OBJECTIVE Increased efficacy without increased toxicity is expected when treating rheumatoid arthritis(RA).However,there are many difficulties associated with currently available RA treatments.Reportedly,CP-25,a new c...OBJECTIVE Increased efficacy without increased toxicity is expected when treating rheumatoid arthritis(RA).However,there are many difficulties associated with currently available RA treatments.Reportedly,CP-25,a new compound developed by our group,significantly inhibits the progression of arthritis in animal models through reducing membrane expression of GRK2.This study observed CP-25 monotherapy and combined administration with MTX/LEF in treating animal arthritis model and investigated possible mechanisms.METHODS We set up AA rat and collageninduced arthritis(CIA)mice model.Experimental groups were divided into normal group,vehicle group,monotherapy groups and CP-25-combined MTX/LEF groups.We focused on the role of GRK2 on macrophage polarization and fibro⁃blast-like synoviocytes(FLS)proliferation.We measured cytokine levels,phosphorylation and protein expression,and interactions between proteins.Targeted disruption of GRK2 in FLS and macrophages through GRK2 siRNA and CRIS⁃PR/Cas9.RESULTS Equivalent therapeutic effects were observed between CP-25-combination groups and high-dose MTX/LEF groups.In the vehicle group,GRK2 membrane expression increased leading to the decreased GRK2-p-ERK interactions in FLS(leading to the phosphorylation of ERK related with FLS over-proliferation),and increased GRK2-EP4 interaction in macrophage(leading to the abnormal PGE2-EP4-cAMP-CREB signal related with imbalance of macro⁃phage polarization).CONCLUSION CP-25 monotherapy and combined administration with MTX/LEF ameliorate the progression of animal arthritis model.CP-25 inhibited p-ERK by reducing the membrane expression of GRK2 in FLS from AA rats.CP-25 restored normal PGE2-EP4-cAMP-CREB signal through inhibiting GRK2 transferring to membrane.These results highlighted CP-25 a kind of potential for treating patients with RA.展开更多
The photodegradation of mefenpyrdiethyl （MFD）, an herbicide safener, was investigated in aqueous suspensions by using Degussa P-25 and Hombikat UV100 titanium oxide under simulated sunlight irradiation. The effects ...The photodegradation of mefenpyrdiethyl （MFD）, an herbicide safener, was investigated in aqueous suspensions by using Degussa P-25 and Hombikat UV100 titanium oxide under simulated sunlight irradiation. The effects of initial concentration of the herbicide, pH, catalysts and hydrogen peroxide doses as well as their combinations were studied and optimized. Accordingly, the kinetic parameters were determined and the effectiveness of the processes was assessed by calculating the rate constants. A pseudo first-order kinetics was observed. Under experimental conditions, the degradation rate constants were strongly influenced using P-25 and no noticeable effect was observed for Hombikat UV100. DFT calculations with B3LYP/6-311＋G（2d,p）//B3LYP/6-31＋G（d,p） level of theory were performed to check whether significant conformational changes occur when the charge state of the MFD substrate changes and whether these changes could play a role in the dependency of photodegradation rate constant on the studied pH. High resolution mass spectrometry （FT-ICR/MS） was implemented to identify the main degradation products.展开更多
肺癌是发病率和死亡率均较高的肿瘤之一,现有的预防和治疗方法均收效甚微。维生素D的生物学特性除了通过促进机体钙的吸收进而调节多种生理功能外,其在肿瘤的预防和治疗方面也有一定的作用。肺癌的发生、发展与维生素D或其代谢物25-一...肺癌是发病率和死亡率均较高的肿瘤之一,现有的预防和治疗方法均收效甚微。维生素D的生物学特性除了通过促进机体钙的吸收进而调节多种生理功能外,其在肿瘤的预防和治疗方面也有一定的作用。肺癌的发生、发展与维生素D或其代谢物25-一羟维生素D[25(OH)D]或1,25-二羟维生素D[1,25(OH)2D]有密切的关系。在这一代谢通路中,25-羟维生素D 1-α-羟化酶和25-羟基维生素D3-24-羟化酶的活性决定了1,25(OH)2D的含量,而维生素D受体(vitamin D receptor,VDR)的表达决定了1,25(OH)2D是否能有效发挥作用。本文就维生素D与肺癌的发生和预后之间的关系以及维生素D的代谢通路做一综述。展开更多
A new triterpene, 25-methylenecyclopholidonyl p-hydroxy-trans-cinnamate, was isolated from a orchid Pholidota yunnanensis. The structure elucidation and H, 1 13 C-NMR assignments were achieved by spectral and chemical...A new triterpene, 25-methylenecyclopholidonyl p-hydroxy-trans-cinnamate, was isolated from a orchid Pholidota yunnanensis. The structure elucidation and H, 1 13 C-NMR assignments were achieved by spectral and chemical method.展开更多
