The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administratio...The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.展开更多
Summary: The antinephritic effect of lipo-prostaglandin E1. prostaglandin E1 incorporated in lipid mierospheres was investigated using an experimental model of mesangial proliferative glomerulonephritis (MsPGN). Tw...Summary: The antinephritic effect of lipo-prostaglandin E1. prostaglandin E1 incorporated in lipid mierospheres was investigated using an experimental model of mesangial proliferative glomerulonephritis (MsPGN). Twenty-two female rats were randomly divided into nephritic group (N, n=6), lipo-prostaglandin E1 treated group (NL, n=8) and control group (C, n=6). Lipo-prostaglandin E1 was given intravenously at 40 μg·kg^-1·d^-1 from the 6th week to the 8th week. Twenty-four h urinary protein contents and blood ereatinine (Cr) were determined and the pathological changes were observed in the experiment. The expression of proliferating cell nuclear antigen (PCNA), extraeellular matrix (fibroneetin, FN; collagen type Ⅳ , Col Ⅳ ) and transforming growth factor β1 (TGFβ1) was detected by using immunohistoehemistry. The results showed that lipo-prostaglandin E1 significantly inhibited the glomerular histopathologieal changes as well as the elevation of plasma Cr (P〈0.05). The overexpression of PCNA, FN, Col Ⅳ and TGFβ1 were also obviously inhibited in group NL as compared with the group N (P〈0.01). It was suggested that lipo-prostaglandin E1 could improve renal function, inhibit the proliferation of glomerular cells and reduce the deposition of extraeellular matrix, which may be related to the down-regulation of the TGFβ1 expression.展开更多
The selection of proper treatment is based on identification of the causes of massive hemorrhage of gastrointestinal tract after pericardial devascularization.The combined use of prostaglandin E1 indirect portal vein ...The selection of proper treatment is based on identification of the causes of massive hemorrhage of gastrointestinal tract after pericardial devascularization.The combined use of prostaglandin E1 indirect portal vein angiography, DSA of celiac artery and color Doppler can provide detailed information about portal vein system,including the presence of embolism, spongioid changes and devasculization of left gastric vein and left gastric artery and the direction of blood flow. If these techniques failed to reveal the causes of digestive tract bleeding, the endoscopy may show lesions of gastric mucosa, which could be accountable for the bleeding.展开更多
The availability of many high-degree Global Geopotential Models(GGMs), namely EGM2008, EIGEN-6C4,GECO, SGG-UGM-1, SGG-UGM-2, XGM2019e_2159, and GGMPlus, challenges users regarding which model is best for Vietnam. This...The availability of many high-degree Global Geopotential Models(GGMs), namely EGM2008, EIGEN-6C4,GECO, SGG-UGM-1, SGG-UGM-2, XGM2019e_2159, and GGMPlus, challenges users regarding which model is best for Vietnam. This study, therefore, evaluates their performance by comparing them with GNSS/leveling data over Vietnam. Results show that their absolute and relative performances are largely independent of topographic conditions and geographical location and can be ranked into three classes:(1)XGM2019e_2159 has the highest accuracy,(2) the models EIGEN-6C4, GECO, SGG-UGM-1, SGG-UGM-2, and GGMPlus, have a very similar level of medium accuracy, while(3) EGM2008 is found to be the least accurate. In an absolute sense, the differences between GNSS/leveling and EGM2008-based height anomalies have a standard deviation(STD) of 0.290 ± 0.010 m, whereas, for XGM2019e_2159, this is 0.156 ± 0.006 m.All other models have STDs of(0.18-0.19) ± 0.007 m. Regarding relative performance without fitting, all GGMs have comparable accuracies for baseline length of 5-20 km, while for baselines longer than 20 km,the STD of XGM2019e_2159 is 1.5 ppm-0.5 ppm(approximately 19%-40%) lower compared with EGM2008, and 0.5 ppm-0.25 ppm(approximately 7%-36%) lower compared with EIGEN6C4, GECO,SGG-UGM-1, SGG-UGM-2, and GGMPlus. In addition, the STDs decrease significantly from 20 to 12 ppm in the range of 5-10 km, slightly from 12 to 6 ppm for 10-35 km, very slightly from 6 to 2.5 ppm for35-200 km, and then remain almost unchanged for longer baselines. After fitting, the relative accuracies of all GGMs are at the same level with negligible STD/RMSE values. Furthermore, only EGM2008 experiences significant regional differences, while other GGMs show more homogeneous spatial variation of absolute accuracy over Vietnam. These findings can contribute to the development of local quasigeoid models in Vietnam and may be helpful with the improvement of GGMs in the future.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82073934,81872937,and 81673513).
