旨在研究成纤维细胞生长因子(FGF20)及受体FGFR2和FGFR3在小鼠胚胎期毛囊形成期的表达情况,了解FGF20及受体FGFR2和FG-FR3在小鼠毛囊形成期的作用。采用实时荧光定量PCR、Western blot和免疫组织化学技术检测胚胎期13 d (E13)至18 d (E...旨在研究成纤维细胞生长因子(FGF20)及受体FGFR2和FGFR3在小鼠胚胎期毛囊形成期的表达情况,了解FGF20及受体FGFR2和FG-FR3在小鼠毛囊形成期的作用。采用实时荧光定量PCR、Western blot和免疫组织化学技术检测胚胎期13 d (E13)至18 d (E18)小鼠背部皮肤中FGF20、FGFR2和FGFR3 mRNA及蛋白的差异表达。免疫组化结果显示,FGF20蛋白和FGFR3蛋白E13在表层细胞微弱表达,E14主要表达在表层细胞,且在基底层细胞也有微弱表达,E15主要表达在基板和表层细胞,E16强表达在毛钉与表层细胞,E17和E18主要表达在表层细胞和未成熟的毛囊;FGFR2蛋白在表层细胞、基底层细胞、基板、毛钉、未成熟的毛囊等处均有表达,且E18强表达在表层细胞和未成熟毛囊;RT-PCR及Western blot数据分析结果显示:FGF20 mRNA及蛋白在E16相对表达量最高;FGFR2 mRNA及蛋白在E13相对表达量最低,E18相对表达量最高;FGFR3 mRNA及蛋白表达趋势和FGF20相似。研究结果提示,在毛囊形成期,FGF20可能通过与FGFR3结合从而参与毛囊的诱导和激活,促进毛囊形成并决定其生长方向。FGFR2可能在毛囊形成过程调控表层细胞增殖,促进毛囊形成,诱导毛囊进入第一生长周期。展开更多
Objective:To evaluate the efficacy of ponatinib plus gossypol against colorectal cancer HCT-116 and Caco-2 cells.Methods:Cells were treated with ponatinib and/or gossypol at increasing concentrations to evaluate syner...Objective:To evaluate the efficacy of ponatinib plus gossypol against colorectal cancer HCT-116 and Caco-2 cells.Methods:Cells were treated with ponatinib and/or gossypol at increasing concentrations to evaluate synergistic drug interactions by combination index.Cell viability,FGF19/FGFR4,and apoptotic and autophagic cell death were studied.Results:Ponatinib(1.25-40μM)and gossypol(2.5-80μM)monotherapy inhibited HCT-116 and Caco-2 cell viability in a doseand time-dependent manner.The combination of ponatinib and gossypol at a ratio of 1 to 2 significantly decreased cell viability(P<0.05),with a>2-and>4-fold reduction in IC50,respectively,after 24 h and 48 h,as compared to the IC50 of ponatinib.Lower combined concentrations showed greater synergism(combination index<1)with a higher ponatinib dose reduction index.Moreover,ponatinib plus gossypol induced morphological changes in HCT-116and Caco-2 cells,increased beclin-1 and caspase-3,and decreased FGF19,FGFR4,Bcl-2 and p-Akt as compared to treatment with drugs alone.Conclusions:Gossypol enhances ponatinib's anticancer effects against colorectal cancer cells through antiproliferative,apoptotic,and autophagic mechanisms.This may open the way for the future use of ponatinib at lower doses with gossypol as a potentially safer targeted strategy for colorectal cancer treatment.展开更多
Objective:To investigate the expression of miR-195 in intrauterine adhesion(IUA)and its relationship with TGF-β1/Smads and FGF2/FGFR1/ERK pathways.Methods:118 cases of IUA patients who underwent hysteroscopic treatme...Objective:To investigate the expression of miR-195 in intrauterine adhesion(IUA)and its relationship with TGF-β1/Smads and FGF2/FGFR1/ERK pathways.Methods:118 cases of IUA patients who underwent hysteroscopic treatment in our hospital between September 2017 and February 2019 were regarded as IUA group,80 cases of dysfunctional uterine bleeding patients who underwent hysteroscopic curettage in our hospital during the same period were regarded as control group.Differences in the expression levels of miR-195 as well as TGF-β1/Smads and FGF2/FGFR1/ERK signaling pathway-related molecules in the focal tissues obtained by hysteroscopy were compared between the two groups.Pearson test was used to evaluate the correlation of miR-195 expression in the intrauterine adhesion tissues with TGF-β1/Smads and FGF2/FGFR1/ERK pathways in IUA patients.Results:miR-195 expression in intrauterine adhesion