Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 ...Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs.The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes.This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China(For human study:Approval No.20170135)in December 2016.All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University(approval No.20180248)in December 2017.展开更多
The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor（IL-17R） in intestinal mucosa tissue in patients with ulcerative colitis（UC） and con-trols, and evaluate their r...The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor（IL-17R） in intestinal mucosa tissue in patients with ulcerative colitis（UC） and con-trols, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein（CRP） levels were determined by ELISA and immu-nonephelometry, respectively. The IL-17 R m RNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls（P〈0.05）. Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase（P〈0.05）, and correlated with CRP levels（r=0.578, P〈0.01）. IL-17 R expression levels were higher in active UC patients than in healthy con-trols（P〈0.05）. It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.展开更多
17-β-estradiol (estrogen) is a steroid hormone important to human development;however, high levels of this molecule are associated with increased risk of breast cancer primarily due to estrogen’s ability to bind and...17-β-estradiol (estrogen) is a steroid hormone important to human development;however, high levels of this molecule are associated with increased risk of breast cancer primarily due to estrogen’s ability to bind and activate the estrogen receptor (ER) and initiate gene transcription. Currently, estrogen mechanisms of action are classified as genomic and non-genomic and occur in an ER-dependent and ER-independent manner. In this study, we examine estrogen signaling pathways, by measuring changes in protein expression as a function of time of exposure to estrogen in both ER-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. Using a robust experimental design utilizing isotopic labeling, two-dimensional LC-MS, and bioinformatics analysis, we report genomic and non-genomic ER regulated estrogen responsive proteins. We find a little over 200 proteins differentially expressed after estrogen treatment. Cell proliferation, transcription, actin filament capping and cell to cell signaling are significantly enriched in the MCF-7 cell line alone. Translational elongation and proteolysis are enriched in both cell lines. Subsets of the proteins presented in this study are for the first time directly associated with estrogen signaling in mammary carcinoma cells. We find that estrogen affected the expression of proteins involved in numerous processes that are related to tumorigenesis such as increased cellular division and invasion in an ER-dependent manner. Moreover, we identified negative regulation of apoptosis as a non-genomic process of estrogen. This study complements gene expression studies and highlights the need for both genomic and proteomic analyses in unraveling the complex mechanisms by which estrogen affects progression of breast cancer.展开更多
目的探讨苗药金乌健骨方总提物对类风湿关节炎滑膜组织成纤维样滑膜细胞(RA-FLS)白细胞介素6(IL-6)、转化生长因子-β(TGF-β)、白细胞介素17(IL^(-1)7)分泌及IL^(-1)7受体(IL^(-1)7R)蛋白的影响。方法采用组织块法体外培养原代RA-FLS;...目的探讨苗药金乌健骨方总提物对类风湿关节炎滑膜组织成纤维样滑膜细胞(RA-FLS)白细胞介素6(IL-6)、转化生长因子-β(TGF-β)、白细胞介素17(IL^(-1)7)分泌及IL^(-1)7受体(IL^(-1)7R)蛋白的影响。方法采用组织块法体外培养原代RA-FLS;分为金乌健骨方低、中、高剂量组(0.06,0.6,6.0 mg·m L^(-1)),雷公藤多苷组(0.03 mg·m L^(-1))及空白对照组,共5组。采用ELISA法检测IL-6、TGF-β、IL^(-1)7含量;PCR法检测IL^(-1)7R m RNA表达;Western Blot法检测IL^(-1)7R蛋白表达。结果与空白对照组比较,各给药组细胞培养上清液中IL-6、TGF-β、IL^(-1)7的浓度均有不同程度的降低(P<0.01),IL^(-1)7R m RNA及蛋白表达水平均明显下降(P<0.01)。与雷公藤多苷组比较,金乌健骨方高剂量组IL-6、TGF-β、IL^(-1)7水平及IL^(-1)7R蛋白表达量明显降低(P<0.05),金乌健骨方中、高剂量组IL^(-1)7R m RNA表达水平明显降低(P<0.05)。结论苗药金乌健骨方总提物能够下调RA-FLS中IL-6、TGF-β、IL^(-1)7的分泌,降低IL^(-1)7R m RNA及蛋白表达量。展开更多
基金supported by the Natural Science Foundation of Anhui Province of China,No.1708085MH211(to HWC)the College Top-notch Talent Foundation of Anhui Province of China,No.KJ2018A0207(to HWC)
文摘Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs.The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes.This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China(For human study:Approval No.20170135)in December 2016.All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University(approval No.20180248)in December 2017.
