Isocitrate dehydrogenase 2(IDH2)and glutamate dehydrogenase 1(GLUD1)are key enzymes involved in the production ofα-ketoglutarate(α-KG),a metabolite central to the tricarboxylic acid cycle and glutamine metabolism.In...Isocitrate dehydrogenase 2(IDH2)and glutamate dehydrogenase 1(GLUD1)are key enzymes involved in the production ofα-ketoglutarate(α-KG),a metabolite central to the tricarboxylic acid cycle and glutamine metabolism.In this study,we investigated the impact of IDH2 and GLUD1 on early porcine embryonic development following IDH2 and GLUD1 knockdown(KD)via doublestranded RNA(dsRNA)microinjection.Results showed that KD reducedα-KG levels,leading to delayed embryonic development,decreased blastocyst formation,increased apoptosis,reduced blastomere proliferation,and pluripotency.Additionally,IDH2 and GLUD1 KD induced abnormally high levels of trimethylation of lysine 20 of histone H4(H4K20me3)at the 4-cell stage,likely resulting in transcriptional repression of embryonic genome activation(EGA)-related genes.Notably,KD of lysine methyltransferase 5C(KMT5C)and supplementation with exogenousα-KG reduced H4K20me3 expression and partially rescued these defects,suggesting a critical role of IDH2 and GLUD1 in the epigenetic regulation and proper development of porcine embryos.Overall,this study highlights the significance of IDH2 and GLUD1 in maintaining normal embryonic development through their influence onα-KG production and subsequent epigenetic modifications.展开更多
Geometry optimization of p-C_(6)H_(4)-connected cyclo[20]carbon(p-C_(6)H_(4)-C_(20))was carried out at M062X/6-311G(d,p)level,three kinds of bond orders(Mayer,Laplacian,and Wiberg),electron-hole distributions,localize...Geometry optimization of p-C_(6)H_(4)-connected cyclo[20]carbon(p-C_(6)H_(4)-C_(20))was carried out at M062X/6-311G(d,p)level,three kinds of bond orders(Mayer,Laplacian,and Wiberg),electron-hole distributions,localized orbital locators(LOL),and infrared(IR)spectrum were also performed at the same level.Based on TD-DFT M062X/6-311G(d,p)method,the first 20 excited states and ultraviolet(UV)spectra of p-C_(6)H_(4)-C_(20) were calculated.Calculation results of π-electron delocalization analyses prove thatπ-electron delocalization of p-C_(6)H_(4)-C_(20) is more likely to occur on shorter C-C bonds rather than longer C-C bonds,and inside/outside of the ring plane rather than above/below the ring plane.Two absorption peaks of p-C_(6)H_(4)-C_(20) locate at about 319 nm and 236 nm,respectively.展开更多
[Objectives]To prepare 20(S)-protopanaxadiol PLGA nanoparticles(20(S)-PPD-PLGA-NPs).[Methods]20(S)-PPD-PLGA-NPs were prepared by emulsion solvent evaporation method,and the optimal formulation was screened by Box-Behn...[Objectives]To prepare 20(S)-protopanaxadiol PLGA nanoparticles(20(S)-PPD-PLGA-NPs).[Methods]20(S)-PPD-PLGA-NPs were prepared by emulsion solvent evaporation method,and the optimal formulation was screened by Box-Behnken experiment with particle size and drug loading as the indicators through single factor experiment,and the drug release in vitro was carried out.[Results]The average diameter of the nanoparticles was(119.60±2.29)nm and the polydispersity index was(0.12±0.02),the size was uniform.The encapsulation efficiency and drug loading of protopanaxadiol were(87.99±1.29)%and(14.86±0.25)%,respectively.[Conclusions]The 20(S)-PPD-PLGA-NPs were successfully prepared by emulsion solvent evaporation method,and the 20(S)-PPD-PLGA-NPs had good stability,to lay a foundation for the study of 20(S)-PPD-PLGA-NPs in vitro and in vivo.展开更多
We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal degeneration.Here,we extended our...We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal degeneration.Here,we extended our investigation in two clinically-relevant ways.First,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors.Second,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of degeneration.We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors.In agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice.However,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin BNN-20.Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20.Interestingly,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.展开更多
Objective： To investigate the expressions of cytokeratin 19 （CK19） and cytokeratin 20 （CK20） in bladder transitional cell carcinoma （TCC） and their clinical significance. Methods： The expression of CK19 and CK...Objective： To investigate the expressions of cytokeratin 19 （CK19） and cytokeratin 20 （CK20） in bladder transitional cell carcinoma （TCC） and their clinical significance. Methods： The expression of CK19 and CK20 was detected in 54 cases of TCC by immunohistochemical methods and image processing techniques. Results： The expression of CK19 and CK20 was significantly stronger in the recurrent group than in the non-recurrent group （P〈0.01, P〈0.001, respectively）. Conclusion： The expression of CK19 and CK20 was obviously related with biological behaviors of TCC, suggesting that CK19 and CK20 could be used to predict the recurrence of TCC.展开更多
