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Liu N.,The 455th Hospital of PLA | Liu N.,Charite - Medical University of Berlin | Patzak A.,Charite - Medical University of Berlin | Zhang J.,The 455th Hospital of PLA
American Journal of Physiology - Renal Physiology | Year: 2013

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) can repair acute kidney injury (AKI), but with limited effect. We test the hypothesis that CXCR4 overexpression improves the repair ability of BMSCs and that this is related to increased homing of BMSCs and increased release of cytokines. Hypoxia/reoxygenation-pretreated renal tubular epithelial cells (HR-RTECs) were used. BMSCs, null- BMSCs, and CXCR4-BMSCs were cocultured with HR-RTECs. The number of migrating BMSCs was counted. Proliferating cell nuclear antigen (PCNA) expression, cell death, and expressions of cleaved caspase-3 and Bcl-2 in cocultured HR-RTECs were measured. Cytokeratin 18 (CK18) expression and cytokine secretions of the BMSCs cultured with HR-RTEC supernatant were detected. BMSC homing, renal function, proliferation, and cell death of tubular cells were assayed in the AKI mouse model. CXCR4-BMSCs showed a remarkable expression of CXCR4. Stromal cell-derived factor-1 in the HR-RTEC supernatant was increased. Migration of BMSCs was CXCR4-dependent. Proportions of CK18+ cells in BMSCs, null- BMSCs, and CXCR4-BMSCs showed no difference. However, CXCR4 overexpression in BMSCs stimulated secretion of bone morphogenetic protein-7, hepatocyte growth factor, and interleukin 10. The neutralizing anti-CXCR4 antibody AMD3100 abolished this. In cocultured HR-RTECs the proportions of PCNA+ cells and Bcl-2 expression were enhanced; however, the proportion of annexin V+ cells and expression of cleaved caspase-3 were reduced. The in vivo study showed increased homing of CXCR4-BMSCs in kidneys, which was associated with improved renal function, reduced acute tubular necrosis scoring, accelerated mitogenic response of tubular cells, and reduced tubular cell death. The enhanced homing and paracrine actions of BMSCs with CXCR4 overexpression suggest beneficial effects of such cells in BMSC-based therapy for AKI. © 2013 the American Physiological Society.

Liu Y.,Nanjing University | Yu M.,Shanghai University | Zhang L.,Fudan University | Cao Q.,The 455th Hospital of PLA | And 2 more authors.
Molecular and Cellular Biochemistry | Year: 2016

Vascular dysfunction including vascular remodeling and endothelial dysfunction in hypertension often results in poor clinical outcomes and increased risk of vascular accidents. We investigate the effect of treatment with soluble receptor for advanced glycation end products (sRAGE) on vascular dysfunction in spontaneously hypertensive rats (SHR). Firstly, the aortic AGE/RAGE pathway was investigated in SHR. Secondly, SHR received intraperitoneal injections of sRAGE daily for 4 weeks. Effect of sRAGE against vascular dysfunction in SHR and underlying mechanism was investigated. SHR aortas exhibited enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE. Treatment of SHR with sRAGE had no significant effect on blood pressure, but alleviated aortic hypertrophy and endothelial dysfunction. In vitro, treatment with sRAGE reversed the effect of incubation with AGE on proliferation of smooth muscle cells and endothelial function. Treatment of SHR with sRAGE abated oxidative stress, suppressed inflammation and NF-κB activation, improved the balance between Ang II and Ang-(1-7) through reducing angiotensin-converting enzyme (ACE) activity and enhancing ACE2 expression, and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in aortas. In conclusion, treatment with sRAGE alleviated vascular adverse remodeling in SHR, possibly via suppression of oxidative stress and inflammation, improvement in RAS balance, and activation of PPAR-γ pathway. © 2016, Springer Science+Business Media New York.

