Effects of Ge-Xia Zhu-Yu Decoction on Hepatic Thioredoxin System in Rats with Hepatic Fibrosis / 世界科学技术-中医药现代化

This study was aimed to verify the hypothesis that Ge-Xia Zhu-Yu (GXZY) decoction protects liver from porcine serum-induced oxidative stress through the thioredoxin system.SD rats were randomly divided into the blank control group,model group,normal rat + GXZY decoction group,model rat + GXZY group.The rat autoimmune hepatic fibrosis model was induced with porcine serum by intraperitoneal injection (0.5 mL/each rat) twice a week.And GXZY decoction (7.37 g raw material/kg· d) was simultaneously administered daily by gavage.Lipid peroxidation (LPO) levels and thioredoxin reductase (TrxR) activity in liver tissues were determined by the colorimetric method.Polymerase chain reaction (PCR) was used to analyze the transcription factor nuclear factor erythroid 2-related factor 2 (Nfe2l2,previously known as Nrf2) mRNA expression.And the western blot was used to analyze the thioredoxin-1 (Trx1) protein expression and Akt phosphorylation in the liver.The results showed that compared to the model control group,the GXZY decoction group attenuated porcine serum-induced oxidative stress,as indicated by the LPO level,in liver tissues.Furthermore,GXZY decoction significantly enhanced TrxR activity,Trx1 protein expression,Nfe2l2 mRNA expression,and Akt phosphorylation (all P＜0.05).It was concluded that the strong antioxidant properties of GXZY decoction in the porcine serum rat model was due to the enhancement of the hepatic thioredoxin system via activating Akt-Nrf2 signaling pathway.The study results provided experimental evidences for the supporting of this hypothesis.

Protective effects of recombinant human erythropoietin on oligodendrocyte after cerebral infarction / 中华病理学杂志

<p><b>OBJECTIVE</b>To study biological effect of recombinant human erythropoietin (RhEPO) on the expression of oligodendrocyte in the neuron glia antigen 2(NG2), Nogo receptor-interacting protein 1(LINGO-1), myelin basic protein (MBP) and myelin associated glycoprotein (MAG), and to explore the protective mechanism of RhEPO for oligodendrocyte after cerebral infarction.</p><p><b>METHODS</b>Experimental rats were randomly divided into the treatment group (RhEPO at a dose of 3 000 U/kg) or saline control group. Both groups received intraperitoneal injection of RhEPO after cerebral ischemia in 30 min, 3 h, 6 h, 12 h and 24 h, which was administered daily for 7 days. The modified neurological severity score (mNSS) and histology were analyzed, and immunohistochemistry was used to detect the protein expression of NG2, MAG, MBP and LINGO-1.</p><p><b>RESULTS</b>The overall mNSS of RhEPO treatment group significantly decreased compared with the saline control group on the seventh day after cerebral infarction (P<0.05). Such treatment effect was more obvious in the treatment group at 30 min and 3 h (P<0.01). Compared with the saline control group, the numbers of NG2 positive cells increased in RhEPO treatment group. In contrast, the expression of LINGO-1 protein significantly decreased (P<0.05), with a dramatic decrease observed at 30 min and 3 h (P<0.01). However, the expression of MBP protein decreased more significantly in saline control group, while the level of the MAG protein expression increased. The differences were statistically significant (P<0.05), especially at 30 min (P<0.01).</p><p><b>CONCLUSIONS</b>After cerebral ischemia, RhEPO promotes the proliferation of NG2 positive cells, and inhibits the expression of LINGO-1 and MAG proteins. RhEPO improves the proliferation and differentiation of oligodendrocyte precursor cells, which in turn protects neuronal function, particularly at the early phase of ischemia.</p>

Expression and Significance of Epithelial-to-mesenchymal Transition in the Progression of Gastric Carcinoma and Lymph Node Metastasis / 中国医科大学学报

Objective To investigate the association between expression of the epithelial?to?mesenchymal transition(EMT)biomarkers and the malignant progression of gastric cancer in primary tumors and metastases and their possible correlation with progression of gastric cancer(GC). Methods The EMT biomarkers including E?cadherin,β?catenin,N?cadherin,Snail and TGF?β1 were detected by immunohistochemical method for 145 cases of gastric cancer(GC),25 cases of abnormal hyperplasia,13 cases of intestinal metaplasia,42 cases of lymph node metastasis and 40 cases of normal gastric mucosa tissues. Results Positive rates of TGF?β1,Snail,E?cadherin,β?catenin and N?cadherin were 73.5%,65.5%, 14.5%,53.1%and 35.9%,respectively,in gastric cancer tissues and 100%,100%,0%,27.5%and 2.5%,respectively,in normal gastric tissues, with a significant difference between the two groups(P<0.05). The decreased expression of E?cadherin andβ?catenin and the increased expression of TGF?β1 were related to the depth of invasion of gastric cancer(P<0.05). The expression of E?cadherin was correlated positively with the expres?sion ofβ?catenin,but negatively with the expression of TGF?β1. Whereas,the expression of N?cadherin was correlated positively with the expression of TGF?β1(P<0.05). The expression of E?cadherin andβ?catenin in lymph node metastasis was significantly higher than that in gastric cancer tis?sues,while the expression of TGF?β1 was lower than in gastric cancer tissues(P<0.05). Conclusion The increased expression of TGF?β1 and Snail and the decreased expression of E?cadherin,β?catenin,and N?cadherin are involved in the processes of invasion and metastasis of GC. The transformation of E?cadherin to N?cadherin and the expression of TGF?β1 may play an important role in the development of GC. In lymph node me?tastasis,the phenomenon of mesenchymal?to?epithelial transition(MET)occurs.

