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Han D.,Shanghai JiaoTong University | Li J.,China Medical University at Heping
Cell and Tissue Research | Year: 2013

A large hurdle in orthopedics today is the difficulty of dealing with the non-union of fractured bones. We therefore evaluated the effects of runt-related transcription factor II (Runx II), a factor used to create gene-modified tissue-engineered bone, combined with vascular bundle implantation for repairing segmental bone defects. Adenovirus Runx II gene (Ad-Runx II)-modified rabbit adipose-derived stem cells (ADSCs) were seeded onto polylactic acid/polycaprolacton (PLA/PCL) scaffolds to construct gene-modified tissue-engineered bone. The following four methods were used for repair in rabbit radial-defect (1.5 cm long) models: gene-modified tissue-engineered bone with vascular bundle (Group A), gene-modified tissue-engineered bone (Group B), non-gene-modified tissue-engineered bone with vascular bundle (Group C), and PLA/PCL scaffolds only (Group D). X-ray, histological examination, biomechanics analysis, and micro-angiography were conducted 4, 8, and 12 weeks later to determine angiogenesis and osteogenesis. The volume and speed of production of newly formed bones in Group A were significantly superior to those in other groups, and de-novo vascular network circulation from the vessel bundle through newly formed bone tissue was observed, with the defect being completely repaired. Group B showed a slightly better effect in terms of speed and quality of bone formation than Group C, whereas the bone defect in Group D was replaced by fibrous tissue. The maximal anti-bending strength in Group A was significantly higher than that in the other groups. Runx II gene therapy combined with vascular bundle implantation thus displays excellent abilities for osteoinduction and vascularization and is a promising method for the treatment of bone non-union and defect. © 2013 Springer-Verlag Berlin Heidelberg.

The polymorphism Pro12Ala in peroxisome proliferator-activated receptor-γ2 gene (PPARγ2) has been reported to be associated with diabetic nephropathy (DN) in some studies, though the results remain inconclusive. To explore this relationship between PPARγ2 Pro12Ala polymorphism and the susceptibility for DN, a cumulative meta-analysis was performed in this study. PubMed, Medline, Embase and Web of Science databases have been systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. 18 studies were included in this meta-analysis, involving 3,361 cases and 5,815 controls. The PPARγ2 Ala12 allele was significantly associated with decreased risk of DN based on dominant model (OR=0.778; 95%CI=0.618-0.981; Pheterogeneity=0.008; P=0.034). In the stratified analysis by ethnicity, significantly decreased risks were found among Caucasians for dominant model (OR=0.674; 95%CI=0.500-0.909; Pheterogeneity=0.079; P=0.010), while there was no significant association was found in Asians. The results from the present meta-analysis indicated that the Pro12Ala polymorphism in PPARγ2 gene is not a risk factor for DN in type 2 diabetes (T2D). Further large and well-designed studies are needed to confirm this conclusion. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7491348341027320.

Sun Y.-B.,China Medical University at Heping | Xu S.,China Medical University at Heping
International Journal of Oncology | Year: 2013

Lung cancer is the most commonly diagnosed cancer worldwide. Loss of KISS1 expression has been associated with progression and poor prognosis of various cancers, however, the precise role of KISS1 expression in non-small cell lung cancer (NSCLC) is not well defined. KISS1 receptor (KISS1R, also named GPR54) coupled to KISS1, has been shown to play a pivotal role in suppressing cancer metastasis. In this study, 56 NSCLC specimens were divided into stage IIIB (locally advanced) and stage IV (metastatic). The mRNA and protein levels of KISS1 and KISS1R in cancer tissues were found to be lower compared to that in normal tissues using RT-PCR and western blot analysis, respectively. In addition, the expression of both KISS1 and KISS1R in stage IV NSCLC was lower compared to that in stage IIIB stage NSCLC. The cumulative survival rate of the patients with KISS1 or KISS1R expression was significantly higher compared to that without expression. KISS1 or KISS1R expression in NSCLC can be used to indicate favorable prognosis for disease outcome. Metastin, the product of the KISS1 gene, was lower in the serum of patients with stage IV NSCLC compared to that in stage IIIB NSCLC.

