Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiolog...Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, wesummarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.展开更多
Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome prolifera...Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1α pathway and improving mitochondrial function.展开更多
Endogenous neural stem cells become ＂activated＂ after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relatio...Endogenous neural stem cells become ＂activated＂ after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chronological changes of neural stem cells by 5-bromo-2′-deoxyuridine（BrdU） incorporation. Hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. Hypoxia-inducible factor-1α immunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-infarct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3–7 days. Nestin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neurons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and vascular endothelial growth factor after ischemia made 展开更多
Background Hypoxia-inducible factor- 1α （HIF- 1α） is a transcriptional factor that could improve the stimulation of angiogenesis and the metabolic adaptation of tumor cells to hypoxia. A recent study showed that H...Background Hypoxia-inducible factor- 1α （HIF- 1α） is a transcriptional factor that could improve the stimulation of angiogenesis and the metabolic adaptation of tumor cells to hypoxia. A recent study showed that HIF- 1α could induce colon cancer cells epithelial-mesenchymal transition （EMT）. However, no evidence indicates a similar correlation in human prostate cancer cells. This study was designed to evaluate the effect of HIF- 1α over-expression on the EMT in human prostate cancer cells. Methods We selected the appropriate cell line for HIF- 1α induction from those EMT negative prostate cell lines through vimentin gene detection by RT-PCR. As the result, LNCaP cell line is the best one for further experiment. LNCaP cells were transfected with recombinant plasmid pcDNA3.1 （-）/HIF- 1α and pcDNA3.1 （-） control vector by Lipofectamine 2000 system. The positive cell colonies were confirmed by indirect immunofluorescence labeling. Then Transwell polycarbonate filter was used to analyze the invasive potency. The expression of EMT associated proteins, E-cadherin and vimentin, was detected by Western blotting. Results Among four of the EMT negative cell lines, LNCaP was the only one expressed the vimentin gene but not the associated protein. The expression level of HIF- 1α in LNCaP/HIF- 1α was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. The cell numbers of LNCaP/HIF- 1α that penetrated through the Transwell filter were higher than that of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1 and LNCaP cells, the expression of vimentin was up-regulated in LNCaP/HIF- 1α, whereas the expression of E-cadherin was down-regulated.Conclusions Over-expression of HIF- 1α stimulates the invasion potency of human prostate carcinoma cells through EMT pathway. The expression of E-cadherin and vimentin, playing established roles in EMT, could be regulated by HIF- 1α in human prostate cancer cell line.展开更多
Two new pentacyclic triterpene acids, 1a, 3b-dihydroxyl-olean-12-en-28-oic acid and 1a, 2a, 3b-trihydroxyl-olean-12-en-28-oic acid, were isolated from the arial parts of Sabia parviflora.
维生素D是一种具有神经活性的类固醇激素,维生素D受体(vitamin D receptor,VDR)在胚胎期以及成年大脑组织的不同区域均有表达。越来越多的流行病学数据表明,VDR基因多态性以及维生素D缺乏与阿尔茨海默氏症、帕金森氏症等中枢神经系统疾...维生素D是一种具有神经活性的类固醇激素,维生素D受体(vitamin D receptor,VDR)在胚胎期以及成年大脑组织的不同区域均有表达。越来越多的流行病学数据表明,VDR基因多态性以及维生素D缺乏与阿尔茨海默氏症、帕金森氏症等中枢神经系统疾病易感性有关。VDR对中枢神经系统可能具有重要作用。现综述VDR调控大脑发育以及神经保护作用的研究进展,以期为维生素D促进脑发育以及预防和治疗中枢神经系统疾病的应用提供理论参考。展开更多
DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-bu...DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-butylphthalide action by various means.We used hydrogen peroxide to induce injury to PC12cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of DI-3-n-butylphthalide.We found that DI-3-nbutylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis.Furthermore,DI-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3.DI-3-nbutylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α,the key transcription factor that regulates Bax and Bnip3 genes.These findings suggest that DI-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81770562,81602166 and 81703807)grants from the Science and Technology Planning Project of Luzhou,Sichuan Province,China(Nos.2016LZXNYD-Z04 and 2017LZXNYD-J02)
文摘Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, wesummarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.
