目的探讨骨外膜素(Periostin)、Notch跨膜受体-1(Notch1)m RNA、维生素D(VitD)与自身免疫性甲状腺炎(AIT)淋巴细胞浸润程度、调节性T细胞/辅助性T细胞17(Treg/Th17)的相关性。方法选取2021年7月至2023年12月郑州大学第一附属医院收治的9...目的探讨骨外膜素(Periostin)、Notch跨膜受体-1(Notch1)m RNA、维生素D(VitD)与自身免疫性甲状腺炎(AIT)淋巴细胞浸润程度、调节性T细胞/辅助性T细胞17(Treg/Th17)的相关性。方法选取2021年7月至2023年12月郑州大学第一附属医院收治的92例AIT患者纳入AIT组,另选取同期50例无甲状腺疾病的健康人群纳入对照组。比较两组受检者的淋巴细胞浸润程度及抗体水平,采用Spearman、Pearson相关系数分析淋巴细胞浸润程度、Treg/Th17与甲状腺功能、抗体水平的相关性,比较两组受检者的Periostin、Notch1 m RNA、VitD及Treg/Th17,采用Pearson相关系数分析Periostin、Notch1 mRNA、VitD与淋巴细胞浸润程度及Treg/Th17的相关性。结果AIT组患者的CD3^(+)、CD3^(+)CD4^(+)、CD4^(+)CD25^(+)CD127^(-)、TgAb、TPOAb、TRAb水平及甲亢/亚临床甲亢、甲减/亚临床甲减患者占比明显高于对照组,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,CD3^(+)(r=0.579、0.602、0.563)、CD3^(+)CD4^(+)(r=0.612、0.637、0.606)、CD~4+CD25^(+)CD127^(-)(r=0.655、0.643、0.687)与TgAb、TPOAb、TRAb呈正相关(P<0.05);AIT组患者的Periostin、Notch1 m RNA分别为(4.27±1.40)μg/L、1.73±0.56,明显高于对照组的(2.86±0.49)μg/L、1.02±0.14,VitD、Treg/Th17分别为(17.82±5.09)ng/mL、2.82±0.97,明显低于对照组的(22.30±3.76)ng/mL、12.36±2.03,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,Periostin(r=0.792、0.811、0.737)、Notch1 mRNA(r=0.812、0.775、0.792)与CD3^(+)、CD3^(+)CD4^(+)、CD4^(+)CD25+CD127-呈正相关(P<0.05),VitD(r=-0.687、-0.753、-0.799)与之呈负相关(P<0.05),且Periostin(r=-0.823)、Notch1 m RNA(r=-0.772)与Treg/Th17呈负相关(P<0.05),VitD(r=0.745)与之呈正相关(P<0.05)。结论Periostin、Notch1 mRNA在AIT患者血清中表达上调,VitD表达下调,各指标与AIT淋巴细胞浸润程度及Treg/Th17均具有一定相关性,可为临床判断病情提供参考,并对后续临床治疗具有一定指导价值。展开更多
目的 探讨MYB、Notch1免疫组化染色在经典型乳腺腺样囊性癌(classic adenoid cystic carcinoma of the breast, C-AdCC)、具有基底细胞样特征的实体型乳腺腺样囊性癌(solid-basaloid adenoid cystic carcinoma of the breast, SB-AdCC)...目的 探讨MYB、Notch1免疫组化染色在经典型乳腺腺样囊性癌(classic adenoid cystic carcinoma of the breast, C-AdCC)、具有基底细胞样特征的实体型乳腺腺样囊性癌(solid-basaloid adenoid cystic carcinoma of the breast, SB-AdCC)鉴别诊断中的应用价值。方法 收集病理科存档的20例C-AdCC、6例SB-AdCC及65例其他乳腺病变组织,分别行MYB、Notch1免疫组化染色,并对26例AdCC行FISH检测,6例SB-AdCC行NGS检测。结果 (1)MYB免疫组化染色显示:C-AdCC(20/20)弥漫中等或强阳性,SB-AdCC(4/6)弥漫中等或强阳性;胶原小体病(5/5)局灶或弥漫弱阳性;恶性腺肌上皮瘤(3/3)局灶中等或强阳性;8例产基质的癌、9例分泌性癌及40例非特殊型三阴型乳腺癌均阴性。(2)Notch1免疫组化显示:SB-AdCC(3/6)弥漫中等阳性,C-AdCC(20/20)均阴性;3例恶性腺肌上皮瘤、5例胶原小体病、8例产基质的癌、9例分泌性癌及40例非特殊型三阴型乳腺癌均阴性。(3)FISH检测显示C-AdCC(12/19)MYB基因断裂,NGS检测显示SB-AdCC(3/6)Notch1突变。结论 免疫组化MYB、Notch1中等或强的弥漫性表达,可辅助鉴别C-AdCC、SB-AdCC的分型;与恶性腺肌上皮瘤鉴别困难时,可借助分子检测进一步明确。展开更多
