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The role of stroma is fundamental in the development and behavior of epithelial tumors. In this regard, limited growth of squamous cell carcinomas (SCC) or cell-lines derived from them has been achieved in immunodeficient mice. Moreover, lack of faithful recapitulation of the original human neoplasia complexity is often observed in xenografted tumors. Here, we used tissue engineering techniques to recreate a humanized tumor stroma for SCCs grafted in host mice, by combining CAF (cancer associated fibroblasts)-like cells with a biocompatible scaffold. The stroma was either co-injected with epithelial cell lines derived from aggressive SCC or implanted 15 days before the injection of the tumoral cells, to allow its vascularization and maturation. None of the mice injected with the cell lines without stroma were able to develop a SCC. In contrast, tumors were able to grow when SCC cells were injected into previously established humanized stroma. Histologically, all of the regenerated tumors were moderately differentiated SCC with a well-developed stroma, resembling that found in the original human neoplasm. Persistence of human stromal cells was also confirmed by immunohistochemistry. In summary, we provide a proof of concept that humanized tumor stroma, generated by tissue engineering, can facilitate the development of epithelial tumors in immunodeficient mice.BACKGROUND The promotion of health literacy is seen as an urgent goal in public health and education and, hence, should be integrated in the school context as a component of the holistic health promoting school (HPS) approach. However, only limited empirical studies have addressed health literacy of school staff so far. Hence, this study aimed to examine the level of health literacy among school leaders and its association with the extent of HPS implementation. METHODS A cross-sectional study with n = 680 school principals and members of the school management board from Germany was carried out at the end of 2018. Individual health literacy, attitudes, and competencies towards HPS and occupational self-efficacy served as independent variables and the level of HPS implementation was the dependent variable. Data were analyzed using univariate and bivariate analysis as well as multiple binary logistic regression. RESULTS 29.3% of school leaders show a limited health literacy with significantly higher values found for male respondents. Regression analyses revealed that male gender (OR 1.91, 95% CI 1.22-2.99), HPS attitudes (OR 3.17, 95% CI 2.13-4.72), and HPS competencies (OR 3.66, 95% CI 2.43-5.50) were associated with a lower level of HPS implementation. Furthermore, regression analyses differentiated by gender showed that limited health literacy is associated with a low level of HPS implementation for male school leaders only (OR 2.81, 95% CI 1.22-6.45). CONCLUSIONS The promotion of health literacy especially for male leaders would not only result in positive effects on an individual level but also could contribute to a stronger implementation of activities on school health promotion. We suggest integrating health literacy, HPS attitudes, and competencies more strongly into the qualification and in further training of school leaders.Gut microbiota-derived tryptophan metabolites such as indole derivatives are an integral part of host metabolome that could mediate gut-brain communication and contribute to host homeostasis. We previously reported that infant-type Human-Residential Bifidobacteria (HRB) produced higher levels of indole-3-lactic acid (ILA), suggesting the former might play a specific role in microbiota-host crosstalk by producing ILA in human infants. Nonetheless, the biological meaning of bifidobacteria-derived ILA in infant health development remains obscure. Here, we sought to explore the potential role of ILA in neuronal differentiation. We examined the neurite outgrowth and acetylcholinesterase (AchE) activity of PC12 cells following exposure to ILA and NGF induction. We found that ILA substantially enhanced NGF-induced neurite outgrowth of PC12 cells in a dose-dependent manner, and had the most prominent effect at 100 nM. Significant increases in the expression of TrkA receptor, ERK1/2 and CREB were observed in ILA-treated PC12 cells, suggesting ILA potentiated NGF-induced neurite outgrowth through the Ras/ERK pathway. Additionally, ILA was found to act as the aryl hydrocarbon receptor (AhR) agonist and evoked NGF-induced neurite outgrowth in an AhR-mediated manner. These new findings provide clues into the potential involvement of ILA as the mediator in bifidobacterial host-microbiota crosstalk and neuronal developmental processes.The concept of merging pre-processed textile materials with tailored mechanical properties into soft matrices is so far rarely used in the field of soft robotics. PLX4032 in vitro The herein presented work takes the advantages of textile materials in elastomer matrices to another level by integrating a material with highly anisotropic bending properties. A pre-fabricated textile material consisting of oriented carbon fibers is used as a stiff component to precisely control the mechanical behavior of the robotic setup. The presented robotic concept uses a multi-layer stack for the robot's body and dielectric elastomer actuators (DEAs) on both outer sides of it. The bending motion of the whole structure results from the combination of its mechanically adjusted properties and the force generation of the DEAs. We present an antagonistic switching setup for the DEAs that leads to deflections to both sides of the robot, following a biomimetic principle. To investigate the bending behavior of the robot, we show a simulation model utilizing electromechanical coupling to estimate the quasi-static deflection of the structure. Based on this model, a statement about the bending behavior of the structure in general is made, leading to an expected maximum deflection of 10 mm at the end of the fin for a static activation. Furthermore, we present an electromechanical network model to evaluate the frequency dependent behavior of the robot's movement, predicting a resonance frequency of 6.385 Hz for the dynamic switching case. Both models in combination lead to a prediction about the acting behavior of the robot. These theoretical predictions are underpinned by dynamic performance measurements in air for different switching frequencies of the DEAs, leading to a maximum deflection of 9.3 mm located at the end of the actuators. The herein presented work places special focus on the mechanical resonance frequency of the robotic setup with regard to maximum deflections.
My Website: https://www.selleckchem.com/products/PLX-4032.html
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