Epigenetic modifications in valproic acid-induced teratogenesis

Exposure to the anticonvulsant drug valproic acid (VPA) in utero is associated with a 1-2% increase in neural tube defects (NTDs), however the molecular mechanisms by which VPA induces teratogenesis are unknown. Previous studies demonstrated that VPA, a direct inhibitor of histone deacetylase, can induce histone hyperacetylation and other epigenetic changes such as histone methylation and DNA demethylation. The objective of this study was to determine if maternal exposure to VPA in mice has the ability to cause these epigenetic alterations in the embryo and thus contribute to its mechanism of teratogenesis. Pregnant CD-1 mice (GD 9.0) were administered a teratogenic dose of VPA (400 mg/kg, s.c.) and embryos extracted 1, 3, 6, and 24 h after injection. To assess embryonic histone acetylation and histone methylation, Western blotting was performed on whole embryo homogenates, as well as immunohistochemical staining on embryonic sections. To measure DNA methylation changes, the cytosine extension assay was performed. Results demonstrated that a significant increase in histone acetylation that peaked 3 h after VPA exposure was accompanied by an increase in histone methylation at histone H3 lysine 4 (H3K4) and a decrease in histone methylation at histone H3 lysine 9 (H3K9). Immunohistochemical staining revealed increased histone acetylation in the neuroepithelium, heart, and somites. A decrease in methylated histone H3K9 staining was observed in the neuroepithelium and somites, METHYLATED histone H3K4 staining was observed in the neuroepithelium. No significant differences in global or CpG island DNA methylation were observed in embryo homogenates. These results support the possibility that epigenetic modifications caused by VPA during early mouse organogenesis results in congenital malformations.     

Epigenetic gene regulation: linking early developmental environment to adult disease

Traditional studies on the combined effects of genetics and the environment on individual variation in disease susceptibility primarily focus on single nucleotide polymorphisms that influence toxicant uptake and metabolism. A growing body of evidence, however, suggests that epigenetic mechanisms of gene regulation, such as DNA methylation and chromatin modification, are also influenced by the environment, and play an important role in the fetal basis of adult disease susceptibility. Studying the influence of early environmental exposures on metastable epialleles and imprinted genes offers insight into the mechanisms affecting the fetal epigenome and subsequent adult disease susceptibility. In this review, we introduce the reader to the field of environmental epigenomics, provide information on the important epigenetic control mechanisms and epigenetic phenomena in mammals, and summarize the current body of literature on nutritional and environmental influences affecting the epigenome.     

Epigenetic modifications in rheumatoid arthritis,a review

1. Download : Download high-res image (218KB)
2. Download : Download full-size image

Highlights► RA synovial fibroblasts display an aberrant DNA methylome signature. ► Histone deacetylase inhibitors have beneficial effects in RA. ► Histone deacetylase inhibitors have epigenetic and non-epigenetic effects.     

An elective course on lifestyle modifications in pharmacotherapy

Objectives

Develop and implement a pharmacy course explaining basic lifestyle modification components and assess changes in student knowledge, skills, beliefs, and confidence after completing the course.

Design

A 2-credit hour elective course was offered to pharmacy students in which basic lifestyle modification components were applied to case-based patients with hypertension, dyslipidemia, diabetes mellitus, obesity, and metabolic syndrome in the pharmacy practice setting through comprehensive wellness programs. Knowledge, skills, beliefs, and confidence assessments were embedded into the course.

Assessment

There were significant improvements in students'' skills and confidence, and in most knowledge areas, but not in their beliefs regarding health behaviors.

Conclusion

Implementing an elective course on lifestyle modifications is an effective means of teaching students about wellness and disease prevention.     

Epigenetic modifications in multiple myeloma: recent advances on the role of DNA and histone methylation

Introduction: Multiple Myeloma (MM) is a clonal late B-cell disorder accounting for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent studies on the molecular pathogenesis and biology of MM have highlighted a complex epigenomic landscape contributing to MM onset, prognosis and high individual variability.

Areas covered: We describe here the current knowledge on epigenetic events characterizing MM initiation and progression, focusing on the role of DNA and histone methylation and on the most promising epi-therapeutic approaches targeting the methylation pathway.

Expert opinion: Data published so far indicate that alterations of the epigenetic framework, which include aberrant global or gene/non-coding RNA specific methylation profiles, feature prominently in the pathobiology of MM. Indeed, the aberrant expression of components of the epigenetic machinery as well as the reversibility of the epigenetic marks make this pathway druggable, providing the basis for the design of epigenetic therapies against this still fatal malignancy.