Fu R.-G.,Xian Jiaotong University |
Xue R.-L.,Xian Jiaotong University |
Wang J.,Hanzhong Central Hospital |
Ma L.-Q.,Xian Jiaotong University |
And 7 more authors.
Neuroscience Letters | Year: 2012
Background/aims: Ghrelin can act as a signal for mealtime hunger and meal initiation. Amygdala is indispensable in appetitive behavior motivated by learned emotions. This study was to investigate the alteration of ghrelin in the amygdala of rats with chronic renal failure (CRF) and its relation with uremic anorexia. Methods: SD rats were randomly classified into CRF group and control group (n= 16 per group). The CRF model was constructed using 5/6 nephrectomy. When plasma creatinine (PCr) and blood urea nitrogen (BUN) in the CRF group were twice more than the normal level, food intake (g/24. h) was measured and then all rats were killed for detection of ghrelin protein expression in the amygdala using immunohistochemical analysis and mRNA expression using RT-PCT. Statistics was conducted with one-way analysis of variance, Student-Newman-Keuls- q test and correlation analysis. Results: By the 8th week after the surgery, the BUN and PCr of CRF rats exceeded double the normal level, and their food intake was obviously decreased compared with the controls (P< 0.05). The protein and mRNA expression of ghrelin in the amygdala of CRF group were significantly reduced, and there was a positive correlation between this reduction and the decrease in food intake (P< 0.05). Conclusion: The reduction of amygdala's ghrelin in CRF rats may be associated with uremic anorexia. © 2012 Elsevier Ireland Ltd.
Li G.,PLA Fourth Military Medical University |
Jin T.-B.,Life Detection Systems |
Wei X.-B.,Hanzhong Central Hospital |
He S.-M.,PLA Fourth Military Medical University |
And 6 more authors.
Cancer Epidemiology | Year: 2012
Background: Current evidence suggests that a majority of the inherited risks play a major role in glioma susceptibility, and glioma is due to the co-inheritance of multiple low-risk variants. These variants can be identified through association studies including such as genome-wide association studies (GWAS), which has led the glioma epidemiology researchers to focus on identifying potential disease-causing factors. Methods: We evaluated and validated 10 tag single nucleotide polymorphisms (tSNPs) in seven genes associated with glioma susceptibility in a Han Chinese population, including 301 glioma cases and 302 controls, using a multiplexed single nucleotide polymorphism (SNP) MassEXTEND assay. We ascertained the genotypic frequencies for each tSNP in control subjects were within Hardy-Weinberg equilibrium (HWE) using an exact test, and then compared the genotype and allele frequencies of glioma patients and control subjects using the χ2 test. We then applied three genetic models (dominant, recessive, and additive) using PLINK software to assess the association of each tSNP with glioma risk. Results: We identified two tSNPs to be associated with glioma susceptibility (rs1695, GSTP1, P=0.019; rs2853676, TERT, P=0.039), which we confirmed using dominant and additive model analyses. The genotype “GA” for rs1695 was recognized to be a protective genotype for glioma (OR, 0.67; 95% CI, 0.47-0.96; P=0.027), while the genotype “AG” for rs2853676 was shown to be a risk genotype for glioma (OR, 1.50; 95% CI, 1.05-2.15; P=0.025). Conclusion: Our results, and those from previous studies, suggest potential genetic contributes for GSTP1 and TERT in glioma development. © 2012 Elsevier Ltd.
Yin G.,Xian Jiaotong University |
Zhou H.,Hanzhong Central Hospital |
Xue Y.,Xian Jiaotong University |
Yao B.,Xian Jiaotong University |
Zhao W.,Xian Jiaotong University
Oncology Reports | Year: 2016
Aberrant expression and function of microRNAs (miRNAs) play a critical role in the development and progression of various human cancers including gastric cancer. However, the clinical significance and underlying mechanisms of miR-340 remain largely unknown in gastric cancer. In the present study, we demonstrated that the expression of miR-340 was aberrantly elevated in both gastric cancer tissues and cells. Moreover clinical association analyses disclosed that the elevated level of miR-340 was significantly associated with unfavorable clinicopathological characteristics of the gastric cancer patients, such as poor differentiation, large tumor size and advanced tumor-node-metastasis (TNM) stage. Gastric cancer patients with high expression of miR-340 had prominently shorter overall survival and disease-free survival. Functionally, forced expression of miR-340 promoted cell viability, proliferation, colony formation and cell cycle progression in the SGC-7901 cells, while miR-340 silencing reduced cell viability, proliferation, colony formation and cell cycle progression in MGC-803 cells. Furthermore, in vivo experiments indicated that miR-340 knockdown suppressed the tumor growth of MGC-803 cells. Notably, alteration of miR-340 expression affected the luciferase activity of wildtype 3'-UTR of cyclin G2 (CCNG2) and regulated CCNG2 abundance in gastric cancer cells, indicating that CCNG2 is a direct target of miR-340. Moreover, CCNG2 knockdown eradicated the effects of miR-340 silencing on gastric cancer cells. In conclusion, our data suggest that miR-340 may potentially serve as a novel prognostic biomarker and therapeutic target for gastric cancer.
