Fluid shear stress promotes periodontal ligament cells proliferation via p38-AMOT-YAP.

Periodontal ligament (PDL) cells are a promising tool for periodontal regeneration therapy. Achieving a sufficient number of PDL cells is essential to PDL regeneration. In our study, appropriate flow shear stress (FSS, 1-6 dyn/cm2) promotes the proliferation of PDL cells. FSS remodels cytoskeleton and focal adhesion in a duration-dependent manner. FSS induces PDL cells to form the actin cap within 10 min, flattens the nuclei, and increases the nuclear pore size, which promotes nuclear translocation of Yes-associated protein (YAP). FSS activates p38, which plays a dual function in YAP regulation. p38 regulates the phosphorylation of Akt and cofilin, as well as induced F-actin polymerization to induce YAP activity. In addition, p38 inhibits pLATS and consecutively regulates angiomotin (AMOT) and YAP phosphorylation. AMOT competitively binds to F-actin and YAP to participate in FSS-mediated YAP nuclear translocation and cell proliferation. Taken collectively, our results provide mechanistic insights into the role of p38-AMOT-YAP in FSS-mediated PDL cells proliferation and indicate potential applications in dental regenerative medicine.

Experiment and hydro-mechanical coupling simulation study on the human periodontal ligament.

In this paper, a new method involving an experiment in vivo and hydro-mechanical coupling simulations was proposed to investigate the biomechanical property of human periodontal ligament (PDL). Teeth were loaded and their displacements were measured in vivo. The finite element model of the experiment was built and hydro-mechanical coupling simulations were conducted to test some PDL's constitutive models. In the simulations, the linear elastic model, the hyperfoam model, and the Ogden model were assumed for the solid phase of the PDL coupled with a model of the fluid phase of the PDL. The displacements of the teeth derived from the simulations were compared with the experimental data to validate these constitutive models. The study shows that a proposed constitutive model of the PDL can be reliably tested by this method. Furthermore, the influence of species, areas, and the fluid volume ratio on PDL's mechanical property should be considered in the modeling and simulation of the mechanical property of the PDL.

A fixed-jaw method to protect critical organs during intensity-modulated radiotherapy.

Intensity-modulated radiotherapy (IMRT) plays an important role in cancer radiotherapy. For some patients being treated with IMRT, the extremely low tolerances of critical organs (such as lens, ovaries, and testicles) cannot be met during treatment planning. The aim of this article is to introduce a new planning method to overcome that problem. In current planning practice, jaw positions are automatically set to cover all target volumes by the planning system (e.g., Pinnacle(3) system). Because of such settings, critical organs may be fully blocked by the multileaf collimator (MLC), but they still sit in the field that is shaped by collimator jaws. These critical organs receive doses from the transmission and leakage of MLC leaves. We manually fixed jaw positions to block them to further reduce such doses. This method has been used for different treatment sites in our clinic, and it was thoroughly evaluated in patients with radical hysterectomy plus ovarian transposition after surgery. For each patient, 2 treatment plans were designed with the same optimization parameters: the original plan with automatically chosen jaw positions (called O-plan) and the plan with fixed-jaw positions (named F-plan). In the F-plan, the jaws were manually fixed to block the ovaries. For target coverage, the mean conformity index (CI) of the F-plan (1.28 ± 0.02) was remarkably lower than that of the O-plan (1.53 ± 0.09) (p < 0.05). The F-plan and the O-plan performed similarly in target dose homogeneity. Meanwhile, for the critical organ sparing, the mean dose of both ovaries were much lower in the F-plan than that in the O-plan (p < 0.05). The V20, V30, and V40 of bladder were also lower in the F-plan (93.57 ± 1.98, 73.99 ± 5.76, and 42.33 ± 3.7, respectively) than those in the O-plan (97.98 ± 1.11, 85.07 ± 4.04, and 49.71 ± 3.63, respectively) (p < 0.05). The maximum dose to the spinal cord planning organ at risk (OAR) volume (PRV) in the O-plan (3940.24 ± 102.8) was higher than that in the F-plan (3628.18 ± 131.45) with significant differences (p < 0.01). For other OARs, there were no significant differences in doses between these 2 plans except that the high-dose regions of the rectum were higher for V40 in the O-plan than that in the F-plan (p < 0.01). But the monitor units (MUs) in the F-plan were 1.4 times as much as that in the O-plan. Thus the treatment time could be longer by using the F-plan. As it results in more MUs in spite of better plan quality, it is recommended to be used only in situations in which clinical requirements to critical organs cannot be met with the regular method.