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Introduction: IL-6 influences several biological processes, including cardiac stem cell and cardiomyocyte physiology. Although JAK-STAT3 activation is the defining feature of IL-6 signaling, signaling molecules such as PI3K, PKCs, and ERK1/2 are also activated and elicit different responses. Moreover, most studies on the specific role of these signaling molecules focus on the adult heart, and few studies are available on the biological effects evoked by IL-6 in embryonic cardiomyocytes. Aim: The aim of this study was to clarify the biological response of embryonic heart derived cells to IL-6 by analyzing the morphological modifications and the signaling cascades evoked by the cytokine in H9c2 cells. Results: IL-6 stimulation determined the terminal differentiation of H9c2 cells, as evidenced by the increased expression of cardiac transcription factors (NKX2.5 and GATA4), structural proteins (α-myosin heavy chain and cardiac Troponin T) and the gap junction protein Connexin 43. This process was mediated by the rapid modulation of PI3K, Akt, PTEN, and PKCζ phosphorylation levels. PI3K recruitment was an upstream event in the signaling cascade and when PI3K was inhibited, IL-6 failed to modify PKCζ, PTEN, and Akt phosphorylation. Blocking PKCζ activity affected only PTEN and Akt. Finally, the overexpression of a constitutively active form of PKCζ in H9c2 cells largely mimicked the morphological and molecular effects evoked by IL-6. Conclusions: This study demonstrated that IL-6 induces the cardiac differentiation of H9c2 embryonic cells though a signaling cascade that involves PI3K, PTEN, and PKCζ activities. J. Cell. Physiol. 231: 576-586, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Human amniotic fluid (hAF) cells share characteristics of both embryonic and adult stem cells. They proliferate rapidly and can differentiate into cells of all embryonic germ layers but do not form teratomas. Embryoid-bodies obtained from hAF have cardiac differentiation potential, but terminal differentiation to cardiomyocytes (CMs) has not yet been described. Our purpose was to promote cardiac differentiation in hAFcells. Cells were exposed to inducing factors for up to 15 days. Only the subset of hAF cells expressing the multipotency markers SSEA4, OCT4 and CD90 (CardiopoieticAF cells) responded to the differentiation process by increasing the expression of the cardiac transcription factors Nkx2.5 and GATA4, sarcomeric proteins (cTnT, α-MHC, α-SA), Connexin43 and atrial and ventricular markers. Furthermore, up to 90% of differentiated cells were positive for the calcium pumps CACNA1C and SERCA2a, with approximately 30% of CardiopoieticAF-derived CM-like cells responding to caffeine or adrenergic stimulation. Some spontaneous beating foci were also observed. In conclusion, we demonstrated that CardiopoieticAF cells can differentiate into a population of CM-like cells, characterized by cardiac-specific molecular, structural, and functional properties, that are useful for the development of in vitro models of genetic cardiac disorders, for drug discovery and testing, and for the regenerative medicine. [ABSTRACT FROM AUTHOR]

Rationale. Human amniotic fluid-derived (hAF) stem cells are considered a novel class of multipotent stem cells, sharing characteristics of both embryonic and adult stem cells. In fact, they proliferate rapidly, are able to differentiate into cells of all the embryonic germ layers, but do not form teratoma. It has been already reported that the embryoid bodies (EBs) obtained from hAFs have a cardiac potential, but it has not been described a functional terminal differentiation in cardiomyocytes (CMs)yet. Objective. Aim of this study was to foster the cardiomyogenic potential of hAFs in order to obtain a cellular population with morphological and functional features of CMs. Methods and Results. AFCs were exposed sequentially to inducing factors (Ascorbic Acid, 5-Azacytidine, BMP4, ActivinA, VEGF) up to 15 days and differentiation was monitored. Only the hAF samples expressing the multipotency markers SSEA4, OCT4 and CD90 (CardiopoieticAF) responded to the differentiation process loosing their stemness and increasing the cardiac nuclear factors NKX2.5 and GATA4. After the differentiation cells expressed high levels of the sarcomeric proteins (cTnT, αMHC and αSA), the gap junction marker Connexin43 and both atrial and ventricular markers; moreover, up to 90% of the cells was positive for CACNA1C and SERCA2a, cardiac calcium pumps involved in the excitation/contraction coupling, and about 30% of the CardiopoieticAF-derived cells presented spontaneous intracellular Ca2+ waves and Ca2+ fluctuation in response to caffeine or adrenergic stimulation. Some spontaneous beating foci were also observed. Conclusion. Our results demonstrate that CardiopoietichAFs can fully differentiate into a homogenous population of CM-like cells, characterized by cardiac specific molecular, structural, and functional properties. Thus, CardiopoietichAFs can hold great promise for the development of in vitro models of cardiac genetic disorders, for drug discovery and testing, and for the emerging field of cardiovascular regenerative medicine. [ABSTRACT FROM AUTHOR]

