X-box-binding protein-1 （XBP-1） is an essential transcription factor in endoplasmic reticulum stress In this study, XBP-1 gene-transfected neural stem cells （NSCs） were transplanted into lesion sites to ensure sta...X-box-binding protein-1 （XBP-1） is an essential transcription factor in endoplasmic reticulum stress In this study, XBP-1 gene-transfected neural stem cells （NSCs） were transplanted into lesion sites to ensure stability and persistent expression of XBP-1, resulting in the exertion of anti-apoptotic effects. Simultaneously, XBP-1 gene transfection promotes the survival and differentiation of transplanted NSCs. Results from this study demonstrated that survival, proliferation and differentiation of XBP-1 g^ne-modified NSCs were enhanced when compared to unmodified NSCs at 28 days post-transplantation （P 〈 0.05）. A diminished number of apoptotic neural cells increased Bcl-2 expression and reduced Bax expression, and were observed in the ischemic region of the XBP-1-NSCs group （P 〈 0.05）. These results indicated that modification of the XBP-1 gene enhances the survival and migration of NSCs in vivo and decreases the occurrence of apoptosis.展开更多
X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson＇s disease. The survival capacities and differentiation rates of cells ...X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson＇s disease. The survival capacities and differentiation rates of cells expressing the dopaminergic marker tyrosine hydroxylase were higher in X-box-binding protein 1-transfected neural stem cells compared to non-transfected cells. Moreover, dopamine and 3,4-dihydroxyphenylacetic acid levels in the substantia nigra were significantly increased, α-synuclein expression was decreased, and neurological behaviors were significantly ameliorated in rats following transplantation of X-box-binding protein 1-transfected neural stem cells. These results indicate that transplantation of X-box-binding protein 1-transfected neural stem cells can promote stem cell survival and differentiation into dopaminergic neurons, increase dopamine and 3,4-dihydroxyphenylacetic acid levels, reduce α-synuclein aggregation in the substantia nigra, and improve the symptoms of Parkinson＇s disease in rats.展开更多
BACKGROUND： Neural stem cell （NSC） survival is closely associated with cell apoptosis in ischemic-hypoxic regions following transplantation. Numerous studies have revealed that X-box binding protein 1 （XBP1） is a...BACKGROUND： Neural stem cell （NSC） survival is closely associated with cell apoptosis in ischemic-hypoxic regions following transplantation. Numerous studies have revealed that X-box binding protein 1 （XBP1） is a transcription factor during endoplasmic reticulum unfolded protein response and is essential for cell survival, differentiation, and anti-apoptotic effects. OBJECTIVE： To determine the effects of the XBP1 gene on NSC proliferation and apoptosis under hypoxic conditions following XBP1 gene transfection into rat embryonic hippocampal NSCs using recombinant adenovirus vector. DESIGN, TIME AND SETTING： In vitro experiments were performed at the Laboratory of Cell Biology of Jilin University and Laboratory of Proteomics, Department of Neurology, Jilin University China from September 2008 to November 2009. MATERIALS： Recombinant adenovirus package XBP1 gene and Ad-XBPl-enhanced green fluorescent protein plasmid （Guangzhou Easywin BioMed Technology, China）, rabbit anti-XBP1 and its target gene estrogen receptor degradation-enhancing a-mannosidase-like protein （EDEM） glucose-regulated protein 78 （GRP78）, anti-apoptotic molecule Bcl-2 and proapoptotic molecule Bax polyclonal antibody （Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA）, and COCI2 （Sigma, St. Louis, MO, USA） were used in the present study. METHODS： Hippocampi from embryonic, Sprague Dawley rats on gestational day 16 were harvested for NSC isolation and cloning, followed by immunofluorescence for Nestin and