tissues of IUA group was higher than that in endometrial tissues of control group(P<0.05).TGF-β1,Smad2 and Smad3 mRNA expression in intrauterine adhesion tissues of IUA group were higher than those in endometrial tissues of control group;FGF2,FGFR1 and ERK mRNA expression in intrauterine adhesion tissues were higher than those in endometrial tissues of control group(P<0.05).Pearson test showed that the miR-195 expression in intrauterine adhesion tissues of IUA group was positively correlated with the TGF-β1/Smads pathway-related molecules TGF-β1,Smad2 and Smad3 mRNA expression,and positively correlated with the FGF2/FGFR1/ERK pathway-related molecules FGF2,FGFR1 and ERK mRNA expression(P<0.05).Conclusion:miR-195 is highly expressed in IUA lesion tissues and may promote disease progression by activating TGF-β1/Smads and FGF2/FGFR1/ERK signaling pathways.展开更多
目的研究Rbp4(Retinol binding protein 4)、Gpc3(Glypican family of growth factor binding protein 3)、C1qtnf3(Collagenous repeat-containing sequence of 26 KDa protein)等新致病基因在颅缝早闭症中的发病机制,为疾病非手术治...目的研究Rbp4(Retinol binding protein 4)、Gpc3(Glypican family of growth factor binding protein 3)、C1qtnf3(Collagenous repeat-containing sequence of 26 KDa protein)等新致病基因在颅缝早闭症中的发病机制,为疾病非手术治疗奠定理论基础。方法以Crouzon综合征Fgfr2cC342Y/+小鼠为实验模型,应用MicroCT和组织学染色,研究小鼠颅缝闭合模式;以Fgfr2cC342Y/+模型,RT-qPCR研究Rbp4、Gpc3、C1qtnf3等新致病基因的表达差异,初步探讨其在颅缝闭合过程中的调控作用;以体外培养的Fgfr2cC342Y/+小鼠颅缝细胞为模型,研究基因突变动物细胞增殖与代谢改变。结果获得Fgfr2cC342Y/+小鼠后额缝、冠状缝、人字缝、矢状缝等颅缝闭合模式,随颅骨发育、颅缝闭合,OC(Osteocalcin)、ALP(Alkalinephosphatase)表达增加,目的基因Rbp4、Gpc3、C1qtnf3表达下降,Msx2(Muscle segment homeobox gene 2)表达增加,杂合子与野生型小鼠之间均存在显著统计学差异,与前期人颅缝组织Microarray研究结果一致。Gpc1(Glypican family ofgrowth factor binding protein 1)、FliI(Flightless I)在颅缝闭合中的表达较恒定,野生型与杂合子之间未见明显统计学差异。体外培养Fgfr2cC342Y/+小鼠颅缝细胞,CellTiter96 MTS和Quant-iT Picogreen dsDNA细胞增殖与代谢分析结果显示,Fgfr2功能获得性突变可促进冠状缝细胞的增殖,从而导致成骨增加,颅缝早闭。结论 Fgfr2cC342Y/+模型新致病基因表达趋势与前期人颅缝组织Microarray研究结果一致,Rbp4、Gpc3、C1qtnf3可能在颅缝早闭中具重要调控作用。展开更多
基金financial support from the Theodor Bilharz Research InstituteWarrak El-Hadar+1 种基金ImbabaGiza 12411,Egypt。
文摘Objective:To evaluate the efficacy of ponatinib plus gossypol against colorectal cancer HCT-116 and Caco-2 cells.Methods:Cells were treated with ponatinib and/or gossypol at increasing concentrations to evaluate synergistic drug interactions by combination index.Cell viability,FGF19/FGFR4,and apoptotic and autophagic cell death were studied.Results:Ponatinib(1.25-40μM)and gossypol(2.5-80μM)monotherapy inhibited HCT-116 and Caco-2 cell viability in a doseand time-dependent manner.The combination of ponatinib and gossypol at a ratio of 1 to 2 significantly decreased cell viability(P<0.05),with a>2-and>4-fold reduction in IC50,respectively,after 24 h and 48 h,as compared to the IC50 of ponatinib.Lower combined concentrations showed greater synergism(combination index<1)with a higher ponatinib dose reduction index.Moreover,ponatinib plus gossypol induced morphological changes in HCT-116and Caco-2 cells,increased beclin-1 and caspase-3,and decreased FGF19,FGFR4,Bcl-2 and p-Akt as compared to treatment with drugs alone.Conclusions:Gossypol enhances ponatinib's anticancer effects against colorectal cancer cells through antiproliferative,apoptotic,and autophagic mechanisms.This may open the way for the future use of ponatinib at lower doses with gossypol as a potentially safer targeted strategy for colorectal cancer treatment.
