Mao Q.-X.,Chongqing Medical University |
Mao Q.-X.,DaPing Hospital |
Yang T.-D.,Chongqing Medical University
Brain Research Bulletin | Year: 2010
Excitatory amino acid transporters (EAATs) appear to participate in the pathogenesis of neuropathic pain. The present study was performed to evaluate the effects of the tricyclic antidepressant amitriptyline on the expressions of EAATs in neuropathic pain rats. Using spared nerve injured (SNI) male Sprague Dawley rats, we found that SNI induced an initial EAATs upregulation on postoperative day 1 within the ipsilateral spinal cord dorsal horn, followed by a downregulation on postoperative days 3 and 5. Intraperitoneal administration of amitriptyline reversed the downregulation of EAATs in SNI rats on postoperative days 3-5 and attenuated the mechanical allodynia. We further demonstrated that administration of amitriptyline alone induced an upregulation of EAATs in sham-operated rat but do not produce an antinociceptive effect. These results indicate that amitriptyline could increase the expression of EAATs which may be one of its mechanisms in the treatment of neuropathic pain. © 2009 Elsevier Inc. All rights reserved.
Xu Z.-Q.,Flinders University |
Xu Z.-Q.,Daping Hospital |
Sun Y.,Flinders University |
Li H.-Y.,Flinders University |
And 3 more authors.
European Journal of Neuroscience | Year: 2011
The majority of newborn neurons migrate from their birthplace to final destination in the developing brain. Migration of cerebellar granule cells (CGCs) requires multiple factors. Mature brain-derived neurotrophic factor (BDNF) positively regulates the proliferation, migration, survival and differentiation of CGCs in rodents. However, the role of the BDNF precursor, proBDNF, in neuronal development remains unknown. In this study, we investigated the effect of proBDNF in vivo and in vitro on migration of CGCs. We demonstrate that proBDNF and its receptors p75 neurotrophin receptor (p75NTR) and sortilin are highly expressed in the cerebella as determined by immunohistochemistry and Western blot. ProBDNF is released from cultured cerebellar neurons, and this release is increased by high potassium stimulation. ProBDNF inhibits migration of CGCs in vitro, and the neutralizing antibodies to proBDNF enhance such migration as assayed by transwell culture. In addition, proBDNF incorporated into an agarose plug reduces granule cell migration from such plugs, whereas the neutralizing antibodies attract these cells towards the plug. The application of proBDNF into the lateral ventricle significantly inhibits migration of CGCs out of the proliferative zone into the internal granular cell layer, whereas the neutralizing antibodies enhance this migration. Furthermore, the effects of proBDNF on cell migration are lost in p75NTR-/- mice. Our data suggest that proBDNF negatively regulates migration of CGCs and this effect is mediated by p75NTR. We conclude that proBDNF has an opposing role in migration of CGCs to that of mature BDNF. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
Yu H.,Daping Hospital |
Yu H.,Second Affiliated Hospital |
Jin H.,Peking University |
Gong W.,First Affiliated Hospital |
And 2 more authors.
Molecules | Year: 2013
Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodiae fructus. With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, Alzheimer's disease, infectious diseases and themoregulative effects. Evodiamine has evolved a superior ability to bind various proteins, so we also argue that it is good starting point for multi-target drugs. This review is primarily addressed to the description of the recent advances in the biological activity studies of evodiamine, with a focus on pharmacological mechanism. The present review also includes the pharmacokinetics and the detailed exploration of target-binding properties of evodiamine in an attempt to provide a direction for further multi-target drug design. © 2013 by the authors.
Wu G.,Daping Hospital |
Wu G.,Harvard University |
Cai J.,Daping Hospital |
Han Y.,Daping Hospital |
And 18 more authors.
Circulation | Year: 2014
Background: Long noncoding RNAs (lncRNAs) have recently been implicated in many biological processes and diseases. Atherosclerosis is a major risk factor for cardiovascular disease. However, the functional role of lncRNAs in atherosclerosis is largely unknown. Methods and Results: We identified lincRNA-p21 as a key regulator of cell proliferation and apoptosis during atherosclerosis. The expression of lincRNA-p21 was dramatically downregulated in atherosclerotic plaques of ApoE-/-mice, an animal model for atherosclerosis. Through loss- and gain-of-function approaches, we showed that lincRNA-p21 represses cell proliferation and induces apoptosis in vascular smooth muscle cells and mouse mononuclear macrophage cells in vitro. Moreover, we found that inhibition of lincRNA-p21 results in neointimal hyperplasia in vivo in a carotid artery injury model. Genome-wide analysis revealed that lincRNA-p21 inhibition dysregulated many p53 targets. Furthermore, lincRNA-p21, a transcriptional target of p53, feeds back to enhance p53 transcriptional activity, at least in part, via binding to mouse double minute 2(MDM2), an E3 ubiquitin-protein ligase. The association of lincRNA-p21 and MDM2 releases MDM2 repression of p53, enabling p53 to interact with p300 and to bind to the promoters/enhancers of its target genes. Finally, we show that lincRNA-p21 expression is decreased in patients with coronary artery disease. Conclusions: Our studies identify lincRNA-p21 as a novel regulator of cell proliferation and apoptosis and suggest that this lncRNA could serve as a therapeutic target to treat atherosclerosis and related cardiovascular disorders.
