sensitive and reliable method to measure muscle strength, and it can be applied to small animals in different models of muscle atrophy.

The effects of methylmercury (MeHg) on exposed populations are a public health problem. In contrast to widely studied neurological damage, few cardiovascular changes have been described. Our group evaluated the cardiotoxicity of a cumulative dose of 70 mg.kg⁻¹ fractioned over a 14-day exposure period in mice (MeHg70 group). The effects of MeHg on proteins relevant to cardiac mitochondrial function were also investigated. The results obtained showed a reduction in oxygen consumption in the two settings. In cardiac tissue samples in oxygraphy studies, this reduction was related to a lower efficiency of complexes II and V, which belong to the oxidative phosphorylation system. In vivo, mice in the MeHg70 group presented lower oxygen consumption and running tolerance, as shown by ergometric analyses. Cardiac stress was evident in the MeHg70 group, as indicated by a marked increase in the level of the mRNA encoding atrial natriuretic peptide. Electrocardiogram studies revealed a lower heart rate at rest in the animals from the MeHg70 group, as well as prolonged left ventricular depolarisation and repolarisation. Through echocardiographic analysis, reductions in the left ventricular ejection fraction and left ventricular wall thickness of approximately 10% and 20%, respectively, were detected. These results indicate that the oral intake of MeHg can decrease cardiac function and oxidative metabolism. This finding highlights the importance of monitoring MeHg levels in humans and animals in contaminated areas, as well as periodically carrying out cardiac function tests.