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
就近年来白细胞介素6/非受体酪氨酸蛋白激酶/信号转导和转录激活因子3(interleukin-6/janus activated kinase/signal transducer and activator of transcription 3,IL-6/JAK/STAT3)信号通路在多种消化系统肿瘤中发挥的效应、中药单体...就近年来白细胞介素6/非受体酪氨酸蛋白激酶/信号转导和转录激活因子3(interleukin-6/janus activated kinase/signal transducer and activator of transcription 3,IL-6/JAK/STAT3)信号通路在多种消化系统肿瘤中发挥的效应、中药单体及其活性成分、中药复方对与IL-6/JAK/STAT3信号通路调控有关的消化系统肿瘤中的防治作用进行综述,探究中医药在延缓、阻抑甚至逆转炎-癌转化中发挥的作用,为防治肿瘤提供更有力的理论指导。展开更多
目的探讨信号传导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)和磷酸化STAT3(p-STAT3)在肝癌组织及癌旁肝硬化组织中的转录表达,以及p-STAT3表达与肝癌临床病理特征的关系。方法收集73例肝癌患者术后...目的探讨信号传导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)和磷酸化STAT3(p-STAT3)在肝癌组织及癌旁肝硬化组织中的转录表达,以及p-STAT3表达与肝癌临床病理特征的关系。方法收集73例肝癌患者术后肝癌组织及癌旁肝硬化组织,RT-PCR检测STAT3转录情况,免疫组化方法检测STAT3和p-STAT3蛋白表达水平;对比分析p-STAT3阳性表达组患者和阴性表达组患者年龄、性别、肿瘤大小、肿瘤计数、组织病理分化、TNM分期、是否存在包膜、门静脉系统侵犯、血清甲胎蛋白(AFP)浓度以及血清HBsAg阳性率的差异。结果肝癌组织中STAT3转录水平高于对应癌旁肝硬化组织,肝癌组织中STAT3和p-STAT3蛋白阳性表达率均高于癌旁肝硬化组织。肝癌组织p-STAT3阳性表达组与阴性表达组比较,患者在肿瘤大小、组织病理分化、TNM分期、门静脉系统侵犯存在统计学差异。结论肝癌中存在STAT3的异常表达和活化,p-STAT3是评估患者预后可能指标之一。展开更多
目的优化信号转导和转录活化因子5(signal transducers and activators of transcription,STAT5)诱骗寡核苷酸(decoyoli-godeoxynucleotide,decoyODNs)技术的实验条件,为阻断K562细胞STAT5信号转导途径,进而诱导细胞表型转变奠定基础。...目的优化信号转导和转录活化因子5(signal transducers and activators of transcription,STAT5)诱骗寡核苷酸(decoyoli-godeoxynucleotide,decoyODNs)技术的实验条件,为阻断K562细胞STAT5信号转导途径,进而诱导细胞表型转变奠定基础。方法设计并合成STAT5decoyODNs、FAM荧光标记的decoyODNs和decoyODNs突变型(M-decoyODNs);SDS-PAGE检测不同退火缓冲液条件下decoyODNs双链形成率;倒置荧光显微镜下通过阳性细胞计数比较DEAE、lipofectin和DMRIE-C3种转染试剂对decoyODNs的转染效率;流式细胞仪(FCM)检测转染12、24和72h时FAM-decoyODNs摄取率和荧光强度,检测decoyODNs的稳定性;MTT实验检测decoyODNs对K562细胞活力的影响;RT-PCR检测decoyODNs对pim-1和c-myc基因表达的影响。结果退火缓冲液(10mmol/LTris,pH8.0,50mmol/LNaCl,1mmol/LEDTA)更有利于decoyODNs双链形成。DMRIE-C的转染效率(99.2±4.6)%高于DEAE和lipofectin(67.15±7.3)%、(83.2±3.8)%,P<0.05,并且DMRIE-C介导decoyODNs转染12、24、72h的转染效率均>98%。MTT实验发现DMRIE-C的细胞毒性低,细胞活性为94.23%,decoyODNs处理组能显著抑制K562细胞MTT还原能力,与其余组相比具有显著性差异(P<0.05);RT-PCR结果发现decoyODNs处理组pim-1基因下降了71.20%,c-myc下降了59.46%,与其余组相比有统计学意义(P<0.05)。结论建立了decoyODNs最佳的双链形成条件;DMRIE-C能显著增强decoyODNs转染K562细胞的效率;decoyODNs能抑制K562细胞活力,抑制STAT5靶基因的转录。展开更多
目的通过体外沉默信号传导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)基因转录,探讨阻断JAK2/STAT3信号通路对肝癌细胞HepG2增殖能力的影响及其机制。方法 siRNA体外沉默肝癌细胞株HepG2STAT3基因转录...目的通过体外沉默信号传导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)基因转录,探讨阻断JAK2/STAT3信号通路对肝癌细胞HepG2增殖能力的影响及其机制。方法 siRNA体外沉默肝癌细胞株HepG2STAT3基因转录,检测细胞内STAT3mRNA和蛋白的表达变化证实基因沉默效果,MTT检测细胞增殖能力的变化,流式细胞仪检测细胞周期,RT-PCR检测JAK2/STAT3信号通路下游分子survivin及caspase3表达的变化。结果阻断JAK2/STAT3信号通路后肝癌细胞株HepG2增殖能力下降,细胞分裂停滞于G0-G1期,伴随survivin转录下降,caspase3转录上升。结论阻断JAK2/STAT3信号通路可抑制肝癌细胞增殖,可能同调控survivin及caspase3有关。展开更多
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.