Wang L.,The 455th Hospital of PLA | Xu X.P.,The 455th Hospital of PLA | Zhan H.,The 455th Hospital of PLA | Zhang S.M.,The 455th Hospital of PLA
Annals of Thoracic and Cardiovascular Surgery | Year: 2014

This report presents the extracorporeal membrane oxygenation (ECMO)-assisted surgical as a treatment of benign double tracheoesophageal fistula. The patient was a 43-yearold woman who presented the airway obstruction for 3 weeks after the esophagus metal stent implantation for the tracheoesophageal fistula 1 year ago. The airway obstruction was due to the expansion and piercing of the metal stent through the upper part of the esophagus into the tracheal cavity. In view of the failure of endotracheal intubation, we finally used ECMO-assisted surgery to remove the stent. And at the same time, cervical esophagostomy externa, exclusion of the thoracic tracheoesophageal fistulas and gastrostomy were performed. © 2014 The Editorial Committee of Annals of Thoracic and Cardiovascular Surgery. All rights reserved.

Liu N.,Shanghai University | Tian J.,The 455th Hospital of PLA | Cheng J.,The 455th Hospital of PLA | Zhang J.,The 455th Hospital of PLA
Experimental Cell Research | Year: 2013

Bone marrow-derived mesenchymal stem cells (BMSCs) preferentially migrate to the injured tissue but with limited efficiency. Here we investigated the effect of erythropoietin (EPO) treatment on the BMSC migration to the acute kidney injury (AKI) microenvironment. The possible mechanisms were also discussed. A hypoxia/re-oxygenation (HR) model of renal tubular epithelial cells (RTECs) was established to generate AKI in vitro, and a chemotaxis experiment was conducted using the transwell chamber. EPO treatment enhanced the BMSC migration to the HR-RTEC culturing chamber in a SDF-1 level-dependent manner, which was fully inhibited by the treatment of anti-SDF-1 antibody. The BMSC migration could also be partly blocked by LY294002 (phosphoinositide 3-kinase (PI3K) inhibitor) and PD98059 (MAPK inhibitor). Western blot analysis showed that phosphorylated Akt and phosphorylated MAPK in BMSCs were enhanced by EPO treatment. In the in vivo experiment, BMSCs were transplanted into the AKI mice and EPO was subcutaneously injected. The results showed that EPO injection increased the SDF-1 protein expression and BMSC accumulation in the renal tissue, which was consistent with a decent improvement of renal function. In addition, the BMSC accumulation in the renal tissue was blocked by anti-SDF-1 antibody, LY294002 or PD98059. Our data suggest that AKI microenvironment had a directional chemotactic effect on BMSCs, which could be further enhanced by the EPO treatment. The increased SDF-1 level in the AKI microenvironment and the activations of PI3K/AKT and MAPK in BMSCs were the possible mechanisms for the effect of EPO. Therefore, BMSC transplantation combined with EPO injection can be a novel and effective approach for AKI repair. © 2013 Elsevier Inc.

Gu J.-F.,The 455th Hospital of PLA | Ding W.,The 455th Hospital of PLA | Hu J.,The 455th Hospital of PLA | Li Z.-Y.,The 455th Hospital of PLA | Li M.-F.,The 455th Hospital of PLA
World Chinese Journal of Digestology | Year: 2014

Aim: To investigate the efficacy and safety of endoscopic self-expandable metal stent implantation with argon plasma coagulation in the treatment of malignant gastric outlet obstruction. Methods: Clinical data for 54 patients with malignant gastric outlet obstruction diagnosed from February 2010 to November 2013 were retrospectively analyzed. The patients were divided two groups: a control group (n = 27) and a treatment group (n = 27). The control group was treated by implantation of simple metal stents, while the treatment group was treated by implantation of self-expandable metal stents with argon plasma coagulation. Results: Self-expandable metal stent placement was successful in all patients. Fifty-four patients were able to take liquid food and soft food within 24 h after the procedure. Pain developed in 4 cases in the control group, and 2 cases in the treatment group. Three cases in the control group developed restenosis 2 mo after surgery, while only one case in the treatment group had restenosis 4.3 mo after surgery. No bleeding or perforation occurred. Two cases in the control group died after 6 mo. The treatment group was superior to the control group in terms of symptoms, food intake, survival and quality of life. Conclusion: Placement of a self-expandable metal stent combined with argon plasma coagulation in patients with malignant gastric outlet obstruction is safe and effective for resolving obstruction symptoms. © 2014 Baishideng Publishing Group Inc. All rights reserved.

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