Li X.,Shanghai Minhang District Central Hospital |
Fan X.,Shanghai Minhang District Central Hospital |
Ren F.,Shanghai Minhang District Central Hospital |
Zhang Y.,Shanghai Minhang District Central Hospital |
And 7 more authors.
Diabetes Research and Clinical Practice | Year: 2011
Objective: Fibroblast growth factor (FGF21) has beneficial effects on lipolysis. Highly sensitive C-reactive protein (hs-CRP) is a predictor of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the levels of serum FGF21 and hs-CRP in newly diagnosed type 2 diabetes patients with and without NAFLD, and further explored the correlation between FGF21 with hs-CRP in newly diagnosed type 2 DM. Research design and methods: 69 patients with newly diagnosed type 2 DM and 30 normal subjects were included in the study. FGF21 and hs-CRP were measured by ELISA kits. The severity of NAFLD was measured by ultrasound. Results: Serum FGF21 in newly diagnosed type 2 DM with NAFLD group were significantly increased (p< 0.01). There was no difference for the FGF21 level in normal control group and newly diagnosed type 2 DM without NFALD group. In type 2 DM group, the FGF21 level was positively correlated with hsCRP (r=0.417, p< 0.001). In multiple stepwise regression models, only hsCRP was a significantly independent determinant for serum FGF21. Conclusions: Serum levels of FGF21 are closely related to liver steatosis in newly diagnosed type 2 DM patients. © 2011 Elsevier Ireland Ltd.
Wan H.,Shanghai Minhang District Central Hospital |
Yuan Y.,Shanghai JiaoTong University |
Liu J.,Shanghai Minhang District Central Hospital |
Chen G.,Shanghai Songjiang District Central Hospital
Translational Research | Year: 2012
The purpose of this study was to test the hypothesis that activation of endogenous peroxisome proliferator-activated receptor (PPARγ) inhibits induction of early growth response factor-1 (Egr-1), which is rapidly induced in the pancreas following cerulein intraperitoneal injection. Acute pancreatitis was induced in mice by hourly intraperitoneal injection of cerulein. Pioglitazone was administered prophylactically and pancreatic inflammation was assessed. AR42J cells were stimulated with caerulein10 -8M co-incubated in presence of different concentration of pioglitazone. The expression of PPARγ, Egr-1, and the target genes of Egr-1 were studied by real-time reverse transcriptase polymerase chain reaction (PCR), Western blot, and immunohistochemistry. In vitro, a PPAR-γ activator (pioglitazone) strikingly diminished Egr-1 mRNA and protein expression corresponding to Egr-1. In vivo, treatment with pioglitazone prior to the intraperitoneal injection of cerulein induction of Egr-1 and its target genes such as, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). The inhibitory effect of pioglitazone on Egr-1 expression induced by cerulein was almost fully restored by GW9662. Activation of PPAR-γ suppressed the activation of Egr-1 and its inflammatory gene targets and provided potent protection against pancreas injury. These data suggest a new mechanism in which PPAR-γ activation may decrease tissue inflammation in response to a cerulein insult. © 2012 Mosby, Inc. All rights reserved.
Jin R.,Shanghai JiaoTong University |
Jin R.,University of Sydney |
Liu W.,Shanghai JiaoTong University |
Liu W.,University of Sydney |
And 6 more authors.
Journal of Cell Science | Year: 2014
N-myc downstream-regulated gene 1 (NDRG1) is a potent metastasis suppressor that has been demonstrated to inhibit the transforming growth factor ß (TGF-ß)-induced epithelial-to-mesenchymal transition (EMT) by maintaining the cell-membrane localization of E-cadherin and ß-catenin in prostate and colon cancer cells. However, the precise molecular mechanism remains unclear. In this investigation, we demonstrate that NDRG1 inhibits the phosphorylation of b-catenin at Ser33/37 and Thr41 and increases the levels of non-phosphorylated ß-catenin at the plasma membrane in DU145 prostate cancer cells and HT29 colon cancer cells. The mechanism of inhibiting ß-catenin phosphorylation involves the NDRG1-mediated upregulation of the GSK3ß-binding protein FRAT1, which prevents the association of GSK3ß with the Axin1-APC-CK1 destruction complex and the subsequent phosphorylation of ß-catenin. Additionally, NDRG1 is shown to modulate the WNT-ß-catenin pathway by inhibiting the nuclear translocation of ß-catenin. This is mediated through an NDRG1-dependent reduction in the nuclear localization of p21-activated kinase 4 (PAK4), which is known to act as a transporter for ß-catenin nuclear translocation. The current study is the first to elucidate a unique molecular mechanism involved in the NDRG1-dependent regulation of ß-catenin phosphorylation and distribution. © 2014. Published by The Company of Biologists Ltd.
