The Janus kinase and signal transducer and activator of transcription （JAK/STAT） signal transduction pathway is involved in sepsis-induced functional damage to the heart, liver, kidney, and other organs. However, th...The Janus kinase and signal transducer and activator of transcription （JAK/STAT） signal transduction pathway is involved in sepsis-induced functional damage to the heart, liver, kidney, and other organs. However, the cellular and molecular mechanisms underlying sepsis-induced brain damage remain elusive. In the present study, we found severe loss of neurons in the hippocampal CA1 region in rats with sepsis-induced brain damage following intraperitoneal injection of endotoxin, The expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 was significantly increased in brain tissues following lipopolysaccharide exposure. AG490 （JAK2 antagonist） and rapamycin （STAT3 antagonist） significantly reduced neuronal loss and suppressed the increased expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 in the hippocampal CA1 region in sepsis-induced brain damaged rats. Overall, these data suggest that blockade of the JAK/STAT signal transduction pathway is neuroprotective in sepsis-induced brain damage via the inhibition of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 exoression.展开更多
AIM： To study the effect of Hepatitis C virus nonstructural 5A （HCV NSSA） on IFNα induced signal transducer and activator of transcription-1 （STAT1） phosphorylation and nuclear translocation.METHODS： Expression...AIM： To study the effect of Hepatitis C virus nonstructural 5A （HCV NSSA） on IFNα induced signal transducer and activator of transcription-1 （STAT1） phosphorylation and nuclear translocation.METHODS： Expression of STAT1 Tyr701 phosphorylation at different time points was confirmed by Western blot, and the time point when p-STAT1 expressed most, was taken as the IFN induction time for further studies. Immunocytochemistry was used to confirm the successful transient transfection of NS5A expression plasmid. Immunofluorescene was performed to observe if there was any difference in IFNα-induced STAT1 phosphorylation and nuclear translocation between HCV NSSA-expressed and non-HCV NSSA-expressed cells. Western blot was used to compare the phosphorylated STAT1 protein of the cells.RESULTS： Expression of HCV NS5A was found in the cytoplasm of pCNS5A-transfected Huh7 cells, but not in the PRC/ CMV transfected or non-transfected cells, STAT1 Tyr701 phosphorylation was found strongest in 30 min of IFN induction, STAT1 phosphorylation and nuclear import were much less in the presence of HCV NS5A protein in contrast to pRC/CMV-transfected and non-transfected cells under fluorescent microscopy, which was further confirmed by Western blot.CONCLUSION： HCV NSSA expression plasmid is successfully transfected into Huh7 cells and HCV NS5A protein is expressed in the cytoplasm of the cells. IFN-α is able to induce STAT1 phosphrylation and nuclear translocation, and this effect is inhibited by HCV NS5A protein, which might be another possible resistance mechanism to interferon alpha therapy.展开更多
目的分析信号转导子及转录激活因子4(signal transducer and activator of transcription4,STAT4)基因启动子区域单核苷酸多态(single nucleotide polymorphism,SNP)位点rs16833431A>G多态性与山东汉族人群支气管哮喘发生的相关性。...目的分析信号转导子及转录激活因子4(signal transducer and activator of transcription4,STAT4)基因启动子区域单核苷酸多态(single nucleotide polymorphism,SNP)位点rs16833431A>G多态性与山东汉族人群支气管哮喘发生的相关性。方法采用聚合酶链式反应-限制性片断长度多态(polymerase chain reactionand restrictionfragment length polymorphism,PCR-RFLP)方法检测220例哮喘患者和233例正常对照STAT4基因启动子区域多态位点rs16833431A>G的基因型,计算基因型与基因频率,采用χ2检验进行组间比较。结果STAT4基因rs16833431多态位点AA、AG、和GG基因型频率在病例组中分别为0.536、0.377和0.086,在对照组中分别为0.515、0.399和0.086,A和G等位基因的频率在病例组分别为0.725和0.275,在对照组分别为0.715和0.285,该位点基因型和等位基因分布在病例组与对照组均无统计学差异。结论STAT4基因启动子区域rs16833431A>G位点单核苷酸多态与山东汉族人群哮喘发生无明显相关性。展开更多