基金Middle-young Subject Backbone Training Projects(No.FCYY201710)
文摘Objective:To investigate the expression of miR-195 in intrauterine adhesion(IUA)and its relationship with TGF-β1/Smads and FGF2/FGFR1/ERK pathways.Methods:118 cases of IUA patients who underwent hysteroscopic treatment in our hospital between September 2017 and February 2019 were regarded as IUA group,80 cases of dysfunctional uterine bleeding patients who underwent hysteroscopic curettage in our hospital during the same period were regarded as control group.Differences in the expression levels of miR-195 as well as TGF-β1/Smads and FGF2/FGFR1/ERK signaling pathway-related molecules in the focal tissues obtained by hysteroscopy were compared between the two groups.Pearson test was used to evaluate the correlation of miR-195 expression in the intrauterine adhesion tissues with TGF-β1/Smads and FGF2/FGFR1/ERK pathways in IUA patients.Results:miR-195 expression in intrauterine adhesion tissues of IUA group was higher than that in endometrial tissues of control group(P<0.05).TGF-β1,Smad2 and Smad3 mRNA expression in intrauterine adhesion tissues of IUA group were higher than those in endometrial tissues of control group;FGF2,FGFR1 and ERK mRNA expression in intrauterine adhesion tissues were higher than those in endometrial tissues of control group(P<0.05).Pearson test showed that the miR-195 expression in intrauterine adhesion tissues of IUA group was positively correlated with the TGF-β1/Smads pathway-related molecules TGF-β1,Smad2 and Smad3 mRNA expression,and positively correlated with the FGF2/FGFR1/ERK pathway-related molecules FGF2,FGFR1 and ERK mRNA expression(P<0.05).Conclusion:miR-195 is highly expressed in IUA lesion tissues and may promote disease progression by activating TGF-β1/Smads and FGF2/FGFR1/ERK signaling pathways.
文摘目的研究Rbp4(Retinol binding protein 4)、Gpc3(Glypican family of growth factor binding protein 3)、C1qtnf3(Collagenous repeat-containing sequence of 26 KDa protein)等新致病基因在颅缝早闭症中的发病机制,为疾病非手术治疗奠定理论基础。方法以Crouzon综合征Fgfr2cC342Y/+小鼠为实验模型,应用MicroCT和组织学染色,研究小鼠颅缝闭合模式;以Fgfr2cC342Y/+模型,RT-qPCR研究Rbp4、Gpc3、C1qtnf3等新致病基因的表达差异,初步探讨其在颅缝闭合过程中的调控作用;以体外培养的Fgfr2cC342Y/+小鼠颅缝细胞为模型,研究基因突变动物细胞增殖与代谢改变。结果获得Fgfr2cC342Y/+小鼠后额缝、冠状缝、人字缝、矢状缝等颅缝闭合模式,随颅骨发育、颅缝闭合,OC(Osteocalcin)、ALP(Alkalinephosphatase)表达增加,目的基因Rbp4、Gpc3、C1qtnf3表达下降,Msx2(Muscle segment homeobox gene 2)表达增加,杂合子与野生型小鼠之间均存在显著统计学差异,与前期人颅缝组织Microarray研究结果一致。Gpc1(Glypican family ofgrowth factor binding protein 1)、FliI(Flightless I)在颅缝闭合中的表达较恒定,野生型与杂合子之间未见明显统计学差异。体外培养Fgfr2cC342Y/+小鼠颅缝细胞,CellTiter96 MTS和Quant-iT Picogreen dsDNA细胞增殖与代谢分析结果显示,Fgfr2功能获得性突变可促进冠状缝细胞的增殖,从而导致成骨增加,颅缝早闭。结论 Fgfr2cC342Y/+模型新致病基因表达趋势与前期人颅缝组织Microarray研究结果一致,Rbp4、Gpc3、C1qtnf3可能在颅缝早闭中具重要调控作用。
