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Lopez-Sanchez C.,University of Extremadura | Franco D.,University of Jaen | Bonet F.,University of Jaen | Garcia-Lopez V.,Minimally Invasive Surgery Center | And 2 more authors.
Developmental Biology | Year: 2015

It is known that secreted proteins from the anterior lateral endoderm, FGF8 and BMP2, are involved in mesodermal cardiac differentiation, which determines the first cardiac field, defined by the expression of the earliest specific cardiac markers Nkx-2.5 and Gata4. However, the molecular mechanisms responsible for early cardiac development still remain unclear. At present, microRNAs represent a novel layer of complexity in the regulatory networks controlling gene expression during cardiovascular development. This paper aims to study the role of miR130 during early cardiac specification.Our model is focused on developing chick at gastrula stages. In order to identify those regulatory factors which are involved in cardiac specification, we conducted gain- and loss-of-function experiments in precardiac cells by administration of Fgf8, Bmp2 and miR130, through in vitro electroporation technique and soaked beads application. Embryos were subjected to in situ hybridization, immunohistochemistry and qPCR procedures. Our results reveal that Fgf8 suppresses, while Bmp2 induces, the expression of Nkx-2.5 and Gata4. They also show that Fgf8 suppresses Bmp2, and vice versa. Additionally, we observed that Bmp2 regulates miR-130 -a putative microRNA that targets Erk1/2 (Mapk1) 3'UTR, recognizing its expression in precardiac cells which overlap with Erk1/2 pattern. Finally, we evidence that miR-130 is capable to inhibit Erk1/2 and Fgf8, resulting in an increase of Bmp2, Nkx-2.5 and Gata4. Our data present miR-130 as a necessary linkage in the control of Fgf8 signaling, mediated by Bmp2, establishing a negative feed-back loop responsible to achieve early cardiac specification. © 2015 Elsevier Inc.

Ji W.,Yale University | Li Y.,Sun Yat Sen University | Wan T.,Yale University | Wang J.,Minimally Invasive Surgery Center | And 4 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2012

Objective-The proinflammtory cytokine tumor necrosis factor (TNF), primarily via TNF receptor 1 (TNFR1), induces nuclear factor-κB (NF-κB)-dependent cell survival, and c-Jun N-terminal kinase (JNK) and caspase-dependent cell death, regulating vascular endothelial cell (EC) activation and apoptosis. However, signaling by the second receptor, TNFR2, is poorly understood. The goal of this study was to dissect how TNFR2 mediates NF-κB and JNK signaling in vascular EC, and its relevance to in vivo EC function. Methods and Results-We show that TNFR2 contributes to TNF-induced NF-κB and JNK signaling in EC as TNFR2 deletion or knockdown reduces the TNF responses. To dissect the critical domains of TNFR2 that mediate the TNF responses, we examine the activity of TNFR2 mutant with a specific deletion of the TNFR2 intracellular region, which contains conserved domain I, domain II, domain III, and 2 TNFR-associated factor-2-binding sites. Deletion analyses indicate that different sequences on TNFR2 have distinct roles in NF-κB and JNK activation. Specifically, deletion of the TNFR-associated factor-2-binding sites (TNFR2-59) diminishes the TNFR2-mediated NF-κB, but not JNK activation; whereas, deletion of domain II or domain III blunts TNFR2-mediated JNK but not NF-κB activation. Interestingly, we find that the TNFR-associated factor-2-binding sites ensure TNFR2 on the plasma membrane, but the di-leucine LL motif within the domain II and aa338-355 within the domain III are required for TNFR2 internalization as well as TNFR2-dependent JNK signaling. Moreover, domain III of TNFR2 is responsible for association with ASK1-interacting protein-1, a signaling adaptor critical for TNF-induced JNK signaling. While TNFR2 containing the TNFR-associated factor-2-binding sites prevents EC cell death, a specific activation of JNK without NF-κB activation by TNFR2-59 strongly induces caspase activation and EC apoptosis. Conclusion-Our data reveal that both internalization and ASK1-interacting protein-1 association are required for TNFR2-dependent JNK and apoptotic signaling. Controlling TNFR2-mediated JNK and apoptotic signaling in EC may provide a novel strategy for the treatment of vascular diseases. © 2012 American Heart Association, Inc.