目的:观察白藜芦醇(Res)对急性T淋巴细胞白血病(T-ALL)小鼠的影响,并进一步探讨其对Notch1信号通路的作用机制。方法:将25只6-8周龄雌性C57BL/6小鼠随机分为正常对照组、T-ALL组和Res组,其中Res组又进一步分为low-Res(L-Res)、middle-Re...目的:观察白藜芦醇(Res)对急性T淋巴细胞白血病(T-ALL)小鼠的影响,并进一步探讨其对Notch1信号通路的作用机制。方法:将25只6-8周龄雌性C57BL/6小鼠随机分为正常对照组、T-ALL组和Res组,其中Res组又进一步分为low-Res(L-Res)、middle-Res(M-Res)和high-Res(H-Res)3个浓度给药组。应用流式细胞术和瑞氏-吉姆萨染色法检测外周血及脾细胞悬液中白血病细胞百分比,HE染色法观察脾脏和骨髓组织病理形态,RT-q PCR法检测脾脏组织中Notch1、Hes-1、c-Myc、mi R-19b和PTEN m RNA表达水平,Western blot法检测Notch1、Hes-1、c-Myc、p-PTEN和PTEN蛋白表达水平。结果:与对照组相比,T-ALL组小鼠外周血中白血病细胞明显增多,脾脏及骨髓组织中白血病细胞弥漫性浸润,脾脏中Notch1、Hes-1、c-Myc、mi R-19b m RNA表达水平和Notch1、Hes-1、c-Myc蛋白表达水平均明显增高(P<0.01),PTEN m RNA及其蛋白水平显著降低(P<0.01),经白藜芦醇处理后,H-Res组以上各项指标较T-ALL组均获得逆转。结论:白藜芦醇具有抗小鼠T-ALL的作用,其机制可能通过抑制Notch1信号通路发挥作用。展开更多
Intracellular Notch (ICN) initiates DNA transcription in cooperation with CSL that acts as repressor in the absence of ICN. The ICN mediates recruitment of MAML protein, leading to the formation of minimal transcripti...Intracellular Notch (ICN) initiates DNA transcription in cooperation with CSL that acts as repressor in the absence of ICN. The ICN mediates recruitment of MAML protein, leading to the formation of minimal transcriptional complex, MAML/ICN/CSL/DNA. Crystal structure reveals that different conformations exist between the free (CSL/DNA) and bound (ICN/MAML/CSL/DNA) forms. The significance of this modulation of the CSL/DNA molecular complex can be better understood by experimental approaches that aim to elucidate the cause and timing of these events. There are four orthologues of human ICN (ICN1-4). We studied interactions between human full-length ICN1 and CSL/DNA without involvement of MAML, in vitro, and found that 1) the EMSA profile of CSL/DNA is altered in the presence of ICN1 as a consequence of an intrinsic change(s) in CSL/DNA, and not due to the formation of an ICN/CSL/DNA molecular complex;2) ICN1 destabilizes CSL/DNA. These findings indicate that human ICN1 functions to modulate the CSL/DNA molecular complex for subsequent recruitment of MAML, and that modulated CSL/DNA cannot accommodate ICN1 in the absence of MAML. The latter in turn, implies that the formation of the MAML/ICN1/CSL/DNA is likely to be a collective event, wherein preassembly of MAML and ICN1 as a binary