Objective:To construct a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in hippocampal neuronsin vitro, and to explore the inhibitory effect of anti-miR-146b on the apoptosis of ...Objective:To construct a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in hippocampal neuronsin vitro, and to explore the inhibitory effect of anti-miR-146b on the apoptosis of hippocampal neurons of ischemic/reperfusion injury. Methods: Primary rat hippocampal neurons were cultured, and oxygen-glucose deprivation and reoxygenation (OGD/R) were constructed. The anti-miR-146b lentivirus was used to transfect the hippocampal neurons, and the cells were divided into the normal group, the OGD/R group and the OGD/R + anti-miR-146b group. Real time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of miR-146b, KLF7, Caspase-3, Bcl-2 and Bax in each group. Cell viability was detected by CCK8 assay, and apoptosis was detected by Hoechst33342/PI double staining.Results: Compared with the normal group, the cell morphology of the OGD/R group and the OGD/R + anti-miR-146b group was damaged, the cell activity was decreased, and the cell apoptosis rate was increased significantly (P<0.05). However, Compared with OGD/R group, the cell morphology of the OGD/R + KLF7 group was improved, the cell activity was increased, and the apoptosis rate was decreased significantly (P<0.05). Compared with the normal group, the mRNA expression levels of miR-146b, KLF7, Caspase-3, Bax and Bcl-2 in the OGD/R group and the OGD/R + KLF7 group was increased (P<0.05). Compared with the OGD/R group, the mRNA expression of KLF7, Bcl-2 were increased in the OGD/R + KLF7 group significantly, however, the mRNA expression of miR-146b, Caspase-3, Bax were decreased significantly (P<0.05).Conclusion:Anti-miR-146b play protective effect on hippocampal neurons of OGD/R-induced injury. The mechanism may be related to upregulation of KLF7 signaling pathway, downregulation expression of Caspase-3 and Bax, upregulation expression of Bcl-2, and inhibition of apoptosis induced by OGD/R.展开更多
BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases ...BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.展开更多
基金National Natural Science Foundation of China,Projects No:81371362the Scientific Research Foundation of Heilongjiang Province,China,Projects No:H2018068+1 种基金the Basic Research Operating Expenses Program of Heilongjiang Provincial Universities,China,Projects No:2017-KYYWFMY-0661Research project of colege students in Mudanjiang Medical University,Projects No:2018-28.
文摘Objective:To construct a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in hippocampal neuronsin vitro, and to explore the inhibitory effect of anti-miR-146b on the apoptosis of hippocampal neurons of ischemic/reperfusion injury. Methods: Primary rat hippocampal neurons were cultured, and oxygen-glucose deprivation and reoxygenation (OGD/R) were constructed. The anti-miR-146b lentivirus was used to transfect the hippocampal neurons, and the cells were divided into the normal group, the OGD/R group and the OGD/R + anti-miR-146b group. Real time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of miR-146b, KLF7, Caspase-3, Bcl-2 and Bax in each group. Cell viability was detected by CCK8 assay, and apoptosis was detected by Hoechst33342/PI double staining.Results: Compared with the normal group, the cell morphology of the OGD/R group and the OGD/R + anti-miR-146b group was damaged, the cell activity was decreased, and the cell apoptosis rate was increased significantly (P<0.05). However, Compared with OGD/R group, the cell morphology of the OGD/R + KLF7 group was improved, the cell activity was increased, and the apoptosis rate was decreased significantly (P<0.05). Compared with the normal group, the mRNA expression levels of miR-146b, KLF7, Caspase-3, Bax and Bcl-2 in the OGD/R group and the OGD/R + KLF7 group was increased (P<0.05). Compared with the OGD/R group, the mRNA expression of KLF7, Bcl-2 were increased in the OGD/R + KLF7 group significantly, however, the mRNA expression of miR-146b, Caspase-3, Bax were decreased significantly (P<0.05).Conclusion:Anti-miR-146b play protective effect on hippocampal neurons of OGD/R-induced injury. The mechanism may be related to upregulation of KLF7 signaling pathway, downregulation expression of Caspase-3 and Bax, upregulation expression of Bcl-2, and inhibition of apoptosis induced by OGD/R.
基金Supported by Chronic Disease Management Center for Thoracic Tumor,The Affiliated Hospital of Medical School of Ningbo University,No.2021MGZX-07Natural Science Foundation of Ningbo,No.2019A610238.
文摘BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.