Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduc- tion pathways during cer...Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduc- tion pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups： in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-hep-arinized blood into the Brain. In the acupuncture group, modeled rats had Baihui （DU20） and Qubin （GBT） acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 μg/mL DAPT solution （10 mL） infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch 1 and Hesl protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by in- hibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.展开更多
Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but al...Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but also hinders DNA transactions.Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions.The high mobility group box(HMGB)proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion.They play a major role in chromatin dynamics.The Saccharomyces cerevisiae(yeast hereafter)HMGB protein Hmo1 contains two HMGB motifs.However,unlike a canonical HMGB protein that has an acidic C-terminus,Hmo1 ends with a lysine rich,basic,C-terminus,resembling linker histone H1.Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions.For instance,Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones.Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome.This minireview reviews the functions of Hmo1 and the underlying mechanisms,highlighting recent discoveries.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
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
Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,h...Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.展开更多
Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and test...Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test.Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism.Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.展开更多
基金supported by the National Natural Science Foundation of China,No.81273824,30772840Ministry of Education Doctoral Fund in China,No.20102327110003+1 种基金the Natural Science Foundation of Heilongjiang Province in China,No.ZD201204Special funds for Technological Innovation Research of Harbin,China,No.2012RFXXS062
文摘Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduc- tion pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups： in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-hep-arinized blood into the Brain. In the acupuncture group, modeled rats had Baihui （DU20） and Qubin （GBT） acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 μg/mL DAPT solution （10 mL） infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch 1 and Hesl protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by in- hibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.
文摘Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but also hinders DNA transactions.Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions.The high mobility group box(HMGB)proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion.They play a major role in chromatin dynamics.The Saccharomyces cerevisiae(yeast hereafter)HMGB protein Hmo1 contains two HMGB motifs.However,unlike a canonical HMGB protein that has an acidic C-terminus,Hmo1 ends with a lysine rich,basic,C-terminus,resembling linker histone H1.Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions.For instance,Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones.Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome.This minireview reviews the functions of Hmo1 and the underlying mechanisms,highlighting recent discoveries.
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Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.
基金supported by the priority academic program development of Jiangsu Higher education institutionsthe National Natural Science Foundation of China [31801538, 32072200]China Postdoctoral Science Foundation[2019M651747].
文摘Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test.Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism.Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.
