Quercetin Prevents Radiation-Induced Oral Mucositis by Upregulating BMI-1.

Radiation-induced oral mucositis is a major adverse event of radiotherapy. Severe oral mucositis may cause unwanted interruption in radiotherapy and reduce long-term survival in cancer patients receiving radiotherapy, but until now, there have been no effective options for preventing radiation-induced oral mucositis. Quercetin is a flavonoid that is widely found in food species and has anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated a new role of quercetin in preventing radiation-induced oral mucositis. Quercetin exerted preventive effects against radiation-induced oral mucositis induced by single-dose (25 Gy) ionizing radiation or fractionated ionizing radiation (8 Gy × 3) in C57BL/6 mice and maintained the proliferation ability of basal epithelial cells. Quercetin pretreatment alleviated reactive oxygen species generation, NF-κB pathway activation, and downstream proinflammatory cytokine production and reduced DNA double-strand breaks and cellular senescence induced by ionizing radiation. Quercetin also upregulated BMI-1 expression in oral epithelial cells and promoted ulcer repair. In addition, quercetin exerted similar radioprotective effects in irradiated primary cultured normal human keratinocytes, reduced reactive oxygen species generation and proinflammatory cytokine release, and promoted DNA double-strand break repair and wound healing by upregulating the expression of BMI-1, which is a polycomb group protein. Thus, quercetin can block multiple pathological processes of radiation-induced oral mucositis by targeting BMI-1 and may be a potential treatment option for preventing radiation-induced oral mucositis.

Modeling of the through-the-thickness electric potentials of a piezoelectric bimorph using the spectral element method.

An efficient spectral element (SE) with electric potential degrees of freedom (DOF) is proposed to investigate the static electromechanical responses of a piezoelectric bimorph for its actuator and sensor functions. A sublayer model based on the piecewise linear approximation for the electric potential is used to describe the nonlinear distribution of electric potential through the thickness of the piezoelectric layers. An equivalent single layer (ESL) model based on first-order shear deformation theory (FSDT) is used to describe the displacement field. The Legendre orthogonal polynomials of order 5 are used in the element interpolation functions. The validity and the capability of the present SE model for investigation of global and local responses of the piezoelectric bimorph are confirmed by comparing the present solutions with those obtained from coupled 3-D finite element (FE) analysis. It is shown that, without introducing any higher-order electric potential assumptions, the current method can accurately describe the distribution of the electric potential across the thickness even for a rather thick bimorph. It is revealed that the effect of electric potential is significant when the bimorph is used as sensor while the effect is insignificant when the bimorph is used as actuator, and therefore, the present study may provide a better understanding of the nonlinear induced electric potential for bimorph sensor and actuator.