sub-culturing. The recombinant adenovirus Ad-XBPl-enhanced green fluorescent protein plasmid was transfected into rat embryonic hippocampal NSCs, and then CoCl2 was applied to induce hypoxia. MAIN OUTCOME MEASURES： Cell quantification and 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide colorimetric assay were utilized to detect proliferation in XBPl-transfected NSCs for 7 consecutive days. Western blot assay was utilized to quantify XBP1 GRP78, EDEM, Bcl-2, and Bax expression. Flow cytometry was used to measure apoptosis. RESULTS： NSC proliferation was significantly enhanced following XBP1 gene transfection （P 〈 0.05）. Under hypoxic conditions, GRP78, EDEM, and Bcl-2 levels increased, but Bax levels decreased. In addition, NSC apoptosis decreased following transfection （P 〈 0.05）. CONCLUSION： The XBP1 gene was successfully transfected into rat embryonic hippocampal NSCs using a recombinant adenovirus vector. NSC proliferation following transfection, as well as anti-apoptotic effects under hypoxia, was significantly increased.展开更多
Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinic...Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinicopathological significance and to analyze their potential use as biomarkers of breast cancer metastasis. Methods: The study included ninety subjects sub-grouped equally into metastatic BC, non-metastatic BC and healthy volunteers. Serum YBX-1 and IL-6 were quantified using ELISA technique while CA 15-3 was quantified using IRMA kit. Clinical data were collected from patients’ records. Results: YBX-1 (p < 0.001), IL-6 (p < 0.001) and CA15-3 (p = 0.017, 0.001) were significantly elevated in metastatic and non-metastatic BC patients compared to healthy controls, however, only YBX-1 (p 0.001) showed a significant difference with cancer metastasis. Generally, YBX-1 and IL-6 were correlated with worse histological grade and late clinical stage in breast cancer patients and they were also associated with axillary lymph nodes involvement and positive vascular invasion in metastatic BC patients. Serum YBX-1 and IL-6 levels were positively correlated to each other (rs = 0.615, p < 0.001) and they showed high sensitivity and specificity compared to CA 15-3 (p < 0.001 and p = 0.004 for YBX-1 and IL-6 respectively) for predicting cancer metastasis. Conclusions: Serum YBX-1 and IL-6 are potential biomarkers of breast cancer patients with significant correlation with bad clinicopathological characteristics. Serum YBX-1 and IL-6 have superior sensitivity and specificity compared to CA15-3 and can serve as potential follow up and prognostic markers.展开更多
目的:探讨富含丝氨酸结构域1的RNA结合蛋白(RNA-binding protein with serine-rich domain 1,RNPS1)在胰腺癌进展中的作用及可能分子机制。方法:免疫组织化学与免疫荧光检测RNPS1与Notch3在胰腺癌组织及癌旁组织的表达;RTq PCR、免疫荧...目的:探讨富含丝氨酸结构域1的RNA结合蛋白(RNA-binding protein with serine-rich domain 1,RNPS1)在胰腺癌进展中的作用及可能分子机制。方法:免疫组织化学与免疫荧光检测RNPS1与Notch3在胰腺癌组织及癌旁组织的表达;RTq PCR、免疫荧光检测RNPS1与Notch3在胰腺癌细胞中的表达情况;Hoechst与CCK-8实验检测胰腺癌细胞凋亡与增殖;划痕实验与transwell实验检测胰腺癌细胞迁移与侵袭能力;Western blot实验检测胰腺癌细胞中N-Cadherin和E-Cadherin的表达;Western blot与RT-q PCR实验检测胰腺癌细胞中Notch3与HEY1的表达。结果:与癌旁组织与正常细胞系相比较,RNPS1与Notch3在胰腺癌组织中及胰腺癌细胞的表达均增高(F=121.612、34.649,均P<0.05);与对照组相比较,敲低RNPS1抑制生物标志物N-Cadherin的表达(t=39.922,P<0.05),促进E-Cadherin的表达(t=8.281,P<0.05),敲低RNPS1可减弱癌细胞的生存、迁移侵袭的能力(t=2.017、4.874、19.747,均P<0.05,),促进了细胞凋亡(t=33.673,P<0.05);敲低RNPS1降低了癌细胞中Notch3与HEY1的表达(t=17.546、6.258,均P<0.05)。结论:RNPS1的表达与胰腺癌细胞生存、恶性表型有关,RNPS1可能通过调控Notch3/HEY1信号通路促进胰腺癌细胞的生存及肿瘤进展。展开更多
文摘X-box-binding protein-1 （XBP-1） is an essential transcription factor in endoplasmic reticulum stress In this study, XBP-1 gene-transfected neural stem cells （NSCs） were transplanted into lesion sites to ensure stability and persistent expression of XBP-1, resulting in the exertion of anti-apoptotic effects. Simultaneously, XBP-1 gene transfection promotes the survival and differentiation of transplanted NSCs. Results from this study demonstrated that survival, proliferation and differentiation of XBP-1 g^ne-modified NSCs were enhanced when compared to unmodified NSCs at 28 days post-transplantation （P 〈 0.05）. A diminished number of apoptotic neural cells increased Bcl-2 expression and reduced Bax expression, and were observed in the ischemic region of the XBP-1-NSCs group （P 〈 0.05）. These results indicated that modification of the XBP-1 gene enhances the survival and migration of NSCs in vivo and decreases the occurrence of apoptosis.
