Echinacea Supplementation Does Not Impact Aerobic Capacity and Erythropoiesis in Athletes: A Meta-Analysis.

Athletes are increasingly relying on natural supplements to improve athletic performance. Echinacea, a common herbal supplement, has been studied for its potential erythropoietin-enhancing effects, with mixed results in the literature. The purpose of this meta-analysis is to determine whether echinacea supplementation has erythropoietic or ergogenic effects in athletes. A search strategy was developed to identify trials studying the impact of echinacea supplementation on erythropoiesis and maximal oxygen uptake. The database search yielded 502 studies, 496 of which were excluded in the two-reviewer screening process. Six studies with a total of 107 athletes were included in the analysis. For hemoglobin and hematocrit levels, there were small, positive effect sizes when comparing the difference in pre- and post-intervention levels between the echinacea and placebo groups, at 0.38 (p = 0.02, 95% CI -0.04-0.80, I2 = 70%) and 0.34 (p < 0.01, 95% CI -0.10-0.78, I2 = 86%), respectively, though they did not reach statistical significance. There was also no statistically significant change in erythropoietin (effect size -0.29, p = 0.05, 95% CI -0.75-0.17, I2 = 67%) or maximal oxygen uptake (effect size -0.20, p = 0.95, 95% CI -0.60-0.21, I2 = 0%). Echinacea supplementation did not influence erythropoietin, hemoglobin, hematocrit, or maximal oxygen uptake in athletes; however, the evidence base is limited.

APT2 Inhibition Restores Scribble Localization and S-Palmitoylation in Snail-Transformed Cells.

The multidomain scaffolding protein Scribble (Scrib) organizes key signaling complexes to specify basolateral cell polarity and suppress aberrant growth. In many human cancers, genetically normal Scrib mislocalizes from cell-cell junctions to the cytosol, correlating with enhanced growth signaling and malignancy. Here we confirm that expression of the epithelial-to-mesenchymal transcription factor (EMT-TF) Snail in benign epithelial cells leads to Scrib displacement from the plasma membrane, mimicking the mislocalization observed in aggressive cancers. Upon further examination, Snail promotes a transcriptional program that targets genes in the palmitoylation cycle, repressing many protein acyl transferases and elevating expression and activity of protein acyl thioesterase 2 (APT2). APT2 isoform-selective inhibition or knockdown rescued Scrib membrane localization and palmitoylation while attenuating MEK activation. Overall, inhibiting APT2 restores balance to the Scrib palmitoylation cycle, promoting membrane re-localization and growth attenuation. These findings emphasize the importance of S-palmitoylation as a post-translational gatekeeper of cell polarity-mediated tumor suppression.