Quan Y.,Shanghai JiaoTong University |
Quan Y.,Shanghai Institute of Digestive Surgery |
Jin R.,Shanghai JiaoTong University |
Huang A.,Shanghai Institute of Digestive Surgery |
And 5 more authors.
Cancer Biology and Therapy | Year: 2014
Previous reports have associated GRHL2 with tumor progression. However, the biological role of GRHL2 in human colorectal cancer (CRC) has not been explored. We examined the expression of GRHL2 in 75 CRC samples, as well as the paired non-tumor tissues, by immunohistochemistry, qRT-PCR, and western blot analysis. The association between GRHL2 expression and various clinicopathological parameters including Ki-67, a marker of proliferative activity, was also evaluated. We performed lentivirus-mediated shRNA transfection to knock down GRHL2 gene expression in HT29 and HCT116 CRC cells. Cell proliferation was examined by the CCK-8 (Cell Counting Kit-8) assay, colony formation, and cell cycle assay in vitro. Tumorigenesis in vivo was assessed using a mouse xenograft model. Moreover, we transiently silenced ZEB1 expression in GRHL2-knockdown CRC cells using specific shRNA, and then examined the effects on GRHL2 and E-cadherin expression, as well as cell proliferation. Herein, we demonstrated that enhanced GRHL2 expression was detected in CRC, and correlated with higher levels of Ki-67 staining, larger tumor size, and advanced clinical stage. Knocking down GRHL2 in HT29 and HCT116 CRC cells significantly inhibited cell proliferation by decreasing the number of cells in S phase and increasing that in the G0/G1 phaseof the cell cycle. This resulted in inhibition of tumorigenesis in vivo, as well as increased expression of ZEB1. Furthermore, transient ZEB1 knockdown dramatically enhanced cell proliferation and increased GRHL2 and E-cadherin expression. Collectively, our study has identified ZEB1 as a target of GRHL2 and suggested a reciprocal GRHL2-ZEB1 repressive relationship, providing a novel mechanism through which proliferation may be modulated in CRC cells. © 2014 Landes Bioscience.
Liang C.,Fudan University |
Liang C.,Shanghai Medical College |
Xue Z.,Fudan University |
Wang H.,Fudan University |
Li P.,Shanghai Minhang District Central Hospital
Journal of Neurosurgical Anesthesiology | Year: 2011
BACKGROUND: Heme oxygenase-1 (HO-1) is an important cytoprotective agent. We examined the effect of propofol on the regulation of HO-1 expression and its activity in human umbilical vein endothelial cells (HUVECs) under oxidative stress conditions. We further assessed whether extracellular signal-regulated kinases (ERKs), cJun-N-terminal kinases (JNKs), and p38-mitogen-activated protein kinase mediate propofol-induced HO-1 expression. METHODS: Hydrogen peroxide (100 μmol/L) was used to induce oxidative stress. HUVECs were treated with different concentrations (1025 and 50 μmol/L) of propofol for various periods of time. Finally, cells were pretreated with SB203580 (10 μmol/L), a p38-mitogen-activated protein kinase inhibitor; PD98059 (25 μmol/L), an ERKs inhibitor; SP600125 (10 μmol/L), a JNKs inhibitor; and ZnPPIX (10 μmol/L), an HO-1 activity inhibitor, followed by propofol incubation. Reverse transcriptase polymerase chain reaction was used to detect HO-1 mRNA expression. HO-1 activity was determined in microsomal fractions from HUVECs by monitoring the conversion of heme into bilirubin. HO-1 protein and phosphorylated ERKs were measured by western blot analysis. Cell apoptosis was detected using terminal transferase deoxyuridine triphosphate-biotin nick-end labeling. RESULTS: Under oxidative stress conditions, HO-1 expression and activity were increased by propofol in a dose-dependent and time-dependent manner. PD98059, but not SB203580 or SP600125, effectively reduced propofol-induced HO-1 protein levels. The phosphorylation of ERKs was significantly increased by propofol, and this process was also inhibited by PD98059. Hydrogen peroxide-induced apoptosis in HUVECs was attenuated by propofol, which was partly reversed by ZnPPIX. CONCLUSIONS: These findings show that, under oxidative stress conditions, propofol induces HO-1 expression in HUVECs and this effect is mediated, at least in part, via ERKs pathways. Copyright © 2011 by Lippincott Williams & Wilkins.
