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.
Wen S.-Y.,Shanghai JiaoTong University |
Lin Y.,Shanghai JiaoTong University |
Yu Y.-Q.,Shenyang Medical College |
Cao S.-J.,Shanghai Songjiang District Central Hospital |
And 11 more authors.
Oncogene | Year: 2014
Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.Oncogene advance online publication, 10 March 2014; doi:10.1038/onc.2014.9.
PubMed | Boston University, Tongji University, Brown University and Shanghai Songjiang District Central Hospital
Type: Journal Article | Journal: Oncotarget | Year: 2016
Bromodomain and extra-terminal (BET) protein inhibitors have been shown to effectively inhibit tumorgenesis and ameliorate pulmonary fibrosis by targeting bromodomain proteins that bind acetylated chromatin markers. However, their pharmacological effects in renal fibrosis remain unclear. In this study, we examined the effect of I-BET151, a selective and potent BET inhibitor, on renal fibroblast activation and renal fibrosis. In cultured renal interstitial fibroblasts, exposure of cells to I-BET151, or silencing of bromodoma in-containing protein 4 (Brd4), a key BET protein isoform, significantly reduced their activation as indicated by decreased expression of -smooth muscle actin, collagen 1 and fibronectin. In a murine model of renal fibrosis induced by unilateral ureteral obstruction (UUO), administration of I-BET151 suppressed the deposition of extracellular matrix proteins, renal fibroblast activation and macrophage infiltration. Mechanistically, I-BET151 treatment abrogated UUO-induced phosphorylation of epidermal growth factor receptor and platelet growth factor receptor-. It also inhibited the activation of Smad-3, STAT3 and NF-B pathways, as well as the expression of c-Myc and P53 transcription factors in the kidney. Moreover, BET inhibition resulted in the reduction of renal epithelial cells arrested at the G2/M phase of cell cycle after UUO injury. Finally, injury to the kidney up-regulated Brd4, and I-BET151 treatment abrogated its expression. Brd4 was also highly expressed in human fibrotic kidneys. These data indicate that BET proteins are implicated in the regulation of signaling pathways and transcription factors associated with renal fibrogenesis, and suggest that pharmacological inhibition of BET proteins could be a potential treatment for renal fibrosis.
Yu M.,Fudan University |
Chen X.,Hainan Provincial Nong Ken Hospital |
Lv C.,Fudan University |
Yi X.,Shanghai Songjiang District Central Hospital |
And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2014
Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases. © 2014 Elsevier Inc. All rights reserved.
Sheng F.,Shanghai Songjiang District Central Hospital |
Chen B.,East Hospital |
He M.,Shanghai Songjiang District Central Hospital |
Zhang M.,Shanghai Songjiang District Central Hospital |
Shen G.,Shanghai Songjiang District Central Hospital
Archives of Medical Research | Year: 2016
Background and Aims ST-segment resolution ≥70% on consecutive electrocardiograms (ECGs) before administration of definitive reperfusion therapy is considered as an electrocardiographic sign of spontaneous reperfusion (SR) in STEMI patients and it indicates not only the patency of the infarct-related artery (IRA) but also the microvascular and myocardial reperfusion. Neutrophil/lymphocyte (N/L) ratio has been demonstrated to be associated with the patency of the IRA and no-reflow in patients with STEMI before mechanical reperfusion therapy. However, the association between N/L ratio and ST-segment resolution in STEMI patients with SR was not investigated. The aim of this study was to focus on the relation between N/L ratio and ST-segment resolution in STEMI patients with SR. Methods One hundred sixty two consecutive patients with their first diagnosed STEMI were enrolled in this study. ECGs of all the patients at admission and 1 h later were obtained. According to electrocardiographic sign of SR, the patients were divided into two groups as SR group and non-SR group. Clinical data between two groups were evaluated. Results Patients in SR group had lower neutrophil counts, higher lymphocyte counts, and lower N/L ratio than patients in non-SR group. Moreover, after undertaking primary PCI, patients in SR group had lower peak cTnT value and higher LVEF than patients in non-SR group. Furthermore, N/L ratio was an independent predictor of electrocardiographic sign of SR in patients with STEMI. Conclusion N/L ratio, an easily available laboratory data, may be related to microvascular reperfusion in STEMI patients with electrocardiographic sign of SR. © 2016 IMSS
PubMed | Shanghai Songjiang District Central Hospital and East Hospital
Type: Journal Article | Journal: Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc | Year: 2016
Augmentation of the amplitude of QRS complexes with diuretic therapy for patients with congestive heart failure has been well documented. However, the effect of diuresis on the paced QRS complexes in pacing-dependent patients with heart failure is scarce.To investigate the effect of diuresis on the paced QRS complexes in pacing-dependent patients with heart failure.Thrity-two consecutive pacing-dependent patients with heart failure were enrolled in this study. Before and after diuresis, the sums of paced QRS amplitude of leads I+II (pQRSI+II ), six limb leads (pQRS6L ), leads V1 -V3 (pQRSV1-V3 ), leads V4 -V6 (pQRSV4-V6 ), leads V1 -V6 (pQRSV1-V6 ), and lead aVR (pQRSaVR ), paced QRS duration (pQRSd ), paced QT intervals (pQT) and the body weight of each patient were measured, then the % changes (%) in paced electrocardiogram (ECG) variables and the % in body weight were evaluated.Compared with before diuresis, paced ECG variables significantly increased and body weight significantly decreased after diuresis, % in paced QRS amplitude(s) in all ECG variables (pQRSI+II, pQRS6L, pQRSV1-V3 , pQRSV4-V6 , pQRSV1-V6 , and pQRSaVR ) correlated well with % in body weight (r = 0.416, r = 0.849, r = 0.901, r = 0.371, r = 0.837, r = 0.619, and P = 0.018, P < 0.001, P < 0.001, P = 0.037, P < 0.001, P < 0.001), while there was no correlation between % in pQRSd and pQT and % in body weight.The changes in amplitude of paced QRS complexes may be useful for the monitoring of therapy of pacing-dependent patients with heart failure.
