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Wu X.-H.,Fudan University | Qian C.,Fudan University | Yuan K.,Changzhou Second Peoples Hospital
Chinese Medical Journal | Year: 2011

Background Hypoxia-inducible factor (HIF) may play an important role in the process of tumorigenesis as well as tumor progression. The aim of this study was to compare the expression between HIF-1α and HIF-2α in tumor angiogenesis and the overall impact on patient prognosis in human non-small cell lung cancer (NSCLC). Methods In the current work we compared the immunohistochemical expression of HIF-1α and HIF-2α in surgical specimens of 140 patients with NSCLC in a tissue microarray study. Relationships between HIF-α expression and clinicopathological or angiogenic factors, including prognosis, were analyzed. Results High HIF-1α and HIF-2α expression was noted in 49/140 (35.0%) and in 64/140 (45.7%) of the cases, respectively. There was no direct correlation between HIF-1α and HIF-2α expression. Patients with advanced stage tumors had frequent high expression of HIF-2α (P=0.007), and we also found a significant correlation between HIF-2α and T or N stage (P=0.030 and 0.043, respectively). HIF-1α showed a marginal association with T stage (P=0.084), which showed a higher expression in early stage tumors. A significant correlation (P=0.045) was noticed between HIF-1α and vascular endothelial growth factor (VEGF) expression while the expression levels of thymidine phosphorylase (TP), cyclooxygenase (COX)-2 and microvessel density (MVD) were significantly higher in high HIF-2α tumors (P=0.020, 0.004, and 0.046, respectively). In addition, univariate analysis of overall survival demonstrated that HIF-2α expression, but not HIF-1α, was related to poor outcome (P=0.001) and it retained significant in multivariate analysis (P=0.036). Conclusions Taken together, we conclude that HIF-1α and HIF-2α may differentially regulate the major angiogenic factors in different stages of the tumor process in NSCLC. HIF-2α may play a dominant role in tumor angiogenesis and appears to be of obvious value as a significant prognostic factor in NSCLC. Source

Zhang Y.-P.,Capital Medical University | Zhang Y.-Y.,Changzhou Second Peoples Hospital | Duan D.D.,University of Nevada, Reno
Progress in Molecular Biology and Translational Science | Year: 2016

Obesity is a condition in which excess body fat has accumulated over an extent that increases the risk of many chronic diseases. The current clinical classification of obesity is based on measurement of body mass index (BMI), waist-hip ratio, and body fat percentage. However, these measurements do not account for the wide individual variations in fat distribution, degree of fatness or health risks, and genetic variants identified in the genome-wide association studies (GWAS). In this review, we will address this important issue with the introduction of phenome, phenomics, and phenome-wide association study (PheWAS). We will discuss the new paradigm shift from GWAS to PheWAS in obesity research. In the era of precision medicine, phenomics and PheWAS provide the required approaches to better definition and classification of obesity according to the association of obese phenome with their unique molecular makeup, lifestyle, and environmental impact. © 2016. Source

Wei J.,Changzhou Second Peoples Hospital | Cheng J.,Changzhou Second Peoples Hospital
Pakistan Journal of Medical Sciences | Year: 2014

Objective: To evaluate correlations between insulin secretion and resistance in patients with gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT). Methods: Three hundred thirty six pregnant women with an oral glucose tolerance test (OGTT) were tested and measured insulin function indices (IFI), insulin resistance indices (HOMA-IR) as well as blood serum triglycerides (TG), total cholesterol (TCH) and low density lipoprotein cholesterol (LDL-C) concentrations. GIGT patients were further divided into subgroups according to hyperglycemia appearance 1, 2 or 3 hours after glucose ingestion. Results: GDM and GIGT correlated with age (p<0.05), family history of diabetes (p<0.05) and pre-pregnancy body mass indices (BMIs) (p<0.05). Blood pressures were higher in GDM than in GIGT and normal glucose tolerance (NGT) patients (p<0.05). The IFIs were gradually reduced (p<0.05), whereas HOMA-IR was gradually enhanced (p<0.05) in the GIGT and GDM patients. Blood serum TG, TCH and LDL-C concentrations were higher in the GIGT and GDM groups (p<0.05) and the GIGT 1 hour hyperglycemia subgroup had highest pregnancy weight gain and HOMA-IR values (p<0.05). Conclusions: Advanced age, family history of diabetes, high BMIs and blood pressure were risk factors for GIGT and GDM, which were both caused by reduced insulin secretion and enhanced insulin resistance. © 2014, Professional Medical Publications. All rights reserved. Source

Ruan L.,Wenzhou University | Chen R.,Wenzhou University | Wang R.,Taizhou Institution for Food and Drug Control | Xie X.,Wenzhou University | And 9 more authors.
Metabolic Brain Disease | Year: 2015

The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects. © 2015, Springer Science+Business Media New York. Source

Gao J.,Shanghai University | Zhou X.-L.,Changzhou Second Peoples Hospital | Kong R.-N.,Shanghai University | Ji L.-M.,Shanghai University | And 2 more authors.
Experimental and Molecular Pathology | Year: 2016

Objective: The purpose of our study was to elucidate the impact of microRNA-126 (miR-126) targeting PIK3R2 gene on cell proliferation and apoptosis of rheumatoid arthritis synovial fibro-blasts (RASFs) by regulating PI3K/AKT signal pathway. Methods: The synovial tissue samples of this study were from 55 RA patients undergoing joint replacement and 27 healthy people undergoing joint repair due to trauma. The target genes of miR-126 were collected by the TargetScan and PIK3R2 as the direct target gene of miR-126 was confirmed by dual-luciferase reporter assay system. Our experiment had five groups including the blank control, miR-126 mimic, miR-126 mimic control, miR-126 inhibitor and miR-126 inhibitor control groups. Additionally, real-time quantitative polymerase chain reaction (RT-qPCR), Western-Blot, cell counting kit (CCK-8) and flow cytometry were carried out in this study. Results: Compared with healthy individuals, the RA patients had increased miR-126, but decreased PIK3R2 mRNA expressions in the synovial tissues. Pearson correlation analysis indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression (all P<. 0.05). When compared with the blank group respectively, the miR-126 mimic group had raising cell proportions in S and G2/M phases with reduced rate of cell apoptosis, while the miR-126 inhibitor group had raising cell proportions in G0/G1 and G2/M phases with increased rate of cell apoptosis (all P<. 0.05). Besides, compared with the blank control group, the miR-126 mimic group had declined expression of PIK3R2 protein with ascended expression of PI3K and p-AKT (all P<. 0.05), while the miR-126 inhibitor group had increased expression of PIK3R2 protein with decreased expression of PI3K and p-AKT (all P<. 0.05). Conclusion: Our study demonstrated that down-regulation of miR-126 may indirectly inhibit PI3K/AKT signaling pathway to disrupt the imbalance between growth and death of RASFs by targeting PIK3R2, which may be clinically helpful to find therapeutic strategies directed toward miR-126 function for RA patients. © 2015 Elsevier Inc.. Source

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