Ke C.-W.,Minimally Invasive Surgery Center | Cai J.-L.,Minimally Invasive Surgery Center | Cai J.-L.,Wenzhou Medical College | Chen D.-L.,Minimally Invasive Surgery Center | Zheng C.-Z.,Minimally Invasive Surgery Center
Surgical Endoscopy and Other Interventional Techniques | Year: 2010

Background: Laparoscopic resection of gastric stromal tumors is being performed with increased frequency. This study aims to evaluate the feasibility and safety of the extraluminal laparoscopic gastric wedge resection (ELWR) technique. Methods: Clinical data of 84 patients who underwent ELWR for gastric submucosal tumors between September 2000 and December 2007 were reviewed and analyzed retrospectively. The operation includes: localization of the tumor, dissection of the omentum, mobilization of the upper stomach and the upper pole of the spleen, exposure of esophago-cardiac junction (ECJ), and wedge resection of the upper part of gastric body and/or the gastric fundus with endoscopic gastrointestinal anastomosis (Endo GIA) stapler. Results: All of the procedures were performed successfully, with mean operation time of 62.6 ± 8.9 min and mean intraoperative blood loss of 86.2 ± 8.1 ml. Through extraluminal laparoscopic wedge resection, complete R0 resection was achieved for all tumors. All surgical margins were negative microscopically. No lesions were missed, nor were there any significant postoperative complications or intraoperative conversions to open surgery. A total of 78.6% of the patients recovered their gastrointestinal functions and began to eat and ambulate within 36 h of the operation. The smallest surgical margins were 0.7-2.5 cm, with a mean distance of 1.4 ± 0.5 cm. Of the 84 cases of gastric submucosal tumors, 29 cases were leiomyomas, 51 cases were various types of stromal tumors, and 4 other cases were neurofibromas. Mean follow-up duration was 51 ± 4.3 months (overall follow-up rate 73.8%, 62/84 cases), during which no recurrences or metastases were found. Conclusion: ELWR is a safe, simple, and effective procedure for treating submucosal tumors in the upper part of the stomach. It can avoid intraperitoneal contamination, possible tumor spillage, and postoperative esophageal stenosis, and provides unlimited scope for gastric resection. © 2010 Springer Science+Business Media, LLC.

Siow A.,Minimally Invasive Surgery Center | Ng S.,Minimally Invasive Surgery Unit
Journal of Minimally Invasive Gynecology | Year: 2011

The objectives of this retrospective case series were to report our experience with laparoscopic management of recurrent cornual ectopic pregnancy in a tertiary care center and to present a review of the literature. Four patients experienced recurrent cornual ectopic pregnancy, and 1 patient had 2 consecutive recurrences. Laparoscopic surgery was performed to treat recurrent cornual ectopic pregnancy in all 4 patients. These 4 cases together with 10 cases collated from the literature review confirm that this entity is rare. Cornual ectopic pregnancy can recur as early as 4 months and as late as 5 years after the first ectopic pregnancy. There seems to be no correlation between the treatment method of the first ectopic pregnancy and the risk of recurrence. The etiology of recurrent cornual ectopic pregnancy is not fully understood, although it shares similar risk factors with tubal ectopic pregnancy. Both medical therapy and surgery are used to treat recurrent cornual ectopic pregnancy, with surgery often performed via laparotomy. These 4 cases constitute the largest case series of recurrent cornual ectopic pregnancy treated laparoscopically. Our experience with laparoscopic management of recurrent cornual ectopic pregnancy in a tertiary care center reveals that it is effective and safe. © 2011 AAGL.

Qin M.,Minimally Invasive Surgery Center | Ding G.,Minimally Invasive Surgery Center | Ding G.,Tianjin Medical University | Yang H.,Minimally Invasive Surgery Center
Journal of Laparoendoscopic and Advanced Surgical Techniques | Year: 2013

Aim: To compare the advantages and disadvantages of laparoscopic Nissen and Toupet fundoplication in the treatment of gastroesophageal reflux disease (GERD) and their indications. Patients and Methods: From June 2001 to December 2011, 383 patients with GERD were randomized into two groups according to the last number in their hospitalization number. Overall, 215 patients underwent laparoscopic Nissen fundoplication, and 168 underwent laparoscopic Toupet fundoplication. Results: No conversions to laparotomy or deaths were observed, and the symptoms disappeared completely postoperatively in both groups. Average follow-up was 5.6 years. No recurrence of symptoms was observed in the Nissen group. Eighteen patients experienced recurrence of symptoms in the Toupet group and were administered acid-suppressing drugs. Esophageal manometry and acid reflux testing were performed 4 months postoperatively, with normal results in both groups. The cure rate of esophageal inflammation was 88.4% in the Nissen group and 67.7% in the Toupet group. Four days postoperatively, the incidences of dysphagia and abdominal distension were significantly higher in the Nissen group compared with the Toupet group (28.4% and 16.7%, respectively); the difference between the two groups significantly decreased 1 year postoperatively (1.5% and 0.8%, respectively). Conclusions: In the short term, the incidence of dysphagia was significantly lower after Toupet fundoplication, but the difference decreased significantly with extension of the postoperative recovery period. For patients with moderate to severe GERD, the laparoscopic Nissen fundoplication may be optimal; for elderly patients or for patients with significantly reduced esophageal peristalsis detected in preoperative examinations, the laparoscopic Toupet fundoplication should be considered. © 2013, Mary Ann Liebert, Inc.

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