Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were se...Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Y展开更多
肿瘤转移与多种细胞信号通路作用有关,其中与JAK2/STAT3/SOCS3通路关系尤为密切,JAK2/STAT3信号通路的激活参与了肿瘤发生、发展、侵袭和转移等多个环节。细胞因子信号转导抑制蛋白3(suppressors of cytokine signaling 3,SOCS3)负性调...肿瘤转移与多种细胞信号通路作用有关,其中与JAK2/STAT3/SOCS3通路关系尤为密切,JAK2/STAT3信号通路的激活参与了肿瘤发生、发展、侵袭和转移等多个环节。细胞因子信号转导抑制蛋白3(suppressors of cytokine signaling 3,SOCS3)负性调控JAK2/STAT3通路,进而抑制肿瘤的增殖和生长;信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)信号通路的激活促成了肿瘤炎性微环境的形成,参与了肿瘤血管生成、上皮间质转化和细胞外基质降解等多个环节,在肿瘤的侵袭和转移过程中发挥重要作用。本文着重对JAK2/STAT3/SOCS3信号通路与肿瘤转移的关系进行综述,针对JAK2/STAT3/SOCS3细胞信号动态网络在肿瘤中作用机制研究和药物设计为肿瘤治疗提供了新方向。展开更多
目的:观察电针对神经病理性疼痛大鼠痛行为学及脊髓细胞因子信号转导抑制蛋白3(SOCS3)表达的影响。方法:SD大鼠随机分为正常组、假手术组、模型组、电针组、非电针组,每组10只。采用坐骨神经结扎压迫建立慢性限制性损伤(CCI)神经痛模型...目的:观察电针对神经病理性疼痛大鼠痛行为学及脊髓细胞因子信号转导抑制蛋白3(SOCS3)表达的影响。方法:SD大鼠随机分为正常组、假手术组、模型组、电针组、非电针组,每组10只。采用坐骨神经结扎压迫建立慢性限制性损伤(CCI)神经痛模型,电针组选取双侧"阳陵泉"、"环跳"穴进行电针治疗,观察大鼠痛行为学和脊髓SOCS3、IL-6基因表达的变化,检测脊髓SOCS3神经细胞定位情况。结果:与模型组相比,电针可显著提高CCI大鼠机械痛及热痛阈值(P<0.01);与正常组相比,模型组大鼠脊髓SOCS3、IL-6 m RNA表达显著上调(P<0.01),而电针可显著降低IL-6m RNA表达,并进一步上调脊髓SOCS3表达水平(P<0.01)。在CCI大鼠中,SOCS3主要表达于脊髓星形胶质细胞和小胶质细胞中。结论:电针可能通过下调IL-6基因表达,并上调SOCS3表达,减轻神经痛大鼠痛敏反应。展开更多
T-cells critically contribute to protection against Mycobacterium tuberculosis infection,and impaired T-cell responses can lead to disease progression.Pro-inflammatory and immunosuppressive cytokines affect T-cells,an...T-cells critically contribute to protection against Mycobacterium tuberculosis infection,and impaired T-cell responses can lead to disease progression.Pro-inflammatory and immunosuppressive cytokines affect T-cells,and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function.Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases.We characterized blood samples from tuberculosis patients(n=28)and healthy contacts(n=28)from Ghana for M.tuberculosis-specific T-cell responses,constitutive cytokine production,and SOCS3 and pSTAT3 expression.Lentiviral modulation of primary CD4+T-cells was performed to determine the effects of SOCS3 on T-cell functions.T-cells from tuberculosis patients expressed higher levels of IL-10 and IL-6 and lower levels of T helper type(TH)17 cytokines after M.tuberculosis-specific stimulation compared to healthy contacts.In addition,tuberculosis patients had higher IL-10 and IL-6 levels in the supernatants of non-stimulated immune cells and plasma samples compared to healthy contacts.Notably,aberrant cytokine expression was accompanied by high constitutive pSTAT3 levels and SOCS3 expression in T-cells.Multivariate analysis identified an IL-6/IL-10 co-expression-based principal component in tuberculosis patients that correlated with high pSTAT3 levels.SOCS3 contributed to a regulatory component,and tuberculosis patients with high SOCS3 expression showed decreased TH1 cytokine expression and impaired IL-2-induced STAT5 phosphorylation.SOCS3 over-expression in primary CD4+T-cells confirmed the SOCS3 inhibitory function on IL-2-induced STAT5 phosphorylation.We conclude that constitutive pSTAT3 and high SOCS3 expression are influential factors that indicate impaired T-cell functions in tuberculosis patients.展开更多
