This review provides a brief overview of the basic principles of epigenetic gene regulation and then focuses on recent development of epigenetic drugs for cancer treatment and prevention with an emphasis on the molecular mechanisms of action. The approved epigenetic drugs are either inhibitors of DNA methyltransferases or histone deacetylases (HDACs). Future epigenetic drugs could include inhibitors for histone methyltransferases and histone demethylases and other epigenetic enzymes. Epigenetic drugs often function in two separate yet interrelated ways. First, as epigenetic drugs per se, they modulate the epigenomes of premalignant and malignant cells to reverse deregulated epigenetic mechanisms, leading to an effective therapeutic strategy (epigenetic therapy). Second, HDACs and other epigenetic enzymes also target non-histone proteins that have regulatory roles in cell proliferation, migration and cell death. Through these processes, these drugs induce cancer cell growth arrest, cell differentiation, inhibition of tumor angiogenesis, or cell death via apoptosis, necrosis, autophagy or mitotic catastrophe (chemotherapy). As they modulate genes which lead to enhanced chemosensitivity, immunogenicity or dampened innate antiviral response of cancer cells, epigenetic drugs often show better efficacy when combined with chemotherapy, immunotherapy or oncolytic virotherapy. In chemoprevention, dietary phytochemicals such as epigallocatechin-3-gallate and sulforaphane act as epigenetic agents and show efficacy by targeting both cancer cells and the tumor microenvironment. Further understanding of how epigenetic mechanisms function in carcinogenesis and cancer progression as well as in normal physiology will enable us to establish a new paradigm for intelligent drug design in the treatment and prevention of cancer.
The crystal structure of the title compound D(H)LAP with chemical formula (D2N)2CND · (CH2)3CH(ND3)CO2 · D2PO4 · D2O has been determined by single crystal neutron diffraction. Positional and thermal parameters of atoms were refined by block diagonal matrix least-squares technique. A final Rf value of 0.048 was obtained for 1040 observed independent reflections. The crystal structure consists of alternate layers of phosphate groups and ariginine molecules stacked along the a-axis and held together by hydrogen bonds. By deuteration of HLAP, the deuteriums occupy hydrogen positions except those hydrogen atoms bonded to carbon atoms. All the D(H) bond lengths in D(H)LAP are about 10% to 30% longer than those in HLAP And bond angles are obviously different from references  and .
The plasticity, elastic modulus and thermal stability restrict the applications of electrodeposited nanocrystalline Ni-Fe alloy foils. To improve its mechanical properties, the electrodeposited Ni-Fe alloy foils were heat treated within the temperature 900–1,150 °C. The microstructure and texture of the samples were further analyzed with a combination of SEM, XRD and EBSD. The experimental results indicated that the electrodeposited Ni-Fe alloy foil had poor mechanical properties at about 1,000 °C, which was mainly attributed to the development of a mixed grain microstructure. At 900–950 °C, the plastic and elastic modulus were greatly improved, which were owed to the uniformed microstructure and the decrease of structure defects. At 1,050–1,150 °C, the degree of the mixed grain microstructure decreased, resulting in improved plasticity and higher elastic modulus. However, the strength of the foil obviously decreased, which was mainly associated with the increase of the average grain size.
Background: Mesenchymal stem cells (MSCs) known to be sensitive to mechanical stimulus. This type of stimulus plays a role in cellular differentiation, so that it might affect MSCs differentiation toward cardiomyocytes.
Objectives: Investigate the effect of mechanical stimulus on MSCs differentiation toward cardiomyocytes.
Methods: The adipose tissue-derived MSCs were induced to differentiate with 5-azacytidine, and stimulated by one Hz mechanical stretching up to 8%. After 10 days, the cell’s cardiac markers and cardiogenesis-related genes were detected by immumohistochemistrical staining and reverse transcriptase-polymerase chain reaction, and the cell’s ATPase activity was detected.
Results: The cyclic mechanical stretching enhanced the expression of cardiogenesis-related genes and cardiac markers, and stimulated the activity of Na+-K+-ATPase and Ca2+-ATPase in the MSCs treated with 5-azacytidine. Without 5-azacytidine pre-treatment, cyclic mechanical stretch alone has little effect.
Conclusion: Mechanical stretch combined with 5-azacytidine treatment could accelerate MSCs differentiation toward cardiomyocytes.