Mesenchymal stem cells (MSCs) exert therapeutic effect on treating acute myocardial infarction. Recent evidence showed that paracrine function rather than direct differentiation predominately contributes to the beneficial effects of MSCs, but how the paracrine factors function are not fully elucidated. In the present study, we tested if extracellular vesicles (EVs) secreted by MSC promotes angiogenesis in infracted heart via microRNAs. Immunostaining of CD31 and matrigel plug assay were performed to detect angiogenesis in a mouse myocardial infarction (MI) model. The cardiac function and structure was examined with echocardiographic analysis. Capillary-like tube formation, migration and proliferation of human umbilical vein endothelial cells (HUVECs) were determined. As a result, MSC-EVs significantly improved angiogenesis and cardiac function in post-MI heart. MSC-EVs increased the proliferation, migration and tube formation capacity of HUVECs. MicroRNA (miR)-210 was found to be enriched in MSC-EVs. The EVs collected from MSCs with miR-210 silence largely lost the pro-angiogenic effect both in-vitro and in-vivo. The miR-210 target gene Efna3, which plays a role in angiogenesis, was down-regulated by MSC-EVs treatment in HUVECs. In conclusion, MSC-EVs are sufficient to improve angiogenesis and exert therapeutic effect on MI, its pro- angiogenesis effect might be associated with a miR-210-Efna3 dependent mechanism. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.

Mn2+-doped ZnSe nanocrystals (Mn:ZnSe d-dots) with high optical qualityhigh dopant emission quantum yield with monoexponential dopant-emission decay dynamicsenable systematic and quantitative studies of temperature- and Mn2+ concentration-dependent optical properties of the dopant emission, especially its relationship with magnetic coupling. While temperature-dependent steady-state and transient dopant emission of d-dots with dilute Mn2+ concentrations originated from isolated Mn2+ ions, and can be quantitatively treated as a result of exciton–phonon coupling of isolated paramagnetic emission centers. Dopant emission of d-dots with high Mn2+ concentrations (up to 50% of Zn2+ ions being replaced by Mn2+ ions in the core nanocrystals) are found solely related to magnetically coupled Mn2+ emission. Magnetic coupling effects on steady-state dopant emission of d-dots with high Mn2+ concentrations are much stronger than those observed for doped bulk semiconductors, which is found to follow a strong and universe shell-thickness dependence for the epitaxial ZnSe and/or ZnS shells of the d-dots. By exciting the magnetically coupled Mn2+ ions directly, dopant-emission of d-dots with high Mn2+ concentrations exhibit monoexponential decay dynamics. In addition to this emission channel, a minor channel with slightly longer decay lifetime appears when the host nanocrystals with high Mn2+ concentrations are excited, which is barely visible at room temperature and increases its fraction by decreasing temperature.

Transition metal doped semiconductor nanocrystals (d-dots) possess fundamentally different emission properties upon photo- or electroexcitation, which render them as unique emitters for special applications. However, in comparison with intrinsic semiconductor nanocrystals, the potential of d-dots has been barely realized, because many of their unique emission properties mostly rely on precise control of their photoluminescence (PL) decay dynamics. Results in this work revealed that it would be possible to obtain bright d-dots with nearly single-exponential PL decay dynamics. By tuning the number of Mn2+ ions per dot from ∼500 to 20 in Mn2+ doped ZnSe nanocrystals (Mn:ZnSe d-dots), the single-exponential PL decay lifetime was continuously tuned from ∼50 to 1000 μs. A synthetic scheme was further developed for uniform and epitaxial growth of thick ZnS shell, ∼7 monolayers. The resulting Mn:ZnSe/ZnS core/shell d-dots were found to be essential for necessary environmental durability of the PL properties, both steady-state and transient ones, for the d-dot emitters. These characteristics combined with intense absorption and high PL quantum yields (70 ± 5%) enabled greatly simplified schemes for various applications of PL lifetime multiplexing using Mn:ZnSe/ZnS core/shell d-dots.

Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and redifferentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that inhibition of the epigenetic modification enzyme enhancer of zeste homolog 2 (EZH2), histone deacetylases 1 and 3 (HDAC1 and -3), lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines. The regulatory effect of these enzymes in neuronal differentiation resided in their intrinsic activity in embryonic neural precursor/progenitor cells. We further found that a major part of pan-cancer-promoting genes and the signal transducers of the pan-cancer-promoting signaling pathways, including the epithelial-to-mesenchymal transition (EMT) mesenchymal marker genes, display neural specific expression during embryonic neurulation. In contrast, many tumor suppressor genes, including the EMT epithelial marker gene that encodes cadherin 1 (), exhibited non-neural or no expression. This correlation indicated that cancer cells and embryonic neural cells share a regulatory network, mediating both tumorigenesis and neural development. This observed similarity in regulatory mechanisms suggests that cancer cells might share characteristics of embryonic neural cells.