China Medical University at Heping
Heping, China
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Yang X.,China Medical University at Heping | Yan J.,China Medical University at Heping | Feng J.,China Medical University at Heping
European Journal of Pharmacology | Year: 2016

Tanshinone IIA (TSIIA), one of the major bioactive components of the traditional Chinese herb Salvia miltiorrhiza, has been reported to have both anti-inflammatory and immunoregulatory effects. The effect of treatment with TSIIA in multiple sclerosis, an autoimmune inflammatory neurodegenerative disease, however, remains poorly understood. In the present study, experimental autoimmune encephalomyelitis (EAE), a classical experimental model of MS, was used to investigate the therapeutic effect of TSIIA. TSIIA attenuated motor dysfunction and improved inflammation and demyelination associated with EAE in a dose-dependent manner. TSIIA also significantly reduced the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule-1 (Iba-1), and protected the integrity of the blood-brain barrier (BBB) by increasing the expression of critical endothelial tight junction (TJ) proteins. TSIIA also inhibited the expression of some adhesion molecules and chemokines, which are considered to be critical for adhesion of immune cells and migration across the BBB. TSIIA was thus shown to be effective in the treatment of EAE through preventing the infiltration of immune cells into the CNS, strengthening the integrity of the BBB and decreasing the numbers of adhesion molecules and chemokines. © 2015 Elsevier B.V.

Xia M.,China Medical University at Heping | Zhu Y.,China Medical University at Heping
Journal of Molecular Neuroscience | Year: 2013

Spinal cord injury is characterized by an inflammatory response that includes the increased expression of several cytokines and chemokines. Extracellular adenosine triphosphate (ATP) acts as a critical endogenous signaling molecule in inflammation and immunity. However, the molecular and cellular mechanisms of the proinflammatory cytokines stimulated by ATP are poorly understood. Mammalian forkhead members of the class O (FOXO) are involved in a variety of signaling pathways. In this study, we have found that ATP could selectively decrease the expression of FOXO1 and FOXO3a via the phosphorylation of epidermal growth factor receptor (EGFR) and Akt in spinal cord astrocytes. However, ATP had no effect on the expression of FOXO4 and FOXO6, and EGFR, Akt, and ERK1/2 all involve in the release of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) induced by ATP. In addition, we have researched that the overexpressed FOXO3a could specially inhibit the release of TNF-α increased by ATP, but the level of IL-6 induced by ATP was not decreased. Meanwhile, there was no change in the release of IL-6 and TNF-α after FOXO1 was overexpressed. Understanding the critical role of FOXO3a in astrocytes stimulated by ATP may provide a potential target for therapeutic intervention after spinal cord injury. © 2013 Springer Science+Business Media New York.

Zhang W.,China Medical University at Heping | Zhang X.-A.,Shenyang Sport University
NeuroReport | Year: 2014

Inflammation plays a crucial role in the pathogenesis and prognosis of stroke. This study aims to investigate the relationship between acute ischemic stroke (AIS) and lipoprotein(a) [Lp(a)] levels and to determine the prognosis value of Lp(a) to predict the functional outcome. A total of 153 patients with AIS and 120 controls were included in the study. Serum Lp(a) levels were examined in both groups. Severity of the stroke was assessed using the National Institutes of Health Stroke Scale. The modified Rankin Scale scores at discharge were determined to establish the prognosis of stroke patients. The prognostic value of Lp(a) to predict the functional outcome within the time of discharge was analyzed by logistic regression analysis, after adjusting for the possible confounders. The results indicated that the serum Lp(a) levels were significantly higher in AIS patients as compared with normal controls [303 {interquartile range (IQR) 170-529 mg/l} and 144 (IQR 66-252 mg/l), respectively; P=0.000]. In the 52 patients with an unfavorable functional outcome, serum Lp(a) levels were higher compared with those in patients with a favorable outcome [213 (IQR 143-347 mg/l) and 559 (IQR 357-845 mg/l), respectively; P=0.000]. In multivariate analysis, there was an increased risk of unfavorable outcome associated with Lp(a) levels 300 mg/l or more (odds ratio 3.12; 95% confidence interval 1.55-5.28; P=0.001) after adjusting for possible confounders. Serum Lp(a) can be considered as an independent short-term prognostic marker of functional outcome in Chinese patients with AIS even after correcting for possible confounding factors.

Xia M.,China Medical University at Heping | Zhu Y.,China Medical University at Heping
GLIA | Year: 2011

Traumatic spinal cord injury is characterized by an immediate, irreversible loss of tissue at the lesion site, as well as a secondary expansion of tissue damage over time. Although secondary injury should, in principle, be preventable, no effective treatment options currently exist for patients with acute spinal cord injury (SCI). Excessive release of ATP by the traumatized tissue, triggers the rapid release of arachidonic acid (AA) and prostaglandin E2 (PGE2), and has beenimplicated in acute and chronic neuropathic pain and inflammation. But the intracellular pathways between ATP and PGE2 remain largely unknown. We have explored the signaling events involved in this synthesis by primarily culturing spinal cord astrocytes: (1) we determined significant PGE2 production increased by ATP is mainly via Subtype 1 of P2 purinoceptors (P2Y1) but not P2Y2; (2) we found that ATP strongly increased the level of intracellular Ca2+ via P2Y1 receptor; (3) we indicated that ATP stimulates the definitely release of AA and PGE2 which involved the transactivation of epidermal growth factor (EGF) receptor, the phosphorylation of extracellular-regulated protein kinases 1 and 2 (ERK1/2) and the activation of cytosolic phospholipase A2 (cPLA2); (4) we examined ATP could increase the phosphorylation of Akt via P2Y1 receptor which also depend on the transactivation of EGFR, but the activation of Akt has no effect on the downstream of cPLA2 phosphorylation. ATP induced by SCI could mobilize the release of AA and PGE2. And inhibition of PGE2 release reduces behavioral signs of pain after SCI and peripheral nerve injury. © 2011 Wiley-Liss, Inc.

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:

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.

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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