Protective effect of γ‐tocopherol‐enriched diet on N‐methyl‐N‐nitrosourea‐induced epithelial dysplasia in rat ventral prostate

Despite recent advances in understanding the biological basis of prostate cancer (PCa), the management of this disease remains a challenge. Chemoprotective agents have been used to protect against or eradicate prostate malignancies. Here, we investigated the protective effect of γ‐tocopherol on N‐methyl‐N‐nitrosourea (MNU)‐induced epithelial dysplasia in the rat ventral prostate (VP). Thirty‐two male Wistar rats were divided into four groups (n = 8): control (CT): healthy control animals fed a standard diet; control+γ‐tocopherol (CT+γT): healthy control animals without intervention fed a γ‐tocopherol‐enriched diet (20 mg/kg); N‐methyl‐N‐nitrosourea (MNU): rats that received a single dose of MNU (30 mg/kg) plus testosterone propionate (100 mg/kg) and were fed a standard diet; and MNU+γ‐tocopherol (MNU+γT): rats that received the same treatment of MNU plus testosterone and were fed with a γ‐tocopherol‐enriched diet (20 mg/kg). After 4 months, the VPs were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase‐2 (Cox‐2), glutathione‐S‐transferase‐pi (GST‐pi) and androgen receptor (AR) protein expression, and matrix metalloproteinase‐9 (MMP‐9) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the MNU group was accompanied by augmented cell proliferation, GST‐pi and Cox‐2 immunoexpression and pro‐MMP‐9 activity. Stromal thickening and inflammatory foci were also observed. The administration of a γ‐tocopherol‐enriched diet significantly attenuated the adverse effects of MNU in the VP. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, GST‐pi and Cox‐2 immunoexpression. The gelatinolytic activity of pro‐MMP‐9 returned to the levels observed for the CT group. These results suggest that γ‐tocopherol acts as a protective agent against MNU‐induced prostatic disorders in the rat ventral prostate.     

FOS蛋白在胶质瘤中的表达及其对胶质瘤细胞生长的影响

目的 探讨FOS蛋白在胶质瘤中的表达及其对胶质瘤细胞生长的影响.方法 用免疫组化染色法检测FOS蛋白在各级别胶质瘤组织中的表达水平.应用RNA干扰技术降低FOS表达后,应用四甲基偶氮唑盐微量酶反应比色法和流式细胞技术检测胶质瘤细胞的增殖和周期的改变;应用Transwell实验检测胶质瘤细胞侵袭能力的改变;采用Western印迹法检测FOS下游功能蛋白的变化.结果 胶质瘤组织中FOS的表达随着级别的增高而增高;抑制FOS的表达后,U87和U251细胞生长受抑制,细胞生长阻滞在G1期且细胞侵袭能力下降,下游的功能蛋白CyclinD1和MMP9表达水平降低.结论 FOS在胶质瘤中高表达;抑制其表达可以下调功能蛋白CyclinD1和MMP9的表达,进而调控细胞的生长和侵袭能力.     

Propolis ameliorates cerebral injury in focal cerebral ischemia/reperfusion (I/R) rat model via upregulation of TGF-β1

Neuroprotective impact of transforming growth factor β1 (TGF-β1) is increasingly recognized in different brain injuries. Propolis exhibits a broad spectrum of biological and pharmacological properties including neuroprotective action. The objective of the investigation was to explore the involvement of TGF-β1 signaling in the neuroprotective mechanism of propolis in I/R rats. In this study, focal cerebral ischemia model was built by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The investigation was carried out on 48 rats that were arranged into four groups (n = 12): the sham group, I/R control group, I/R + propolis (50 mg/kg) group and I/R + propolis (100 mg/kg) group. The results revealed that propolis preserved rats against neuronal injury induced by cerebral I/R. It significantly reduced neurological deficit scores and improved motor coordination and locomotor activity in I/R rats. Propolis antagonized the damage induced by cerebral I/R through suppression of malondialdehyde (MDA) and elevation of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), brain-derived neurotropic factor (BDNF) and dopamine levels in the brain homogenates of I/R rats. Other ameliorations were also observed based on reduction of neurodegeneration and histological alterations in the brain tissues. These results also proposed that the neuroprotective effect of propolis might be related to upregulation of TGF-β1 and suppressed matrix metallopeptidase-9 (MMP9) mRNA expression.     

金属蛋白酶类及其抑制剂在椎间盘退变中作用研究进展

椎间盘退变(intervertebral disc degeneration,IVDD)可导致多种脊柱相关疾病的发生.细胞外基质(extracellularmatrix,ECM)的降解被认为是IVDD的主要病理过程.基质金属蛋白酶(matrix metalloproteinases,MMPs)及含凝血酶敏感蛋白模体的解整合素样金属蛋白酶(a disintegrin and metalloproteinase with thrombospondin motif,ADAMTSs)是参与ECM降解的主要蛋白酶类.本文总结在IVDD中MMPs、ADAMTSs及金属蛋白酶组织抑制剂(tissue inhibitors of metalloproteinases,TIMPs)的基因表达调控相关研究.研究发现人IVDD中MMP-1、2、3、7、8、10、13,ADAMTS-1、4、5出现表达上调,TIMP-3下调、TIMP-1上调.MMPs、ADAMTSs的表达受多因素共同调节,包括机械应力、炎症、氧化应激等,部分参与P38途径.遗传因素也在MMP 1、2、3、9的表达中起重要作用.MMPs、ADAMTSs蛋白表达及酶活性的上调导致ECM降解,进一步导致IVDD的发展.未来的治疗将靶向于导致ECM病理降解的特定MMPs及ADAMTSs.