目的:分析信号转导及转录激活因子4(signal transducer and activator of transcription 4,STAT4)基因单核苷酸多态性(single nucleotide polymorphism,SNP)位点rs7574865 G>T的多态性与中国汉族人群克罗恩病发生的相关性。方法:选...目的:分析信号转导及转录激活因子4(signal transducer and activator of transcription 4,STAT4)基因单核苷酸多态性(single nucleotide polymorphism,SNP)位点rs7574865 G>T的多态性与中国汉族人群克罗恩病发生的相关性。方法:选取汉族克罗恩病患者318例与健康对照者318例作为研究对象,抽提基因组DNA,采用聚合酶链式反应和直接测序方法检测STAT4基因SNP位点rs7574865的基因型,计算基因型与基因频率,采用χ2检验进行组间比较。结果:STAT4基因rs7574865多态位点GG、GT和TT基因型频率在病例组中分别为0.110、0.431和0.459,在对照组中分别为0.097、0.450和0.453,G和T等位基因的频率在病例组分别为0.325和0.675,在对照组分别为0.322和0.678,该位点基因型和等位基因分布在病例组与对照组均无统计学差异(P>0.05)。结论:STAT4基因rs7574865 G>T位点单核苷酸多态性与中国汉族人群克罗恩病发生无明显相关性。展开更多
Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid ...Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.展开更多
Summary： Cancer stem cells （CSCs） are considered responsible for the high recurrence rate in cervical carcinoma. It has been demonstrated that the signal transducer and activator of transcription 3 （STAT3） is inv...Summary： Cancer stem cells （CSCs） are considered responsible for the high recurrence rate in cervical carcinoma. It has been demonstrated that the signal transducer and activator of transcription 3 （STAT3） is involved in the oncogenesis and takes part in mediating the effects of maintaining stem cell phenotype and pluripotency by regulating the expression of stem cell-related transcription factors. However, the correlation between STAT3 and stem cell-related transcription factors in cervical cancer has not been elucidated. In this study, we established overexpressing plasmid （GV316-STAT3） and siRNA-STAT3 for transfecting Siha cells. Cells negative or positive for Nanog, Oct4, or Sox2 were selected by flow cytometry. Proliferation and differentiation rate of Siha cells was determined by detecting the efficiency of tumor sphere formation. The expression of Nanog, Oct4 and Sox2 （cancer stem cell markers） and STAT3 was detected by quantitative real-time PCR and immunoblotting for Siha cells and by immuno- histochemistry （IHC） for cervical tissues, respectively. The results showed that Nanog＋, Oct4＋, and Sox2＋ Siha-STAT3 over-expressing cells displayed the typical non-adherent spheres. The sphere for- mation efficiency was significantly different between Siha-STAT3 overexpressing cells and siRNA-STAT3 cells （P〈0.05）. Meanwhile, the expression levels of Oct4, Nanog and Sox2 rrtRNA and protein were significantly higher in Siha-STAT3 overexprssing cells than in siRNA-STAT3 cells （P〈0.05）. In addition, the positive rate of STAT3, Nanog, Oct4 and Sox2 in cervical cancer tissues was higher than that in chronic cervicitis group （P〈0.05）. There was a significantly positive relationship between STAT3 and Nanog or Oct4 or Sox2 expression （all P〈0.001）. These results suggested that Oct4＋, Sox2＋, and Nanog＋ cell population possesses stem cell properties in cervical cancer, which may contribute to cervical carcinogenesis and be regulated by STAT3.展开更多
文摘The Janus kinase and signal transducer and activator of transcription （JAK/STAT） signal transduction pathway is involved in sepsis-induced functional damage to the heart, liver, kidney, and other organs. However, the cellular and molecular mechanisms underlying sepsis-induced brain damage remain elusive. In the present study, we found severe loss of neurons in the hippocampal CA1 region in rats with sepsis-induced brain damage following intraperitoneal injection of endotoxin, The expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 was significantly increased in brain tissues following lipopolysaccharide exposure. AG490 （JAK2 antagonist） and rapamycin （STAT3 antagonist） significantly reduced neuronal loss and suppressed the increased expression of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 in the hippocampal CA1 region in sepsis-induced brain damaged rats. Overall, these data suggest that blockade of the JAK/STAT signal transduction pathway is neuroprotective in sepsis-induced brain damage via the inhibition of toll-like receptor 4, tumor necrosis factor a, and interleukin-6 exoression.
