Alcohol exposure during pregnancy may cause congenital heart disease (CHD), but the underlying mechanisms are not clear. Recent evidence suggests that ethanol and its metabolites can selectively increase histone H3 acetylation at lysine 9 (H3AcK9) residue in rat hepatocytes. This may be a mechanism by which ethanol alters gene expression. The goal of current study is to investigate the effect of ethanol and its metabolites on H3AcK9 acetylation and the mRNA expression of heart development-related genes (GATA4, Mef2c, and Tbx5) in cardiac progenitor cells. We used mitochondrial activity (MTT) assay to assess the viability of cardiac progenitor cells. Western blotting and real-time PCR were employed to determine H3AcK9 acetylation and gene expression. Low levels of ethanol (50 mM), acetaldehyde (4 mM), and acetate (4 mM) had no effect on cell proliferation. However, high concentrations of ethanol (200 mM), acetaldehyde (12 mM), and acetate (16 mM) reduced cell viability by 30%, respectively (P < 0.05). Low levels of ethanol and acetate increased the acetylation of H3 lysine 9 by 2.4- and 2.2-fold, respectively (P < 0.05), but did not significantly change the expression of the heart development-related genes. High concentrations of ethanol and acetate increased H3 lysine 9 acetylation by 5.3- and 5.6-fold, respectively (P < 0.05). Moreover, high levels of ethanol and acetate significantly augmented the expression of GATA4 and Mef2c. Conversely, acetaldehyde (4 or 12 mM) had little effect on H3 lysine 9 acetylation or the expression of the heart development-related genes. Our studies demonstrate that high levels of ethanol or its metabolites induce H3AcK9 acetylation and impair cardiac progenitor cells. The altered histone H3 acetylation at lysine 9 has an important impact on the expression of the heart development-related genes, which may be one of the mechanisms underlying the alcohol-induced CHD.

Cardiac hypertrophy has become a major cardiovascular problem wordwide and is considered the early stage of heart failure. Treatment and prevention strategies are needed due to the suboptimal efficacy of current treatment methods. Recently, many studies have demonstrated the important role of histone acetylation in myocardium remodelling along with cardiac hypertrophy. A Chinese herbal extract containing anacardic acid (AA) is known to possess strong histone acetylation inhibitory effects. In previous studies, we demonstrated that AA could reverse alcohol‐induced cardiac hypertrophy in an animal model at the foetal stage. Here, we investigated whether AA could attenuate cardiac hypertrophy through the modulation of histone acetylation and explored its potential mechanisms in the hearts of transverse aortic constriction (TAC) mice. This study showed that AA attenuated hyperacetylation of acetylated lysine 9 on histone H3 (H3K9ac) by inhibiting the expression of p300 and p300/CBP‐associated factor (PCAF) in TAC mice. Moreover, AA normalized the transcriptional activity of the heart nuclear transcription factor MEF2A . The high expression of cardiac hypertrophy‐linked genes ( ANP, β‐MHC ) was reversed through AA treatment in the hearts of TAC mice. Additionally, we found that AA improved cardiac function and survival rate in TAC mice. The current results further highlight the mechanism by which histone acetylation is controlled by AA treatment, which may help prevent and treat hypertrophic cardiomyopathy.

While coronary artery abnormality (CAA) has been established as the most serious complication of Kawasaki disease (KD), there have been no detailed systematic reviews of the risk factors associated with this condition. We searched six databases and performed a systematic review and meta-analysis. Study-specific odds ratios (ORs) for each factor were pooled using a random effects model. We identified four risk factors for CAA children with KD: gender (OR, 1.75; 95% confidence interval [CI], 1.59–1.92), intravenous immunoglobulin (IVIG) resistance (OR, 3.43; 95% CI, 2.07–5.67), IVIG treatment beyond 10 days of onset of symptoms (OR, 3.65; 95% CI, 2.23–5.97), and increased C-reactive protein levels (OR, 1.02; 95% CI, 1.01–1.02). More number of the five typical symptoms of KD was identified as a protective factor against CAA (OR, 0.47; 95% CI, 0.33–0.66). Pediatric patients with IVIG resistant were more likely to develop CAA within 1 month of the onset of KD than the general population, even in patients with other risk factors for CAA. Thus, there is a potential risk of CAA misdiagnosis if echocardiography is not carried out frequently. In summary, we report four risk factors for CAA and a protective factor against CAA in children with KD. We recommend that pediatricians consider these factors much more closely. With accurate prediction and early preventive treatment in high-risk patients, we can expect a reduction in CAA rates. Further research is now required to investigate the associations between CAA and other factors including the interval between KD onset and IVIG administration, platelet count, and the duration of fever. We also need to confirm whether the frequency of echocardiography within a month of KD onset should be increased in IVIG-resistant patients.