IDH1 mutation and MGMT expression in astrocytoma and the relationship with prognosis after radiotherapy / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the correlation between IDH1 mutation, MGMT expression, clinicopathologic features and post-radiotherapy prognosis in patients with astrocytoma.</p><p><b>METHODS</b>Detection of IDH1 mutation and MGMT expression was carried out in 48 cases of astrocytoma (WHO grade II to III) by EnVision method with immunohistochemical staining. Follow-up data, including treatment response and overall survival time, were analyzed.</p><p><b>RESULTS</b>The rates of IDH1 mutation and MGMT expression in astrocytomas were 62.7% (30/48) and 47.9% (23/48), respectively. There was a negative correlation between IDH1 mutation and MGMT expression (r = -0.641, P < 0.01). The age of patients with IDH1 mutation was younger at disease onset. The IDH1 mutation rate in patients with WHO grade II astrocytoma was higher than that in patients with WHO grade III tumor (P < 0.05). The age at onset was an independent factor affecting the expression of mutant IDH1. After radiotherapy, patients with IDH1 mutation+/MGMT- tumor carried a longer overall survival time than patients with IDH1 mutation-/MGMT+ tumor (P < 0.05).</p><p><b>CONCLUSIONS</b>There is a correlation between IDH1 mutation and MGMT expression in WHO grade II to III astrocytoma. Age at onset is an independent factor affecting the expression of mutant IDH1. Tumors with IDH1+/MGMT- pattern show better response to radiotherapy than tumors with IDH1-/MGMT+ pattern. Detection of IDH1 mutation and MGMT protein expression can provide some guidance in choice of treatment modalities in patients with astrocytoma.</p>

The study on the relationship between methylation of MGMT, hMSH2 gene promoters and protein ex-pression in glioma patients / 实用肿瘤学杂志

Objective To investigate the relevance between protein expression and methylation of MG-MT and hMSH2 in glioma patimts.Methods Immunohistochemical and methylation specific PCR were adopted respectively to test on 275 cases of glioma patients for the protein expression and methylation situation of MGMT and hMSH2.Results The negative protein expression rate of MGMT and hMSH 2 in the tissue of brain golima were 47.2% and 62.5% respectively;the occurrence of methylation in gene promoter region were accordingly 41.8% and 22.4%.Statistical analysis revealed that MGMT promoter methylation in peripheral blood gene groups was related with the protein negative expression of tumor tissue (P0.05).Conclusion The meth-ylation of MGMT is a common molecular situation in the generation of brain glioma ,which may be connected with that of tumor.However,hMSH2 promoter methylation might not the main reason for inactivation of hMSH 2 pro-tein,there may be other important factors affecting its expression .

Effect of type 2 diabetes on middle cerebral artery occlusion-induced focal cerebral ischemia / 中华神经科杂志

Objective To study the function of vascular endothelial growth factor (VEGF) in type 2 diabetes model rats and its effect on focal cerebral ischemia induced by middle cerebral artery occlusion in these rats. Methods Focal cerebral ischemia was induced by middle cerebral artery occlusion for 6 hours in type 2 diabetes rats and normal control rats.Blood vessels morphology was examined by ink perfusion,infarct size was measured by TTC and expression of VEGF and CD34 were evaluated by immunohistochemistry staining. Results Ink perfusion revealed increased number of small vessels in type 2 diabetes rats. Infarct size was significantly smaller in type 2 diabetes rats ( ( 80. 07 ± 11.21 ) mm3 ) than that in normal controls ((98. 91 ± 14. 86) mm3,t = 2.48,P = 0. 0326). There were more hemorrhage lesions in the ischemic hemisphere in type 2 diabetes rats when comparing with the controls. VEGF and CD34 showed significantly higher expression in type 2 diabetes rats than in normal controls. Conclusions High expression of VEGF and CD34 are found in type 2 diabetes rats after middle cerebral artery occlusion. There is cerebrolvascular remodeling in diabetes rats. While this diabetes-induced remodeling appears to prevent infarct expansion,the changes also increase the risk of hemorrhagic transformation. The latter may result in poor prognosis.