complex co-localizes at the CSL/DNA promoter site, or the MAML/ICN1/CSL complex is pre-assembled prior to binding to the promoter, rather than ICN1 arriving at CSL/DNA ahead of MAML and/or other associated transcription factors. The novel finding that ICN1 destabilizes the CSL/DNA complex opens new possibilities of transcriptional regulation by Notch.展开更多
文摘目的探讨骨外膜素(Periostin)、Notch跨膜受体-1(Notch1)m RNA、维生素D(VitD)与自身免疫性甲状腺炎(AIT)淋巴细胞浸润程度、调节性T细胞/辅助性T细胞17(Treg/Th17)的相关性。方法选取2021年7月至2023年12月郑州大学第一附属医院收治的92例AIT患者纳入AIT组,另选取同期50例无甲状腺疾病的健康人群纳入对照组。比较两组受检者的淋巴细胞浸润程度及抗体水平,采用Spearman、Pearson相关系数分析淋巴细胞浸润程度、Treg/Th17与甲状腺功能、抗体水平的相关性,比较两组受检者的Periostin、Notch1 m RNA、VitD及Treg/Th17,采用Pearson相关系数分析Periostin、Notch1 mRNA、VitD与淋巴细胞浸润程度及Treg/Th17的相关性。结果AIT组患者的CD3^(+)、CD3^(+)CD4^(+)、CD4^(+)CD25^(+)CD127^(-)、TgAb、TPOAb、TRAb水平及甲亢/亚临床甲亢、甲减/亚临床甲减患者占比明显高于对照组,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,CD3^(+)(r=0.579、0.602、0.563)、CD3^(+)CD4^(+)(r=0.612、0.637、0.606)、CD~4+CD25^(+)CD127^(-)(r=0.655、0.643、0.687)与TgAb、TPOAb、TRAb呈正相关(P<0.05);AIT组患者的Periostin、Notch1 m RNA分别为(4.27±1.40)μg/L、1.73±0.56,明显高于对照组的(2.86±0.49)μg/L、1.02±0.14,VitD、Treg/Th17分别为(17.82±5.09)ng/mL、2.82±0.97,明显低于对照组的(22.30±3.76)ng/mL、12.36±2.03,差异均有统计学意义(P<0.05);Pearson相关系数分析结果显示,Periostin(r=0.792、0.811、0.737)、Notch1 mRNA(r=0.812、0.775、0.792)与CD3^(+)、CD3^(+)CD4^(+)、CD4^(+)CD25+CD127-呈正相关(P<0.05),VitD(r=-0.687、-0.753、-0.799)与之呈负相关(P<0.05),且Periostin(r=-0.823)、Notch1 m RNA(r=-0.772)与Treg/Th17呈负相关(P<0.05),VitD(r=0.745)与之呈正相关(P<0.05)。结论Periostin、Notch1 mRNA在AIT患者血清中表达上调,VitD表达下调,各指标与AIT淋巴细胞浸润程度及Treg/Th17均具有一定相关性,可为临床判断病情提供参考,并对后续临床治疗具有一定指导价值。
文摘目的 探讨MYB、Notch1免疫组化染色在经典型乳腺腺样囊性癌(classic adenoid cystic carcinoma of the breast, C-AdCC)、具有基底细胞样特征的实体型乳腺腺样囊性癌(solid-basaloid adenoid cystic carcinoma of the breast, SB-AdCC)鉴别诊断中的应用价值。方法 收集病理科存档的20例C-AdCC、6例SB-AdCC及65例其他乳腺病变组织,分别行MYB、Notch1免疫组化染色,并对26例AdCC行FISH检测,6例SB-AdCC行NGS检测。结果 (1)MYB免疫组化染色显示:C-AdCC(20/20)弥漫中等或强阳性,SB-AdCC(4/6)弥漫中等或强阳性;胶原小体病(5/5)局灶或弥漫弱阳性;恶性腺肌上皮瘤(3/3)局灶中等或强阳性;8例产基质的癌、9例分泌性癌及40例非特殊型三阴型乳腺癌均阴性。(2)Notch1免疫组化显示:SB-AdCC(3/6)弥漫中等阳性,C-AdCC(20/20)均阴性;3例恶性腺肌上皮瘤、5例胶原小体病、8例产基质的癌、9例分泌性癌及40例非特殊型三阴型乳腺癌均阴性。(3)FISH检测显示C-AdCC(12/19)MYB基因断裂,NGS检测显示SB-AdCC(3/6)Notch1突变。结论 免疫组化MYB、Notch1中等或强的弥漫性表达,可辅助鉴别C-AdCC、SB-AdCC的分型;与恶性腺肌上皮瘤鉴别困难时,可借助分子检测进一步明确。