文摘X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson＇s disease. The survival capacities and differentiation rates of cells expressing the dopaminergic marker tyrosine hydroxylase were higher in X-box-binding protein 1-transfected neural stem cells compared to non-transfected cells. Moreover, dopamine and 3,4-dihydroxyphenylacetic acid levels in the substantia nigra were significantly increased, α-synuclein expression was decreased, and neurological behaviors were significantly ameliorated in rats following transplantation of X-box-binding protein 1-transfected neural stem cells. These results indicate that transplantation of X-box-binding protein 1-transfected neural stem cells can promote stem cell survival and differentiation into dopaminergic neurons, increase dopamine and 3,4-dihydroxyphenylacetic acid levels, reduce α-synuclein aggregation in the substantia nigra, and improve the symptoms of Parkinson＇s disease in rats.
文摘BACKGROUND： Neural stem cell （NSC） survival is closely associated with cell apoptosis in ischemic-hypoxic regions following transplantation. Numerous studies have revealed that X-box binding protein 1 （XBP1） is a transcription factor during endoplasmic reticulum unfolded protein response and is essential for cell survival, differentiation, and anti-apoptotic effects. OBJECTIVE： To determine the effects of the XBP1 gene on NSC proliferation and apoptosis under hypoxic conditions following XBP1 gene transfection into rat embryonic hippocampal NSCs using recombinant adenovirus vector. DESIGN, TIME AND SETTING： In vitro experiments were performed at the Laboratory of Cell Biology of Jilin University and Laboratory of Proteomics, Department of Neurology, Jilin University China from September 2008 to November 2009. MATERIALS： Recombinant adenovirus package XBP1 gene and Ad-XBPl-enhanced green fluorescent protein plasmid （Guangzhou Easywin BioMed Technology, China）, rabbit anti-XBP1 and its target gene estrogen receptor degradation-enhancing a-mannosidase-like protein （EDEM） glucose-regulated protein 78 （GRP78）, anti-apoptotic molecule Bcl-2 and proapoptotic molecule Bax polyclonal antibody （Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA）, and COCI2 （Sigma, St. Louis, MO, USA） were used in the present study. METHODS： Hippocampi from embryonic, Sprague Dawley rats on gestational day 16 were harvested for NSC isolation and cloning, followed by immunofluorescence for Nestin and sub-culturing. The recombinant adenovirus Ad-XBPl-enhanced green fluorescent protein plasmid was transfected into rat embryonic hippocampal NSCs, and then CoCl2 was applied to induce hypoxia. MAIN OUTCOME MEASURES： Cell quantification and 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide colorimetric assay were utilized to detect proliferation in XBPl-transfected NSCs for 7 consecutive days. Western blot assay was utilized to quantify XBP1 GRP78, EDEM, Bcl-2, and Bax expression. Flow cytometry was used to measure apoptosis. RESULTS： NSC proliferation was significantly enhanced following XBP1 gene transfection （P 〈 0.05）. Under hypoxic conditions, GRP78, EDEM, and Bcl-2 levels increased, but Bax levels decreased. In addition, NSC apoptosis decreased following transfection （P 〈 0.05）. CONCLUSION： The XBP1 gene was successfully transfected into rat embryonic hippocampal NSCs using a recombinant adenovirus vector. NSC proliferation following transfection, as well as anti-apoptotic effects under hypoxia, was significantly increased.
