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Objective:To study the protective effect of glucagon-like peptide-1 (GLP-1) on the inflammatory damage induced by high glucose(HG) in placental trophoblasts HTR8/SVneo and its molecular mechanism.Methods:Trophoblasts HTR8/SVneo cells were cultured and divided into low glucose(LG) group treated with low glucose (5 mmol/L), HG group treated with high glucose (25 mmol/L), GLP-1 group treated with high glucose combined with GLP-1, miR-137+ GLP-1 group treated with high glucose combined with GLP-1 after the transfection of miR-137 mimic, miR-137 mimic group transfected with miR-137 mimic, negative control (NC) mimic group transfected with NC mimic, and miR-137 inhibitor group transfected with miR-137 inhibitor, NC inhibitor group transfected with NC inhibitor. Apoptotic rate, expression of miR-137 and IL-6 were measured.Results:The apoptotic rate and the expression levels of miR-137 and IL-6 in HG group were significantly higher than those in LG group. The apoptotic rate and the expression levels of miR-137 and IL-6 in GLP-1 group were significantly lower than those in HG group. The apoptotic rate and the expression levels of miR-137 and IL-6 in miR-137+ GLP-1 group were significantly higher than those in GLP-1 group. The apoptotic rate and the expression level of IL-6 in miR-137 mimic group were significantly higher than those of NC mimic group, the apoptotic rate and the expression level of IL-6 in miR-137 inhibitor group were significantly lower than those in the NC inhibitor group.Conclusion:GLP-1 is able to alleviate the inflammation injury of HTR8/SVneo induced by high glucose through the miR-137/IL-6 pathway.
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Objective To investigate the effects of glucagon like peptide 1 (GLP-1) agonist on myocardial hypoxia reoxygenation injury and its molecular mechanism. Methods H9C2 cells were divided into control group, hypoxia reoxygenation(H/ R) group, H/ R+GLP-1 group, and H/ R+GLP-1+phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 group. The cell proliferation activity, apoptosis rate, enzyme contents in the medium and the expressions of apoptosis-related genes were detected. After animal model of myocardial ischemia reperfusion injury (I/ R) was established and was treated with GLP-1 agonist and PI3K inhibitor, serum enzyme contents were detected. Results Hypoxia reoxygenation decreased the myocardial cell proliferation activity and phosphorylated-PI3K(p-PI3K), phosphorylated-protein kinase B (p-Akt), Bcl-2 protein expressions, increased the apoptotic cell number and creatine kinase ( CK), creatine kinase-MB ( CK-MB), lactate dehydrogenase ( LDH) contents in cell culture medium and Bax, caspase-3 protein expressions, which were ameliorated by GLP-1 ( all P < 0. 05). The myocardial cell proliferation activity and Bcl-2 protein expression of H/ R+GLP-1+LY294002 group were significantly lower than those of H/ R+GLP-1 group while the apoptotic cell number and CK, CK-MB, LDH contents in cell culture medium and Bax, Caspase-3 protein expressions were significantly higher (all P<0. 05). Serum CK, CK-MB, and LDH contents in rats of I/ R group were significantly higher than those in control group and I/ R+GLP-1 group. Serum CK, CK-MB, and LDH contents in rats of I/ R+GLP-1+LY294002 group were significantly higher than those in I/ R+GLP-1 group(all P < 0. 05). Conclusion GLP-1 agonist is able to protect the myocardial hypoxia reoxygenation injury via activating PI3K/ Akt signaling pathway.
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Objective:To investigate the extracellular signal-regulated kinase 5 (ERK5) and matrix metallo proteinase-9 (MMP-9) expres-sion levels in osteosarcoma tissues and their clinical significance. Methods:The ERK5 and MMP-9 expression levels in 71 specimens of osteosarcoma tissue and 40 specimens of normal bone tissue were detected by immunohistochemistry. The relationship between ERK5 and MMP-9 expression levels, their clinical characteristics, and prognosis of patients with osteosarcoma were analyzed. Results:The positive expression of ERK5 and MMP-9 in osteosarcoma tissues was 85.9%(61/71) and 74.65%(53/71), respectively, which were significantly higher than those in normal bone tissues at 12.5%(5/40) and 10.0%(4/40) (all P<0.05). The positive expression of ERK5 and MMP-9 was associated with Enneking stage and metastasis (all P<0.05). Kaplan-Meier analysis showed that the survival duration of patients with positive ERK5 and MMP-9 expression levels was shorter than those of the patients in the negative expression groups (all P<0.05). Univariate analysis of COX proportional hazards regression model revealed that tumor size, Enneking stage, metastasis, and positive ERK5 and MMP-9 expression levels are relevant to the overall survival of patients with osteosarcoma (all P<0.05). Multi-variate analysis of COX proportional hazards regression model confirmed that Enneking stage, metastasis, and positive ERK5 and MMP-9 expression levels can act as independent prognostic factors for osteosarcoma patients (all P<0.05). Conclusion:The ERK5 and MMP-9 expression levels are high in osteosarcoma tissues and are related to the clinical characteristics and prognosis of patients with osteo-sarcoma. Thus, ERK5 and MMP-9 expression levels may play important roles in osteosarcoma development and progression.
