Fu K.,Harbin Medical University |
Piao T.,Harbin Children Hospital |
Wang M.,Second Peoples Hospital of Guangdong Province |
Zhang J.,Harbin Medical University |
And 3 more authors.
International Immunopharmacology | Year: 2014
Catalpol, an iridiod glucoside isolated from Rehmannia glutinosa, has been reported to have anti-inflammatory properties. Although anti-inflammatory activity of catalpol already reported, its involvement in lung protection has not been reported. Thus, we investigated the role of catalpol on lipopolysaccharide (LPS)-induced acute lung injury in this study. Mice acute lung injury model was induced by intranasal instillation of LPS. Catalpol was administrated 1 h prior to or after LPS exposure. The severity of pulmonary injury was evaluated 12 h after LPS administration. The results showed that catalpol inhibited lung W/D ratio, myeloperoxidase activity of lung samples, the amounts of inflammatory cells and TNF-α, IL-6, IL-4 and IL-1β in BALF induced by LPS. The production of IL-10 in BALF was up-regulated by catalpol. In vitro, catalpol inhibited TNF-α, IL-6, IL-4 and IL-1β production and up-regulated IL-10 expression in LPS-stimulated alveolar macrophages. Moreover, western blot analysis showed that the activation of NF-κB and MAPK signaling pathways was inhibited by catalpol. Furthermore, catalpol was found to inhibit TLR4 expression induced by LPS. In conclusion, catalpol potently protected against LPS-induced ALI. The protective effect may attribute to the inhibition of TLR4-mediated NF-κB and MAPK signaling pathways. © 2014 Published by Elsevier B.V.
Chen X.-R.,Sun Yat Sen University |
Liao S.-J.,Sun Yat Sen University |
Ye L.-X.,Sun Yat Sen University |
Gong Q.,Second Peoples Hospital of Guangdong Province |
And 3 more authors.
Brain Research | Year: 2014
Focal cerebral infarction causes secondary damage in the ipsilateral ventroposterior thalamic nucleus (VPN). Chondroitin sulfate proteoglycans (CSPGs) are a family of putative inhibitory components, and its degradation by chondroitinase ABC (ChABC) promotes post-injury neurogenesis. This study investigated the role of ChABC in the primary and secondary injury post stroke in hypertension. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO), and were subjected to continuous intra-infarct infusion of ChABC (0.12 U/d for 7 days) 24 h later. Neurological function was evaluated by a modified neurologic severity score. Neurons were counted in the peri-infarct region and the ipsilateral VPN 8 and 14 days after MCAO by Nissl staining and NeuN labeling. The expressions of CSPGs, growth-associated protein-43 (GAP-43) and synaptophysin (SYN) were detected with immunofluorescence or Western blotting. The intra-infarct infusion of ChABC, by degrading accumulated CSPGs, rescued neuronal loss and increased the levels of GAP-43 and SYN in both the ipsilateral cortex and VPN, indicating enhancd neuron survival as well as augmented axonal growth and synaptic plasticity, eventually improving overall neurological function. The study demonstrated that intra-infarct ChABC infusion could salvage the brain from both primary and secondary injury by the intervention on the neuroinhibitory environment post focal cerebral infarction. © 2013 Elsevier B.V.
Zhang H.,Central South University |
Cai X.U.,Second Peoples Hospital of Guangdong Province |
Yi B.,Central South University |
Huang J.,Central South University |
And 2 more authors.
