Prenatal alcohol exposure may cause cardiac development defects, however, the underlying mechanisms are not yet clear. In the present study we have investigated the roles of histone modification by curcumin on alcohol induced fetal cardiac abnormalities during the development. Q-PCR and Western blot results showed that alcohol exposure increased gene and active forms of caspase-3 and caspase-8, while decreased gene and protein of bcl-2. ChIP assay results showed that, alcohol exposure increased the acetylation of histone H3K9 near the promoter region of caspase-3 and caspase-8, and decreased the acetylation of histone H3K9 near the promoter region of bcl-2. TUNEL assay data revealed that alcohol exposure increased the apoptosis levels in the embryonic hearts. In vitro experiments demonstrated that curcumin treatment could reverse the up-regulation of active forms of caspase-3 and caspase-8, and down-regulation of bcl-2 induced by alcohol treatment. In addition, curcumin also corrected the high level of histone H3K9 acetylation induced by alcohol. Moreover, the high apoptosis level induced by alcohol was reversed after curcumin treatment in cardiac cells. These findings indicate that histone modification may play an important role in mediating alcohol induced fetal cardiac apoptosis, possibly through the up-regulation of H3K9 acetylation near the promoter regions of apoptotic genes. Curcumin treatment may correct alcohol-mediated fetal cardiac apoptosis, suggesting that curcumin may play a protective role against alcohol abuse caused cardiac damage during pregnancy.

Bone marrow derived stem cells (BMSCs) have the potential to differentiate into cardiomyocytes, but the rate of differentiation is low and the mechanism of differentiation is unclear completely. Here, we aimed to investigate the role of miR1-2 in differentiation of mouse BMSCs into cardiomyocyte-like cells and reveal the involved signaling pathways in the procedure. Mouse BMSCs were treated with miR1-2 and 5-azacytine (5-aza). The expression of cardiac cell markers: NKx2.5, cTnI and GATA4 in BMSCs were examined by qPCR. The apoptosis rate was detected by flow cytometry and the activity of the Wnt/β-catenin signaling pathway was evaluated by measuring the upstream protein of this signaling pathway. After over-expression of miR1-2 in mouse BMSCs, the apoptosis rate was significantly lower than the 5-aza group, while the expressions of cardiac-specific genes: such as Nkx2.5, cTnI and GATA4 were significantly increased compared to the control group and the 5-aza group. Meanwhile, over-expression of miR1-2 in mouse BMSCs enhanced the expression of wnt11, JNK, β-catenin and TCF in the Wnt/β-catenin signaling pathway. Use of LGK-974, an inhibitor of Wnt/β-catenin signaling pathway, significantly reduced the expression of cardiac-specific genes and partially blocked the role of the miR1-2. Over-expression of miR1-2 in mouse BMSCs can induce them toward promoted cardiomyocyte differentiation via the activation of the Wnt/β-catenin signaling pathway. Compared to 5-aza, miR1-2 can induce differentiation of BMSCs into cardiomyocytes more effectively with a less cytotoxicity.

This review summarizes recent advances in understanding the development of coronary arteritis in Kawasaki disease. Kawasaki disease is the most common cause of acquired heart disease among children characterized with coronary artery abnormalities, which can cause myocardial ischemia, infarction, and even death. The pathogenic factors of Kawasaki disease and the pathological process of coronary artery disease are not clear at present, which brings challenges to the prevention and treatment of the disease. The treatment of Kawasaki disease focuses mainly on timely administration of intravenous high doses of immunoglobulin and aspirin. However, there are still some patients who do not respond well to this standard treatment, and its management remains a challenge. As a result, coronary artery lesions still occur in patients and affect their quality of life. In this review, we discuss updated research data of Kawasaki disease coronary artery lesions.

Accurate evaluation of individual risk of intravenous immunoglobin (IVIG)-resistance is critical for adopting regimens for the first treatment and prevention of coronary artery lesions (CALs) in patients with Kawasaki disease (KD). Methods: The KD patients hospitalized in Chongqing Children’s Hospital, in west China, from October 2007 to December 2017 were retrospectively reviewed. Data were collected and compared between IVIG-resistant group and IVIG-responsive group. The independent risk factors were determined using multivariate regression analysis. A new prediction model was built and compared with the previous models. Results: A total of 5277 subjects were studied and eight independent risk factors were identified including higher red blood cell distribution width (RDW), lower platelet count (PLT), lower percentage of lymphocyte (P-LYM), higher total bile acid (TBA), lower albumin, lower serum sodium level, higher degree of CALs (D-CALs) and younger age. The new predictive model showed an AUC of 0.74, sensitivity of 76% and specificity of 59%. For individual’s risk probability of IVIG-resistance, an equation was given. Conclusions: IVIG-resistance could be predicted by RDW, PLT, P-LYM, TBA, albumin, serum sodium level, D-CALs and age. The new model appeared to be superior to those previous models for KD population in Chongqing city.