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Huang S.-D.,Changhai Hospital | Yuan Y.,Changhai Hospital | Zhuang C.-W.,Fuzhou General Hospital of Nanjing Command | Li B.-L.,Changhai Hospital | And 4 more authors.
Molecular Cancer | Year: 2012

Background: The enhancer of zeste homolog 2 (EZH2) was found to be overexpressed and associated with tumor metastasis in esophageal squamous cell carcinoma (ESCC). On the other hand, it was reported that miR-26a, miR-98, miR-101, miR-124, miR-138 and miR-214 could inhibit the expression of EZH2 in some tumors. However, the role of miRNAs in the regulation of EZH2 expression in human ESCC has not been documented. The aim of this study was to determine the role of these miRNAs in the regulation of tumor metastasis via EZH2 overexpression in human ESCC.Methods and results: The expression of these miRNAs and EZH2 mRNA were examined by qPCR and the expression of EZH2 protein was detected by western blot. The role of these miRNAs in migration and invasion was studied in ESCC cell line (Eca109) transfected with miRNA mimics or cotransfected with miRNA mimics and pcDNA-EZH2 plasmid (without the 3'-UTR of EZH2). Through clinical investigation, we found that miR-98 and miR-214 expression was significantly lower in ESCC tissues than in matched normal tissues, and the expression level of miR-98 and miR-214 was inversely correlated to EZH2 protein expression and the clinical features such as pathological grade, tumor stage and lymph node metastasis in ESCC. In Eca109 cells, overexpression of miR-98 and miR-214 significantly inhibited the migration and invasion of ESCC cells, which was reversed by transfection of EZH2.Conclusions: These findings suggest that decreased expression of miR-98 and miR-214 might promote metastasis of human ESCC by inducing accumulation of EZH2 protein. © 2012 Yuan et al.; licensee BioMed Central Ltd.

Yuan Y.,Shanghai University | Zeng Z.-Y.,Fuzhou General Hospital of Nanjing Command | Liu X.-H.,Shanghai University | Gong D.-J.,Shanghai University | And 3 more authors.
BMC Cancer | Year: 2011

Background: This study was performed to investigate the effect of microRNA-203 (miR-203) and ΔNp63 on cell proliferation and the functional connection between miR-203 and ΔNp63 in ESCC.Methods: We employed 2 human ESCC cell lines, Eca109 and TE-1, as the model system. The effect of miR-203 and ΔNp63 on cell proliferation was determined in cells transfected with miR-203 mimic and ΔNp63 small interfering RNA (siRNA), respectively. The regulation of ΔNp63 expression in ESCC cells by miR-203 was studied by luciferase reporter assay, RT-PCR and western blot analysis in cells transfected with miR-203. The effect of ΔNp63 re-expression on miR-203 induced inhibition of cell proliferation was studied by cell proliferation assay in cells cotransfected with miR-203 and pcDNA-ΔNp63 plasmid (without the 3'-UTR of ΔNp63).Results: We found that both miR-203 and ΔNp63 siRNA signicantly inhibited cell proliferation in ESCC. MiR-203 could down-regulate endogenous ΔNp63 expression at the posttranscriptional level. Moreover, re-expression of ΔNp63 in cells transfected with miR-203 significantly attenuated the miR-203 induced inhibition of cell proliferation.Conclusions: Our data implied that miR-203 could inhibit cell proliferation in human ESCC through ΔNp63-mediated signal pathway. Therefore, we propose that miR-203 might be used as a therapeutic agent for human ESCC. © 2011 Yuan et al; licensee BioMed Central Ltd.

Ye Y.-P.,Fuzhou General Hospital of Nanjing Command | Xu H.,Fuzhou General Hospital of Nanjing Command | Chen D.,Military Command of Fujian Province
Archives of Orthopaedic and Trauma Surgery | Year: 2013