These data indicate a time course of H3K9 acetylation change during heart development and demonstrate that alcohol exposure in utero may induce an increase of HAT activities, which results in H3K9 hyperacetylation and an increase of the expression of heart development-related genes. These findings reveal a novel epigenetic mechanism that connects the alcohol consumption during the pregnancy and the development of CHD in the fetus.

Cardiac hypertrophy is a complex process involving highly coordinated but tight regulation of multiple elements, such as in epigenetics, which make an important contribution to myocardium remodeling and cardiac hypertrophy. Epigenetic regulations, particularly histone acetylation, have been implicated in cardiac hypertrophy, however, the exact mechanism is still largely unknown. In the present study, we explored the potential attenuating effects of Chinese herbal extract anacardic acid on phenylephrine-induced cardiac hypertrophy and the underlying mechanism. The mouse cardiac hypertrophy model was established and the hearts were collected from C57BL/6 mice for further analyses. The data showed that anacardic acid modulated the cardiac genes expression and attenuated the phenylephrine-induced cardiac hypertrophy via the suppression of histone acetylases activity and downstream cardiac genes. In addition, anacardic acid abrogated histone and MEF2A acetylation and DNA-binding activity by blocking p300-HAT and PCAF-HAT activities. In addition, anacardic acid normalized the cardiac hypertrophy-related genes expressions (ANP, BNP, cTnT, cTnI, β-MHC, and Cx43) induced by phenylephrine at the level of transcription and translation. In addition, anacardic acid did not affect the blood routine index, hepatic function, renal function, and myocardial enzymes. Therefore, anacardic acid may prove to be a candidate drug to cure hypertrophic cardiomyopathy.

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Investigating how seed germination of multiple species in an ecosystem responds to environmental conditions is crucial for understanding the mechanisms for community structure and biodiversity maintenance. However, knowledge of seed germination response of species to environmental conditions is still scarce at the community level. We hypothesized that responses of seed germination to environmental conditions differ among species at the community level, and that germination response is not correlated with seed size. To test this hypothesis, we determined the response of seed germination of 20 common species in the Siziwang Desert Steppe, China, to seasonal temperature regimes (representing April, May, June, and July) and drought stress (0, −0.003, −0.027, −0.155, and −0.87 MPa). Seed germination percentage increased with increasing temperature regime, but Allium ramosum , Allium tenuissimum , Artemisia annua , Artemisia mongolica, Artemisia scoparia , Artemisia sieversiana , Bassia dasyphylla, Kochia prastrata, and Neopallasia pectinata germinated to >60% in the lowest temperature regime (April). Germination decreased with increasing water stress, but Allium ramosum , Artemisia annua , Artemisia scoparia , Bassia dasyphylla, Heteropappus altaicus , Kochia prastrata , Neopallasia pectinata, and Potentilla tanacetifolia germinated to near 60% at −0.87 MPa. Among these eight species, germination of six was tolerant to both temperature and water stress. Mean germination percentage in the four temperature regimes and the five water potentials was not significantly correlated with seed mass or seed area, which were highly correlated. Our results suggest that the species‐specific germination responses to environmental conditions are important in structuring the desert steppe community and have implications for predicting community structure under climate change. Thus, the predicted warmer and dryer climate will favor germination of drought‐tolerant species, resulting in altered proportions of germinants of different species and subsequently change in community composition of the desert steppe.

BackgroundCardiovascular malformations can be caused by abnormalities in Gata4 expression during fetal development. In a previous study, we demonstrated that ethanol exposure could lead to histone hyperacetylation and Gata4 over-expression in fetal mouse hearts. However, the potential mechanisms of histone hyperacetylation and Gata4 over-expression induced by ethanol remain unclear.Methods and ResultsPregnant mice were gavaged with ethanol or saline. Fetal mouse hearts were collected for analysis. The results of ethanol fed groups showed that global HAT activity was unusually high in the hearts of fetal mice while global HDAC activity remained unchanged. Binding of P300, CBP, PCAF, SRC1, but not GCN5, were increased on the Gata4 promoter relative to the saline treated group. Increased acetylation of H3K9 and increased mRNA expression of Gata4, α-MHC, cTnT were observed in these hearts. Treatment with the pan-histone acetylase inhibitor, anacardic acid, reduced the binding of P300, PCAF to the Gata4 promoter and reversed H3K9 hyperacetylation in the presence of ethanol. Interestingly, anacardic acid attenuated over-expression of Gata4, α-MHC and cTnT in fetal mouse hearts exposed to ethanol.ConclusionsOur results suggest that P300 and PCAF may be critical regulatory factors that mediate Gata4 over-expression induced by ethanol exposure. Alternatively, P300, PCAF and Gata4 may coordinate over-expression of cardiac downstream genes in mouse hearts exposed to ethanol. Anacardic acid may thus protect against ethanol-induced Gata4, α-MHC, cTnT over-expression by inhibiting the binding of P300 and PCAF to the promoter region of these genes.