Background:Zinc-finger E-box-binding homeobox-1(ZEB1)is predominantly found in type-H vessels.However,the roles of ZEB1 and type-H vessels in steroid-i nduced osteonecrosis of the femoral head(SONFH)are unclear.Method...Background:Zinc-finger E-box-binding homeobox-1(ZEB1)is predominantly found in type-H vessels.However,the roles of ZEB1 and type-H vessels in steroid-i nduced osteonecrosis of the femoral head(SONFH)are unclear.Methods:Human femoral heads were collected to detect the expression of ZEB1and the levels of type-H vessels.Then,the SONFH model was developed by injecting C57BL/6 mice with lipopolysaccharide and methylprednisolone.Microcomputed tomography,angiography,double calcein labeling,immunofluorescence,immunohistochemistry,quantitative real-time polymerase chain reaction,and Western blotting were performed to detect the expression of ZEB1,the Wnt/β-catenin pathway,type-H vessels,and the extent to which ZEB1 mediates angiogenesis and osteogenesis.Human umbilical vein endothelial cells were also used to explore the relationship between ZEB1 and the Wnt/β-catenin pathway.Results:We found that ZEB1 expression and the formation of type-H vessels decreased in SONFH patients and in a mouse model.The number of vascular endothelial growth factors in the femoral heads also decreased.Moreover,the bone mineral density,trabecular number,mineral apposition rate,and expression of genes related to osteogenesis decreased.After ZEB1 knockdown,angiogenesis and osteogenesis decreased.However,the numbers of type-H vessels and the extent of angiogenesis and osteogenesis improved after activation of the Wnt/β-catenin pathway.Conclusions:The ZEB1 expression decreased in SONFH,causing a decrease in type-H vessel,and it mediated angiogenesis and osteogenesis by regulating the Wnt/β-catenin pathway,ultimately accelerating the process of SONFH.展开更多
BACKGROUND Oral squamous cell carcinoma(OSCC)is a frequent cancer affecting the oral cavity.OSCC is usually preceded by occurrence of precursor lesions,which demonstrate a varying degree of malignant transformation po...BACKGROUND Oral squamous cell carcinoma(OSCC)is a frequent cancer affecting the oral cavity.OSCC is usually preceded by occurrence of precursor lesions,which demonstrate a varying degree of malignant transformation potential.Epithelialmesenchymal transition is a significant biological phenomenon that facilitates tumor growth and metastasis through the involvement of diverse epithelial and mesenchymal proteins.E-cadherin down regulation and over-expression of zincfinger E-box-binding homeobox 1(ZEB1)has been reported in several cancers.AIM To evaluate the role of E-cadherin and ZEB1 in oral leukoplakia and OSCC.METHODS A total of 60 cases i.e.,oral leukoplakia/oral epithelial dysplasia(OED)(n=30)and OSCC(n=30)were included.Immunohistochemistry was performed utilizing two markers:E-cadherin and ZEB1.The Mann-Whitney U test was employed to compare individual markers across the study groups.Spearman’s correlation was done followed by discriminant function analysis.RESULTS Reduction in the expression E-cadherin and altered localization were noted from OED to OSCC.Overexpression of ZEB1 along with cytoplasmic accumulation was noted in OED,with marked expression in OSCC.ZEB1 epithelium intensity and ZEB1 connective tissue percentage contributed to the discriminant function with an accuracy of 85%for the classification of OED from OSCC.CONCLUSION Loss of E-cadherin and up-regulation of ZEB1 from OED to OSCC,predisposes to induction of epithelial-mesenchymal transition.Discriminant formulas are developed to classify cases of OED and OSCC with 85%accuracy.展开更多
基金China Postdoctoral Science Foundation,Grant/Award Number:2021M692575Fundamental Research Funds for the Central Universities,Grant/Award Number:xzy022024016National Natural Science Foundation of China,Grant/Award Number:82002311。
文摘Background:Zinc-finger E-box-binding homeobox-1(ZEB1)is predominantly found in type-H vessels.However,the roles of ZEB1 and type-H vessels in steroid-i nduced osteonecrosis of the femoral head(SONFH)are unclear.Methods:Human femoral heads were collected to detect the expression of ZEB1and the levels of type-H vessels.Then,the SONFH model was developed by injecting C57BL/6 mice with lipopolysaccharide and methylprednisolone.Microcomputed tomography,angiography,double calcein labeling,immunofluorescence,immunohistochemistry,quantitative real-time polymerase chain reaction,and Western blotting were performed to detect the expression of ZEB1,the Wnt/β-catenin pathway,type-H vessels,and the extent to which ZEB1 mediates angiogenesis and osteogenesis.Human umbilical vein endothelial cells were also used to explore the relationship between ZEB1 and the Wnt/β-catenin pathway.Results:We found that ZEB1 expression and the formation of type-H vessels decreased in SONFH patients and in a mouse model.The number of vascular endothelial growth factors in the femoral heads also decreased.Moreover,the bone mineral density,trabecular number,mineral apposition rate,and expression of genes related to osteogenesis decreased.After ZEB1 knockdown,angiogenesis and osteogenesis decreased.However,the numbers of type-H vessels and the extent of angiogenesis and osteogenesis improved after activation of the Wnt/β-catenin pathway.Conclusions:The ZEB1 expression decreased in SONFH,causing a decrease in type-H vessel,and it mediated angiogenesis and osteogenesis by regulating the Wnt/β-catenin pathway,ultimately accelerating the process of SONFH.
文摘BACKGROUND Oral squamous cell carcinoma(OSCC)is a frequent cancer affecting the oral cavity.OSCC is usually preceded by occurrence of precursor lesions,which demonstrate a varying degree of malignant transformation potential.Epithelialmesenchymal transition is a significant biological phenomenon that facilitates tumor growth and metastasis through the involvement of diverse epithelial and mesenchymal proteins.E-cadherin down regulation and over-expression of zincfinger E-box-binding homeobox 1(ZEB1)has been reported in several cancers.AIM To evaluate the role of E-cadherin and ZEB1 in oral leukoplakia and OSCC.METHODS A total of 60 cases i.e.,oral leukoplakia/oral epithelial dysplasia(OED)(n=30)and OSCC(n=30)were included.Immunohistochemistry was performed utilizing two markers:E-cadherin and ZEB1.The Mann-Whitney U test was employed to compare individual markers across the study groups.Spearman’s correlation was done followed by discriminant function analysis.RESULTS Reduction in the expression E-cadherin and altered localization were noted from OED to OSCC.Overexpression of ZEB1 along with cytoplasmic accumulation was noted in OED,with marked expression in OSCC.ZEB1 epithelium intensity and ZEB1 connective tissue percentage contributed to the discriminant function with an accuracy of 85%for the classification of OED from OSCC.CONCLUSION Loss of E-cadherin and up-regulation of ZEB1 from OED to OSCC,predisposes to induction of epithelial-mesenchymal transition.Discriminant formulas are developed to classify cases of OED and OSCC with 85%accuracy.