Xu J.,Shanghai Minhang District Central Hospital |
Yin X.-F.,Shanghai Minhang District Central Hospital |
Gu H.-J.,Shanghai Minhang District Central Hospital |
Qin Q.,Shanghai Minhang District Central Hospital
Chinese Journal of Tissue Engineering Research | Year: 2014
BACKGROUND: Currently, bone graft is mainly used for repair of bone defects, and tricalcium phosphate is the most used artificial bone material. But the effectiveness of the tricalcium phosphate bone graft is still controversial, and there is also no detailed report about its function during the healing of bone defect. OBJECTIVE: To observe the concentration changes of bone morphogenetic protein-2 and vascular endothelial growth factor as well as bone healing after tricalcium phosphate graft in bone defects. METHODS: Forty-eight C57 mice were randomly divided to experimental group and control group. A 2-mm-long diaphyseal segment and periosteum from the middle of the right femur was cut to prepare unilateral bone defect models. Tricalcium phosphate bone graft was used in the experimental group, and no bone graft in the control group. During the following 4 weeks, X-ray examination was done once a week to observe the bone healing, and then the animals were executed for collecting samples in the graft area. The concentrations of bone morphogenetic protein-2 and vascular endothelial growth factor in samples which were taken from the bone graft area were determined by using ELISA assay. RESULTS AND CONCLUSION: X-ray films showed that 2 weeks later, bone fracture healed mostly in the experimental group except a small part of cortical bone; 3 weeks later, bone fracture was basically healed, and only a small amount of tricalcium phosphate remained; 4 weeks later, bone fracture was completely healed, and the callus grew obviously, and the tricalcium phosphate was nearly absorbed. In the control group, the fracture line was still visible at 1-2 weeks, but it became vague at 3 weeks; then, the fracture was healed at 4 weeks except some of the cortical bone. The levels of bone morphogenetic protein-2 and vascular endothelial growth factor were significantly higher in the experimental group than in the control group at different time points (P < 0.05). These results suggest that tricalcium phosphate bone graft can up-regulate the expression of bone morphogenetic protein-2 and vascular endothelial growth factor and accelerate bone healing. © 2014, Journal of Clinical Rehabilitative Tissue Engineering Research All Rights Reserved.
Man W.,Shanghai Minhang District Central Hospital |
Ming D.,Fudan University |
Fang D.,Fudan University |
Chao L.,Fudan University |
Jing C.,Fudan University
Journal of Cellular Biochemistry | Year: 2014
The antioxidant property of dimethyl sulfoxide (DMSO) was formerly attributed to its direct effects. Our former study showed that DMSO is able to induce heme oxygenase-1 (HO-1) expression in endothelial cells, which is a potent antioxidant enzyme. In this study, we hypothesized that the antioxidant effects of DMSO in cardiomyocytes are mediated or partially mediated by increased HO-1 expression. Therefore, we investigated whether DMSO exerts protective effects against H2O2-induced oxidative damage in cardiomyocytes, and whether HO-1 is involved in DMSO-imparted protective effects, and we also explore the underlying mechanism of DMSO-induced HO-1 expression. Our study demonstrated that DMSO pretreatment showed a cytoprotective effect against H2O2-induced oxidative damage (impaired cell viability, increased apopototic cells rate and caspase-3 level, and increased release of LDH and CK) and this process is partially mediated by HO-1 upregulation. Furthermore, our data showed that the activation of p38 MAPK and Nrf2 translocation are involved in the HO-1 upregulation induced by DMSO. This study reports for the first time that the cytoprotective effect of DMSO in cardiomyocytes is partially mediated by HO-1, which may further explain the mechanisms by which DMSO exerts cardioprotection on H 2O2 injury. © 2014 Wiley Periodicals, Inc.
