Asiatic acid mitigates hyperglycemia and reduces islet fibrosis in Goto-Kakizaki rat, a spontaneous type 2 diabetic animal model / 中国天然药物

The Goto-Kakizaki (GK) rat is a spontaneous type 2 diabetic animal model, which is characterized by a progressive loss of beta islet cells with fibrosis. In the present study, the hypoglycemic effect of asiatic acid (AA) in GK rats was examined. GK rats receiving AA at a daily dose of 25 mg·kg(-1) for four weeks showed a significant reduction in blood glucose levels. Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose (CMC-Na) solution for the same periods and used as control. Compared to the normal Wistar rats, GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level (P < 0.01) and insulin level (P < 0.05). Furthermore, the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats. Fibronectin, a key protein related to islet fibrosis, was over-expressed in GK rats, which was reversed significantly by AA treatment (P < 0.05). These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes, which may play a role in the prevention of islets dysfunction.

Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase / 中国天然药物

AIM@#To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects.@*METHOD@#HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a (GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β (IRβ), protein kinase B (also known as Akt), and glycogen synthase kinase-3β (GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet (HFD).@*RESULTS@#The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content.@*CONCLUSION@#The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.

Expression of interleukin-1β and apoptosis in hippocampus of rat with prolonged febrile seizures / 中华实用儿科临床杂志

Objective To investigate the expression of interleukin-1 β(IL-1 β) and apoptosis in the hippocampus of rats with prolonged febrile seizures(PFS),and to provide the theoretical basis for exploring the brain damage of PFS and the effective prevention and control measures.Methods Ninety-six 14-day-old Sprague-Dawley rats were randomly divided into 3 groups:normal control group(NC group,n =32),hyperthermia group(HC group,n =32) and PFS group(n =32).Lipopolysaccharide combined low-dose Kainic acid of intraperitoneal injection were used to induce PFS.Then the histopathologic changes in hippocampus were viewed by HE staining and electronmicroscope,the expression of IL-1β protein in hippocampus of rats was detected with immunohistochemistry methods,the neuron apoptosis was observed by TdT-mediated dUTP nick end labeling,and the relationship of both was researched.Results 1.Thirty-two rats all appeared seizures in PFS group,the average rectal temperature was (39.3 ± 0.4) ℃ ; while the rats in other groups were not convulsions.2.The TUNEL positive cells in hippocampus CA1 of PFS group were more than that of NC group and HC group at 6 h after the PFS(all P ＜0.01),reached its highest level at 24 h.3.Measured by immunohistochemistry,the level of IL-1β in the hippocampus of PFS group was significantly higher than that of the NC group and HC group at 6 h after the PFS(all P ＜ 0.01).There was a positive correlation between the expression of IL-1 β and the apoptotic index in hippocampus(r =0.789,P ＜ 0.01).Conclusions IL-1 β expression in the hippocampus increases following PFS in rats,and the increased IL-1 β expression was correlated with neurocyte apoptosis.

Clinicopathologic features of delayed radiation-induced brain injury after radiotherapy for brain tumor / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of delayed radiation-induced brain injury after radiotherapy for brain tumor.</p><p><b>METHODS</b>The clinical, histopathologic and immunohistochemical features of 9 cases with delayed radiation-induced injury were evaluated.</p><p><b>RESULTS</b>The disease occurred from 6 months to 12 years after radiotherapy and often presented with headache and muscle weakness. Magnetic resonance imaging showed peripheral enhancing lesions with slight mass effect and surrounding edema. Microscopically, the major changes included coagulative necrosis, fibrinoid necrosis of vessels, vascular hyalinization with luminal stenosis and peripheral reactive gliosis. Immunostaining for hypoxia-inducible factors 1α was positive in reactive astrocytes.</p><p><b>CONCLUSIONS</b>Delayed radiation-induced brain injury is a relatively common complication of radiation therapy. The lesion was frequently misdiagnosed as brain tumor. Correct diagnosis relies on clinical, radiologic and pathologic correlation.</p>