基金Supported by the National Natural Science Foundation of China(No.81473639)the Fundamental Research Funds for the Central Universities(No.3332018037)
文摘Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1α pathway and improving mitochondrial function.
基金supported by the National Research Foundation of Korea Grant funded by the Korean Government,No.NRF-013-2011-1-E00045
文摘Endogenous neural stem cells become ＂activated＂ after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chronological changes of neural stem cells by 5-bromo-2′-deoxyuridine（BrdU） incorporation. Hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. Hypoxia-inducible factor-1α immunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-infarct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3–7 days. Nestin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neurons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and vascular endothelial growth factor after ischemia made
文摘Background Hypoxia-inducible factor- 1α （HIF- 1α） is a transcriptional factor that could improve the stimulation of angiogenesis and the metabolic adaptation of tumor cells to hypoxia. A recent study showed that HIF- 1α could induce colon cancer cells epithelial-mesenchymal transition （EMT）. However, no evidence indicates a similar correlation in human prostate cancer cells. This study was designed to evaluate the effect of HIF- 1α over-expression on the EMT in human prostate cancer cells. Methods We selected the appropriate cell line for HIF- 1α induction from those EMT negative prostate cell lines through vimentin gene detection by RT-PCR. As the result, LNCaP cell line is the best one for further experiment. LNCaP cells were transfected with recombinant plasmid pcDNA3.1 （-）/HIF- 1α and pcDNA3.1 （-） control vector by Lipofectamine 2000 system. The positive cell colonies were confirmed by indirect immunofluorescence labeling. Then Transwell polycarbonate filter was used to analyze the invasive potency. The expression of EMT associated proteins, E-cadherin and vimentin, was detected by Western blotting. Results Among four of the EMT negative cell lines, LNCaP was the only one expressed the vimentin gene but not the associated protein. The expression level of HIF- 1α in LNCaP/HIF- 1α was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. The cell numbers of LNCaP/HIF- 1α that penetrated through the Transwell filter were higher than that of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1 and LNCaP cells, the expression of vimentin was up-regulated in LNCaP/HIF- 1α, whereas the expression of E-cadherin was down-regulated.Conclusions Over-expression of HIF- 1α stimulates the invasion potency of human prostate carcinoma cells through EMT pathway. The expression of E-cadherin and vimentin, playing established roles in EMT, could be regulated by HIF- 1α in human prostate cancer cell line.
文摘Two new pentacyclic triterpene acids, 1a, 3b-dihydroxyl-olean-12-en-28-oic acid and 1a, 2a, 3b-trihydroxyl-olean-12-en-28-oic acid, were isolated from the arial parts of Sabia parviflora.
文摘维生素D是一种具有神经活性的类固醇激素,维生素D受体(vitamin D receptor,VDR)在胚胎期以及成年大脑组织的不同区域均有表达。越来越多的流行病学数据表明,VDR基因多态性以及维生素D缺乏与阿尔茨海默氏症、帕金森氏症等中枢神经系统疾病易感性有关。VDR对中枢神经系统可能具有重要作用。现综述VDR调控大脑发育以及神经保护作用的研究进展,以期为维生素D促进脑发育以及预防和治疗中枢神经系统疾病的应用提供理论参考。
文摘DI-3-n-butylphthalide is used to treat mild and moderate acute ischemic stroke.However,the precise underlying mechanism requires further investigation.In this study,we investigated the molecular mechanism of DI-3-n-butylphthalide action by various means.We used hydrogen peroxide to induce injury to PC12cells and RAW264.7 cells to mimic neuronal oxidative stress injury in stroke in vitro and examined the effects of DI-3-n-butylphthalide.We found that DI-3-nbutylphthalide pretreatment markedly inhibited the reduction in viability and reactive oxygen species production in PC12 cells caused by hydrogen peroxide and inhibited cell apoptosis.Furthermore,DI-3-n-butylphthalide pretreatment inhibited the expression of the pro-apoptotic genes Bax and Bnip3.DI-3-nbutylphthalide also promoted ubiquitination and degradation of hypoxia inducible factor 1α,the key transcription factor that regulates Bax and Bnip3 genes.These findings suggest that DI-3-n-butylphthalide exhibits a neuroprotective effect on stroke by promoting hypoxia inducible factor-1α ubiquitination and degradation and inhibiting cell apoptosis.
