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Drug resistance is a frequent cause of failure in cancer chemotherapy treatments. In this study, a pair of uterine sarcoma cancer lines, MES-SA, and doxorubicin-resistant partners, MES-SA/DxR-2μM cells and MES-SA/DxR-8μM cells, as a model system to investigate resistance-dependent proteome alterations and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to perform this research and the results revealed that doxorubicin-resistance altered the expression of 208 proteins in which 129 identified proteins showed dose-dependent manners in response to the levels of resistance. Further studies have used RNA interference, H2A.X phosphorylation assay, cell viability analysis, and analysis of apoptosis against reticulocalbin-1 (RCN1) proteins, to prove its potency on the formation of doxorubicin resistance as well as the attenuation of doxorubicin-associated DNA double strand breakage. To sum up, our results provide useful diagnostic markers and therapeutic candidates such as RCN1 for the treatment of doxorubicin-resistant uterine cancer.

The prevalence of diabetes around the world is increasing, and the complications of diabetes are becoming worse so that the global burden of diabetes-related complications is rising. The purpose of this study was to simulate the physiological condition of diabetes in the human body by culturing human microvascular endothelial cell 1 (HMEC-1) cells in Dulbecco’s modified Eagle’s medium (DMEM) containing 5.5mM glucose, 25mM glucose, and 50mM glucose. The cell viability of HMEC-1 cells at the indicated glucose concentrations was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The specific epithelial cell junction N-cadherin was measured by immunofluorescence. Furthermore, monocytic initiation of inflammatory reactions was studied by using Western blotting and enzyme-linked immunosorbent assay. Based on our results, hyperglycemia treatment influenced the distribution of N-cadherin-containing structures in HMEC-1 cells, whereas the change of the inflammatory profiles in HMEC-1 cells was affected after their coculture with the supernatant of diabetic THP-1 monocytes. In this study, we conclude that the removal of endothelial N-cadherin caused by hyperglycemia (at the 25mM glucose and 50mM glucose concentrations) may lead to endothelial dysfunction and subsequently endothelial cell death in the late stage of diabetes. Furthermore, the loss of intercellular adhesion molecule 1 and the upregulation of interleukin (IL)-1, IL-6, and tumor necrosis factor alpha mediated by diabetic monocytes showed altered interaction between the vascular endothelium and blood cells in the diabetic microenvironment.

This paper mainly confers the development of tracking controller design for wheeled mobile robots with plant uncertainties and external disturbances. This paper proposes a unified and systematic procedure to design adaptive fuzzy tracking controllers for such system. At first an adaptive fuzzy tracking controller (AFTC) is designed for the nonholonomic constrained wheeled mobile robots without considering the model of DC motors. Furthermore, an AFTC and an adaptive type-2 fuzzy tracking controller (AT2FTC) are presented for wheeled mobile robots with the model of DC motors, where the backstepping techniques are adopted. The stability of closed-loop system and the convergence of the proposed tracking controllers are proved by using the Lyapunov and uniformly ultimately bounded stability theories. Finally, several simulation results of adaptive fuzzy tracking and adaptive type-2 fuzzy tracking controlled wheeled mobile robots are executed, where the AT2FTC provides the best tracking performance.