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To study the effect of glucagon-likepeptide 1(GLP-1)receptor agonist on insulin resistance and hepatic oxidative stress in rats with diabetes mellitus combined with nonalcoholic fatty liver disease. 36 male SD rats were served as the experimental animal and randomly divided into control group, model group, and GLP-1 group. The rats of control group were given routine diet with intraperitoneal injection of normal saline, those in model group were given high fat diet and intraperitoneal injection of normal saline, while GLP-1 group rats were fed with high fat diet and intraperitoneal injection of liraglutide. After 4 weeks of treatment, insulin resistance, lipid metabolism, liver injury and oxidative stress were all assessed. Serum fasting blood glucose, fasting insulin, total cholesterol, triglyceride, alanine transaminase(ALT), aspartate transaminase(AST)levels and total cholesterol, triglyceride contents in liver tissue, and as well as homeostasis model assessment for insulin resistance(HOMA-IR)levels of model group were significantly higher than those of control group, complex insulin sensitivity index(ISIcomp)level was significantly lower than that of control group; serum fasting blood glucose, fasting insulin, total cholesterol, triglyceride, ALT, AST contents and HOMA-IR levels of GLP-1 group were significantly lower than those of model group, ISIcomp level was significantly higher than that of model group; superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), catalase(CAT)contents in liver tissue of model group were significantly lower, while malondialdehyde content and SOD, GSH-Px, CAT, NF-E2 related factor-2(Nrf-2), antioxidant response element(ARE), heme oxygenase-1(HO-1), quinone oxidoreductase-1(NQO-1), glutathione thiol transferase(GST)mRNA expression were significantly higher than control group; SOD, GSH-Px, CAT contents and SOD, GSH-Px, CAT, Nrf-2, ARE, HO-1, NQO-1, GST mRNA expression in the liver tissue of GLP-1 group were significantly higher, while malondialdehyde content was significantly lower than that of model group. GLP-1 receptor agonist reduces insulin resistance and liver oxidative stress injury in diabetic rats with nonalcoholic liver disease.
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Objective: To investigate the effects of receptor interacting protein kinase 4 (RIPK 4) gene-silencing on epithelial-mesenchymal transition (EMT) of osteosarcoma U-2OS cells. Methods: The specific siRNA targeting RIPK 4 gene was transfected into U-2OS cells by liposome to establish RIPK 4 gene-silencing U-2OS cell line. Then the change of RIPK4 expression level was detected by Western blotting. The migration and invasion abilities of U-2OS cells after RIPK 4 gene-silencing were detected by Transwell chamber assay. The morphological changes of U-2OS cells were observed under an inverted optical microscope. Finally, the expression levels of EMT makers E-cadherin and vimentin in U-2OS cells were detected by Western blotting. Results: After transfection with RIPK4-siRNA, the expression level of RIPK4 protein was significantly decreased in U-2OS cells (P < 0.05). The migration and invasion abilities of U-2OS cells in RIPK4-siRNA transfection group were significantly reduced (both P<0.05). The morphology of U-2OS cells conversed from mesenchymal phenotype to epithelial phenotype. The expression level of E-cadherin was significantly up-regulated in RIPK4-siRNA transfection group (P < 0.05), whereas the expression level of vimentin was significantly down-regulated (P < 0.05). Conclusion: RIPK 4 gene-silencing can inhibit the occurrence of EMT in osteosarcoma U-2OS cells, and reduce the migration and invasion abilities of osteosarcoma cells.
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Wnt/β-catenin signaling pathway participates in cancer cell proliferation,invasion and metastasis and effectively induces drug resistance.It is also the key signal to mediate cancer carcinogenesis.Recent studies in vitro indicate that disturbance of Wnt/β-catenin signaling pathway can increase the sensitivity of the cancer cells to chemotherapeutic drugs.In-depth researches and analysis of tumor drug resistance induced by Wnt/β-catenin will provide potential targets and possible therapeutic means for the treatment of tumors.