Molecular Medicine Reports | Year: 2014
Increasing evidence shows that DNA methylation is involved in the development and progression of diabetes mellitus (DM) and its complications. Previous studies conducted by our group have indicated that high glucose levels may induce the demethylation process of the connective tissue growth factor (CTGF) gene promoter and increase the expression of CTGF in human glomerular mesangial cells. Based on these findings, the aim of the present study was to investigate the methylation level of genomic DNA and the CTGF promoter in patients with type 2 DM and to analyze its possible correlation with CTGF expression. Methylation levels of the whole genomic DNA were detected by high-performance liquid chromatography in a non-diabetes control (NDM) group (n=29), a diabetes without nephropathy (NDN) group (n=37) and a diabetes with nephropathy (DN) group (n=38). CTGF promoter methylation levels were detected by methylation-specific polymerase chain reaction and bisulfite sequencing. The levels of serum CTGF were assessed using the enzyme-linked immunosorbent assay. The methylation levels of the whole genomic DNA were not significantly different among the three groups. However, the CTGF methylation levels in the two diabetes groups were significantly lower than those in the NDM group (P<0.05), with the lowest methylation level in the DN group (P<0.05). The CTGF protein levels in the DN group were significantly higher than those in the NDM and NDN groups (P<0.05). Levels of CTGF were negatively correlated with the estimated glomerular filtration rate (eGFR) and the methylation level of the promoter, while they were positively correlated with age, urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen, creatinine, fasting blood sugar and postprandial blood glucose. Multiple stepwise regression analysis showed that CTGF expression was associated with the UACR, CTGF methylation level and eGFR. DNA methylation is a regulatory mechanism of CTGF expression, which is decreased in patients with DM, particularly in those with DN, and may contribute to the pathogenesis of nephropathy.
Huang L.,Sun Yat Sen University |
Huang L.,Nanchang University |
Wang H.-Y.,Sun Yat Sen University |
Li J.-D.,Sun Yat Sen University |
And 7 more authors.
Cell Death and Disease | Year: 2013
Karyopherin alpha 2 (KPNA2), a member of the karyopherin family, has a central role in nucleocytoplasmic transport and is overexpressed in many cancers. Our previous study identified KPNA2 as significantly upregulated in epithelial ovarian carcinoma (EOC), correlating with poor survival of patients. However, the precise mechanism of this effect remains unclear. The aim of the present study was to examine the role of KPNA2 in the proliferation and tumorigenicity of EOC cells, and its clinical significance in tumor progression. Real-time quantitative RT-PCR analysis revealed high expression levels of KPNA2 in 162 out of 191 (84.8%) fresh EOC tissues, which was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, differentiation, histological type, recurrence, and prognosis of EOC patients. Our results showed that upregulation of KPNA2 expression significantly increased the proliferation and tumorigenicity of EOC cells (EFO-21 and SK-OV3) in vitro and in vivo, by promoting cell growth rate, foci formation, soft agar colony formation, and tumor formation in nude mice. By contrast, knockdown of KPNA2 effectively suppressed the proliferation and tumorigenicity of these EOC cells in vitro and in vivo. Our results also indicated that the molecular mechanisms of the effect of KPNA2 in EOC included promotion of G1/S cell cycle transition through upregulation of c-Myc, enhanced transcriptional activity of c-Myc, activation of Akt activity, suppression of FOXO3a activity, downregulation of cyclin-dependent kinase (CDK) inhibitor p21Cip1 and p27Kip1, and upregulation of CDK regulator cyclin D1. Our results show that KPNA2 has an important role in promoting proliferation and tumorigenicity of EOC, and may represent a novel prognostic biomarker and therapeutic target for this disease. © 2013 Macmillan Publishers Limited All rights reserved.
Chen K.Y.,Second Peoples Hospital of Guangdong Province
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010
To evaluate the effect of ROUX-en-Y anastomosis and Billroth-II anastomosis after subtotal gastrectomy on blood glucose in patients with type 2 diabetes. From January 2006 to December 2009, 26 and 24 type 2 diabetic patients underwent subtotal gastrectomy for gastric cancer or gastric ulcer and received subsequent ROUX-en-Y anastomosis and Billroth-II anastomosis, respectively. Perioperative and postoperative blood glucose and glycosylated hemoglobin (HbA1c) were detected in these patients to identify the variations. In ROUX-en-Y group, the fasting blood glucose (FBG) of the patients decreased significantly in the first month after the operation (t=4.46, P<0.05), and the 2-hour postprandial glucose (2hPG) and HbA1c also underwent significant reductions in the first postoperative week and month, respectively (t=3.5, P<0.05; t=2.21, P<0.05). In Billroth-II group, the FBG decreased significantly till 6 months after the operation (t=2.0, P<0.05), and HbA1c reduction occurred 3 months after the operation (t=2.61, P<0.05). There were significant differences in FBG in the first postoperative month, 2hPG in the 6th month, and HbA1c in the 3rd month between the two groups (P<0.05). The ROUX-en-Y anastomosis and Billroth-II anastomosis after subtotal gastrectomy can both reduce blood glucose of type 2 diabetic patients, but the former approach has better effect.