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81.
Wen-Qing Li Nan Hu Zhaoming Wang Kai Yu Hua Su Lemin Wang Chaoyu Wang Stephen J. Chanock Laurie Burdett Ti Ding You-Lin Qiao Jin-Hu Fan Yuan Wang Yi Xu Carol Giffen Xiaoqin Xiong Gwen Murphy Margaret A. Tucker Sanford M. Dawsey Neal D. Freedman Christian C. Abnet Alisa M. Goldstein Philip R. Taylor 《PloS one》2013,8(7)
The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16×10−3). Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not observe a significant pathway-level association (P = 0.72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms. 相似文献
82.
Liqun Chen Guangbo Qu Xue Sun Shuping Zhang Lei Wang Nan Sang Yuguo Du Jun Liu Sijin Liu 《PloS one》2013,8(3)
Mixture toxicity is an important issue for the risk assessment of environmental pollutants, for which an extensive amount of data are necessary in evaluating their potential adverse health effects. However, it is very hard to decipher the interaction between compounds due to limited techniques. Contamination of heavy metals and organophosphoric insecticides under the environmental and biological settings poses substantial health risk to humans. Although previous studies demonstrated the co-occurrence of cadmium (Cd) and chlorpyrifos (CPF) in environmental medium and food chains, their interaction and potentially synergistic toxicity remain elusive thus far. Here we integrated the approaches of thin-layer chromatography and 1H NMR to study the interaction between Cd2+ and CPF in inducing hepatoxicity. A novel interaction was identified between Cd2+ and CPF, which might be the bonding between Cd2+ and nitrogen atom in the pyridine ring of CPF, or the chelation formation between one Cd2+ and two CPF molecules. The Cd-CPF complex was conferred with distinct biological fate and toxicological performances from its parental components. We further demonstrated that the joint hepatoxicity of Cd ion and CPF was chiefly due to the Cd-CPF complex-facilitated intracellular transport associated with oxidative stress. 相似文献
83.
Jiaofen Nan Jixin Liu Guoying Li Shiwei Xiong Xuemei Yan Qing Yin Fang Zeng Karen M. von Deneen Fanrong Liang Qiyong Gong Wei Qin Jie Tian 《PloS one》2013,8(6)
Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients’ dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course. 相似文献
84.
Hong-xia Chen Zeng-liang Jin Li-ming Zhang Rui Xue Xiao-dan Xu Nan Zhao Zhi-kun Qiu Xian-wang Wang You-zhi Zhang Ri-fang Yang Yun-feng Li 《PloS one》2013,8(12)
It has been suggested that drugs combining activities of selective serotonin reuptake inhibitor and 5-HT1A receptor agonist may form a novel strategy for higher therapeutic efficacy of antidepressant. The present study aimed to examine the pharmacology of YL-0919, a novel synthetic compound with combined high affinity and selectivity for serotonin transporter and 5-HT1A receptors. We performed in vitro binding and function assays and in vivo behavioral tests to assess the pharmacological properties and antidepressant-like efficacy of YL-0919. YL-0919 displayed high affinity in vitro to both 5-HT1A receptor and 5-HT transporter prepared from rat cortical tissue. It exerted an inhibitory effect on forskolin-stimulated cAMP formation and potently inhibited 5-HT uptake in both rat cortical synaptosomes and recombinant cells. After acute p.o. administration, very low doses of YL-0919 reduced the immobility time in tail suspension test and forced swimming test in mice and rats, with no significant effect on locomotor activity in open field test. Furthermore, WAY-100635 (a selective 5-HT1A receptor antagonist, 0.3 mg/kg) significantly blocked the effect of YL-0919 in tail suspension test and forced swimming test. In addition, chronic YL-0919 treatment significantly reversed the depressive-like behaviors in chronically stressed rats. These findings suggest that YL-0919, a novel structure compound, exerts dual effect on the serotonergic system, as both 5-HT1A receptor agonist and 5-HT uptake blocker, showing remarkable antidepressant effects in animal models. Therefore, YL-0919 may be used as a new option for the treatment of major depressive disorder. 相似文献
85.