文摘目的:观察白藜芦醇(Res)对急性T淋巴细胞白血病(T-ALL)小鼠的影响,并进一步探讨其对Notch1信号通路的作用机制。方法:将25只6-8周龄雌性C57BL/6小鼠随机分为正常对照组、T-ALL组和Res组,其中Res组又进一步分为low-Res(L-Res)、middle-Res(M-Res)和high-Res(H-Res)3个浓度给药组。应用流式细胞术和瑞氏-吉姆萨染色法检测外周血及脾细胞悬液中白血病细胞百分比,HE染色法观察脾脏和骨髓组织病理形态,RT-q PCR法检测脾脏组织中Notch1、Hes-1、c-Myc、mi R-19b和PTEN m RNA表达水平,Western blot法检测Notch1、Hes-1、c-Myc、p-PTEN和PTEN蛋白表达水平。结果:与对照组相比,T-ALL组小鼠外周血中白血病细胞明显增多,脾脏及骨髓组织中白血病细胞弥漫性浸润,脾脏中Notch1、Hes-1、c-Myc、mi R-19b m RNA表达水平和Notch1、Hes-1、c-Myc蛋白表达水平均明显增高(P<0.01),PTEN m RNA及其蛋白水平显著降低(P<0.01),经白藜芦醇处理后,H-Res组以上各项指标较T-ALL组均获得逆转。结论:白藜芦醇具有抗小鼠T-ALL的作用,其机制可能通过抑制Notch1信号通路发挥作用。
文摘Intracellular Notch (ICN) initiates DNA transcription in cooperation with CSL that acts as repressor in the absence of ICN. The ICN mediates recruitment of MAML protein, leading to the formation of minimal transcriptional complex, MAML/ICN/CSL/DNA. Crystal structure reveals that different conformations exist between the free (CSL/DNA) and bound (ICN/MAML/CSL/DNA) forms. The significance of this modulation of the CSL/DNA molecular complex can be better understood by experimental approaches that aim to elucidate the cause and timing of these events. There are four orthologues of human ICN (ICN1-4). We studied interactions between human full-length ICN1 and CSL/DNA without involvement of MAML, in vitro, and found that 1) the EMSA profile of CSL/DNA is altered in the presence of ICN1 as a consequence of an intrinsic change(s) in CSL/DNA, and not due to the formation of an ICN/CSL/DNA molecular complex;2) ICN1 destabilizes CSL/DNA. These findings indicate that human ICN1 functions to modulate the CSL/DNA molecular complex for subsequent recruitment of MAML, and that modulated CSL/DNA cannot accommodate ICN1 in the absence of MAML. The latter in turn, implies that the formation of the MAML/ICN1/CSL/DNA is likely to be a collective event, wherein preassembly of MAML and ICN1 as a binary complex co-localizes at the CSL/DNA promoter site, or the MAML/ICN1/CSL complex is pre-assembled prior to binding to the promoter, rather than ICN1 arriving at CSL/DNA ahead of MAML and/or other associated transcription factors. The novel finding that ICN1 destabilizes the CSL/DNA complex opens new possibilities of transcriptional regulation by Notch.
