In contrast to lower vertebrates, the mammalian heart has limited capacity to regenerate after injury in part due to ineffective reactivation of cardiomyocyte proliferation. We show that the microRNA cluster miR302–367 is important for cardiomyocyte proliferation during development and is sufficient to induce cardiomyocyte proliferation in the adult and promote cardiac regeneration. In mice, loss of miR302–367 led to decreased cardiomyocyte proliferation during development. In contrast, increased miR302–367 expression led to a profound increase in cardiomyocyte proliferation, in part through repression of the Hippo signal transduction pathway. Postnatal reexpression of miR302–367 reactivated the cell cycle in cardiomyocytes, resulting in reduced scar formation after experimental myocardial infarction. However, long-term expression of miR302–367 induced cardiomyocyte dedifferentiation and dysfunction, suggesting that persistent reactivation of the cell cycle in postnatal cardiomyocytes is not desirable. This limitation can be overcome by transient systemic application of miR302–367 mimics, leading to increased cardiomyocyte proliferation and mass, decreased fibrosis, and improved function after injury. Our data demonstrate the ability of microRNA-based therapeutic approaches to promote mammalian cardiac repair and regeneration through the transient activation of cardiomyocyte proliferation.

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Objective Whether arterial elasticity is reduced in preeclampsia has been investigated only rarely. This study aimed to characterize in vivo the carotid arterial intima-media thickness (IMT) Results In pre-eclamptic compared with normotensive pregnancy, carotid arterial IMT (459 ± 95 vs 351 ± 85 µm, P = 0.0001), internal diameter (7.8 ± 0.5 vs 7.2 ± 0.4 mm, P < 0.0001), pulse wave velocity (7.1 ± 1.7 vs 6.0 ± 1.5 m/s, P = 0.007), augmentation index (7.9 ± 9.2 vs −5.0 ± 5.6%, P < 0.0001) and arterial wall tension (55.0 ± 6.5 vs 38.6 ± 4.9 mmHg/cm,

Chinese classrooms present an intriguing paradox to the claim of self-determination theory that autonomy facilitates learning. Chinese teachers appear to be controlling, but Chinese students do not have poor academic performance in international comparisons. The present study addressed this paradox by examining the cultural differences in students' interpretation of teacher controlling behaviors. Affective meanings of teacher controlling behaviors were solicited from 158 Chinese 5th graders and 115 American 5th graders. It was found that the same controlling behaviors of teachers had different affective meanings for different cultural groups (Chinese vs. American) and for groups with different levels of social-emotional relatedness with teachers (high vs. low). Chinese children perceived the behaviors as less controlling than American children and, in tum, reported that they were more motivated in their teachers' class than American children. Regardless of culture, children with high social-emotional relatedness with teachers perceived the behaviors as less controlling than children with low socialemotional relatedness with teachers. It was also found that internalization mediated the relation between social-emotional relatedness and children's learning motivation in both cultures. The fmdings revealed cultural differences as well as similarities in the psychological process of internalization.

Glycogen synthase kinase (GSK)-3beta inhibitors play an anti-inflammatory role in several inflammatory diseases. Recent studies have demonstrated that GSK-3beta inhibitors protect against myocardial ischemia-reperfusion injury. However, the precise mechanisms remain unclear. We aimed to investigate the roles of inflammation and apoptosis induced by ischemia-reperfusion in the cardioprotection by GSK-3beta inhibitor 4-benzyl-2-methyl-1, 2, 4-thiadiazolidine-3, 5-dione (TDZD-8). Anaesthetized Sprague-Dawley rats underwent an open-chest procedure involving 30 min of myocardial ischemia and 6 h of reperfusion with or without TDZD-8 given at reperfusion. TDZD-8 reduced myocardial infarct size by nearly 43% (P < 0.05 vs. myocardial ischemia-reperfusion) and attenuated myeloperoxidase activity (21.80 +/- 1.07 U/100 mg tissue. vs. myocardial ischemia-reperfusion group, P < 0.05). Administration of TDZD-8 significantly suppressed nuclear factor kappa B (NF-kappaB) and p38 MAPK activation (P < 0.05 vs. myocardial ischemia-reperfusion) and the concentrations of the myocardial-derived cytokines tumor necrosis factor-alpha (TNF-alpha, 107.40 +/- 7.34 pg/mg protein vs. myocardial ischemia-reperfusion group, P < 0.05) and interleukin-6 (IL-6, 29.28 +/- 6.3 pg/mg protein vs. myocardial ischemia-reperfusion group, P < 0.05). Treatment with TDZD-8 also inhibited myocardial cell apoptosis compared with the myocardial ischemia-reperfusion group (12 +/- 1% vs. 22 +/- 2%, P < 0.05). Therefore, blocking this protein kinase activity may be a novel approach to the treatment of this condition, which is characterized by inflammation and apoptosis.

Our results, derived from a canine model of MI/R, demonstrate that hyperglycaemia blunts insulin protection against MI/R injury via hyperglycaemia-induced glycosylation and subsequent inactivation of insulin-signalling proteins. Our findings suggest that prevention of hyperglycaemia is critical for achieving maximal insulin cardioprotection for the ischaemic/reperfused hearts.

BackgroundThe adaption of elastic arteries to transient increase in hemodynamic load in normal pregnancy (NP) remains controversial. The purpose of this study was to investigate the NP carotid remodeling and regional arterial stiffness before and after parturition.MethodsFifty-one NP women and 30 age-matched non-pregnant women were included. All women underwent right common carotid artery (RCCA) measurements with MylabTwice ultrasound instrument (Esaote, Italy). Carotid intima-medial thickness (IMT), pulse wave velocity (PWV, m/s), distensibility coefficient (DC, 1/KPa), α, β, augmentation index (AIx, %) and carotid arterial pressure were obtained by the newly developed ultrasound vascular wall tracking methods: automatic QAS (Quality Arterial Stiffness) and QIMT (Quality Intima-Medial Thickness) Follow up study was performed.ResultsCompared to the non-pregnant controls, the arterial pressures were significantly increased and RCCA diameter was significantly enlarged in late gestational NP women. Twenty months after parturition, carotid diameter, DC, AIx, PWV and arterial wall tension were significantly decreased and had no significant difference with those in non-pregnant controls.ConclusionsCarotid arterial remodeling and stiffening could be seen in the normal pregnant women, which seems to be a physiological adaption and could be recovered post partum. QIMT and QAS together could provide a comprehensive assessment of the maternal carotid arterial changes during pregnancy.

Insulin attenuated the contractile response to beta-AR stimulation and suppressed ISO-elicited cardiac dysfunction and cell injury in MI/R. The inhibitory effect of insulin on the beta-adrenergic action involved the inhibition of PKA-mediated Ca2+ transient and promotion of post-ischemic Ca2+ handling.