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71.
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Yan Zhen Yanfen Ye Xiaoli Yu Chunping Mai Ying Zhou Yan Chen Huiling Yang Xiaoming Lyu Ye Song Qiangyun Wu Qiaofen Fu Mengyang Zhao Shengni Hua Hao Wang Zhen Liu Yajie Zhang Weiyi Fang 《PloS one》2013,8(6)
Background
The role of CTGF varies in different types of cancer. The purpose of this study is to investigate the involvement of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC).Experimental design
CTGF expression levels were examined in NPC tissues and cells, nasopharynx (NP) tissues, and NP69 cells. The effects and molecular mechanisms of CTGF expression on cell proliferation, migration, invasion, and cell cycle were also explored.Results
NPC cells exhibited decreased mRNA expression of CTGF compared to immortalized human nasopharyngeal epithelial cell line NP69. Similarly, CTGF was observed to be downregulated in NPC compared to normal tissues at mRNA and protein levels. Furthermore, reduced CTGF was negatively associated with the progression of NPC. Knocking down CTGF expression enhanced the colony formation, cell migration, invasion, and G1/S cell cycle transition. Mechanistic analysis revealed that CTGF suppression activated FAK/PI3K/AKT and its downstream signals regulating the cell cycle, epithelial-mesenchymal transition (EMT) and MMPs. Finally, DNA methylation microarray revealed a lack of hypermethylation at the CTGF promoter, suggesting other mechanisms are associated with suppression of CTGF in NPC.Conclusion
Our study demonstrates that reduced expression of CTGF promoted cell proliferation, migration, invasion and cell cycle progression through FAK/PI3K/AKT, EMT and MMP pathways in NPC. 相似文献73.
Anna Lehner Viktor Magdolen Tibor Schuster Matthias Kotzsch Marion Kiechle Alfons Meindl Fred C. G. J. Sweep Paul N. Span Eva Gross 《PloS one》2013,8(4)
HTRA1 is a highly conserved serine protease which has been implicated in suppression of epithelial-to-mesenchymal-transition (EMT) and cell motility in breast cancer. Its prognostic relevance for breast cancer is unclear so far. Therefore, we evaluated the impact of HTRA1 mRNA expression on patient outcome using a cohort of 131 breast cancer patients as well as a validation cohort including 2809 publically available data sets. Additionally, we aimed at investigating for the presence of promoter hypermethylation as a mechanism for silencing the HTRA1 gene in breast tumors. HTRA1 downregulation was detected in more than 50% of the breast cancer specimens and was associated with higher tumor stage (p = 0.025). By applying Cox proportional hazard models, we observed favorable overall (OS) and disease-free survival (DFS) related to high HTRA1 expression (HR = 0.45 [CI 0.23–0.90], p = 0.023; HR = 0.55 [CI 0.32–0.94], p = 0.028, respectively), with even more pronounced impact in node-positive patients (HR = 0.21 [CI 0.07–0.63], p = 0.006; HR = 0.29 [CI 0.13–0.65], p = 0.002, respectively). Moreover, HTRA1 remained a statistically significant factor predicting DFS among established clinical parameters in the multivariable analysis. Its impact on patient outcome was independently confirmed in the validation set (for relapse-free survival (n = 2809): HR = 0.79 [CI 0.7–0.9], log-rank p = 0.0003; for OS (n = 971): HR = 0.63 [CI 0.48–0.83], log-rank p = 0.0009). In promoter analyses, we in fact detected methylation of HTRA1 in a small subset of breast cancer specimens (two out of a series of 12), and in MCF-7 breast cancer cells which exhibited 22-fold lower HTRA1 mRNA expression levels compared to unmethylated MDA-MB-231 cells. In conclusion, we show that downregulation of HTRA1 is associated with shorter patient survival, particularly in node-positive breast cancer. Since HTRA1 loss was demonstrated to induce EMT and cancer cell invasion, these patients might benefit from demethylating agents or histone deacetylase inhibitors previously reported to lead to HTRA1 upregulation, or from novel small-molecule inhibitors targeting EMT-related processes. 相似文献
74.