基金supported by the National Research Foundation(NRF)of Korea grant funded by the Korean government(MSIT)(2022R1A2C300769),Republic of Korea。
文摘Isocitrate dehydrogenase 2(IDH2)and glutamate dehydrogenase 1(GLUD1)are key enzymes involved in the production ofα-ketoglutarate(α-KG),a metabolite central to the tricarboxylic acid cycle and glutamine metabolism.In this study,we investigated the impact of IDH2 and GLUD1 on early porcine embryonic development following IDH2 and GLUD1 knockdown(KD)via doublestranded RNA(dsRNA)microinjection.Results showed that KD reducedα-KG levels,leading to delayed embryonic development,decreased blastocyst formation,increased apoptosis,reduced blastomere proliferation,and pluripotency.Additionally,IDH2 and GLUD1 KD induced abnormally high levels of trimethylation of lysine 20 of histone H4(H4K20me3)at the 4-cell stage,likely resulting in transcriptional repression of embryonic genome activation(EGA)-related genes.Notably,KD of lysine methyltransferase 5C(KMT5C)and supplementation with exogenousα-KG reduced H4K20me3 expression and partially rescued these defects,suggesting a critical role of IDH2 and GLUD1 in the epigenetic regulation and proper development of porcine embryos.Overall,this study highlights the significance of IDH2 and GLUD1 in maintaining normal embryonic development through their influence onα-KG production and subsequent epigenetic modifications.
文摘Geometry optimization of p-C_(6)H_(4)-connected cyclo[20]carbon(p-C_(6)H_(4)-C_(20))was carried out at M062X/6-311G(d,p)level,three kinds of bond orders(Mayer,Laplacian,and Wiberg),electron-hole distributions,localized orbital locators(LOL),and infrared(IR)spectrum were also performed at the same level.Based on TD-DFT M062X/6-311G(d,p)method,the first 20 excited states and ultraviolet(UV)spectra of p-C_(6)H_(4)-C_(20) were calculated.Calculation results of π-electron delocalization analyses prove thatπ-electron delocalization of p-C_(6)H_(4)-C_(20) is more likely to occur on shorter C-C bonds rather than longer C-C bonds,and inside/outside of the ring plane rather than above/below the ring plane.Two absorption peaks of p-C_(6)H_(4)-C_(20) locate at about 319 nm and 236 nm,respectively.
文摘[Objectives]To prepare 20(S)-protopanaxadiol PLGA nanoparticles(20(S)-PPD-PLGA-NPs).[Methods]20(S)-PPD-PLGA-NPs were prepared by emulsion solvent evaporation method,and the optimal formulation was screened by Box-Behnken experiment with particle size and drug loading as the indicators through single factor experiment,and the drug release in vitro was carried out.[Results]The average diameter of the nanoparticles was(119.60±2.29)nm and the polydispersity index was(0.12±0.02),the size was uniform.The encapsulation efficiency and drug loading of protopanaxadiol were(87.99±1.29)%and(14.86±0.25)%,respectively.[Conclusions]The 20(S)-PPD-PLGA-NPs were successfully prepared by emulsion solvent evaporation method,and the 20(S)-PPD-PLGA-NPs had good stability,to lay a foundation for the study of 20(S)-PPD-PLGA-NPs in vitro and in vivo.
基金co-financed by Greece and the European Union(European Social Fund-ESF)through the Operational Programme《Human Resources Development,Education and Lifelong Learning 2014–2020》in the context of the project“NeuroProPar”(MIS 5047138,to IK)。
文摘We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal degeneration.Here,we extended our investigation in two clinically-relevant ways.First,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors.Second,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of degeneration.We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors.In agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice.However,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin BNN-20.Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20.Interestingly,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.
文摘Objective： To investigate the expressions of cytokeratin 19 （CK19） and cytokeratin 20 （CK20） in bladder transitional cell carcinoma （TCC） and their clinical significance. Methods： The expression of CK19 and CK20 was detected in 54 cases of TCC by immunohistochemical methods and image processing techniques. Results： The expression of CK19 and CK20 was significantly stronger in the recurrent group than in the non-recurrent group （P〈0.01, P〈0.001, respectively）. Conclusion： The expression of CK19 and CK20 was obviously related with biological behaviors of TCC, suggesting that CK19 and CK20 could be used to predict the recurrence of TCC.
