Glioblastoma multiforme (GBM) is the most fatal of all brain cancers, and the standard care protocol for GBM patients is surgical tumor resection followed by radiotherapy and temozolomide (TMZ)-mediated chemotherapy. However, tumor recurrence frequently occurs, and recurrent GBM exhibits more malignancy and less sensitivity in response to chemotherapy. The malignancy and drug resistance primarily reflect the small population of glioma stem-like cells (GSC). Therefore, understanding the mechanism that controls GSC enrichment is important to benefit the prognosis of GBM patients. Nucleolin (NCL), which is responsible for ribosome biogenesis and RNA maturation, is overexpressed in gliomas. However, the role of NCL in GSC development and drug resistance is still unclear. In this study, we demonstrate that NCL attenuated GSC enrichment to enhance the sensitivity of GBM cells in response to TMZ. In GSC enrichment, NCL was significantly reduced at the protein level as a result of decreased protein stability. In particular, the inhibition of HDAC activity by suberoylanilide hydroxamic acid rescued NCL acetylation accompanied by the loss of mouse double minute 2 homolog (MDM2)-mediated ubiquitination. In addition, we found that NCL ubiquitination resulted from the activation of STAT3- and JNK-mediated signaling in GSC. Moreover, NCL inhibited the formation of stem-like spheres by attenuating the expression of Sox2, Oct4, and Bmi1. Furthermore, NCL sensitized the response of GBM cells to TMZ. Based on these findings, NCL expression is a potential indicator to predict chemotherapeutic efficiency in GBM patients.
This paper presents experimental results and analysis of a new high-power Cu/Cu2+ thermogalvanic cell and its comparison with previous results. Past researches were mostly focused on finding the best redox couples and electrode materials [1, 2], however, they generally lacked a comparison of power conversion efficiency (η) dependence on cell geometry. This inspired our interest in exploring the relation of η, internal resistance, maximum power, and cell geometry. Based on previous results [3], a low internal resistance, variable orientation thermogalvanic cell was designed to achieve the highest power output. Experimental results of the Seebeck coefficient (α = ∂E/∂T), power density, and η of Cu/Cu2+ electrolytes in various molar concentrations showed that 0.7M CuSO4 electrolyte has maximum α and power output of 0.7196 mV/°C and 3.17 μW/cm2, respectively. Power output of the new cell has significant improvement which is 219 times greater than previous research. This paper also presents economical aspects of Cu/Cu2+ thermogalvanic cells relative to ferri/ferrocyanide cells.
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