Hao L.,No 324 Hospital Of Pla |
Sun H.,Chongqing Medical University |
Wang J.,Daping Hospital |
Wang T.,Chongqing Medical University |
And 2 more authors.
International Journal of Hematology | Year: 2012
Mesenchymal stromal cells (MSC) have attracted the attention of scientists and clinicians due to their self-renewal, capacity for multipotent differentiation, and immunomodulatory properties. Some essential problems remain to be solved before the clinical application of MSC. Platelet lysate (PL) has recently been used as a substitute for FBS in MSC amplification in vitro to achieve clinically applicable numbers of MSC. In addition to promising trials in regenerative medicine, such as in the treatment of major bone defects and myocardial infarction, MSC have shown therapeutic effect other than direct hematopoiesis support in hematopoietic reconstruction. It has been confirmed that MSC promote hematopoietic cell engraftment and immune recovery after allogeneic hematopoietic stem cell transplantation, probably through the provision of cytokines, matrix proteins, and cell-to-cell contacts. Their suppressive effects on immune cells, including T cells, B cells, NK cells and DC cells, suggest MSCs as a novel therapy for GVHD and other autoimmune disorders. These cells thus present as promising candidates for cellular therapy in the fields of regenerative medicine, allogeneic hematopoietic stem cell transplantation, and autoimmune disorders. © 2011 The Japanese Society of Hematology.
Tu Y.-J.,Daping Hospital |
Tu Y.-J.,174th Hospital of PLA |
Fan X.,Daping Hospital |
Yang X.,Daping Hospital |
And 2 more authors.
Oncology Reports | Year: 2013
Autophagy is a self-defense mechanism that provides nutrition and energy for cell survival by recycling the cytoplasm and organelles. Hence, chemotherapy is rendered less effective against cancer cells. Evodiamine is a previously described biological agent that possesses a cytotoxic activity in multiple cancer cells. However, little is known about evodiamine-induced autophagy in Lewis lung carcinoma (LLC) cells. In this study, LLC cells and a xenograft model were used. By use of a panel of techniques such as MTT assay, flow cytometry, western blotting, immunocytochemistry and TUNEL assay, the effects on the induction of apoptosis and autophagy were evaluated. We demonstrated that evodiamine inhibited LLC cell growth and induced apoptosis through caspase-independent manner in vitro and caspase-dependent pathway in vivo. In addition, we showed for the first time that evodiamine promoted autophagosome formation by enhancing the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II and upregulating the expression of autophagy-specific genes (Atgs). Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, attenuated evodiamine-induced autophagy through decreasing the conversion of LC3-I to LC3-II. The inhibition of autophagy was found to increase cell death and enhance evodiamine-induced apoptosis in vitro in a caspase-independent manner and in vivo in a caspase-dependent manner. In conclusion, evodiamine promoted autophagy in LLC cells and autophagy inhibition enhanced evodiamine-induced apoptosis in vitro and in vivo. These results demonstrate that evodiamine-induced autophagy plays a cytoprotective role in LLC cells and evodiamine combined with autophagy inhibitor therapy could increase the chemosensitivity of LLC cells.
Pi Y.,Daping Hospital |
Zhang L.-L.,Daping Hospital |
Li B.-H.,Daping Hospital |
Guo L.,Daping Hospital |
And 3 more authors.
Laboratory Investigation | Year: 2013
Reactive oxygen species (ROS) are associated with inflammation and vasculature dysfunction. This study aimed to investigate the potential role of the ROS on vascular Toll-like receptor 4 (TLR4)-mediated proinflammatory and proliferative phenotype of vascular smooth muscle cells (VSMCs). A wire-induced carotid injury model was used in male TLR4-deficient (TLR4-/-) and wild-type C57BL/6J mice to induce neointima formation. In the presence or absence of the ROS scavenger apocynin for 14 days, increased TLR4 and proinflammatory cytokines were observed in wire injury-induced carotid neointima and in platelet-derived growth factor-BB (PDGF-BB)-stimulated VSMCs. The TLR4-/- protected the injured carotid from neointimal formation and impaired the cellular proliferation and migration in response to PDGF-BB. Apocynin attenuated intimal hyperplasia. Pre-treatment with apocynin significantly inhibited intracellular ROS generation, accompanied by a significant suppression of TLR4 and proinflammatory cytokines expression, and VSMC proliferation and migration. However, the results were not obvious in TLR4-/- condition. These findings highlight the importance of ROS inhibition in TLR4-mediated proinflammatory and proliferative phenotype of VSMCs, and suggest ROS as an essential therapeutic target for TLR4-associated vascular inflammation and vascular diseases. © 2013 USCAP, Inc All rights reserved.