The purpose of the study was to examine psychobiosocial states, cognitive functions, endocrine responses (i.e., salivary cortisol and chromogranin A), and performance under competitive pressure in orienteering athletes. The study was grounded in the individual zones of optimal functioning (IZOF) and biopsychosocial models. Fourteen junior orienteering athletes (7 girls and 7 boys), ranging in age from 15 to 20 years (M = 16.93, SD = 1.77) took part in a two-day competitive event. To enhance competitive pressure, emphasis was placed on the importance of the competition and race outcome. Psychophysiological and performance data were collected at several points before, during, and after the races. Results showed that an increase in cortisol levels was associated with competitive pressure and reflected in higher perceived exertion (day 1, r = .32; day 2, r = .46), higher intensity of dysfunctional states (day 1, r = .59; day 2, r = .55), lower intensity of functional states (day 1, r = -.36; day 2, r = -.33), and decay in memory (day 1, r = -.27; day 2, r = -.35), visual attention (day 1, r = -.56; day 2, r = -.35), and attention/mental flexibility (day 1, r = .16; day 2, r = .26) tasks. The second day we observed better performance times, lower intensity of dysfunctional states, lower cortisol levels, improved visual attention and attention/mental flexibility (p < .050). Across the two competition days, chromogranin A levels were higher (p < .050) on the most difficult loops of the race in terms of both physical and psychological demands. Findings suggest emotional, cognitive, psychophysiological, and performance variables to be related and to jointly change across different levels of cognitive and physical load. Overall results are discussed in light of the IZOF and biopsychosocial models. The procedure adopted in the study also supports the feasibility of including additional cognitive load for possible practical applications. [ABSTRACT FROM AUTHOR]

Abstract: Mitral valve (MV) is composed of several structures working in synchrony to open during diastole and close in systole within the high-pressure systemic environment. Its morphological features ensure a normal leaflet closure that prevents regurgitation of blood back into the left atrium causing loss of ventricular pressure and forward flow. The complex interactions of the normal MV are reliant on each component playing a complete role for the efficient working of the valve. In this review we firstly discuss the overall MV structure in terms of a complex make up of the annulus, the leaflets, their tendinous cords, and the supporting papillary muscles, and then the anatomical changes of each MV components due to left ventricular geometry and function alterations, underlying functional mitral regurgitation. [Copyright &y& Elsevier]

Abstract: Objective: The main objective of the study was to examine the relation of different biological markers to a variety of pleasant and unpleasant psychobiosocial (PBS) states in response to precompetitive stress in sport. Design: A longitudinal design was adopted to assess biological markers and PBS states before several games. Method: A whole team of high-level professional basketball players (9 men, aged from 23 to 37 years) took part in the study. The biological measures included the salivary concentration of testosterone, cortisol, aamylase, and chromogranin A. The psychological measures involved emotional, cognitive, motivational, bodily, kinesthetic, performance, and communicative components of PBS states assessed according to the dimensions of their intensity, frequency, and direction (i.e., perceived effect on performance). Assessment was conducted within 1 h prior to competition on an approximately weekly basis across the whole championship for a total of 12 games played at the team''s home. Results: A series of canonical correlation analyses showed that an increase in the salivary concentration of biological variables was associated with enhanced intensity and frequency scores of pleasant PBS states, as well as enhanced directional values (i.e., perception of facilitative effects) of a range of both pleasant and unpleasant PBS states. Conclusion: Findings suggest that elevation of testosterone, cortisol, α-amylase, and chromogranin A in basketball players prior to competition can have a perceived functional effect with respect to the upcoming performance. [Copyright &y& Elsevier]

Summary Introduction Several studies have shown that activation of the sympathetic nervous system results in the increased secretion of α-amylase (sAA), an enzyme produced by salivary glands. Recently, chromogranin A (CgA), a soluble protein costored and coreleased with catecholamines from the adrenal medulla and sympathetic nerve endings, has been proposed as a marker of sympathoadrenal medullary system (SAM) activity. The aim of this study was to investigate the behaviour of salivary chromogranin A (sCgA) and sAA during high-intensity exercise and to analyse their possible correlation with cardiovascular and psychological parameters. Methods Before and during a standardized treadmill stress test, and at 5, 15 and 30 min during the recovery phase, sCgA and sAA were monitored in 21 healthy men. The double product (DP) of blood pressure and heart rate responses, and the product of the subjective ratings of perceived exertion recorded at the final step (RPE) and the exercise duration were used as indices of cardiovascular and exercise intensity, respectively. Results With respect to baseline, significant ( P < 0·001) increases in peak sCgA (median 64%) and sAA (median 86%) were observed at the end of exercise. During the recovery phase, sAA levels fell abruptly, whereas sCgA remained elevated ( P < 0·001). Significant correlations emerged only for sCgA with respect to %DP ( r = 0·84; P < 0·001) and last step-RPE ( r = 0·82; P = 0·024). Conclusions These data suggest sCgA as a reliable marker of SAM activation. Furthermore, the relationship between sCgA and exercise intensity highlights the potential use of this noninvasive parameter in monitoring the adrenergic response during intense physical stress. [ABSTRACT FROM AUTHOR]

