Localization of dopamine D1 and D2 receptor mRNAs in the rat systemic and pulmonary vasculatures.

The present study was designed to evaluate the expression of dopamine D1 and D2 receptor mRNAs in systemic and pulmonary vasculatures. Using specific antisense riboprobes for dopamine D1 and D2 receptor cDNAs, in situ hybridization histochemistry was performed in the aorta, common carotid artery, vertebral artery, pulmonary artery, and superior vena cava of the adult male Sprague Dawley rat. In the case of the aorta, common carotid artery, and vertebral artery, dopamine D1 receptor mRNAs localized mainly in the smooth muscle cells of the tunica media. However, the signals of dopamine D2 receptor mRNAs were found in the endothelium and subendothelial layer of tunica intima, and interstitial cells of tunica adventitia. In the case of the pulmonary artery, signals of dopamine D1 receptor mRNAs were detected within the tunica intima, media, and adventitia. Expression of D2 receptor mRNAs was detected in the walls of small blood vessels within the tunica adventitia of the pulmonary artery. There were no detectable signals of dopamine D1 and D2 receptor mRNAs in the vein. The uneven distribution of dopamine D1 and D2 receptor mRNAs in the rat systemic vasculatures and pulmonary artery suggests that dopamine differentially regulates the vasodilation of the systemic and pulmonary arteries through the differential stimulation of dopamine D1 and D2 receptor.     

High‐Capacity Concentration Gradient Li[Ni0.865Co0.120Al0.015]O2 Cathode for Lithium‐Ion Batteries

A Ni‐rich concentration‐gradient Li[Ni_0.865Co_0.120Al_0.015]O₂ (NCA) cathode is prepared with a Ni‐rich core to maximize the discharge capacity and a Co‐rich particle surface to provide structural and chemical stability. Compared to the conventional NCA cathode with a uniform composition, the gradient NCA cathode exhibits improved capacity retention and better thermal stability. Even more remarkably, the gradient NCA cathode maintains 90% of its initial capacity after 100 cycles when cycled at 60 °C, whereas the conventional cathode exhibits poor capacity retention and suffers severe structural deterioration. The superior cycling stability of the gradient NCA cathode largely stemmed from the gradient structure combines with the Co‐rich surface, which provides chemical stability against electrolyte attack and reduces the inherent internal strain observed in all Ni‐rich layered cathodes in their charged state, thus providing structural stability against the repeated anisotropic volume changes during cycling. The high discharge capacity of the proposed gradient NCA cathode extends the driving range of electric vehicles and reduces battery costs. Furthermore, its excellent capacity retention guarantees a long battery life. Therefore, gradient NCA cathodes represent one of the best classes of cathode materials for electric vehicle applications that should satisfy the demands of future electric vehicles.     

Quality of Life and Its Association with Physical Activity among Different Types of Cancer Survivors

PurposeThe main goal of this study was to compare the quality of life (QOL) and its association with physical activity (PA) among patients diagnosed with different types of cancer. Based on the results, we tentatively present suggestions for the cancer health care model.MethodA cross-sectional study was conducted with 2915 cancer survivors recruited from multi-community cancer rehabilitation centers, all of which were affiliated with the Shanghai Cancer Rehabilitation Club. We collected data including socio-demographic characteristics and information about PA. All the subjects included were asked to complete the European Organization for Research and Treatment Quality of Life Questionnaires (EORTC QLQ-C30) and Functional Assessment of Cancer Therapy—General Questionnaire (FACT-G). Multiple linear regression models were employed to control the potential confounding factors.ResultsLung cancer survivors reported the worst dyspnea. Colorectal cancer survivors claimed the highest level of constipation and diarrhea. Liver cancer survivors indicated greatest loss of appetite and financial difficulties. Generally, survivors with PA tended to reported better QOL, although these associations among liver cancer survivors were not statistically significant. Moreover, survivors of all cancer types who performed PA did not report significant lower level of constipation or diarrhea. The relationship between PA frequency and QOL among cancer survivors remained unexplored.ConclusionsBoth QOL and its association with PA vary among survivors of different cancer types. The detailed results can assist clinicians and public health practitioners with improving health care management.     

MACC1 Down-Regulation Inhibits Proliferation and Tumourigenicity of Nasopharyngeal Carcinoma Cells through Akt/β-Catenin Signaling Pathway

The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with β-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and β-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and β-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated β-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), β-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/β-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC.     

Green tea (-)-epigallocatechin-3-gallate inhibits HGF-induced progression in oral cavity cancer through suppression of HGF/c-Met

Hepatocyte growth factor (HGF) and c-Met have recently attracted a great deal of attention as prognostic indicators of patient outcome, and they are important in the control of tumor growth and invasion. Epigallocatechin-3-gallate (EGCG) has been shown to modulate multiple signal pathways in a manner that controls the unwanted proliferation and invasion of cells, thereby imparting cancer chemopreventive and therapeutic effects. In this study, we investigated the effects of EGCG in inhibiting HGF-induced tumor growth and invasion of oral cancer in vitro and in vivo. We examined the effects of EGCG on HGF-induced cell proliferation, migration, invasion, induction of apoptosis and modulation of HGF/c-Met signaling pathway in the KB oral cancer cell line. We investigated the antitumor effect and inhibition of c-Met expression by EGCG in a syngeneic mouse model (C3H/HeJ mice, SCC VII/SF cell line). HGF promoted cell proliferation, migration, invasion and induction of MMP (matrix metalloproteinase)-2 and MMP-9 in KB cells. EGCG significantly inhibited HGF-induced phosphorylation of Met and cell growth, invasion and expression of MMP-2 and MMP-9. EGCG blocked HGF-induced phosphorylation of c-Met and that of the downstream kinases AKT and ERK, and inhibition of p-AKT and p-ERK by EGCG was associated with marked increases in the phosphorylation of p38, JNK, cleaved caspase-3 and poly-ADP-ribose polymerase. In C3H/HeJ syngeneic mice, as an in vivo model, tumor growth was suppressed and apoptosis was increased by EGCG. Our results suggest that EGCG may be a potential therapeutic agent to inhibit HGF-induced tumor growth and invasion in oral cancer.     

ATM mediates interdependent activation of p53 and ERK through formation of a ternary complex with p-p53 and p-ERK in response to DNA damage

DNA damage in eukaryotic cells induces signaling pathways mediated by the ATM, p53 and ERK proteins, but the interactions between these pathways are not completely known. To address this issue, we performed a time course analysis in human embryonic fibroblast cells treated with DNA-damaging agents. DNA damage induced the phosphorylation of p53 at Ser 15 (p-p53) and the phosphorylation of ERK (p-ERK). Inhibition of p53 by a dominant negative mutant or in p53(-/-) fibroblast cells abolished ERK phosphorylation. ERK inhibitor prevented p53 phosphorylation, indicating that phosphorylations of p53 and p-ERK are interdependent each other. A time course analysis showed that ATM interacted with p-p53 and p-ERK in early time (0.5 h) and interaction between ATM-bound p-p53 and p-ERK or ATM-bound p-ERK and p-p53 occurred in late time (3 h) of DNA damage. These results indicate that ATM mediates interdependent activation of p53 and ERK through formation of a ternary complex between p-p53 and p-ERK in response to DNA damage to cause growth arrest.