Adult hearts are hard to recover after cardiac injury due to the limited proliferative ability of cardiomyocytes. Emerging evidence indicates the induction of cell cycle reentry of cardiomyocytes by special treatment or stimulation, which offers adult heart regenerative potential. Herein, a microRNA (miRNA) screening in cardiomyocytes identified miR-301a enriched specially in the neonatal cardiomyocytes from rats and mice. Overexpression of miR-301a in primary neonatal cardiomyocytes and H9C2 cells induced G 1 /S transition of the cell cycle, promoted cellular proliferation, and protected cardiomyocytes against hypoxia-induced apoptosis. Adeno-associated virus (AAV)9-mediated cardiac delivery of miR-301a to the mice model with myocardial infarction (MI) dramatically promoted cardiac repair post-MI in vivo . Phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway was confirmed to mediate miR-301a-induced cell proliferation in cardiomyocytes. Loss of function of PTEN mimicked the miR-301a-induced phenotype, while gain of function of PTEN attenuated the miR-301a-induced cell proliferation in cardiomyocytes. Application of RG7440, a small molecule inhibitor of AKT, blocked the function of miR-301a in cardiomyocytes. The current study revealed a miRNA signaling in inducing the cell cycle reentry of cardiomyocytes in the injured heart, and it demonstrated the miR-301a/PTEN/AKT signaling as a potential therapeutic target to reconstitute lost cardiomyocytes in mammals.

This study aimed to investigate the association of daily branched-chain amino acid (BCAA) intake with the risks of obesity and insulin resistance in children of mothers with gestational diabetes mellitus (GDM). Methods: Daily BCAA intake was calculated by using a validated food frequency questionnaire in 996 children of mothers with GDM. The odds ratios (ORs) (95% CI) of childhood obesity and insulin resistance were obtained using logistic regression models. Results: The multivariable-adjusted ORs for overweight and insulin resistance increased across quartiles of daily BCAA intake (P < 0.05 for trend). Multivariable-adjusted ORs for each 1-SD increase in BCAA intake were 1.37 (1.16-1.62) for overweight and 1.19 (1.02-1.38) for insulin resistance. After additional adjustment of children's daily total energy intake, the OR was still significant for overweight risk but no longer significant for insulin resistance. There were positive associations of daily leucine, isoleucine, and valine intake with the risks for overweight and insulin resistance. Conclusions: Daily BCAA intake was associated with increased risks for overweight and insulin resistance in children of mothers with GDM, but this association was not fully independent of children's daily energy intake. Restriction in dietary BCAA may help prevent childhood obesity and insulin resistance.

Objectives: Either maternal gestational diabetes mellitus (GDM) or hypertensive disorder of pregnancy (HDP) is associated with an increased risk of obesity in the offspring. However, their joint associations with obesity in offspring remain unclear. We investigated the joint associations of maternal GDM and HDP with childhood overweight in offspring.Methods: We performed a large study in 1967 mother-child pairs. Maternal GDM was diagnosed according to the 1999 World Health Organization (WHO) criteria. HDP was defined as self-reported doctor-diagnosed hypertension or treatment of hypertension (including gestational hypertension, preeclampsia, sever preeclampsia or eclampsia) after 20 weeks of gestation on the questionnaire. Body mass index (BMI) for age Z-score and childhood overweight were evaluated according to WHO growth reference. We used the general linear models to compare children's Z score for BMI and logistic regression models to estimate odds ratios of childhood overweight according to maternal different status of GDM and HDP.Results: Offspring of mothers with both GDM and HDP had a higher BMI for age Z-score (0.63 vs. 0.03, P < 0.001) than children born to normotensive and normoglycemic pregnancy. After adjustment for maternal and children's major confounding factors, joint GDM and HDP were associated with increased odds ratios of offspring's overweight compared with normotensive and normoglycemic pregnancy (2.97, 95% confidence intervals [CIs] 1.65–5.34) and GDM alone (2.06, 95% CIs 1.20–3.54), respectively. After additional adjustment for maternal pre-pregnancy BMI and gestational weight gain, joint maternal GDM, and HDP was still associated with an increased risk of offspring's overweight compared with the maternal normotensive, and normoglycemic group but became to have a borderline increased risk compared with the maternal GDM alone group.Conclusions: Maternal GDM alone or joint GDM and HDP were associated with increased ratios of offspring's overweight.