Jiang Z.-C.,Xian Jiaotong University |
Tang X.-M.,Hanzhong Central Hospital |
Zhao Y.-R.,Xian Jiaotong University |
Zheng L.,The Taixing Peoples Hospital
Tumor Biology | Year: 2014
Toll-like receptor 4 (TLR4) plays a key role in prompting the innate or immediate response. A growing body of evidence suggests that genetic variants of TLR4 gene were associated with the development of cancers. This study aimed to investigate the relationship of a functional variant (rs1057317) at microRNA-34a (miR-34a) binding site in toll-like receptor 4 gene and the risk of hepatocellular carcinoma. A single center-based case-control study was conducted. In this study, the polymerase chain reaction (PCR) and direct sequencing were used to genotype sequence variants of TLR4 in 426 hepatocellular carcinoma cases and 438 controls. The modification of rs1057317 on the binding of hsa-miR-34a to TLR4 messenger RNA (mRNA) was measured by luciferase activity assay. Individuals carrying the AA genotypes for the rs1057317 were associated significantly with increased risk of hepatocellular carcinoma comparing with those carrying wild-type homozygous CC genotypes (adjusted odds ratio [OR] by sex and age, from 1.116 to 2.452, P = 0.013). The activity of the reporter vector was lower in the reporter vector carrying C allele than the reporter vector carrying A allele. Furthermore, the expression of TLR4 was detected in the peripheral blood mononucleated cell of hepatocellular carcinoma (HCC) patients, suggesting that mRNA and protein levels of TLR4 might be associated with SNP rs1057317. Collectively, these results suggested that the risk of hepatocellular carcinoma was associated with a functional variant at miR-34a binding site in toll-like receptor 4 gene. miR-34a/TLR4 axis may play an important role in the development of hepatocellular carcinoma. © 2014 International Society of Oncology and BioMarkers (ISOBM).
Liu B.,PLA Fourth Military Medical University |
Liu Q.,Hanzhong Central Hospital |
Song Y.,PLA Fourth Military Medical University |
Li X.,PLA Fourth Military Medical University |
And 4 more authors.
Medical Oncology | Year: 2014
Hypoxia-inducible factor 1α (HIF1α) activates the transcription of genes that are involved in angiogenesis and cell survival. Over-expression of HIF1α caused by intratumoral hypoxia and its genetic alterations are associated with increased mortality in several cancer types including non-small-cell lung cancer (NSCLC). The aim of this study was to investigate the predictive role of single nucleotide polymorphisms (SNPs) in HIF1A gene in NSCLC outcomes. We genotyped two functional SNPs (rs2057482 and rs2301113) in HIF1A gene and assessed their associations with clinicopathological parameters and prognosis of 494 NSCLC patients by Cox proportional hazard model. There was no significant association between the SNPs and clinical outcomes of NSCLC for overall analysis. However, in stratified analysis for NSCLC patients at early stage (I/II), we observed a protective effect conferred by variant genotype of rs2057482 on overall survival (OS) (HR 0.42, 95 % CI 0.22-0.80) and recurrence-free survival (RFS) (HR 0.60, 95 % CI 0.36-0.97) in a dominant model. Additionally, multivariate Cox analysis based on dominant model indicated that significant increased death and recurrence risks were observed in patients with early T-stage (T1 and T2) tumors, who carrying variant-containing genotype of rs2301113, as well as in patients without lymph node involvement (N0 stage) for rs2057482. Genetic variations on HIF1A gene are significantly associated with NSCLC outcomes in patients with early stage disease. © 2014 The Author(s).