Introduction: Primary aim of this study was to compare long-term pain relief and quality of life in adults with isthmic spondylolisthesis (IS) who were treated with posterior lumbar interbody fusion (PLIF) and posterolateral fusion (PLF). Secondary aim was to compare the fusion and infection rates of PLIF- or PLF-treated groups. Materials and methods: We searched four databases and the cited reference lists of the included studies. Inclusion criteria were pain assessment with visual analog scale (VAS), and clinical studies that compared long-term pain relief of PLF and PLIF-treated adults with IS. Exclusion criteria were use of only one treatment and non-English language. Results: Three of five included studies used VAS to assess the decline in low back pain, radicular pain, or leg pains in PLF- or PLIF-treated patients during the follow-up periods (0.5-6 years). Long-term pain relief significantly improved in both treatment groups. Pooled differences in mean improvement of Oswestry disability index after the operation revealed no significant difference in pain relief between the PLF and PLIF groups (P = 0.856). The five studies together indicated that fusion rate was significantly greater in the PLIF group than that in the PLF group. Conclusions: The majority of PLIF- and PLF-treated adults with low-grade IS experienced long-term pain relief to a similar extent in most studies. PLIF treatment provided significantly better fusion rates than PLF treatment. This meta-analysis indicates that the use of separate, well-defined scales for pain relief and functional outcomes are needed in studies of PLF or PLIF-treated patients. © 2013 The Author(s).

Ye Y.-P.,Fuzhou General Hospital of Nanjing Command | Chen D.,Fujian Province Command | Xu H.,Fuzhou General Hospital of Nanjing Command
European Spine Journal | Year: 2014

Purpose: This meta-analysis compared whether fusion with or without instrumentation to treat this disease differed with respect to patient-centered outcomes. Methods: Medline, Cochrane, EMBASE, Google Scholar data bases were searched for randomized control trials that investigated patients with severe chronic lower back pain resulting from localized lumbar or lumbosacral instability caused by either isthmic spondylolisthesis or degenerative spondylolisthesis. Included randomized studies reported quantitative outcomes for low back pain and functional recovery. The primary outcome was the improvement of function and the secondary outcomes were the improvement of pain, patients' satisfactory level, and the fusion rate. Results: A significantly lower function change in patients with instrumented compared with non-instrumented from baseline (pooled standardized mean difference; -1.02 (95 % CI -1.76 to -0.27); Z -2.67; (P = 0.008)]. There was no significant pain change for patients with instrumented compared with that of non-instrumented from baseline [pooled standardized mean difference; -0.07 (95 % CI -1.25 to 1.12); Z -0.11; (P = 0.913)]. There was no significant difference in satisfactory level for patients with instrumented compared with that of non-instrumented [pooled OR; 2.36 (95 % CI 0.91-6.11); Z 1.76; (P = 0.078)]. There was significantly higher fusion rate for patients with instrumented compared with that of non-instrumented [pooled OR; 3.28 (95 % CI 2.22-4.85); Z 5.96; (P < 0.001)]. Conclusions: This meta-analysis found that inclusion of fusion surgery with instrumentation provided no benefit as evaluated by patient-reported outcomes in patients with lumbar spondylolisthesis. Level of evidence: Not applicable. © 2014 Springer-Verlag.

Chen P.,Fuzhou General Hospital of Nanjing Command
Zhonghua nei ke za zhi [Chinese journal of internal medicine] | Year: 2012

To investigate the protective effect of quercetin on diabetic nephropathy and to explore its possible mechanism. Type 2 diabetes mellitus rat model was established by feeding high-carbohydrate-fat diet and injecting with streptozotocin. At 72 hour after injection, blood samples were collected from the tail veins of all rats. Those rats with blood glucose level ≥ 16.7 mmol/L were considered as the diabetes model been successfully established. The model rats were randomly divided into type 2 diabetic group (group DM, n = 9) and quercetin group (group QUE, n = 9). Other rats were used as normal controls (group NC, n = 8). All rats were performed by intragastric administration for 8 weeks. At the end of experiment, the rats were sacrificed and fasting plasma glucose (FPG), fasting insulin(FIns), serum creatinine (SCr), blood urea nitrogen (BUN), TG, TC, LDL-C, 24 h urine protein (24 h UP), and kidney index (KI) were evaluated. Pathological changes of kidney were observed by periodic acid-silver methenamine (PASM). The expressions of ubiquitin and NF-κB p65 on glomeruli were examined by immunohistochemical method, and its association with the incidence of proteinuria was analyzed. In groups DM and QUE, the level of FPG [(25.45 ± 1.23) mmol/L and (19.99 ± 1.20) mmol/L], FIns [(25.67 ± 2.58) mU/L and (19.29 ± 1.80) mU/L], SCr [(44.00 ± 2.53) μmol/L and (34.43 ± 2.23) μmol/L], BUN[(11.60 ± 0.39) mmol/L and (8.20 ± 0.37) mmol/L], TG[(3.32 ± 0.22)mmol/L and (2.43 ± 0.25) mmol/L], TC [(2.95 ± 0.21) mmol/L and (2.24 ± 0.17) mmol/L], LDL-C [(2.03 ± 0.22) mmol/L and (1.49 ± 0.13) mmol/L], 24 h UP[(46.67 ± 2.50) mg/24 h and (25.57 ± 2.82) mg/24 h] and KI [(9.76 ± 0.30)×103 and (8.44 ± 0.26)×103] were significantly increased than the indexes of group NC [(6.56 ± 0.41) mmol/L, (12.63 ± 1.41) mU/L, (22.88 ± 2.36) μmol/L, (5.45 ± 0.51) mmol/L, (1.64 ± 0.11) mmol/L, (1.33 ± 0.17) mmol/L, (0.46 ± 0.05) mmol/L, (12.38 ± 1.19)/24 h and (6.78 ± 0.12)×103]. Moreover, the above indexes in group QUE were obviously lower than group DM. There was evidence of pathological changes associated with diabetes, such as focal and segmental sclerosis and thickened basement and mesangial expansion. The expressions of ubiquitin and NF-κB p65 in renal tissues of group DM increased significantly (P < 0.01). The expression of ubiquitin and NF-κB p65 were positively related with the level of 24 h UP (r = 0.893, 0.879, P < 0.01). Compared with group DM, all above indexes in group QUE were markedly alleviated (P < 0.01). The expression of ubiquitin and NF-κB p65 was reduced but didn't reach level in group NC (P < 0.01). The increased expression of NF-κB induced by ubiquitin-proteasome system may participate in the pathogenesis of proteinuria in diabetic nephropathy. Quercetin has renal protective effects partly through reducing NF-κB p65 expression.

