In the Drosophila larval brain, type I and type Ⅱ neuroblasts（NBs） undergo a series of asymmetric divisions which give rise to distinct progeny lineages. The intermediate neural progenitors（INPs） exist only in ty...In the Drosophila larval brain, type I and type Ⅱ neuroblasts（NBs） undergo a series of asymmetric divisions which give rise to distinct progeny lineages. The intermediate neural progenitors（INPs） exist only in type Ⅱ NB lineages. In this study, we reveal a novel function of Inscuteable（Insc） that acts to maintain type I NB lineage identity. In insc type I NB clones of mosaic analyses with a repressible cell marker（MARCM）, the formation of extra Deadpan（Dpn）tNB-like and GMC-like cells is observed. The lack of Insc leads to the defective localization and segregation of Numb during asymmetric cell division. By the end of cytokinesis, this results in insufficient Numb in ganglion mother cells（GMCs）. The formation of extra Deadpan（Dpn）tcells in insc clones is prevented by the attenuation of Notch activity. This suggests that Insc functions through the Numb/Notch signaling pathway. We also show that in the absence of Insc in type I NB lineages, the cellular identity of GMCs is altered where they adopt an INP-like cell fate as indicated by the initiation of Dpn expression accompanied by a transient presence of Earmuff（Erm）.These INP-like cells have the capacity to divide multiple times. We conclude that Insc is necessary for the maintenance of type I NB lineage identity. Genetic manipulations to eliminate most type I NBs with overproliferating type Ⅱ NBs in the larval brain lead to altered circadian rhythms and defective phototaxis in adult flies. This indicates that the homeogenesis of NB lineages is important for the adult＇s brain function.展开更多
The Musashi （Msi） family is a group of RNA-binding proteins characterized by two RNA recognition motifs （RRMs） and is evolutionarily conserved [1, 2]. In mammals, two isoforms of this family, Msil and Msi2, are co...The Musashi （Msi） family is a group of RNA-binding proteins characterized by two RNA recognition motifs （RRMs） and is evolutionarily conserved [1, 2]. In mammals, two isoforms of this family, Msil and Msi2, are co-expressed in neural precursor cells, including neural stem cells （NSCs）. Msi2 exhibits high sequence homology with Msil, which is more than 90% at the amino acid level within the RNA-binding domain.展开更多
Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling res...Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.展开更多
文摘目的 探讨飞燕草素调节Numb/Notch信号通路诱导卵巢癌细胞A2780凋亡的作用机制。方法 使用顺铂(500μmoL/mL)和低剂量(500μmoL/mL)、高剂量(1000μmoL/mL)飞燕草素处理卵巢癌细胞A2780,同时设立卵巢癌细胞A2780对照组,各组设6个平行样,培养72 h后。实验结束后,采用CCK-8试剂盒测定各组细胞增殖水平,流式细胞术检测细胞凋亡率,Transwell法测定细胞侵袭水平,划痕实验检测细胞迁移水平,实时荧光定量(RT-qPCR)及蛋白印记法(West-blot)检测细胞Numb、Notch1 m RNA和蛋白表达水平。结果 与A2780细胞组比较,顺铂组、飞燕草素低、高剂量组A值、存活率、穿膜数、迁移距离、Notch1 m RNA和蛋白表达降低(P<0.05);与顺铂组比较,飞燕草素低剂量组A值、存活率、穿膜数、迁移距离、Notch1 m RNA和蛋白表达升高(P<0.05),高剂量组A值、存活率、穿膜数、迁移距离、Notch1 m RNA和蛋白表达无明显变化(P>0.05);与飞燕草素低剂量组比较,飞燕草素高剂量组A值、存活率、穿膜数、迁移距离、Notch1 mRNA和蛋白表达降低(P<0.05)。与A2780细胞组比较,顺铂组、飞燕草素低、高剂量组凋亡率、Numb mRNA和蛋白表达升高(P<0.05);与顺铂组比较,飞燕草素低剂量组凋亡率、Numb mRNA和蛋白表达降低(P<0.05),高剂量组凋亡率、Numb mRNA和蛋白表达无明显变化(P>0.05);与飞燕草素低剂量组比较,飞燕草素高剂量组凋亡率、Numb mRNA和蛋白表达升高(P<0.05)。结论 飞燕草素可以通过激活Numb进而抑制Notch1通路来抑制卵巢癌细胞的增殖、迁移、侵袭,促进其凋亡。
基金supported by the National Basic Research Program of China (No.2013CB945600)the National Natural Science Foundation of China (No.31371381)
文摘In the Drosophila larval brain, type I and type Ⅱ neuroblasts（NBs） undergo a series of asymmetric divisions which give rise to distinct progeny lineages. The intermediate neural progenitors（INPs） exist only in type Ⅱ NB lineages. In this study, we reveal a novel function of Inscuteable（Insc） that acts to maintain type I NB lineage identity. In insc type I NB clones of mosaic analyses with a repressible cell marker（MARCM）, the formation of extra Deadpan（Dpn）tNB-like and GMC-like cells is observed. The lack of Insc leads to the defective localization and segregation of Numb during asymmetric cell division. By the end of cytokinesis, this results in insufficient Numb in ganglion mother cells（GMCs）. The formation of extra Deadpan（Dpn）tcells in insc clones is prevented by the attenuation of Notch activity. This suggests that Insc functions through the Numb/Notch signaling pathway. We also show that in the absence of Insc in type I NB lineages, the cellular identity of GMCs is altered where they adopt an INP-like cell fate as indicated by the initiation of Dpn expression accompanied by a transient presence of Earmuff（Erm）.These INP-like cells have the capacity to divide multiple times. We conclude that Insc is necessary for the maintenance of type I NB lineage identity. Genetic manipulations to eliminate most type I NBs with overproliferating type Ⅱ NBs in the larval brain lead to altered circadian rhythms and defective phototaxis in adult flies. This indicates that the homeogenesis of NB lineages is important for the adult＇s brain function.
文摘The Musashi （Msi） family is a group of RNA-binding proteins characterized by two RNA recognition motifs （RRMs） and is evolutionarily conserved [1, 2]. In mammals, two isoforms of this family, Msil and Msi2, are co-expressed in neural precursor cells, including neural stem cells （NSCs）. Msi2 exhibits high sequence homology with Msil, which is more than 90% at the amino acid level within the RNA-binding domain.
基金supported by the National Natural Science Foundation of China(Grant No.82274442)the Key Research Project in Traditional Chinese Medicine of Tianjin Municipal Health Commission(Grant No.202007)the Integrated Traditional Chinese and Western Medicine Research Project of Tianjin Municipal Health Commission(Grant No.2023134).
文摘Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.