文摘Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinicopathological significance and to analyze their potential use as biomarkers of breast cancer metastasis. Methods: The study included ninety subjects sub-grouped equally into metastatic BC, non-metastatic BC and healthy volunteers. Serum YBX-1 and IL-6 were quantified using ELISA technique while CA 15-3 was quantified using IRMA kit. Clinical data were collected from patients’ records. Results: YBX-1 (p < 0.001), IL-6 (p < 0.001) and CA15-3 (p = 0.017, 0.001) were significantly elevated in metastatic and non-metastatic BC patients compared to healthy controls, however, only YBX-1 (p 0.001) showed a significant difference with cancer metastasis. Generally, YBX-1 and IL-6 were correlated with worse histological grade and late clinical stage in breast cancer patients and they were also associated with axillary lymph nodes involvement and positive vascular invasion in metastatic BC patients. Serum YBX-1 and IL-6 levels were positively correlated to each other (rs = 0.615, p < 0.001) and they showed high sensitivity and specificity compared to CA 15-3 (p < 0.001 and p = 0.004 for YBX-1 and IL-6 respectively) for predicting cancer metastasis. Conclusions: Serum YBX-1 and IL-6 are potential biomarkers of breast cancer patients with significant correlation with bad clinicopathological characteristics. Serum YBX-1 and IL-6 have superior sensitivity and specificity compared to CA15-3 and can serve as potential follow up and prognostic markers.
文摘目的:探讨富含丝氨酸结构域1的RNA结合蛋白(RNA-binding protein with serine-rich domain 1,RNPS1)在胰腺癌进展中的作用及可能分子机制。方法:免疫组织化学与免疫荧光检测RNPS1与Notch3在胰腺癌组织及癌旁组织的表达;RTq PCR、免疫荧光检测RNPS1与Notch3在胰腺癌细胞中的表达情况;Hoechst与CCK-8实验检测胰腺癌细胞凋亡与增殖;划痕实验与transwell实验检测胰腺癌细胞迁移与侵袭能力;Western blot实验检测胰腺癌细胞中N-Cadherin和E-Cadherin的表达;Western blot与RT-q PCR实验检测胰腺癌细胞中Notch3与HEY1的表达。结果:与癌旁组织与正常细胞系相比较,RNPS1与Notch3在胰腺癌组织中及胰腺癌细胞的表达均增高(F=121.612、34.649,均P<0.05);与对照组相比较,敲低RNPS1抑制生物标志物N-Cadherin的表达(t=39.922,P<0.05),促进E-Cadherin的表达(t=8.281,P<0.05),敲低RNPS1可减弱癌细胞的生存、迁移侵袭的能力(t=2.017、4.874、19.747,均P<0.05,),促进了细胞凋亡(t=33.673,P<0.05);敲低RNPS1降低了癌细胞中Notch3与HEY1的表达(t=17.546、6.258,均P<0.05)。结论:RNPS1的表达与胰腺癌细胞生存、恶性表型有关,RNPS1可能通过调控Notch3/HEY1信号通路促进胰腺癌细胞的生存及肿瘤进展。