Li T.,Daping Hospital |
Liu Z.,Chongqing Medical University
Medical Hypotheses | Year: 2010
Benign prostatic hyperplasia (BPH) is a world-wide common disease in elderly male patients. A number of invasive physiotherapies have been used to replace prostatectomy. In this article we report our hypothesis of using microbubbles-mediated ultrasound cavitation effects to ablate prostatic tissues. Microbubble ultrasound contrast agent is widely used contrast media in ultrasonography, yet it is also found to act as cavitation nuclei or enhancer. Once excited by a high peak pressure ultrasound pulse, the mechanical effects, like shock wave and microstream, released from cavitation could produce a series of bioeffects, contributing to sonoporation, microvascular rupture and hematoma. BPH is known to have hyperplastic neovasculature and this make it possible to be disrupted by the physical effects of cavitation under existing microbubbles in circulation. Mechanical ablation of prostatic capillary or small vessels could result in pathological alterations such as thrombosis, micro-circulation blockage, prostatic necrosis and atrophia. Thereupon it could effectively treat BPH by nontraumatic ways. © 2009 Elsevier Ltd. All rights reserved.
Fu L.-Y.,Chongqing Medical University |
Dai L.-M.,Chongqing Medical University |
Li X.-G.,Daping Hospital |
Zhang K.,Chongqing Medical University |
Bai Y.,Chongqing Medical University
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2014
Objectives To re-estimate the association between methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism and polycystic ovary syndrome (PCOS) risk by critically reviewing, analyzing and updating the current evidence. MTHFR C677T polymorphism has been studied as a possible risk factor for a variety of common conditions including heart disease, stroke and hypertension. Its association with PCOS was negative in a previous meta-analysis which had possible shortcomings. More studies have now been done but their results remain inconclusive. Study design Available case-control studies containing genotype frequencies of MTHFR C677T were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. Statistical analyses were performed using software Review Manager (Version 5. 2) and Stata (Version 11.0). Results Nine case-control studies including 638 PCOS and 759 healthy controls were identified. Meta-analysis showed a significant effect in the dominant model (TT+CT vs. CC: OR = 1.65, 95%CI = 1.28-2.12, P < 0.0001) and heterozygote comparison (CT vs. CC: OR = 1.83, 95%CI = 1.17-2.87, P = 0.008). In subgroup analysis stratified by ethnicity, MTHFR C677T variant was statistically significantly relevant to PCOS risk in European populations (TT+CT vs. CC: OR = 2.16, 95%CI = 1.50-3.12, P < 0.0001; CT vs. CC: OR = 2.11, 95%CI = 1.15-3.87, P = 0.02) but not in Asian populations (TT+CT vs. CC: OR = 1.29, 95%CI = 0.91-1.82, P = 0.15; CT vs. CC: OR = 1.31, 95%CI = 0.91-1.90, P = 0.15). Conclusions This meta-analysis indicates that the 677T allele increases PCOS susceptibility, and this relevance seems to be more intense in Europeans than in Asians. © 2013 Published by Elsevier Ireland Ltd.
Li Y.,Daping Hospital |
Liu L.,Biowave Center |
Wang B.,Daping Hospital |
Wang J.,Daping Hospital |
Chen D.,Daping Hospital
European Journal of Gastroenterology and Hepatology | Year: 2014
OBJECTIVES: Hematocrit levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) and related to hypoxia and hyperlipidemia. AIM: This study was conducted to investigate the association between elevated hematocrit and liver histology in patients with NAFLD. PATIENTS AND METHODS: We examined 215 consecutive adults with biopsy-proven NAFLD (108 with steatosis alone, 107 with nonalcoholic steatohepatitis) and 110 controls. The stage of fibrosis was measured using a four-point scale. All underwent anthropometric and metabolic profiling. Hematocrit and related hematologic variables such as blood viscosity and red blood cell count were also measured. RESULTS: NAFLD morbidity was found to be positively correlated with hematocrit levels. After adjusting for age, smoking, diabetes, BMI, homeostasis model assessment of insulin resistance, triglycerides, and obstructive sleep apnea, patients with hematocrit levels in the highest quartile were seen to have had an odds ratio of 3.05 (95% confidence interval 2.12-4.36, P=0.015) for NAFLD in males. Hematocrit levels increased significantly (P<0.001) in steatosis (42.4±4.6%) compared with control groups (38.2±4.2%), and in nonalcoholic steatohepatitis (45.1±5.2%) compared with steatosis patients. On multivariate analysis, hematocrit levels were found to be strongly and independently associated with fibrosis (β=0.205, P=0.030). Moreover, hematocrit levels increased with the severity of hepatic fibrosis (P<0.05). CONCLUSION: Our results indicate that hematocrit levels are significantly increased and independently associated with fibrosis in NAFLD patients. Therefore, hematocrit levels may have potential interest as a clinical marker of NAFLD severity. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.