Association of Claudin-1,Ki-67,and CD34 expressions with astrocytic tumor cell proliferation and invasion / 中华神经医学杂志

Objective To investigate the correlation ofClaudin-1, Ki-67 and CD34 expressionsin the tumor tissue to the invasiveness, grading and proliferation of astrocytic tumors. Methods In 50cases of astrocytic tumor, the expressions of Claudin-1, IO-67 and CD34 were detectedimmunohistochemically in the tumor tissue, normal brain tissues and in the junctional area between thetumor and normal tissues. The expressions of Claudin-1, Ki-67, and CD34 were analyzed in relation tothe clinicopathoiogical characteristics of the patients. Results The expression rate of Claudin-1 was70.59% in the astrocytic tumors of histological grades Ⅰ and Ⅱ, significantly higher than that in grade Ⅲand Ⅳ tumors (9.09%, χ2=20.206, P=0.000). In grade Ⅲ and Ⅳ tumors, the positivity rates of Ki-67 inthe normal tissues, junctional area and the tumor tissue were all significantly higher those in grade Ⅲ andⅣ tumors (t=9.144, 5.958, and 6.297; P=0.000, 0.000, and 0.000, respectively). Grade Ⅲ and Ⅳ tumorsdisplayed significantly greater mierovessel density (MVD) than grade Ⅰ and Ⅱ tumors in the tumor tissue(t=3.101, P=0.003) and the junctional area (t=4.139, P=0.000). In all the tumors, significantly higherKi-67 expression was seen in the tumor tissue (12.74±6.93) than in the junctional area (7.42±3.93) andthe normal tissue (3.22±1.57) (F=51.726, P=0.000), and the MVD was also greater in the tumor tissue(27.48±8.26) than in the junctional area (10.72±3.93) and normal tissue (6.48±1.45) (F=215.538, P=0.000).Conclusion Expressions of Claudin-1, Ki-67, and CD34 are closely correlated to the proliferation andinvasion of astrocytic tumors, and these cytokines may serve as important indicators for evaluating themalignancy of astrocytic tumors..

Correlation between the expression of angiopoietins and their receptor and angiogenesis in gastric cancers / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the effects of angiopoietins (Ang-1 and Ang-2) and Tie-2 expression on microvessel density (MVD) in gastric cancers.</p><p><b>METHODS</b>By using semiquantitative RT-PCR, immunohistochemistry and image analysis system, the expression of Ang-1, Ang-2, Tie-2 mRNA and their proteins were detected in 68 primary gastric cancers and their adjacent normal tissues. Microvessel density (MVD) was figured out based on CD34 immunohistochemical staining.</p><p><b>RESULTS</b>The expression of all Ang-1, Ang -2, Tie-2 mRNA and their proteins was detected in gastric cancers and their paired adjacent gastric mucosa tissues. A negative correlation between Ang-1 protein, Tie-2 mRNA and MVD in gastric cancers was observed (r = -0.440, r = -0.267; P < 0.05), while the relation between Ang-2 mRNA and its protein, Ang-2/Ang-1 protein ratio with MVD were positive (r = 0.319, r = 0.729, r = 0.739; P < 0.05). It was found that MVD in groups with Ang-2 mRNA T/N ratio over 1.2 (the ratio of Ang-2 mRNA in gastric cancers and its adjacent normal mucosa) was higher than that in those with a ratio under 1.2, revealed by analysing the effects of Ang-1 and Ang-2 mRNA T/N ratio on MVD in gastric cancers.</p><p><b>CONCLUSION</b>Ang-1 activates Tie-2 receptor, whereas Ang-2 antagonizes Ang-1 in the angiogenesis, and the Ang-2/Ang-1 ratio determines angiogenesis and tumor growth in gastric cancers. When the expression of Ang-2 is high and Ang-1 is low, the angiogenesis in gastric cancers is promoted, otherwise oppositely. The role of Ang-2 is dominant in the effect of Angs and their receptor on angiogenesis in gastric cancers.</p>