Wentao Hu

Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition

Cellular responses to DNA damage induced by intrinsic and extrinsic genotoxic stresses are highly regulated by complex signaling pathways, such as activation of the phosphoinositide-3-kinase-like protein kinase family and their downstream genes. Disruption of these signaling pathways leads to genome instability and cell death, and thus may provide potential novel strategies for cancer therapy. Here, we find that the expression of a human microRNA (miRNA), hsa-miR-185, is downregulated in response to ionizing radiation. Elevation of miR-185 sensitizes renal cell carcinoma cells to X-rays both in vitro and in vivo. Bioinformatic analysis shows that the ATM- and Rad3-related (ATR) kinase, a master conductor of cellular responses to DNA damage and DNA replication stresses, is a target of miR-185. This prediction was validated by luciferase reporter and mutation assays. We also demonstrated that miR-185 negatively regulates ATR expression at post-transcriptional level. miR-185 enhances radiation-induced apoptosis and inhibition of proliferation by repressing ATR pathway. In conclusion, our findings indicate a previously unreported regulatory mechanism for ATR expression mediated by miR-185 and shed light on the potential application of miRNAs both as direct cancer therapeutics and as tools to sensitize tumor cells to radiotherapy.

Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect

Bystander effects can be induced through cellular communication between irradiated cells and non-irradiated cells. The signals that mediate this cellular communication, such as cytokines, reactive oxygen species, nitric oxide and even microRNAs, can be transferred between cells via gap junctions or extracellular medium. We have previously reported that miR-21, a well described DDR (DNA damage response) microRNA, is involved in radiation-induced bystander effects through a medium-mediated way. However, the mechanisms of the microRNA transfer have not been elucidated in details. In the present study, it was found that exosomes isolated from irradiated conditioned medium could induce bystander effects. Furthermore, we demonstrated plenty of evidences that miR-21, which is up-regulated as a result of mimic transfection or irradiation, can be transferred from donor or irradiated cells into extracellular medium and subsequently get access to the recipient or bystander cells through exosomes to induce bystander effects. Inhibiting the miR-21 expression in advance can offset the bystander effects to some extent. From all of these results, it can be concluded that the exosome-mediated microRNA transfer plays an important role in the radiation-induced bystander effects. These findings provide new insights into the functions of microRNAs and the cellular communication between the directly irradiated cells and the non-irradiated cells.

Thermocapillary migration of nondeformable drops

In this paper, we present a numerical study on the thermocapillary migration of drops. The Navier–Stokes equations coupled with the energy conservation equation are solved by the finite-difference front-tracking scheme. The axisymmetric model is adopted in our simulations, and the drops are assumed to be perfectly spherical and nondeformable. The benchmark simulation starts from the classical initial condition with a uniform temperature gradient. The detailed discussions and physical explanations of migration phenomena are presented for the different values of (1) the Marangoni numbers and Reynolds numbers of continuous phases and drops and (2) the ratios of drop densities and specific heats to those of continuous phases. It is found that fairly large Marangoni numbers may lead to fluctuations in drop velocities at the beginning part of simulations. Finally, we also discuss the influence of initial conditions on the thermocapillary migrations.

Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase.

Diploid cells undergoing senescence and mitotic slippage have been reported in the literature. However, the mechanisms triggering senescence in long-term G2-arrested cells are currently unclear. Previously, we reported that the cell cycle of the human uveal melanoma cell line, 92-1, is suspended for up to 6 d upon exposure to 10 Gy ionizing radiation (IR), followed by senescence. In the current study, we initially distinguished senescence in long-term blocked 92-1 cells from mitotic slippage by confirming the blockage of cells in the G2 phase. We subsequently showed that the genes essential for G2-M transition are prematurely downregulated at both the transcriptional and translational levels. Furthermore, levels of the G1-specific markers, Cyclin D1 and Caveolin-1, were distinctly increased, while S/G2-specific markers, Cyclin B1 and Aurora A, were significantly downregulated. These findings collectively imply that long-term G2-arrested cells undergo senescence via G2 slippage. To our knowledge, this is the first study to report that the cellular process of G2 slippage is the mechanism responsible for senescence of cells under long-term G2 arrest.

