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Congenital heart disease (CHD) is the most common type of birth defect and is both a significant pediatric and adult health problem, in light of a growing population of survivors. The etiology of CHD has been considered to be multifactorial with genetic and environmental factors playing important roles. The combination of advances in cardiac developmental biology, which have resulted in the elucidation of molecular pathways regulating normal cardiac morphogenesis, and genome sequencing technology have allowed the discovery of numerous genetic contributors of CHD ranging from chromosomal abnormalities to single gene variants. On the other hand, mechanistic details of the contribution of environmental factors to CHD remain unknown. Maternal diabetes mellitus (matDM) is a well-established and increasingly prevalent environmental risk factor for CHD, but the underlying etiologic mechanisms by which pre-gestational matDM increases the vulnerability of embryos to cardiac malformations remains largely elusive. Here, we will briefly discuss the multifactorial etiology of CHD with a focus on the epidemiologic link between matDM and CHD. We will describe the animal models used to study the underlying mechanisms between matDM and CHD and review the numerous cellular and molecular pathways affected by maternal hyperglycemia in the developing heart. Lastly, we discuss how this increased understanding may open the door for the development of novel prevention strategies to reduce the incidence of CHD in this high-risk population.

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Background:The mechanism of vascular endothelial growth factor (VEGF)-regulated expression of MMPs followed by cancer cell scattering/invasion is poorly understood. Results: VEGF induces MMP-9, MMP-13, and ETS-1 through PI3K/AKT and p38 MAPK pathways in SKOV-3 cells. Conclusion: VEGF induces ETS-1, which activates specific MMPS, leading to the invasion/scattering in SKOV-3 cells. Significance: This study provides useful information that reveals the molecular mechanism of ovarian cancer metastasis.

ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a newly identified component of the transcriptional coregulator network, was found to interact with the Nucleosome Remodeling and Deacetylase (NuRD) complex. Previous reports have shown that ZMYND8 is instrumental in recruiting the NuRD complex to damaged chromatin for repressing transcription and promoting double strand break repair by homologous recombination. However, the mode of transcription regulation by ZMYND8 has remained elusive. Here, we report that through its specific key residues present in its conserved chromatin-binding modules, ZMYND8 interacts with the selective epigenetic marks H3.1K36Me2/H4K16Ac. Furthermore, ZMYND8 shows a clear preference for canonical histone H3.1 over variant H3.3. Interestingly, ZMYND8 was found to be recruited to several developmental genes, including the all-trans-retinoic acid (ATRA)-responsive ones, through its modified histone-binding ability. Being itself inducible by ATRA, this zinc finger transcription factor is involved in modulating other ATRA-inducible genes. We found that ZMYND8 interacts with transcription initiation-competent RNA polymerase II phosphorylated at Ser-5 in a DNA templatedependent manner and can alter the global gene transcription. Overall, our study identifies that ZMYND8 has CHD4-independent functions in regulating gene expression through its modified histone-binding ability.ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8) is a putative chromatin reader/effector harboring a PWWP domain, a bromodomain, and a PHD type zinc finger. It associates with the CHD4 protein of NuRD chromatin remodeling complex implicated in gene transcription, cell cycle progression, and genome integrity (1, 2). Reader proteins specifically recognize histone post-translational modifications (PTMs) 5 and translate such recognition(s) into meaningful biological outcomes by virtue of either their intrinsic activities or those of their interacting partners (3). These readers may interpret histone PTMs via "monovalent" or "multivalent" recognition (4). In monovalent recognition, a chromatin reader recognizes one histone PTM. In contrast, in multivalent recognition, readers recognize multiple histone modifications intra/inter-nucleosomally. An accessible surface is provided by these readers (such as a cavity or surface groove), which accommodates the modified histone residues, and determines the modification (e.g. acetylation versus methylation) or state specificity (such as mono-versus trimethylation of lysine) (3).ZMYND8 is a well known component of the transcription coregulator complex and is associated with several demethylase machinery components, including KDM5A, KDM5C, or LSD1 (5, 6). Through its ability to interact with Xenopus RCoR2, ZMYND8 plays a significant role in embryonic neural differentiation (7). Apart from this, ZMYND8 is also involved in T-cell lymphoma and breast and cervical cancer (8 -10). Another interesting feature is that ZMYND8 is significantly involved...

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Background: Wnt pathway and homeodomain proteins are associated with cancer, but their interaction in ovarian cancer cells has not been studied. Results: PITX2 itself and through inducing Wnt ligands activates the canonical Wnt pathway and cell proliferation. Downregulation of Frizzled receptors limits further Wnt activation. Conclusion: PITX2 enhances proliferation of SKOV-3 cells by inducing canonical Wnt signaling. Significance: This study will help understand the mechanism of proliferation in ovarian cancer cells.