Study of Molecular Dimer Morphology Based on Organic Spin Centers: Nitronyl Nitroxide Radicals.

In this work, in order to investigate the short-range interactions between molecules, the spin-magnetic unit nitronyl nitroxide (NN) was introduced to synthesize self-assembly single radical molecules with hydrogen bond donors and acceptors. The structures and magnetic properties were extensively investigated and characterized by UV-Vis absorption spectroscopy, electron paramagnetic resonance (EPR), and superconducting quantum interference devices (SQUIDs). Interestingly, it was observed that the single molecules can form two different dimers (ring-closed dimer and "L"-type dimer) in different solvents, due to hydrogen bonding, when using EPR to track the molecular spin interactions. Both dimers exhibit ferromagnetic properties (for ring-closed dimer, J/kB = 0.18 K and ΔES-T = 0.0071 kcal/mol; for "L"-type dimer, the values were J/kB = 9.26 K and ΔES-T = 0.037 kcal/mol). In addition, the morphologies of the fibers formed by the two dimers were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM).

Involvement of the PI3K/Akt/Nrf2 Signaling Pathway in Resveratrol-Mediated Reversal of Drug Resistance in HL-60/ADR Cells.

Resistance to chemotherapy drugs, such as adriamycin (ADR), is a common problem in acute myeloid leukemia (AML) patients. We hypothesized that the natural compound resveratrol (Res) may reverse AML drug resistance through the PI3K/Akt/Nrf2 pathway. We investigated the in vitro effect of Res using human promyelocytic leukemia cells (HL-60) and the ADR-resistant cell line (HL-60/ADR) and treated with either Res or ADR + Res. Cellular proliferation inhibition rate, auto-fluorescence intensity of ADR in HL-60/ADR cells and HL-60 cells, mRNA expression of Nrf2 and the drug-resistant gene MRP1, and protein expression of PI3K, Akt, p-Akt, Nrf2, and MRP1 were measured. Results showed ADR + Res had a more significant inhibitory effect than ADR alone on HL-60/ADR cells. Auto-fluorescence intensity of ADR in HL-60/ADR cells treated with ADR + Res significantly increased. No difference of the auto-fluorescence intensity of ADR was observed in HL-60 cells treated with ADR and ADR + Res. mRNA expression of Nrf2 and MRP1 significantly decreased in HL-60/ADR cells treated with both Res and ADR + Res; protein expression of PI3K, p-Akt, Nrf2, and MRP1 significantly decreased in HL-60/ADR cells treated with PI3K inhibitor, Res and ADR + Res. In conclusion, Res reverses the drug resistance of AML HL-60/ADR cells through regulation of the PI3K/Akt/Nrf2 signaling pathway and MRP1 expression.

Effects of nicotine on proliferation and survival in human umbilical cord mesenchymal stem cells.

Cigarette smoking is known to have negative effects on tissue repair and healing. The aim of this study is to investigate the effects of nicotine in human umbilical cord mesenchymal stem cells (MSCs). After nicotine treatment, MSCs became pyknotic, vacuoles appeared in the cytoplasm and nucleus, and the nuclear boundary became fuzzy as observed using atomic force microscopy. Cell proliferation was inhibited in a dose-dependent manner (P < 0.05 for all concentrations). The proportion of apoptotic MSCs was significantly increased in a dose-dependent manner. The mitochondrial membrane potential was significantly decreased (P < 0.05). Nicotine-treated MSCs had a significantly higher G0/G1 ratio (P < 0.05). Peptide mass fingerprinting identified 27 proteins that were differentially expressed between MSCs with and without nicotine treatment. These nicotine exerted toxic effects on MSCs are likely related, at least in part, to the altered expression of multiple proteins that are essential to the health and proliferation of these cells.

Close-packed nitronyl nitroxide radicals by Au-S self-assembly: strong ferromagnetic coupling.