基金National Natural Science Foundation of China(8133008181673444+3 种基金3120067581573443)Anhui Province Natural Science Fund(outstanding youth)(170808J10)Key Projects of Outstanding young Talent Support Program in Colleges and Universities(gxyq ZD2016043)
文摘OBJECTIVE Increased efficacy without increased toxicity is expected when treating rheumatoid arthritis(RA).However,there are many difficulties associated with currently available RA treatments.Reportedly,CP-25,a new compound developed by our group,significantly inhibits the progression of arthritis in animal models through reducing membrane expression of GRK2.This study observed CP-25 monotherapy and combined administration with MTX/LEF in treating animal arthritis model and investigated possible mechanisms.METHODS We set up AA rat and collageninduced arthritis(CIA)mice model.Experimental groups were divided into normal group,vehicle group,monotherapy groups and CP-25-combined MTX/LEF groups.We focused on the role of GRK2 on macrophage polarization and fibro⁃blast-like synoviocytes(FLS)proliferation.We measured cytokine levels,phosphorylation and protein expression,and interactions between proteins.Targeted disruption of GRK2 in FLS and macrophages through GRK2 siRNA and CRIS⁃PR/Cas9.RESULTS Equivalent therapeutic effects were observed between CP-25-combination groups and high-dose MTX/LEF groups.In the vehicle group,GRK2 membrane expression increased leading to the decreased GRK2-p-ERK interactions in FLS(leading to the phosphorylation of ERK related with FLS over-proliferation),and increased GRK2-EP4 interaction in macrophage(leading to the abnormal PGE2-EP4-cAMP-CREB signal related with imbalance of macro⁃phage polarization).CONCLUSION CP-25 monotherapy and combined administration with MTX/LEF ameliorate the progression of animal arthritis model.CP-25 inhibited p-ERK by reducing the membrane expression of GRK2 in FLS from AA rats.CP-25 restored normal PGE2-EP4-cAMP-CREB signal through inhibiting GRK2 transferring to membrane.These results highlighted CP-25 a kind of potential for treating patients with RA.
基金supported by the German Academic Exchange Service (DAAD) within the Morrocan/German exchange program
文摘The photodegradation of mefenpyrdiethyl （MFD）, an herbicide safener, was investigated in aqueous suspensions by using Degussa P-25 and Hombikat UV100 titanium oxide under simulated sunlight irradiation. The effects of initial concentration of the herbicide, pH, catalysts and hydrogen peroxide doses as well as their combinations were studied and optimized. Accordingly, the kinetic parameters were determined and the effectiveness of the processes was assessed by calculating the rate constants. A pseudo first-order kinetics was observed. Under experimental conditions, the degradation rate constants were strongly influenced using P-25 and no noticeable effect was observed for Hombikat UV100. DFT calculations with B3LYP/6-311＋G（2d,p）//B3LYP/6-31＋G（d,p） level of theory were performed to check whether significant conformational changes occur when the charge state of the MFD substrate changes and whether these changes could play a role in the dependency of photodegradation rate constant on the studied pH. High resolution mass spectrometry （FT-ICR/MS） was implemented to identify the main degradation products.
文摘肺癌是发病率和死亡率均较高的肿瘤之一,现有的预防和治疗方法均收效甚微。维生素D的生物学特性除了通过促进机体钙的吸收进而调节多种生理功能外,其在肿瘤的预防和治疗方面也有一定的作用。肺癌的发生、发展与维生素D或其代谢物25-一羟维生素D[25(OH)D]或1,25-二羟维生素D[1,25(OH)2D]有密切的关系。在这一代谢通路中,25-羟维生素D 1-α-羟化酶和25-羟基维生素D3-24-羟化酶的活性决定了1,25(OH)2D的含量,而维生素D受体(vitamin D receptor,VDR)的表达决定了1,25(OH)2D是否能有效发挥作用。本文就维生素D与肺癌的发生和预后之间的关系以及维生素D的代谢通路做一综述。
文摘A new triterpene, 25-methylenecyclopholidonyl p-hydroxy-trans-cinnamate, was isolated from a orchid Pholidota yunnanensis. The structure elucidation and H, 1 13 C-NMR assignments were achieved by spectral and chemical method.