MiR-663 inhibits radiation-induced bystander effects by targeting TGFB1 in a feedback mode.

The mechanisms of radiation-induced bystander effects (RIBE) have been investigated intensively over the past two decades. Although quite a few reports demonstrated that cytokines such as TGF-β1 are induced within the directly irradiated cells and play critical roles in mediating the bystander effects, little is known about the signaling pathways that occur in bystander cells. The crucial question as to why RIBE signals cannot be infinitely transmitted, therefore, remains unclear. In the present study, we showed that miR-663, a radiosensitive microRNA, participates in the regulation of biological effects in both directly irradiated and bystander cells via its targeting of TGF-β1. MiR-663 was downregulated, while TGFB1 was upregulated in directly irradiated cells. The regulation profile of miR-663 and TGFB1, on the other hand, was reversed in bystander cells, in which an elevated miR-663 expression was exhibited and led to downregulation of TGF-β1. Further studies revealed that miR-663 interacts with TGFB1 directly and that through its binding to the core regulation sequence, miR-663 suppresses the expression of TGFB1. Based on the results, we propose that miR-663 inhibits the propagation of RIBE in a feedback mode, in which the induction of TGF-β1 by reduced miR-663 in directly irradiated cells leads to increased level of miR-663 in bystander cells. The upregulation of miR-663 in turn suppresses the expression of TGF-β1 and limits further transmission of the bystander signals.

Pressure drop of bubbly two-phase flow in a square channel at reduced gravity

A new set of experimental pressure drop data, collected aboard the Russian IL-76MDK, is reported for bubbly airwater two-phase flow in a square channel with a cross-sectional area of 12x 12mm(2). The present data are compared to several frequently used empirical models, e.g. homogeneous model, Lockhart-Martinelli-Chisholm correlation and Friedels model. It is shown that the predictions of the models mentioned above are generally not satisfied. A new homogeneous model is developed based on the analysis of the characteristics of bubbly two-phase flow at reduced gravity. It is tested with the present data and other data collected by other researchers in circular pipes. Some questions related to the present model are also discussed

Two bifurcation transitions of the floating half zone convection in a fat liquid bridge of larger Pr

The transient process of the thermocapillary convection was obtained for the large Pu floating half zone by using the method of three-dimensional and unsteady numerical simulation. The convection transits directly from steady and axisymmetric state to oscillatory flow for slender liquid bridge, and transits first from steady and axisymmetric convection to the steady and non-axisymmetric convection, then, secondly to the oscillatory convection for the fatter liquid bridge. This result implies that the volume of liquid bridge is not only a sensitive critical parameter for the onset of oscillation, but also relates to the new mechanism for the onset of instability in the floating half zone convection even in case of large Prandtl number fluid.

Thermocapillary flow in an annular liquid layer painted on a moving fiber

In the present paper, a theoretical model is studied on the flow in the liquid annular film, which is ejected from a vessel with relatively higher temperature and painted on the moving solid fiber. A temperature gradient, driving a thermocapillary flow, is formed on the free surface because of the heat transfer from the liquid with relatively higher temperature to the environmental gas with relatively lower temperature. The thermocapillary flow may change the radii profile of the liquid film. This process analyzed is based on the approximations of lubrication theory and perturbation theory, and the equation of the liquid layer radii and the process of thermal hydrodynamics in the liquid layer are solved for a temperature distribution on the solid fiber.

Experimental investigation of thermocapillary convection in half floating zone

Abstract The vibrations of free surface deformations are directly measured by an optical video system for an oscillatory thermocapillary convection in liquid bridge of half floating zone. The vibration frequency of free surface is agreed with one of temperature measured by inserted thermal couple. The basic features of free surface vibrations are discussed.

The influence of buoyancy on the onset of oscillatory convection in a half floating zone

Abstract The critical Marangoni number is determined by the optical method, a new parameter describing the free surface shape is sensitive to the onset of oscillation. The experiments are performed for half floating-zone with either a upper rod heated (URH) or a lower rod heated (LRH). The results agree with the instability analyses of buoyancy influence (see, for examples, /1–3/).