The study of the magnetism of tightly arranged nitronyl nitroxide (NN) radicals via Au-S self-assembly is interesting. In this study, a series of radicals (S-NN, D-NN, BS-NN, BD-NN) along with two types of nanomaterials (S-NPs, D-NPs) were synthesized. NN was chosen for the magnetic units. Their structures have been successfully synthesized and analyzed. The spin magnetic properties were characterized by electron paramagnetic resonance (EPR) and superconducting quantum interference device (SQUID) measurement. The analysis revealed that the self-assembled NN formed via Au-S bonds exhibits high packing density. Furthermore, it was gratifying to observe that the AuNPs exhibit ferromagnetism after the surface modification by NN. This results in strong ferromagnetic exchange interactions of S-NPs and D-NPs : J S-NPs = +279.715 K and J D-NPs = +254.913 K, respectively.

Hypoxia-mimetic agents inhibit proliferation and alter the morphology of human umbilical cord-derived mesenchymal stem cells.

BACKGROUND: The therapeutic efficacy of human mesenchymal stem cells (hMSCs) for the treatment of hypoxic-ischemic diseases is closely related to level of hypoxia in the damaged tissues. To elucidate the potential therapeutic applications and limitations of hMSCs derived from human umbilical cords, the effects of hypoxia on the morphology and proliferation of hMSCs were analyzed. RESULTS: After treatment with DFO and CoCl2, hMSCs were elongated, and adjacent cells were no longer in close contact. In addition, vacuole-like structures were observed within the cytoplasm; the rough endoplasmic reticulum expanded, and expanded ridges were observed in mitochondria. In addition, DFO and CoCl2 treatments for 48 h significantly inhibited hMSCs proliferation in a concentration-dependent manner (P < 0.05). This treatment also increased the number of cells in G0/G1 phase and decreased those in G2/S/M phase. CONCLUSIONS: The hypoxia-mimetic agents, DFO and CoCl2, alter umbilical cord-derived hMSCs morphology and inhibit their proliferation through influencing the cell cycle.

[Mechanism of Apoptosis for Resveratrol-mediated Reversing the Drug-resistance of AML HL-60/ADR cells].

OBJECTIVE: To explore the mechanism of apoptosis for resvertrol-mediated reversing the drug-resistance of AML HL-60/ADR cells. METHODS: The HL-60/ADR cells were divided into 4 groups: control group, adriamycin (ADR)-treated group, resveratrol(Res)-treated group and ADR+Res-treated group. The inhibitory rate of cell proliferation was analyzed by CCK-8 method. The auto-fluorescence intensity of intracellular ADR and the apoptotic rate of HL-60/ADR cells were detected by flow cytometry. The mRNA expression levels of multidrug-resistance associated protein-1(MRP1), anti-apoptotic gene BCL-2 and pro-apoptotic gene BAX were analyzed by real-time fluorescence quantitative RT-PCR. The protein expression levels of MRP1, BCL-2 and BAX were detected by Western blot. RESULTS: The maximal inhibition rates of cell proliferation were 44%, 61%, 76% and 81%, respectively in different concentration of Res (25, 50, 100, 200 µmol/L) and with concentration-dependent manner(r=0.876, P<0.05). Compared with ADR group (IC50: 8.534±1.111 µmol/L), the half inhibitory concentration (IC50) of HL-60/ADR cells [(1.591±0.373) µmol/L] decreased significantly in ADR+Res group(P<0.05). The auto-fluorescence intensity of ADR in HL-60/ADR cells of ADR+Res group increased significantly (P<0.05). The apoptotic rate of HL-60/ADR cells in Res or ADR+Res group increased significantly (P<0.05). The mRNA expression levels of MRP1 and Bcl-2 in Res or ADR+Res groups decreased and BAX increased significantly (P<0.05). The protein expression levels of MRP1 and BCL-2 were decreased, BAX increased significantly in Res or ADR+Res group (P<0.05). CONCLUSION: Resveratrol shows the effect of reversing the drug resisitance of HL-60/ADR cells in acute myeloid leukemia, possibly via promoting the apoptosis of HL-60/ADR cells and inhibiting the expression of MRP1, which may be related with the inhibition of BCL-2 expression and the promotion of BAX expression.