文摘就近年来白细胞介素6/非受体酪氨酸蛋白激酶/信号转导和转录激活因子3(interleukin-6/janus activated kinase/signal transducer and activator of transcription 3,IL-6/JAK/STAT3)信号通路在多种消化系统肿瘤中发挥的效应、中药单体及其活性成分、中药复方对与IL-6/JAK/STAT3信号通路调控有关的消化系统肿瘤中的防治作用进行综述,探究中医药在延缓、阻抑甚至逆转炎-癌转化中发挥的作用,为防治肿瘤提供更有力的理论指导。
文摘目的探讨信号传导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)和磷酸化STAT3(p-STAT3)在肝癌组织及癌旁肝硬化组织中的转录表达,以及p-STAT3表达与肝癌临床病理特征的关系。方法收集73例肝癌患者术后肝癌组织及癌旁肝硬化组织,RT-PCR检测STAT3转录情况,免疫组化方法检测STAT3和p-STAT3蛋白表达水平;对比分析p-STAT3阳性表达组患者和阴性表达组患者年龄、性别、肿瘤大小、肿瘤计数、组织病理分化、TNM分期、是否存在包膜、门静脉系统侵犯、血清甲胎蛋白(AFP)浓度以及血清HBsAg阳性率的差异。结果肝癌组织中STAT3转录水平高于对应癌旁肝硬化组织,肝癌组织中STAT3和p-STAT3蛋白阳性表达率均高于癌旁肝硬化组织。肝癌组织p-STAT3阳性表达组与阴性表达组比较,患者在肿瘤大小、组织病理分化、TNM分期、门静脉系统侵犯存在统计学差异。结论肝癌中存在STAT3的异常表达和活化,p-STAT3是评估患者预后可能指标之一。
文摘目的优化信号转导和转录活化因子5(signal transducers and activators of transcription,STAT5)诱骗寡核苷酸(decoyoli-godeoxynucleotide,decoyODNs)技术的实验条件,为阻断K562细胞STAT5信号转导途径,进而诱导细胞表型转变奠定基础。方法设计并合成STAT5decoyODNs、FAM荧光标记的decoyODNs和decoyODNs突变型(M-decoyODNs);SDS-PAGE检测不同退火缓冲液条件下decoyODNs双链形成率;倒置荧光显微镜下通过阳性细胞计数比较DEAE、lipofectin和DMRIE-C3种转染试剂对decoyODNs的转染效率;流式细胞仪(FCM)检测转染12、24和72h时FAM-decoyODNs摄取率和荧光强度,检测decoyODNs的稳定性;MTT实验检测decoyODNs对K562细胞活力的影响;RT-PCR检测decoyODNs对pim-1和c-myc基因表达的影响。结果退火缓冲液(10mmol/LTris,pH8.0,50mmol/LNaCl,1mmol/LEDTA)更有利于decoyODNs双链形成。DMRIE-C的转染效率(99.2±4.6)%高于DEAE和lipofectin(67.15±7.3)%、(83.2±3.8)%,P<0.05,并且DMRIE-C介导decoyODNs转染12、24、72h的转染效率均>98%。MTT实验发现DMRIE-C的细胞毒性低,细胞活性为94.23%,decoyODNs处理组能显著抑制K562细胞MTT还原能力,与其余组相比具有显著性差异(P<0.05);RT-PCR结果发现decoyODNs处理组pim-1基因下降了71.20%,c-myc下降了59.46%,与其余组相比有统计学意义(P<0.05)。结论建立了decoyODNs最佳的双链形成条件;DMRIE-C能显著增强decoyODNs转染K562细胞的效率;decoyODNs能抑制K562细胞活力,抑制STAT5靶基因的转录。
文摘目的通过体外沉默信号传导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)基因转录,探讨阻断JAK2/STAT3信号通路对肝癌细胞HepG2增殖能力的影响及其机制。方法 siRNA体外沉默肝癌细胞株HepG2STAT3基因转录,检测细胞内STAT3mRNA和蛋白的表达变化证实基因沉默效果,MTT检测细胞增殖能力的变化,流式细胞仪检测细胞周期,RT-PCR检测JAK2/STAT3信号通路下游分子survivin及caspase3表达的变化。结果阻断JAK2/STAT3信号通路后肝癌细胞株HepG2增殖能力下降,细胞分裂停滞于G0-G1期,伴随survivin转录下降,caspase3转录上升。结论阻断JAK2/STAT3信号通路可抑制肝癌细胞增殖,可能同调控survivin及caspase3有关。