基金supported by Natural Sciences Fund of Zhejiang Province(grant number:LY14H040011)Subject of Zhejiang Provincial Administration of traditional Chinese Medicine(grant number:2013ZB058)
文摘Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Y
文摘肿瘤转移与多种细胞信号通路作用有关,其中与JAK2/STAT3/SOCS3通路关系尤为密切,JAK2/STAT3信号通路的激活参与了肿瘤发生、发展、侵袭和转移等多个环节。细胞因子信号转导抑制蛋白3(suppressors of cytokine signaling 3,SOCS3)负性调控JAK2/STAT3通路,进而抑制肿瘤的增殖和生长;信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)信号通路的激活促成了肿瘤炎性微环境的形成,参与了肿瘤血管生成、上皮间质转化和细胞外基质降解等多个环节,在肿瘤的侵袭和转移过程中发挥重要作用。本文着重对JAK2/STAT3/SOCS3信号通路与肿瘤转移的关系进行综述,针对JAK2/STAT3/SOCS3细胞信号动态网络在肿瘤中作用机制研究和药物设计为肿瘤治疗提供了新方向。
文摘目的:观察电针对神经病理性疼痛大鼠痛行为学及脊髓细胞因子信号转导抑制蛋白3(SOCS3)表达的影响。方法:SD大鼠随机分为正常组、假手术组、模型组、电针组、非电针组,每组10只。采用坐骨神经结扎压迫建立慢性限制性损伤(CCI)神经痛模型,电针组选取双侧"阳陵泉"、"环跳"穴进行电针治疗,观察大鼠痛行为学和脊髓SOCS3、IL-6基因表达的变化,检测脊髓SOCS3神经细胞定位情况。结果:与模型组相比,电针可显著提高CCI大鼠机械痛及热痛阈值(P<0.01);与正常组相比,模型组大鼠脊髓SOCS3、IL-6 m RNA表达显著上调(P<0.01),而电针可显著降低IL-6m RNA表达,并进一步上调脊髓SOCS3表达水平(P<0.01)。在CCI大鼠中,SOCS3主要表达于脊髓星形胶质细胞和小胶质细胞中。结论:电针可能通过下调IL-6基因表达,并上调SOCS3表达,减轻神经痛大鼠痛敏反应。
基金by the German Research Foundation(DFG,JA 1479/5-1)to N Nausch,E.Owusu-Dabo,and M.Jacobsen.K.Harling were supported by the‘Hedwig und Waldemar Hort Stipendienstiftung’.E.Adankwah and M.Jacobsen were supported by the Manchot graduate school‘Molecules of Infection(MOI)-3’.
文摘T-cells critically contribute to protection against Mycobacterium tuberculosis infection,and impaired T-cell responses can lead to disease progression.Pro-inflammatory and immunosuppressive cytokines affect T-cells,and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function.Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases.We characterized blood samples from tuberculosis patients(n=28)and healthy contacts(n=28)from Ghana for M.tuberculosis-specific T-cell responses,constitutive cytokine production,and SOCS3 and pSTAT3 expression.Lentiviral modulation of primary CD4+T-cells was performed to determine the effects of SOCS3 on T-cell functions.T-cells from tuberculosis patients expressed higher levels of IL-10 and IL-6 and lower levels of T helper type(TH)17 cytokines after M.tuberculosis-specific stimulation compared to healthy contacts.In addition,tuberculosis patients had higher IL-10 and IL-6 levels in the supernatants of non-stimulated immune cells and plasma samples compared to healthy contacts.Notably,aberrant cytokine expression was accompanied by high constitutive pSTAT3 levels and SOCS3 expression in T-cells.Multivariate analysis identified an IL-6/IL-10 co-expression-based principal component in tuberculosis patients that correlated with high pSTAT3 levels.SOCS3 contributed to a regulatory component,and tuberculosis patients with high SOCS3 expression showed decreased TH1 cytokine expression and impaired IL-2-induced STAT5 phosphorylation.SOCS3 over-expression in primary CD4+T-cells confirmed the SOCS3 inhibitory function on IL-2-induced STAT5 phosphorylation.We conclude that constitutive pSTAT3 and high SOCS3 expression are influential factors that indicate impaired T-cell functions in tuberculosis patients.