Liang C.,Shanghai Minhang District Central Hospital |
Xue Z.,Fudan University |
Cang J.,Fudan University |
Wang H.,Fudan University |
Li P.,Fudan University
Molecular and Cellular Biochemistry | Year: 2011
Dimethyl sulfoxide (DMSO) has recently been proposed as an anti-inflammatory and free radical scavenging agent. However, the mechanisms by which DMSO mediates its therapeutic effects are unclear. In this paper, we investigated the capability of DMSO to up-regulate heme oxygenase-1(HO-1) expression, as well as the possible underlying mechanisms in human umbilical vein endothelial cells (HUVECs). DMSO induced HO-1 expression both at the level of mRNA and protein in dose-and time-dependent manners in HUVECs, resulting in increased HO-1 activity. The pharmacological inhibition of cJun-N-terminal kinases (JNKs) blocked the DMSO-induced HO-1 up-regulation, while inhibition of extracellular regulated kinase and p38-MAPK did not block heme oxygenase-1 up-regulation. In addition, the phosphorylation of JNKs was initiated by DMSO, indicating the involvement of this kinase in the observed response. DMSO increased the nuclear translocation of NF-E2-related factor 2 (Nrf2) and enhanced its binding to the anti-oxidant response element. Inhibition of Nrf2 synthesis by small interfering RNA molecules subsequently inhibited HO-1 expression induced by DMSO, indicating DMSO's role in inducing HO-1 expression via Nrf2 activation. Utilizing these findings, the present study identified DMSO as a novel inducer of HO-1 expression and identified the underlying mechanisms involved in this process. © 2011 Springer Science+Business Media, LLC.
Liang C.,Shanghai Minhang District Central Hospital |
Chen J.,Shanghai Minhang District Central Hospital |
Gu W.,Shanghai Minhang District Central Hospital |
Wang H.,Fudan University |
Xue Z.,Fudan University
Acta Anaesthesiologica Scandinavica | Year: 2011
Background: The present study was designed to investigate the possible effect of chronic alcohol intake on propofol and remifentanil requirements, which was determined by quantifying the 50% (EC 50) and 95% (EC 95) effective effect-site concentrations for propofol and remifentanil at loss of consciousness (LOC) and after a painful stimulus. Methods: Thirty male patients (alcoholic group; n = 30) with chronic alcoholism and 30 patients (control group; n = 30) with a history of small alcohol intake were anaesthetized with propofol and remifentanil by target-controlled infusion. The predicted drug concentrations and Bispectral Index (BIS) values were recorded at LOC and after no response to painful stimuli. Results: The EC 50 and EC 95 of propofol at LOC in alcoholic group were 3.15 [95% confidence interval (CI), 2.77-3.37] and 4.05 (95% CI, 3.18-5.26) μg/ml, respectively, and those of the control group were 2.21 (95% CI, 1.92-2.86) and 3.04 (95% CI, 2.45-4.64) μg/ml, respectively. The EC 50 and EC 95 of remifentanil measured after no response to painful stimuli in the alcoholic group were 3.02 (95% CI, 2.70-3.38) and 4.98 (95% CI, 4.56-5.89) ng/ml, respectively, and those of the control group were 2.95 (95% CI, 2.68-3.33) and 4.86 (95% CI, 4.55-5.92) ng/ml, respectively. The EC 50 and EC 95 values of propofol at LOC in the control group were significantly lower than that of the alcoholic group. Conclusions: These findings suggest that the induction dose requirements of propofol are increased in alcoholic patients anaesthetized with propofol and remifentanil administered by target controlled infusion. © 2011 The Acta Anaesthesiologica Scandinavica Foundation.
PubMed | Shanghai Minhang District Central Hospital
Type: Journal Article | Journal: Translational research : the journal of laboratory and clinical medicine | Year: 2012
The purpose of this study was to test the hypothesis that activation of endogenous peroxisome proliferator-activated receptor (PPAR) inhibits induction of early growth response factor-1 (Egr-1), which is rapidly induced in the pancreas following cerulein intraperitoneal injection. Acute pancreatitis was induced in mice by hourly intraperitoneal injection of cerulein. Pioglitazone was administered prophylactically and pancreatic inflammation was assessed. AR42J cells were stimulated with caerulein 10 M co-incubated in presence of different concentration of pioglitazone. The expression of PPAR, Egr-1, and the target genes of Egr-1 were studied by real-time reverse transcriptase polymerase chain reaction (PCR), Western blot, and immunohistochemistry. In vitro, a PPAR- activator (pioglitazone) strikingly diminished Egr-1 mRNA and protein expression corresponding to Egr-1. In vivo, treatment with pioglitazone prior to the intraperitoneal injection of cerulein induction of Egr-1 and its target genes such as, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). The inhibitory effect of pioglitazone on Egr-1 expression induced by cerulein was almost fully restored by GW9662. Activation of PPAR- suppressed the activation of Egr-1 and its inflammatory gene targets and provided potent protection against pancreas injury. These data suggest a new mechanism in which PPAR- activation may decrease tissue inflammation in response to a cerulein insult.