Karina D. Thielsen Jakob M. Moser Thomas Schmitt-John Morten S. Jensen Kimmo Jensen Mai Marie Holm 《PloS one》2013,8(12)
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. It is a fatal degenerative disease, best recognized for its debilitating neuromuscular effects. ALS however also induces cognitive impairments in as many as 50% of affected individuals. Moreover, many ALS patients demonstrate cortical hyperexcitability, which has been shown to precede the onset of clinical symptoms. The wobbler mouse is a model of ALS, and like ALS patients the wobbler mouse displays cortical hyperexcitability. Here we investigated if the neocortical aberrations of the wobbler mouse also occur in the hippocampus. Consequently, we performed extracellular field excitatory postsynaptic potential recordings in the CA1 region of the hippocampus on acute brain slices from symptomatic (P45-P60) and presymptomatic (P17-P21) wobbler mice. Significant increased excitation of hippocampal synapses was revealed by leftward shifted input/output-curves in both symptomatic and presymptomatic wobbler mice, and substantiated by population spike occurrence analyses, demonstrating that the increased synaptic excitation precedes the onset of visible phenotypic symptoms in the mouse. Synaptic facilitation tested by paired-pulse facilitation and trains in wobbler and control mice showed no differences, suggesting the absence of presynaptic defects. Immunohistochemical staining revealed that symptomatic wobbler mice have a lower number of parvalbumin positive interneurons when compared to controls and presymptomatic mice. This study reveals that the wobbler mouse model of ALS exhibits hippocampal hyperexcitability. We suggest that the hyperexcitability could be caused by increased excitatory synaptic transmission and a concomitant reduced inhibition due to a decreased number of parvalbumin positive interneurons. Thus we substantiate that wobbler brain impairments are not confined to the motor cortex, but extend to the hippocampus. Importantly, we have revealed more details of the early pathophysiology in asymptomatic animals, and studies like the present may facilitate the development of novel treatment strategies for earlier intervention in ALS patients in the future. 相似文献
75.
Basidiomycete fungi perform fertilizations by incorporation of nuclei into a monokaryotic mycelium to establish a dikaryon. The dikaryon cannot incorporate another type of nucleus, but can still act as a nucleus donor in a dikaryon–monokaryon (di–mon) mating, known as the Buller phenomenon. Previously, it has been observed that: (1) in a particular di–mon mating, one of the nuclear types of the dikaryon generally performs better as a donor than the other, and (2) when nuclei from a dikaryon are separated to form monokaryons again (dedikaryotisation), recovery of monokaryons of the two nuclear types is usually unequal. In this study, we investigated if these two observations of asymmetry are functionally related. We tested this hypothesis by performing both di–mon matings and dedikaryotisation of dikaryons derived from five different monokaryons. When a single mechanism controls both processes, the nucleus better at fertilizing a monokaryon in a Buller pairing should also be recovered upon dedikaryotisation with a higher frequency. The results showed a hierarchical structure for recovery among nuclei in dedikaryotisation, but this hierarchy did not correspond to the fertilization success during di–mon mating. These findings thus show that the mechanism causing asymmetric regeneration of nuclei, is most likely not the same as the mechanism responsible for increased chance of fertilization in di–mon matings. We discuss the complexity of the interactions that occur during di–mon matings with regards to the mating type loci. 相似文献
76.
Integrated Intercalation‐Based and Interfacial Sodium Storage in Graphene‐Wrapped Porous Li4Ti5O12 Nanofibers Composite Aerogel 下载免费PDF全文
Chaoji Chen Henghui Xu Tengfei Zhou Zaiping Guo Lineng Chen Mengyu Yan Liqiang Mai Pei Hu Shijie Cheng Yunhui Huang Jia Xie 《Liver Transplantation》2016,6(13)
Sodium storage in both solid–liquid and solid–solid interfaces is expected to extend the horizon of sodium‐ion batteries, leading to a new strategy for developing high‐performance energy‐storage materials. Here, a novel composite aerogel with porous Li4Ti5O12 (PLTO) nanofibers confined in a highly conductive 3D‐interconnected graphene framework (G‐PLTO) is designed and fabricated for Na storage. A high capacity of 195 mA h g?1 at 0.2 C and super‐long cycle life up to 12 000 cycles are attained. Electrochemical analysis shows that the intercalation‐based and interfacial Na storage behaviors take effect simultaneously in the G‐PLTO composite aerogel. An integrated Na storage mechanism is proposed. This study ascribes the excellent performance to the unique structure, which not only offers short pathways for Na+ diffusion and conductive networks for electron transport, but also guarantees plenty of PLTO–electrolyte and PLTO–graphene interfacial sites for Na+ adsorption. 相似文献
77.
