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Cell permeabilization using shock waves may be a way of introducing macromolecules and small polar molecules into the cytoplasm, and may have applications in gene therapy and anticancer drug delivery. The pressure profile of a shock wave indicates its energy content, and shock-wave propagation in tissue is associated with cellular displacement, leading to the development of cell deformation. In the present study, three different shock-wave sources were investigated; argon fluoride excimer laser, ruby laser, and shock tube. The duration of the pressure pulse of the shock tube was 100 times longer than the lasers. The uptake of two fluorophores, calcein (molecular weight: 622) and fluorescein isothiocyanate-dextran (molecular weight: 71,600), into HL-60 human promyelocytic leukemia cells was investigated. The intracellular fluorescence was measured by a spectrofluorometer, and the cells were examined by confocal fluorescence microscopy. A single shock wave generated by the shock tube delivered both fluorophores into approximately 50% of the cells (p < 0.01), whereas shock waves from the lasers did not. The cell survival fraction was >0.95. Confocal microscopy showed that, in the case of calcein, there was a uniform fluorescence throughout the cell, whereas, in the case of FITC-dextran, the fluorescence was sometimes in the nucleus and at other times not. We conclude that the impulse of the shock wave (i.e., the pressure integrated over time), rather than the peak pressure, was a dominant factor for causing fluorophore uptake into living cells, and that shock waves might have changed the permeability of the nuclear membrane and transferred molecules directly into the nucleus.

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Background: Nuclear factor E2-related factor 2 (Nrf2) is a master regulator of cytoprotective enzymes.Results: Nrf2 overexpression-mediated cytoprotective enzymes' augmentation blocked RANKL signaling via intracellular ROS attenuation and thereby blocked bone destruction.Conclusion: Nrf2-dependent cytoprotective enzyme expressions play a role in the regulation of osteoclastogenesis by controlling intracellular ROS.Significance: The Keap1/Nrf2 axis could be a novel therapeutic target for the treatment of bone destructive disease.

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The motion of single-and two-cavitation bubbles generated by laser beams directly beneath a free surface is studied experimentally, using high-speed photography, and theoretically using the highly accurate boundary integral method. Favorable comparisons of bubble shape history and centroid motion are observed while the numerical calculations provide information on the pressure field surrounding the bubbles. A range of responses, including the null impulse state, is obtained for the two bubbles depending on the bubble size ratio and the interbubble and bubble-free surface distances, although in all cases reported in this article, the bubble nearest the free surface yields a high-speed liquid jet directed away from the free surface. It is also found that when the free-surface-bubble interaction is strong, a fast free-surface spike is formed for both the single-and two-bubble cases.

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The structural change of a phospholipid bilayer in water under the action of a shock wave is numerically studied with unsteady nonequilibrium molecular dynamics simulations. The action of shock waves is modeled by the momentum change of water molecules, and thereby we demonstrate that the resulting collapse and rebound of the bilayer are followed by the penetration of water molecules into the hydrophobic region of the bilayer. The high-speed phenomenon that occurs during the collapse and rebound of the bilayer is analyzed in detail, particularly focusing on the change of bilayer thickness, the acyl chain bend angles, the lateral fluidity of lipid molecules, and the penetration rate of water molecules. The result shows that the high-speed phenomenon can be divided into two stages: in the first stage the thickness of bilayer and the order parameter are rapidly reduced, and then in the second stage they are recovered relatively slowly. It is in the second stage that water molecules are steadily introduced into the hydrophobic region. The penetration of water molecules is enhanced by the shock wave impulse and this qualitatively agrees with a recent experimental result.