This article has been withdrawn at the request of the author(s) and editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Lin B.-Q.,Fuzhou General Hospital of Nanjing Command | Zeng Z.-Y.,Fuzhou General Hospital of Nanjing Command | Yang S.-S.,Fuzhou General Hospital of Nanjing Command | Zhuang C.-W.,Fuzhou General Hospital of Nanjing Command
Lung Cancer | Year: 2013

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide; however, only limited therapeutic treatments are available. The aim of present study was to elucidate the therapeutic effect of dietary restriction in human NSCLC xenografts. Adult female nude mice were injected subcutaneously in the right dorsal flank with NSCLC cell line A549 cells. 5 days after tumor implantation, animals were randomly divided into ad libitum-fed group (AL, 95% of average diary intake) or dietary-restriction-fed group (DR, 70% average diary intake). 24 days after implantation, it was found that DR inhibited tumor growth marked by lower tumor volume and weight. DR suppressed tumor proliferation marked by reduced proliferating cell nuclear antigen (PCNA) expression and activated mitochondria-mediated apoptosis. DR decreased microvessel density marked by decreased CD31 immunostaining and promoted vessel maturation marked by increased alpha-smooth muscle actin (α-SMA) and reduced Factor VIII expression. DR reduced intratumoral interstitial fluid pressure and attenuated tumor hypoxia detected by EF5 immunostaining. In addition, DR suppressed NFκB signaling pathway and downregulated its downstream proteins expression including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). DR suppressed phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. In conclusion, dietary restriction suppresses tumor growth, reduces angiogenesis, and improves tumor microenvironment in human non-small-cell lung cancer xenografts. Dietary restriction could thus be envisaged as a nutritional countermeasure against non-small-cell lung cancer. © 2012 Elsevier Ireland Ltd.

Chen S.-H.,Fuzhou General Hospital of Nanjing Command | Li D.-L.,Fuzhou General Hospital of Nanjing Command | Yang F.,Fuzhou General Hospital of Nanjing Command | Wu Z.,Fuzhou General Hospital of Nanjing Command | And 2 more authors.
Biochimie | Year: 2014

The pancreatic adenocarcinoma remains the most aggressive human malignancy with an extremely low 5-year overall survival. Postoperative gemcitabine could significantly delay recurrence after complete resection of pancreatic cancer. However, the underlying mechanisms are not fully understood. The chemo-resistance factors against gemcitabine still need further characterizations. Here we studied the mechanism of gemcitabine-induced pancreatic cancer cell death by focusing on mammalian sterile 20-like kinase 1 (MST1) and cyclophilin D (Cyp-D). We found that MST1 and Cyp-D expressions were significantly lower in gemcitabine-resistant pancreatic cancer tissues and cell lines. In vitro, gemcitabine activated MST1 through reactive oxygen species (ROS) production, which was prevented by antioxidant n-acetyl-cysteine (NAC). We found that gemcitabine-activated MST1 translocated to mitochondria and formed a complex with the local protein Cyp-D. Gemcitabine-induced cell death was alleviated by MST1 or Cyp-D shRNA silencing, but was aggravated by MST1 or Cyp-D over-expression. Further, cyclosporin A (CsA), the Cyp-D inhibitor, prevented gemcitabine-induced MST1/Cyp-D mitochondrial complexation and cancer cell death. We suggest that gemcitabine-induced death of pancreatic cancer cells requires MST1/Cyp-D mitochondrial complexation. © 2014 Elsevier Masson SAS. All rights reserved.

