Heart rate variability (HRV) is a relevant marker reflecting cardiac modulation by sympathetic and vagal components of the autonomic nervous system (ANS). Although the clinical application of HRV is mainly associated with the prediction of sudden cardiac death and assessing cardiovascular and metabolic illness progression, recent observations have suggested its applicability to physical exercise training. HRV is becoming one of the most useful tools for tracking the time course of training adaptation/maladaptation of athletes and in setting the optimal training loads leading to improved performances. However, little is known regarding the role of HRV and the internal effects of physical exercise on an athlete, which may be useful in designing fitness programs ensuring sufficient training load that may correspond with the specific ability of the athlete. In this review, we offer a comprehensive assessment of investigations concerning the interrelation between HRV and ANS, and examine how the application of HRV to physical exercise may play a role in sports physiology.

Purpose: Rapamycin inhibits the serine-threonine kinase mammalian target of rapamycin (mTOR), blocking phosphorylation of p70 S6 kinase (S6K1) and 4E-binding protein 1 (4E-BP1) and inhibiting protein translation and cell cycle progression. Rapamycin and its analogues are currently being tested in clinical trials as novel-targeted anticancer agents. Although rapamycin analogues show activity in clinical trials, only some of the treated patients respond. The purpose of this study is to identify determinants of rapamycin sensitivity that may assist the selection of appropriate patients for therapy.Experimental Design: Breast cancer cell lines representing a spectrum of aberrations in the mTOR signaling pathway were tested for rapamycin sensitivity. The expression and phosphorylation state of multiple components of the pathway were tested by Western blot analysis, in the presence and absence of rapamycin.Results: Cell proliferation was significantly inhibited in response to rapamycin in 12 of 15 breast cancer cell lines. The ratio of total protein levels of 4E-BP1 to its binding partner eukaryotic initiation factor 4E did not predict rapamycin sensitivity. In contrast, overexpression of S6K1, and phosphorylated Akt independent of phosphatase and tensin homologue deleted from chromosome 10 status, were associated with rapamycin sensitivity. Targeting S6K1 and Akt with small interfering RNA and dominant-negative constructs, respectively, decreased rapamycin sensitivity. Rapamycin inhibited the phosphorylation of S6K1, ribosomal S6 protein, and 4E-BP1 in rapamycin-resistant as well as -sensitive cells, indicating that its ability to inhibit the mTOR pathway is not sufficient to confer sensitivity to rapamycin. In contrast, rapamycin treatment was associated with decreased cyclin D1 levels in the rapamycin-sensitive cells but not in rapamycin-resistant cells.Conclusions: Overexpression of S6K1 and expression of phosphorylated Akt should be evaluated as predictors of rapamycin sensitivity in breast cancer patients. Furthermore, changes in cyclin D1 levels provide a potential pharmacodynamic marker of response to rapamycin.

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The primary objective was to determine the beneficial effects of oat β-glucan (OG) and barley β-glucan (BG) on gut health. A total of 200 male Sprague-Dawley rats were divided into 5 groups of 40 rats each, control group (CON), low-dose OG-administered group (OGL), high-dose OG-administered group (OGH), low-dose BG-administered group (BGL), and high-dose BG-administered group (BGH). OGL and OGH were administered oat β-glucan by intragastric gavage at a dose of 0.35 g/kg of body weight (BW) and 0.70 g/kg of BW daily for 6 weeks, and BGL and BGH were administered barley β-glucan. The CON received normal saline. Intestinal-health-related indexes were analyzed at baseline, week 3, week 6, and week 7. Cereal β-glucan significantly influenced the fecal water content, pH value, ammonia levels, β-glucuronidase activity, azoreductase activity, and colonic short-chain fatty acid (SCFA) concentrations (p < 0.05). Moreover, the population of Lactobacillus and Bifidobacterium increased (p < 0.05), whereas the number of Enterobacteriaceae decreased (p < 0.05) in a dose-dependent manner during the period of cereal β-glucan administration. These results suggested that cereal β-glucan might exert favorable effects on improving intestinal functions and health but the gut-health-promoting effects of oat β-glucan were better than those of barley β-glucan.

Immune checkpoint protein V-domain immunoglobulin suppressor of T-cell activation (VISTA) controls antitumor immunity and is a valuable target for cancer immunotherapy. This study identified a role of VISTA in regulating Toll-like receptor (TLR) signaling in myeloid cells and controlling myeloid cell-mediated inflammation and immunosuppression. VISTA modulated the polyubiquitination and protein expression of TRAF6. Consequently, VISTA dampened TLRmediated activation of MAPK/AP-1 and IKK/NF-κB signaling cascades. At cellular levels, VISTA regulated the effector functions of myeloid-derived suppressor cells (MDSCs) and tolerogenic DC subsets. Blocking VISTA augmented their ability to produce proinflammatory mediators and diminished their T cell-suppressive functions. These myeloid cell-dependent effects resulted in a