Xia M.,China Medical University at Heping | Zhu Y.,China Medical University at Heping
Journal of Orthopaedic Research | Year: 2011

Fibronectin fragments (Fn-f), which are the breakdown products of fibronectin, accumulate in the disc during degeneration and are proved to induce the degeneration of intervertebral disc. The goal of this investigation was to determine the functional role of integrin α5β1, extracellular signal-regulated kinase (ERK), and protein kinase C (PKC) in the process of Fn-f degeneration nucleus pulposus (NP) cells. We found that Fn-f (100 nM, 30 kDa) exposure led to degeneration of NP cells, up-regulation of integrin α5β1 expression and phosphorylation of the ERK1/2. After the expression of integrin a5b1 was silenced in NP cells, the phosphorylation of ERK1/2 and the expression of MMP9, MMP13, and collagen II had no difference with control under the treatment of Fn-f. Finally, when the inhibitor of ERK1/2 and the inhibitor of PKC were added into the medium of NP cells; we found these two inhibitors could eliminate the effect of Fn-f on NP cells. It is concluded that Fn-f had the potential to enhance the NP cell degeneration in a vicious circle. And the integrin α5β1 subunit, ERK, and PKC were all included in this loop. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

To study the protective effect of mitochondrial ATP-sensitive K+ channel (mitoKATP channel) opener, nicorandil, combined with Na+/Ca2+ exchange blocker KB-R7943 on myocardial ischemia-reperfusion injury in isolated rat hearts; the isolated rat heart was perfused by modified Langendorff device, after 15-min balanced perfusion, 45-min ischemia (about left and right coronary perfusion flow reduced to 5% of the original irrigation flow), and 2-h reperfusion were performed. Forty Wistar rats were randomly divided into four groups: control group, nicorandil group, KB-R7943 group, and the combination of nicorandil and KB-R7943 group. After 45-min ischemia and then 2-h reperfusion, the myocardial infarct size was 34. 31% in control group, 26. 35% in nicorandil group, 28. 74% in KB-R7943 group, and 19. 23% in combination of nicorandil and KB-R7943 group. SOD activity in coronary perfusion fluid was the highest in the combination of nicorandil and KB-R7943 group, and MDA content was the lowest. In the combination drug group compared with the control group, myocardial ultrastructural injury was significantly reduced. The combination of nicorandil and KB-R7943 significantly reduced myocardial infarct size, significantly reduced myocardial ultrastructural damage, could increase coronary perfusion fluid SOD activity, and reduced MDA levels. © 2010 Springer Science+Business Media, LLC.

The usage of submental flap is a good method for head and neck reconstruction, but it has some risk also, such as anatomical variations and surgical errors. In this article, we present a modified incision design for the submental flap. We designed a modified submental flap incision method based on the overlap of the incision outline of the submental flap, platysma myocutaneous flap and infrahyoid myocutaneous flap. If we found that the submental flap was unreliable during the neck dissection at the level III, II and Ib areas, the infrahyoid myocutaneous flap or platysma myocutaneous flap was used to replace it. Between 2004 and 2012, we performed 30 cases using this method. As control, 33 radial forearm free flaps were counted. Significant differences were evaluated using the χ(2) test and Mann-Whitney U. Survival and recurrence were analyzed using the Kaplan-Meier method. Of the 30 patients, 27 finally received a submental flap, 1 patient received an infrahyoid myocutaneous flap, and 2 patients received a platysma myocutaneous flap. In patients who received the submental flap, the average operation time was 5.9 hours, 2.4 hours shorter than the radial forearm free flap group; the average age was 61.8, 6.1 years older than the radial forearm free flap group; the survival time and recurrence time did not significantly differ with those of the forearm free flap group; and the success rate was higher than traditional methods. The wider indications, less required time, the similar low risk of recurrence and death as radial forearm free flap, higher success rate than traditional submental flap harvest methods, and ability to safely harvest a submental flap make the modified incision design a reliable method.

To explore the determinants of smoking behaviour in recreational venues and to provide scientific bases for establishing smoke-free measures applying to these locations. The International Tobacco Control (ITC) China Survey--a face-to-face cross-sectional survey of representative adult smokers from six cities (Shenyang, Beijing, Shanghai, Guangzhou, Changsha and Yinchuan)--was conducted between April and August 2006. A total of 4815 smokers were selected using multistage sampling methods, and final analyses were conducted on 2875 smokers who reported patronising recreational venues at least once in the last six months. Multivariate logistic regression models were used to identify factors influencing the smoking behaviour within recreational settings. Outcome measure Whether a smoker reported smoking in recreational venues during the last 6 months. 84% subjects reported smoking in recreational venues. Analyses showed that smoke-free laws had been exempted, 32.0% of the patrons reporting bans on smoking in these locations. The following factors were significant predictors of smoking in recreational venues: absence of bans on smoking, support for non-bans, being aged 18-24 years, positive smoking-related attitudes, low number of health effects reported and not living in Beijing. The findings point to the importance of informing Chinese smokers about the active smoking and passive smoking harmfulness in both building support for smoke-free laws and in reducing smokers' desire to smoke within recreational venues. They also point to the importance of good enforcement of smoke-free laws when implemented. Such strategies could also serve to de-normalise smoking in China, a key strategy for reducing smoking in general.

