Background: Myostatin (MSTN) is a well-known negative regulator of skeletal muscle growth, and its pharmacological blockade, such as with follistatin (FST), an endogenous MSTN inhibitor, is under active investigation as a treatment for muscle-wasting conditions. However, the dynamics of MSTN signaling during in vitro myogenesis and its modulation by culture conditions remain incompletely understood. Methods: Primary myoblasts were isolated from wild-type (WT), Mstn-/-, and FST transgenic (F66) mice to evaluate the effects of MSTN inhibition on myotube formation. Myoblasts were differentiated on Matrigel-coated surfaces in the presence of horse serum. Myotube maturation was evaluated by confocal microscopy and reverse transcription-polymerase chain reaction; protein synthesis was assessed using a puromycin incorporation assay; and MSTN concentrations in serum were quantified by enzyme-linked immunosorbent assay. Results: Mstn expression peaked at 24 hr of differentiation, coinciding with early myotube formation, and progressively declined as myotubes matured. Both Mstn-/- and F66 myotubes showed increased thickness and protein synthesis compared to WT controls, with more pronounced effects observed in F66 myotubes. Consistent with this, F66 myotubes also displayed higher expression of myogenic maturation markers. Notably, horse serum used in the culture medium contained detectable levels of MSTN, which may have partially restored MSTN signaling in Mstn-/- cultures and masked the full knockout phenotype. Conclusions FST overexpression induces greater myotube hypertrophy and protein synthesis than Mstn deletion, likely due to its broader inhibition of both endogenous and serum-derived MSTN. These findings highlight the importance of serum composition in interpreting phenotypes from in vitro knockout models targeting secreted factors such as MSTN.

Glucagon-like peptide-1 (GLP-1) analogs, originally developed as antidiabetic agents, have emerged as groundbreaking drugs for treating obesity, following reports of their remarkable weight-reducing effects. With growing recognition of obesity as a disease in modern society and a sharp rise in its prevalence, pharmacological interventions are now being actively pursued. However, due to their mechanism of action, primarily appetite suppression, GLP-1 analogs have been associated with various adverse effects. Most notably, muscle loss — which may be related to reduced nutritional intake — has become an important issue in the long-term management of patients undergoing GLP-1 therapy. This has drawn attention to myostatin (MSTN) inhibitors for their ability to significantly increase muscle mass. These agents are now being explored not only as a strategy to offset the side effects of GLP-1 analogs, but also as direct therapeutics for a range of metabolic disorders, including obesity and diabetes. In this review, we discuss the emerging therapeutic potential of MSTN inhibitors and examine current clinical trials investigating their use alone or in combination with GLP-1 analogs in metabolic disorders.

PURPOSE: We investigated Doppler ultrasonographic (US) parameters of patients with acute stroke to predict the cerebral vascular reserve (CVR) measured by SPECT. MATERIALS and METHODS: We reviewed the flow velocity and cross-sectional area of the circular vessel at the common, external, and internal carotid arteries (ICA) and the vertebral arteries (VA) in 109 acute stroke patients who underwent SPECT. Flow volume (FV) of each artery was calculated as the product of the angle-corrected time-averaged flow velocity and cross-sectional area of the circular vessel. Total cerebral FV (TCBFV) was determined as the sum of the FVs of the right and left ICA and VA. We compared the Doppler US parameters between 44 cases of preserved and 65 cases of impaired CVR. RESULTS: In the preserved CVR group, ICA FV, anterior circulating FV (ACFV) and TCBFV were higher than in the impaired CVR group (p < 0.05, independent t-test). In the impaired CVR group, the ROC curves showed ACFV and TCBFV were suitable parameters to predict CVR (p < 0.05). CONCLUSION: Doppler US was helpful for understanding the hemodynamic state of acute stroke. FV measurement by Doppler US was useful for predicting CVR.
Arteries ; Carotid Artery, Internal ; Hemodynamics ; Humans ; ROC Curve ; Stroke* ; Tomography, Emission-Computed, Single-Photon ; Vertebral Artery