基金supported by the National Natural Science Foundation of China(No.81200283)
文摘The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor（IL-17R） in intestinal mucosa tissue in patients with ulcerative colitis（UC） and con-trols, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein（CRP） levels were determined by ELISA and immu-nonephelometry, respectively. The IL-17 R m RNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls（P〈0.05）. Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase（P〈0.05）, and correlated with CRP levels（r=0.578, P〈0.01）. IL-17 R expression levels were higher in active UC patients than in healthy con-trols（P〈0.05）. It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.
文摘17-β-estradiol (estrogen) is a steroid hormone important to human development;however, high levels of this molecule are associated with increased risk of breast cancer primarily due to estrogen’s ability to bind and activate the estrogen receptor (ER) and initiate gene transcription. Currently, estrogen mechanisms of action are classified as genomic and non-genomic and occur in an ER-dependent and ER-independent manner. In this study, we examine estrogen signaling pathways, by measuring changes in protein expression as a function of time of exposure to estrogen in both ER-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. Using a robust experimental design utilizing isotopic labeling, two-dimensional LC-MS, and bioinformatics analysis, we report genomic and non-genomic ER regulated estrogen responsive proteins. We find a little over 200 proteins differentially expressed after estrogen treatment. Cell proliferation, transcription, actin filament capping and cell to cell signaling are significantly enriched in the MCF-7 cell line alone. Translational elongation and proteolysis are enriched in both cell lines. Subsets of the proteins presented in this study are for the first time directly associated with estrogen signaling in mammary carcinoma cells. We find that estrogen affected the expression of proteins involved in numerous processes that are related to tumorigenesis such as increased cellular division and invasion in an ER-dependent manner. Moreover, we identified negative regulation of apoptosis as a non-genomic process of estrogen. This study complements gene expression studies and highlights the need for both genomic and proteomic analyses in unraveling the complex mechanisms by which estrogen affects progression of breast cancer.
文摘目的探讨苗药金乌健骨方总提物对类风湿关节炎滑膜组织成纤维样滑膜细胞(RA-FLS)白细胞介素6(IL-6)、转化生长因子-β(TGF-β)、白细胞介素17(IL^(-1)7)分泌及IL^(-1)7受体(IL^(-1)7R)蛋白的影响。方法采用组织块法体外培养原代RA-FLS;分为金乌健骨方低、中、高剂量组(0.06,0.6,6.0 mg·m L^(-1)),雷公藤多苷组(0.03 mg·m L^(-1))及空白对照组,共5组。采用ELISA法检测IL-6、TGF-β、IL^(-1)7含量;PCR法检测IL^(-1)7R m RNA表达;Western Blot法检测IL^(-1)7R蛋白表达。结果与空白对照组比较,各给药组细胞培养上清液中IL-6、TGF-β、IL^(-1)7的浓度均有不同程度的降低(P<0.01),IL^(-1)7R m RNA及蛋白表达水平均明显下降(P<0.01)。与雷公藤多苷组比较,金乌健骨方高剂量组IL-6、TGF-β、IL^(-1)7水平及IL^(-1)7R蛋白表达量明显降低(P<0.05),金乌健骨方中、高剂量组IL^(-1)7R m RNA表达水平明显降低(P<0.05)。结论苗药金乌健骨方总提物能够下调RA-FLS中IL-6、TGF-β、IL^(-1)7的分泌,降低IL^(-1)7R m RNA及蛋白表达量。