Yao D.,China Medical University at Heping | Dai C.,China Medical University at Heping | Peng S.,China Medical University at Heping
Molecular Cancer Research | Year: 2011

Cancer metastasis consists of a sequential series of events, and the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are recognized as critical events for metastasis of carcinomas. A current area of focus is the histopathological similarity between primary and metastatic tumors, and MET at sites of metastases has been postulated to be part of the process of metastatic tumor formation. Here, we summarize accumulating evidence from experimental studies that directly supports the role of MET in cancer metastasis, and we analyze the main mechanisms that regulate MET or reverse EMT in carcinomas. Given the critical role of MET in metastatic tumor formation, the potential to effectively target the MET process at sites of metastasis offers new hope for inhibiting metastatic tumor formation. ©2011 AACR.

Qi L.,China Medical University at Heping | Zhang Y.,China Medical University at Heping
Cellular Physiology and Biochemistry | Year: 2014

Background/Aims: Once tissue destruction has occurred, the differentiation of periodontal ligament (PDL) cells into osteoblasts plays an important role in repairing the oral cavity. Methods: In this work, we measured the proliferation and differentiation of PDL cells after fluid shear stress (FSS) treatment by ALP activity assays and in vitro mineralization assays respectively. The levels of miRNA in PDL cells treated with FSS or not were detected by using microRNA arrays. The possible signaling pathway was determined by western-blot. Results: This study demonstrates that FSS modulates several functions of human PDL cells. Specifically, increasing FSS in fixed increments regulates the proliferation and differentiation of PDL cells. Through microRNA arrays, we find that FSS induced-differentiation is accompanied by a significantly higher level of miR-132 compared to untreated controls. Phosphorylated levels of the P13K, AKT, mTOR, and p70S6K proteins also significantly increases in FSS-treated PDL cells. Finally, the FSS-induced differentiation of PDL cells is inhibited by miR-132 knockdown probe and the mTOR signaling pathway inhibitor BEZ235. Conclusion: Our data support the hypothesis that FSS-induced differentiation and proliferation involves the PI3K/AKT/mTOR signaling axis, through a process involving mir-132. Copyright © 2014 S. Karger AG, Basel.

Glutamate plays a double role in 13C-nuclear magnetic resonance (NMR) spectroscopic determination of glucose metabolism in the brain. Bidirectional exchange between initially unlabeled glutamate and labeled α-ketoglutarate, formed from pyruvate via pyruvate dehydrogenase (PDH), indicates the rate of energy metabolism in the tricarboxylic acid (V TCA) cycle in neurons (V PDH, n) and, with additional computation, also in astrocytes (V PDH, g), as confirmed using the astrocyte-specific substrate [ 13C]acetate. Formation of new molecules of glutamate during increased glutamatergic activity occurs only in astrocytes by combined pyruvate carboxylase (V PC) and astrocytic PDH activity. V PDH, g accounts for ~15% of total pyruvate metabolism in the brain cortex, and V PC accounts for another ~10%. Since both PDH-generated and PC-generated pyruvates are needed for glutamate synthesis, ~20/25 (80%) of astrocytic pyruvate metabolism proceed via glutamate formation. Net transmitter glutamate [γ-aminobutyric acid (GABA)] formation requires transfer of newly synthesized α-ketoglutarate to the astrocytic cytosol, α-ketoglutarate transamination to glutamate, amidation to glutamine, glutamine transfer to neurons, its hydrolysis to glutamate and glutamate release (or GABA formation). Glutamate-glutamine cycling, measured as glutamine synthesis rate (V cycle), also transfers previously released glutamate/GABA to neurons after an initial astrocytic accumulation and measures predominantly glutamate signaling. An empirically established ~1/1 ratio between glucose metabolism and V cycle may reflect glucose utilization associated with oxidation/reduction processes during glutamate production, which together with associated transamination processes are balanced by subsequent glutamate oxidation after cessation of increased signaling activity. Astrocytic glutamate formation and subsequent oxidative metabolism provide large amounts of adenosine triphosphate used for accumulation from extracellular clefts of neuronally released K + and glutamate and for cytosolic Ca 2+ homeostasis. © 2011 Elsevier Inc.

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