OBJECTIVE: To explore the effects of core-binding factor α1 (Cbfα-1) gene silenced by siRNA on osteogenic differentiation and calcification of vascular smooth muscle cells (VSMC) induced by high phosphate in vitro.METHODS: VSMC were cultured in vitro and passaged 3 to 8 times. Four pairs of Cbfα-1 siRNA were designed and synthesized. Transfection was performed with cationic lipid vectors (Lipofectamine 2000). Transfection conditions were optimized by the FAM fluorescent labeling-siRNA to screen effective siRNA sequences by reverse transcription-polymerase chain reaction (RT-PCR). After transfection with effective siRNA sequences, VSMCs were divided into 4 groups: (1) normal phosphate (Pi 1.3 mmol/L); (2) high phosphate (Pi 2.6 mmol/L); (3) siRNA transfection: high phosphate+Cbfα-1-siRNA; (4) negative transfection control: high phosphate+negative control siRNA. Cbfα-1 and osteopontin (OPN) mRNA and protein expression were detected by RT-PCR and Western blotting. Calcium deposition was visualized by Alizarin stain method.RESULTS: The transfection efficiency was around 55% with a concentration of Cbfα-1 siRNA 100 nmol/L and Lipo 8 µl/ well. Cbfα-1 siRNA 1952 was chosen as the effective sequence with a suppression ratio up to 81.8%. At 24 and 48 h post-transfection, the expression of Cbfα-1 mRNA was significantly lower in siRNA transfection group than that in high phosphate group (0.335 ± 0.059 vs 0.714 ± 0.106, 0.574 ± 0.036 vs 0.726 ± 0.086, all P < 0.01) . At 48 and 72 h post-transfection, the expression of Cbfα-1 protein in siRNA transfection group was significantly lower than that in high phosphate group (both P < 0.01) . While Cbfα-1 gene was silenced by siRNA in siRNA transfection group, the mRNA and protein expression of OPN significantly declined (all P < 0.05) and calcium deposition in cell layers decreased.CONCLUSIONS: Cbfα-1 siRNA can effectively inhibit the expression of Cbfα-1 mRNA and protein in VSMC and thus suppress the transformation of VSMC into osteoblast-like cells and calcification induced by high phosphate. Cbfα-1 may become a potential therapeutic target in vascular calcification of chronic kidney disease.

Yu Y.,Fuzhou General Hospital of Nanjing Command | Wang Y.,Fuzhou General Hospital of Nanjing Command | Zhou L.-N.,Fuzhou General Hospital of Nanjing Command | Zheng F.,Fuzhou General Hospital of Nanjing Command
American Journal of Nephrology | Year: 2011

Background: Endothelial progenitor cells (EPCs) are involved in endothelium turnover and play a role in renal capillary repair. Since angiotensin II has been shown to negatively affect EPCs and blockade of angiotensin II decreases the progression of renal diseases, we investigated the effects of losartan on EPCs and renal endothelial cells in remnant kidney. Methods: Sprague-Dawley rats were randomized to receive losartan (25 mg/kg/day) or solvent for 15 weeks after 5/6 nephrectomy. Peripheral blood CD34+ EPCs were counted and the number of CD31+ endothelial colonies was determined. Glomerular and tubulointerstitial capillary endothelial cells were assessed and vascular endothelial growth factor (VEGF) and thrombospondin (TSP-1) expression were determined. Results: EPCs and the number of endothelial colonies were significantly reduced in 5/6 nephrectomized rats, which was associated with a decrease in glomerular and tubulointerstitial endothelial cells, a decrease in VEGF and an increase in TSP-1 expression. Losartan treatment largely prevented changes in both EPCs and remnant kidney. Conclusion: The gradual loss of renal capillaries in remnant kidney was associated with decreased EPCs and endothelial colonies, hindering capillary endothelial repair in remnant kidney. Losartan treatment largely prevented the loss of EPCs and preserved renal endothelial cells, which may be part of the mechanism of how it contributes to renal protection. Copyright © 2011 S. Karger AG, Basel.

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