PubMed | University of Madeira, Shanghai Songjiang District Central Hospital, Donghua University and Leibniz Institute of Polymer Research
Type: Journal Article | Journal: Biomaterials science | Year: 2016
We report the design of the fourth generation poly(propylene imine) (PPI) glycodendrimers for magnetic resonance (MR) imaging applications. The glycodendrimers were designed to have a densely organized maltose shell (MAL DS) and several tetraazacyclododecane tetraacetic acid (DOTA) ligands that were attached to the periphery of the PPI dendrimers for Gd(iii) chelation. We show that the formed MAL DS-modified PPI dendrimers possess good cytocompatibility and hemocompatibility in the studied concentration range. With the longitudinal relaxivity (r
Wan H.,Shanghai Songjiang District Central Hospital |
Chen Y.,Zhengzhou University
International Journal of Psychiatry in Medicine | Year: 2010
Background and Aim: Irritable bowel syndrome (IBS) patients usually manifest autonomic nerve dysfunctions and abnormal psychological behaviors. This study was to assess autonomic nervous system (ANS) response to different stressor as well as evaluate effects of antidepressive treatment of Saint John's Wort Extract in women with IBS. Method: Thirty women with IBS and 20 healthy women underwent serial ANS function tests. Five-minute-short-time heart rate variability (HRV) spectral analysis were assessed at a stress or resting recording period. Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to measure their anxiety and depression conditions. After 8-weeks' antidepressant treatment, groups of IBS repeated the tests above. Subjects also completed a GI symptom diary once daily during the 2 weeks before therapy and for 2 weeks in the last scheduled therapy session. Results: IBS-group showed a higher score in HAMA and HAMD (p < 0.01) and showed a significant increase in the low frequency band/high frequency band ratio (L/H) during the period in different stimuli (p < 0.01), which was significantly different from controls. After 8-weeks' antidepressive treatment, L/H showed a significant decrease (p < 0.05) response to different stressor, which was significantly different from pre-treatment. Gastrointestinal (GI) symptoms of IBS were also relieved significantly. Conclusions: Antidepressive treatment can improve the conditions of psychology and the ANS reactivity to stress in patients with IBS. © 2010, Baywood Publishing Co., Inc.
Cao Y.,Donghua University |
He Y.,Shanghai Songjiang District Central Hospital |
Liu H.,Donghua University |
Luo Y.,Donghua University |
And 3 more authors.
Journal of Materials Chemistry B | Year: 2014
Development of cost-effective nanoscale contrast agents for targeted tumor computed tomography (CT) imaging remains a great challenge. Here, we report the synthesis of dendrimer-entrapped AuNPs (Au DENPs) using generation 2 poly(amidoamine) dendrimers pre-modified with fluorescein isothiocyanate via a thiourea linkage and lactobionic acid (LA) via a polyethylene glycol spacer as templates. The formed Au DENPs were characterized via different techniques and were used as a nanoprobe for targeted CT imaging of hepatocellular carcinoma (HCC). We show that the LA-modified Au DENPs with a mean Au core size of 1.8 nm are water-dispersible, colloidally stable under different temperatures (4-50 °C) and pH (5-8) conditions, and cytocompatible in the studied concentration range. Flow cytometry results reveal that the LA-Au DENPs are able to specifically target HepG2 cells (a human HCC cell line) overexpressing asialoglycoprotein receptors via a receptor-mediated targeting pathway. Importantly, the developed LA-Au DENPs can be used as a nanoprobe for targeted CT imaging of HepG2 cells in vitro and the xenografted tumor model in vivo. With the demonstrated organ compatibility, the developed LA-Au DENPs using low-generation dendrimers as templates can be a good candidate to be used as a highly efficient and cost-effective nanoprobe for targeted CT imaging of HCC. © 2015 The Royal Society of Chemistry.
Li J.,Donghua University |
He Y.,Shanghai Songjiang District Central Hospital |
Sun W.,Donghua University |
Luo Y.,Donghua University |
And 5 more authors.
Biomaterials | Year: 2014
We report a polyethyleneimine (PEI)-mediated approach to synthesizing hyaluronic acid (HA)-targeted magnetic iron oxide nanoparticles (Fe3O4 NPs) for invivo targeted tumor magnetic resonance (MR) imaging applications. In this work, Fe3O4 NPs stabilized by PEI were first synthesized via a one-pot hydrothermal method. The formed PEI-stabilized Fe3O4 NPs were then modified with fluorescein isothiocyanate (FI) and HA with two different molecular weights to obtain two different Fe3O4 NPs (Fe3O4-PEI-FI-HA6K and Fe3O4-PEI-FI-HA31K NPs) with a size of 15-16nm. The formed HA-modified multifunctional Fe3O4 NPs were characterized via different techniques. We show that the multifunctional Fe3O4 NPs are water-dispersible and colloidal stable in different aqueous media. Invitro cell viability and hemolysis studies reveal that the particles are quite cytocompatible and hemocompatible in the given concentration range. Furthermore, confocal microscopy and flow cytometry data demonstrate that HA-targeted Fe3O4 NPs are able to be uptaken specifically by cancer cells overexpressing CD44 receptors, and be used as efficient probes for targeted MR imaging of cancer cells invitro and xenografted tumor models invivo. With the tunable amine-based conjugation chemistry, the PEI-stabilized Fe3O4 NPs may be functionalized with other biological ligands or drugs for diagnosis and therapy of different biological systems. © 2014 Elsevier Ltd.