Sedentary behavior (SB) in post-menopause has been associated with an elevated cardiovascular risk, in particular venous thrombosis, regardless of physical activity (PA) levels. Interrupting SB with intermittent light-intensity or moderate to vigorous-intensity physical activity (LPA and MVPA, respectively) can avoid hypercoagulation associated with prolonged sitting. However, no studies examined this effect in free-living context using objectively measured SB and PA. This study was aimed to investigate the association between objectively measured SB patterns (i.e. duration and number of sedentary bouts) and hemostatic parameters. Fifty-two non-smoker post-menopausal women (age: 59.7 ± 6.2 yo; BMI: 27.3 ± 4.4) worn a multisensory device (Sensewear Armband, BodyMedia, Inc., Pittsburgh, PA) for at least three days to measure SB and PA. Blood samples were collected to measure hemostatic parameters. Data were log-transformed (log-) when non-normally distributed. Correlation was analyzed by Pearson's correlation coefficient, controlling for BMI, log-MVPA or total sedentary time (ST), depending on the need. Difference between women with daily SB bouts lasting at least 1 hr and women with shorter bouts was analyzed by Mann-Whitney U-test. Women were really active (102.5 ± 82.6 min/d MVPA) and with a large amount of SB (589.2 ± 132.5 min/d SB). Plasma fibrinogen was directly correlated with both ST and lying time, independently from BMI and log-MVPA (r = .338, P = .016; r = .374, P = .007) and inversely correlated with log-MVPA (r = -.376, P = .006). No correlation was found for sleep time. The number of bouts of SB lower than 5 or 10 min were not associated with fibrinogen, while the number of bouts of SB between 11 and 15, 11 and 20, and 21 and 30 min were directly correlated with plasma fibrinogen, regardless of BMI, ST, and log-MVPA (r = .276, P = .05; r = .315, P = .028; r = .275, P = .05, respectively). Furthermore, women with daily uninterrupted SB longer than 1 hr had higher plasma fibrinogen than other participants (323.9 ± 41.4 mg/dl; 287.7 ± 48.8 mg/dl, respectively; Z = -2.53, P = .011). In conclusion, uninterrupted SB is associated with adverse fibrinogen levels, regardless of ST and PA, while shorter bouts of SB are not directly associated with it. These results suggest that activity breaks mitigate the procoagulant effects of uninterrupted sitting, in post-menopausal women. [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study: The gastrointestinal peptide hormone ghrelin (Ghr) was discovered in 1999 as the endogenous ligand for the growth hormone secretagogue receptor (GHSR-1a). It is a pleiotropic peptide that modulates a wide spectrum of biological activities, such as growth hormone (GH) release, feeding stimulation, adiposity and cardiovascular actions. The presence of Ghr mRNA in the iris and ciliary body (CB) epithelium was recently demonstrated in animal models, where a possible myorelaxing effect on the iris muscles has been suggested. Based on these observations, the aim of our study was to investigate the Ghr and GHSR-1a expression and localization in the normal human eye. Material: Five different ciliary body/iris samples from normal eyes were subjected to Western blot analysis. Immunohistochemical detection was performed on three enucleated eyes. Twenty aqueous humor (AqH) samples obtained from patients submitted to cataract surgery were analyzed with an ELISA for the presence of Ghr. Results: Ghr and GHSR-1a were co-expressed by the pigmented epithelium (PE) of the CB, by the retinal pigmented epithelium (RPE) and by the anterior limiting layer (ALL) of the iris. No reaction was detected at the subepithelial level in the ciliary or pupillae smooth muscle cells. The AqH samples were positive for the presence of Ghr. Conclusion: This study provides the first evidence that Ghr and GHSR-1a are expressed in the human eye by specific cells. The understanding of the functional role of Ghr at the human eye level needs more efforts and investigation, but a hypothetical action on the GH retinal synthesis and/or on the circadian clock system could be suggested. [Copyright &y& Elsevier]

Purpose: To evaluate the effect of walking-training on serum angiogenic potential in postmenopausal women. Materials and Methods: Thirty-four postmenopausal women (56.18 ± 4.24 yr) participated in a 13 weeks program of walking-training. Anthropometric measures, VEGF, IL-1α, IL-1ß, IL-2, IL-8, IL-10, IL-12p70, TNF-α, C-reactive protein, insulin, IGF-1, cortisol, DHEA-S, leptin, visfatin, resistin and adiponectin were evaluated before and after training. Moreover, serum samples were tested for their ability to chemo – attract endothelial cells and to support the in vitro formation of capillary – like structures. Results: After training, the levels of IL-8, TNF-α, leptin and resistin were significantly lower, levels of DHEA-S and adiponectin increased, serum angiogenic properties improved, whereas no changes in anthropometric parameters or VEGF were detected. Conclusions: Walking training reduces inflammatory status and leads to a significant improvement in serum angiogenic properties in the absence of modifications in body composition and VEGF level. [ABSTRACT FROM AUTHOR]