文摘The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.
文摘Summary: The antinephritic effect of lipo-prostaglandin E1. prostaglandin E1 incorporated in lipid mierospheres was investigated using an experimental model of mesangial proliferative glomerulonephritis (MsPGN). Twenty-two female rats were randomly divided into nephritic group (N, n=6), lipo-prostaglandin E1 treated group (NL, n=8) and control group (C, n=6). Lipo-prostaglandin E1 was given intravenously at 40 μg·kg^-1·d^-1 from the 6th week to the 8th week. Twenty-four h urinary protein contents and blood ereatinine (Cr) were determined and the pathological changes were observed in the experiment. The expression of proliferating cell nuclear antigen (PCNA), extraeellular matrix (fibroneetin, FN; collagen type Ⅳ , Col Ⅳ ) and transforming growth factor β1 (TGFβ1) was detected by using immunohistoehemistry. The results showed that lipo-prostaglandin E1 significantly inhibited the glomerular histopathologieal changes as well as the elevation of plasma Cr (P〈0.05). The overexpression of PCNA, FN, Col Ⅳ and TGFβ1 were also obviously inhibited in group NL as compared with the group N (P〈0.01). It was suggested that lipo-prostaglandin E1 could improve renal function, inhibit the proliferation of glomerular cells and reduce the deposition of extraeellular matrix, which may be related to the down-regulation of the TGFβ1 expression.
文摘The selection of proper treatment is based on identification of the causes of massive hemorrhage of gastrointestinal tract after pericardial devascularization.The combined use of prostaglandin E1 indirect portal vein angiography, DSA of celiac artery and color Doppler can provide detailed information about portal vein system,including the presence of embolism, spongioid changes and devasculization of left gastric vein and left gastric artery and the direction of blood flow. If these techniques failed to reveal the causes of digestive tract bleeding, the endoscopy may show lesions of gastric mucosa, which could be accountable for the bleeding.
文摘The availability of many high-degree Global Geopotential Models(GGMs), namely EGM2008, EIGEN-6C4,GECO, SGG-UGM-1, SGG-UGM-2, XGM2019e_2159, and GGMPlus, challenges users regarding which model is best for Vietnam. This study, therefore, evaluates their performance by comparing them with GNSS/leveling data over Vietnam. Results show that their absolute and relative performances are largely independent of topographic conditions and geographical location and can be ranked into three classes:(1)XGM2019e_2159 has the highest accuracy,(2) the models EIGEN-6C4, GECO, SGG-UGM-1, SGG-UGM-2, and GGMPlus, have a very similar level of medium accuracy, while(3) EGM2008 is found to be the least accurate. In an absolute sense, the differences between GNSS/leveling and EGM2008-based height anomalies have a standard deviation(STD) of 0.290 ± 0.010 m, whereas, for XGM2019e_2159, this is 0.156 ± 0.006 m.All other models have STDs of(0.18-0.19) ± 0.007 m. Regarding relative performance without fitting, all GGMs have comparable accuracies for baseline length of 5-20 km, while for baselines longer than 20 km,the STD of XGM2019e_2159 is 1.5 ppm-0.5 ppm(approximately 19%-40%) lower compared with EGM2008, and 0.5 ppm-0.25 ppm(approximately 7%-36%) lower compared with EIGEN6C4, GECO,SGG-UGM-1, SGG-UGM-2, and GGMPlus. In addition, the STDs decrease significantly from 20 to 12 ppm in the range of 5-10 km, slightly from 12 to 6 ppm for 10-35 km, very slightly from 6 to 2.5 ppm for35-200 km, and then remain almost unchanged for longer baselines. After fitting, the relative accuracies of all GGMs are at the same level with negligible STD/RMSE values. Furthermore, only EGM2008 experiences significant regional differences, while other GGMs show more homogeneous spatial variation of absolute accuracy over Vietnam. These findings can contribute to the development of local quasigeoid models in Vietnam and may be helpful with the improvement of GGMs in the future.