Objective To investigate the expression of midkine (MK) and its relation with angiogenesis, biological features and prognosis of pancreatic carcinoma (PC). Methods MK expression and microvessel density (MVD) were dete...Objective To investigate the expression of midkine (MK) and its relation with angiogenesis, biological features and prognosis of pancreatic carcinoma (PC). Methods MK expression and microvessel density (MVD) were determined in 52 cases of human PC with immunohistochemistry and results were compared with pathology. Results Mean MVD of PC was 64 ± 18 and positive expression of MK was detected in 38 cases (73%). The positive rate of MK was significantly lower in cases of without metastasis and at early clinical stage (stage Ⅰ - Ⅱ) than that with metastasis and at stage Ⅲ - Ⅳ. MVD was significantly higher in MK-positive PC than in MK-negative PC (P 【 0. 01). Follow-up showed that postoperative survival time was shorter in patients with positive expression of MK. Conclusion MK is closely related to angiogenesis PC. MK expression is one of the predictors for the biological behavior of PC. 4 refs, 1fig.展开更多
Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by ...Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by the investigators revealed that the upregulation of CREB improves the MK801-related SZ cognitive deficit.The present study further investigates the mechanism on how CREB deficiency is associated with SZ-related cognitive impairment.Methods MK-801 was used to induce SZ in rats.Western blotting and immunofluorescence were performed to investigate CREB and the CREB-related pathway implicated in MK801 rats.The long-term potentiation and behavioral tests were performed to assess the synaptic plasticity and cognitive impairment,respectively.Results The phosphorylation of CREB at Ser133 decreased in the hippocampus of SZ rats.Interestingly,among the upstream kinases of CREB,merely ERK1/2 was downregulated,while CaMKII and PKA remained unchanged in the brain of MK801-related SZ rats.The inhibition of ERK1/2 by PD98059 reduced the phosphorylation of CREB-Ser133,and induced synaptic dysfunction in primary hippocampal neurons.Conversely,the activation of CREB attenuated the ERK1/2 inhibitor-induced synaptic and cognitive impairment.Conclusion These present findings partially suggest that the deficiency of the ERK1/2-CREB pathway is involved in MK801-related SZ cognitive impairment.The activation of the ERK1/2-CREB pathway may be therapeutically useful for treating SZ cognitive deficits.展开更多
目的探讨中期因子(midkine,MK)在人乳腺癌MDA-MB-231细胞体外血管生成中的作用及其机制。方法采用shRNA干扰技术降低MDA-MB-231细胞MK表达,应用Western blot技术检测肿瘤细胞中内皮蛋白C受体(endothelial protein C receptor,EPCR)的表...目的探讨中期因子(midkine,MK)在人乳腺癌MDA-MB-231细胞体外血管生成中的作用及其机制。方法采用shRNA干扰技术降低MDA-MB-231细胞MK表达,应用Western blot技术检测肿瘤细胞中内皮蛋白C受体(endothelial protein C receptor,EPCR)的表达;干扰MK和EPCR表达或通过抗体阻断活化蛋白酶激活受体1(protease-activated receptor 1,PAR1)作用后,制备肿瘤条件培养基作用于人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs),通过CCK-8试剂盒检测HUVECs增殖、Transwell小室检测迁移以及Matrigel表面培养检测脉管形成能力。结果干扰MK表达后,EPCR表达随之降低。干扰MK和EPCR低表达后,HUVECs增殖、迁移及脉管形成能力均低于对照组(P<0.05),EPCR干扰组低于MK干扰组(P<0.05)。应用抗PAR1作用后,HUVECs增殖、迁移及脉管形成能力低于对照组和EPCR干扰组(P<0.05)。结论 MK可通过EPCR/PAR1通路促进乳腺癌MDA-MB-231细胞体外血管生成。展开更多
文摘Objective To investigate the expression of midkine (MK) and its relation with angiogenesis, biological features and prognosis of pancreatic carcinoma (PC). Methods MK expression and microvessel density (MVD) were determined in 52 cases of human PC with immunohistochemistry and results were compared with pathology. Results Mean MVD of PC was 64 ± 18 and positive expression of MK was detected in 38 cases (73%). The positive rate of MK was significantly lower in cases of without metastasis and at early clinical stage (stage Ⅰ - Ⅱ) than that with metastasis and at stage Ⅲ - Ⅳ. MVD was significantly higher in MK-positive PC than in MK-negative PC (P 【 0. 01). Follow-up showed that postoperative survival time was shorter in patients with positive expression of MK. Conclusion MK is closely related to angiogenesis PC. MK expression is one of the predictors for the biological behavior of PC. 4 refs, 1fig.
基金supported in part by grants from National Natural Science Foundation of China(No.31929002,No.82201326 No.82071440 and No.92049107)Science,Technology and Innovation Commission of Shenzhen Municipality(No.JCYJ20210324141405014)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2020B1515120017)the Academic Frontier Youth Team Project to Xiao-chuan WANG from Huazhong University of Science and Technology.
文摘Objective Schizophrenia(SZ)is associated with cognitive impairment,and it is known that the activity of cAMP response element binding protein(CREB)decreases in the brain of SZ patients.The previous study conducted by the investigators revealed that the upregulation of CREB improves the MK801-related SZ cognitive deficit.The present study further investigates the mechanism on how CREB deficiency is associated with SZ-related cognitive impairment.Methods MK-801 was used to induce SZ in rats.Western blotting and immunofluorescence were performed to investigate CREB and the CREB-related pathway implicated in MK801 rats.The long-term potentiation and behavioral tests were performed to assess the synaptic plasticity and cognitive impairment,respectively.Results The phosphorylation of CREB at Ser133 decreased in the hippocampus of SZ rats.Interestingly,among the upstream kinases of CREB,merely ERK1/2 was downregulated,while CaMKII and PKA remained unchanged in the brain of MK801-related SZ rats.The inhibition of ERK1/2 by PD98059 reduced the phosphorylation of CREB-Ser133,and induced synaptic dysfunction in primary hippocampal neurons.Conversely,the activation of CREB attenuated the ERK1/2 inhibitor-induced synaptic and cognitive impairment.Conclusion These present findings partially suggest that the deficiency of the ERK1/2-CREB pathway is involved in MK801-related SZ cognitive impairment.The activation of the ERK1/2-CREB pathway may be therapeutically useful for treating SZ cognitive deficits.