Mechanisms governing the metastasis of endometrial carcinoma (EC) are poorly defined. Recent data support a role for the cell surface receptor tyrosine kinase TrkB in the progression of several human tumors. Here we present evidence for a direct role of TrkB in human EC. Immunohistochemical analysis revealed that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF), are more highly expressed in EC than in normal endometrium. High TrkB levels correlated with lymph node metastasis (p<0.05) and lymphovascular space involvement (p<0.05) in EC. Depletion of TrkB by stable shRNA-mediated knockdown decreased the migratory and invasive capacity of cancer cell lines in vitro and resulted in anoikis in suspended cells. Conversely, exogenous expression of TrkB increased cell migration and invasion and promoted anoikis resistance in suspension culture. Furthermore, over-expression of TrkB or stimulation by BDNF resulted in altered the expression of molecular mediators of the epithelial-to-mesenchymal transition (EMT). RNA interference (RNAi)-mediated depletion of the downstream regulator, Twist, blocked TrkB-induced EMT-like transformation. The use of in vivo models revealed decreased peritoneal dissemination in TrkB-depleted EC cells. Additionally, TrkB-depleted EC cells underwent mesenchymal-to-epithelial transition and anoikis in vivo. Our data support a novel function for TrkB in promoting EMT and resistance to anoikis. Thus, TrkB may constitute a potential therapeutic target in human EC. 相似文献
86.
Li Gao Hao Guo Nan Ye Yudi Bai Xin Liu Ping Yu Yang Xue Shufang Ma Kewen Wei Yan Jin Lingying Wen Kun Xuan 《PloS one》2013,8(6)
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited disorder of the peripheral nervous system resulting from mutations in neurotrophic tyrosine kinase receptor 1 gene (NTRK1), which encodes the high-affinity nerve growth factor receptor TRKA. Here, we investigated the oral and craniofacial manifestations of a Chinese patient affected by autosomal-recessive CIPA and identified compound heterozygosity in the NTRK1 gene. The affected boy has multisystemic disorder with lack of reaction to pain stimuli accompanied by self-mutilation behavior, the inability to sweat leading to defective thermoregulation, and mental retardation. Oral and craniofacial manifestations included a large number of missing teeth, nasal malformation, submucous cleft palate, severe soft tissue injuries, dental caries and malocclusion. Histopathological evaluation of the skin sample revealed severe peripheral nerve fiber loss as well as mild loss and absent innervation of sweat glands. Ultrastructural and morphometric studies of a shed tooth revealed dental abnormalities, including hypomineralization, dentin hypoplasia, cementogenesis defects and a dysplastic periodontal ligament. Genetic analysis revealed a compound heterozygosity- c.1561T>C and c.2057G>A in the NTRK1 gene. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with CIPA and provides additional insight for clinical and molecular diagnosis. 相似文献
87.
88.
Xun Liu Yanni Wang Cheng Wang Chenggang Shi Cailian Cheng Jinxia Chen Huijuan Ma Linsheng Lv Lin Li Tanqi Lou 《PloS one》2013,8(11)
Background
We sought to develop a new equation to estimate glomerular filtration rate (GFR) in Chinese elderly population.Methods
A total of 668 Chinese elderly participants, including the development cohort (n = 433), the validation cohort (n = 235) were enrolled. The new equation using the generalized additive model, and age, gender, serum creatinine as predictor variables was developed and the performances was compared with the CKD-EPI equation.Results
In the validation data set, both bias and precision were improved with the new equation, as compared with the CKD-EPI equation (median difference, −1.5 ml/min/1.73 m2 vs. 7.4 ml/min/1.73 m2 for the new equation and the CKD-EPI equation, [P<0.001]; interquartile range [IQR] for the difference, 16.2 ml/min/1.73 m2 vs. 19.0 ml/min/1.73 m2 [P<0.001]), as were accuracies (15% accuracy, 40.4% vs. 30.6% [P = 0.02]; 30% accuracy, 71.1% vs. 47.2%, [P<0.001]; 50% accuracy, 90.2% vs. 75.7%, [P<0.001]), allowing improvement in GFR categorization (GFR category misclassification rate, 37.4% vs. 53.2% [P = <0.001]).Conclusions
A new equation was developed in Chinese elderly population. In the validation data set, the new equation performed better than the original CKD-EPI equation. The new equation needs further external validations. Calibration of the GFR referent standard to a more accurate one should be an useful way to improve the performance of GFR estimating equations. 相似文献89.
Guo Wenfang Li Gangqiang Wang Nan Yang Caifeng Zhao Yanan Peng Huakang Liu Dehu Chen Sanfeng 《Plant molecular biology》2020,102(4-5):553-567
Plant Molecular Biology - Overexpression of K2-NhaD in transgenic cotton resulted in phenotypes with strong salinity and drought tolerance in greenhouse and field experiments, increased expression... 相似文献
90.
Wang Xuefei Xie Huiqin Ku Yongli Yang Xiangna Chen Yinglong Yang Nan Mei Xueli Cao Cuiling 《Plant and Soil》2020,448(1-2):413-424
Plant and Soil - Mycorrhizal type has been proposed as an effective trait integrator capturing varying biogeochemical syndromes in terrestrial ecosystems. However, for boreal peatlands, it is still... 相似文献