Facilitated long chain fatty acid uptake by adipocytes remains upregulated relative to BMI for more than a year after major bariatric surgical weight loss 下载免费PDF全文
Fengxia Ge José L. Walewski Mehyar Hefazi Torghabeh Harrison Lobdell IV Chunguang Hu Shengli Zhou Gregory Dakin Alfons Pomp Marc Bessler Beth Schrope Aku Ude‐Welcome William B. Inabnet Tianshu Feng Elektra Carras‐Terzian Dieunine Anglade Faith E. Ebel Paul D. Berk 《Obesity (Silver Spring, Md.)》2016,24(1):113-122
78.
Wei Zhu Zanlin Mai Jing Qin Xiaolu Duan Yang Liu Zhijian Zhao Jian Yuan Shaw P. Wan Guohua Zeng 《PloS one》2016,11(2)
Background
Diabetic patients are more likely to develop kidney stones than the general population. The underlying mechanisms for this disparity remain to be elucidated. Little is known about the relationship between urine composition and diabetes mellitus in non-stone-forming individuals. We sought to examine the differences in the 24-hour (24-h) urine composition between diabetic and non-diabetic adults who were not stone formers.Methods
A convenience sample of 538 individuals without a history of nephrolithiasis, gout, hyperparathyroidism, or gastroenteric diseases participated in this study. The 24-h urine profiles of 115 diabetic adults were compared with those of 423 non-diabetic adults. Diabetes was defined by self-reported physician diagnosis or medication use. All participants were non-stone formers confirmed by urinary tract ultrasonography. Participants provided a fasting blood sample and a single 24-h urine collection for stone risk analysis. Student’s t-test was used to compare mean urinary values. Linear regression models were adjusted for age, gender, body mass index, hypertension, fasting serum glucose, serum total cholesterol, estimated creatinine clearance rate and urinary factors.Results
Univariable analysis showed that the diabetic participants had significantly higher 24-h urine volumes and lower urine calcium and magnesium excretions than non-diabetic participants (all P < 0.05). After multivariate adjustment, no significant differences in 24-h urine composition were observed between diabetic and non-diabetic participants except for a slightly increased 24-h urine volume in diabetic participants (all P > 0.05). The main limitation of this study is that the convenience samples and self-reported data may have been sources of bias.Conclusion
Our data showed that there were no differences in 24-h urine composition between diabetic and non-diabetic adults who are not stone formers. The reason for it might be the improved glycemic control in diabetic individuals in our study. Therefore, a tighter glycemic control might reduce stone formation in diabetic adults. 相似文献79.
The internet enables the rapid and easy creation, storage, and transfer of knowledge; however, services that transfer geographic knowledge and facilitate the public understanding of geographic knowledge are still underdeveloped to date. Existing online maps (or atlases) can support limited types of geographic knowledge. In this study, we propose a framework for map-based services to represent and transfer different types of geographic knowledge to the public. A map-based service provides tools to ensure the effective transfer of geographic knowledge. We discuss the types of geographic knowledge that should be represented and transferred to the public, and we propose guidelines and a method to represent various types of knowledge through a map-based service. To facilitate the effective transfer of geographic knowledge, tools such as auxiliary background knowledge and auxiliary map-reading tools are provided through interactions with maps. An experiment conducted to illustrate our idea and to evaluate the usefulness of the map-based service is described; the results demonstrate that the map-based service is useful for transferring different types of geographic knowledge. 相似文献
80.