基金Supported by National Natural Science Foundation of ChinaNo. 39670671, No. 30471531
文摘AIM： To study the effect of Hepatitis C virus nonstructural 5A （HCV NSSA） on IFNα induced signal transducer and activator of transcription-1 （STAT1） phosphorylation and nuclear translocation.METHODS： Expression of STAT1 Tyr701 phosphorylation at different time points was confirmed by Western blot, and the time point when p-STAT1 expressed most, was taken as the IFN induction time for further studies. Immunocytochemistry was used to confirm the successful transient transfection of NS5A expression plasmid. Immunofluorescene was performed to observe if there was any difference in IFNα-induced STAT1 phosphorylation and nuclear translocation between HCV NSSA-expressed and non-HCV NSSA-expressed cells. Western blot was used to compare the phosphorylated STAT1 protein of the cells.RESULTS： Expression of HCV NS5A was found in the cytoplasm of pCNS5A-transfected Huh7 cells, but not in the PRC/ CMV transfected or non-transfected cells, STAT1 Tyr701 phosphorylation was found strongest in 30 min of IFN induction, STAT1 phosphorylation and nuclear import were much less in the presence of HCV NS5A protein in contrast to pRC/CMV-transfected and non-transfected cells under fluorescent microscopy, which was further confirmed by Western blot.CONCLUSION： HCV NSSA expression plasmid is successfully transfected into Huh7 cells and HCV NS5A protein is expressed in the cytoplasm of the cells. IFN-α is able to induce STAT1 phosphrylation and nuclear translocation, and this effect is inhibited by HCV NS5A protein, which might be another possible resistance mechanism to interferon alpha therapy.
基金supported by the National Natural Science Foundation of China(NSFC)(81973316,82173807)the China Postdoctoral Science Foundation(2020M681914)+1 种基金the Fund from Tianjin Municipal Health Commission(ZC200093)the Open Fund of Tianjin Central Hospital of Obstetrics and Gynecology/Tianjin Key Laboratory of human development and reproductive regulation(2021XHY01)。
文摘Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.
基金supported by the National Natural Science Foundation of China(No.81272866)the Wuhan Municipal Science and Technology Bureau Foundation of China(No.20146 0101010043)
文摘Summary： Cancer stem cells （CSCs） are considered responsible for the high recurrence rate in cervical carcinoma. It has been demonstrated that the signal transducer and activator of transcription 3 （STAT3） is involved in the oncogenesis and takes part in mediating the effects of maintaining stem cell phenotype and pluripotency by regulating the expression of stem cell-related transcription factors. However, the correlation between STAT3 and stem cell-related transcription factors in cervical cancer has not been elucidated. In this study, we established overexpressing plasmid （GV316-STAT3） and siRNA-STAT3 for transfecting Siha cells. Cells negative or positive for Nanog, Oct4, or Sox2 were selected by flow cytometry. Proliferation and differentiation rate of Siha cells was determined by detecting the efficiency of tumor sphere formation. The expression of Nanog, Oct4 and Sox2 （cancer stem cell markers） and STAT3 was detected by quantitative real-time PCR and immunoblotting for Siha cells and by immuno- histochemistry （IHC） for cervical tissues, respectively. The results showed that Nanog＋, Oct4＋, and Sox2＋ Siha-STAT3 over-expressing cells displayed the typical non-adherent spheres. The sphere for- mation efficiency was significantly different between Siha-STAT3 overexpressing cells and siRNA-STAT3 cells （P〈0.05）. Meanwhile, the expression levels of Oct4, Nanog and Sox2 rrtRNA and protein were significantly higher in Siha-STAT3 overexprssing cells than in siRNA-STAT3 cells （P〈0.05）. In addition, the positive rate of STAT3, Nanog, Oct4 and Sox2 in cervical cancer tissues was higher than that in chronic cervicitis group （P〈0.05）. There was a significantly positive relationship between STAT3 and Nanog or Oct4 or Sox2 expression （all P〈0.001）. These results suggested that Oct4＋, Sox2＋, and Nanog＋ cell population possesses stem cell properties in cervical cancer, which may contribute to cervical carcinogenesis and be regulated by STAT3.
