Low-dose cytarabine combined with differentiating or DNA hypomethylating agents,such as vitamin D compounds,is a potential regimen to treat acute myeloid leukemia(AML)patients who are unfit for high-intensity chemothe...Low-dose cytarabine combined with differentiating or DNA hypomethylating agents,such as vitamin D compounds,is a potential regimen to treat acute myeloid leukemia(AML)patients who are unfit for high-intensity chemotherapy.The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3(1,25-D3).Here,firstly,c Bio Portal database was used and we found out that vitamin D receptor(VDR)was highly expressed in acute monocytic leukemia(M5)and high VDR expression was associated with a poor survival of AML patients.Then,we confirmed that 1,25-D3 at clinical available concentration could induce more significant differentiation in acute monocytic leukemia cell lines(U937,MOLM-13,THP-1)and blasts from M5 patients than in non-monocytic cell lines(KG1 a and K562)and blasts from M2 patient.Finally,it was shown that the combination of 1,25-D3 and low-dose cytarabine further increased the differentiating rate,growth inhibition and G0/G1 arrest,while mild changes were found in the apoptosis in acute monocytic leukemia cell lines.Our study demonstrates that the enhanced response of acute monocytic leukemia cells to low-dose cytarabine by 1,25-D3 might indicate a novel therapeutic direction for patients with acute monocytic leukemia,especially for elderly and frail ones.展开更多
An optically active intermediate 5 for A-ring of 19-nor-1α,25-dihydroxyvitamin D3 2 has been synthesized in five steps, starting from readily available, inexpensive v（＋）-xylose 6 with good yield.
Objective:To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase(MCT) in asthmatic guinea pigs.Methods:A total of 60 male or female healthy guinea pigs were randomly divided into control group(gro...Objective:To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase(MCT) in asthmatic guinea pigs.Methods:A total of 60 male or female healthy guinea pigs were randomly divided into control group(group A),asthmatic group(group B).and 1,25-dihydroxyvitamin D3 group(group C),with 20 cases in each group.To establish asthmatic guinea pig models,1ml peanut oil was tilled into stomach in the morning in group A and group B.and 1 ml peanut oil with 1,25-dihydroxyvitamin D3 was filled into stomach in group C.Airway resistance(Re) of asthmatic guinea pigs was detected,and the bronchoalveolar lavage fluid(BALF) cells were counted.Lung tissue with HE and MCT immunohistochemical staining were used to observe the pathological changes in lung tissue and the distribution of MCT.Results:After injection of different concentration of acetylcholine chloride,the Re in group B and group C were increased significantly compared with group A(P<0.05):compared with group B.the Re in group C were decreased significantly(t=-5.385.-5.761.-6.184.-13.574.P<0.05):the total number of BALF cells and eosinophils were increased significantly in group B and C(t=19.618.9.598.10.854.5.388.P<0.05);compared with group B.the total number of BALF cells and eosinophils in group C was decreased significantly(t=-5.555.-5.392.P<0.05):the number of tryptase positive cells in group B was increased significantly than that in group A(t=21.312,P<0.05),and in addition to the alveolar septum and submucosa,the cells were also distributed around blood vessels and outside the cells:the number of tryptase positive cells in group C was decreased significantly compared with group B.and the difference was statistically significant(t=5.043.P<0.05).Conclusions:After the asthmatic guinea pigs arc treated with 1,25-dihydroxyvitamin D3,their BALF.Re.infiltration degree of inflammatory cells in the trachea and lung tissue and airway inflammatory reaction are reduced significantly.1,25-dihydroxyvitamin D3 has a certain inhibiting effect on the activation of mast cells and the release of MCT granules.展开更多
The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functi...The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functions.展开更多
Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poo...Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D_3[1,25(OH)_2D_3], the biologically active form of vitamin D_3, significantly attenuated monosodium glutamate(MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemiceuglycemic clamp. Moreover, 1,25(OH)_2D_3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)_2D_3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied byincreased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulintargeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)_2D_3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.展开更多
目的建立基于同位素稀释液相色谱串联质谱技术(liquid phase chromatography tandem mass spectrometry,LC-MS/MS)的血清25羟维生素D3[25-hydroxy vitamin D3,25(OH)D3]的候选参考测量程序。方法采用同位素标准溶液为内标,液液萃取进行...目的建立基于同位素稀释液相色谱串联质谱技术(liquid phase chromatography tandem mass spectrometry,LC-MS/MS)的血清25羟维生素D3[25-hydroxy vitamin D3,25(OH)D3]的候选参考测量程序。方法采用同位素标准溶液为内标,液液萃取进行前处理,正离子电喷雾模式进行监测。参照美国临床实验室标准化协会(Clinical and Laboratory Standards Institute,CLSI)C62-A和EP15-A3等文件,对方法的正确度、精密度、线性范围、定量限、检测下限、相对基质效应等进行验证。采用候选参考测量程序和质谱常规程序检测40份临床血清样本,评价两种方法的一致性。结果候选方法的分析时间为15 min,通过色谱的等度洗脱可有效分离同分异构体3-epi-25(OH)D3,特异度好。测定参考实验室室间比对(RELA)样本,偏倚低于1.5%。批内精密度和批间精密度分别为0.75%~2.31%和1.28%~2.01%。定量限和检测下限分别为0.85 ng/ml和1.84 ng/ml。在2.5~220ng/ml浓度范围内线性良好。无相对基质效应和携带污染。质谱常规程序与候选参考程序的相关性较好(r=0.982),但低浓度样本处的偏差超出卫健委临检中心室间质评的允许总误差±25%。结论成功建立了基于LC-MS/MS技术的血清25(OH)D3的候选参考测量程序,分析性能符合要求,可用于临床常规方法的量值溯源。展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81400172 and No.81470330)
文摘Low-dose cytarabine combined with differentiating or DNA hypomethylating agents,such as vitamin D compounds,is a potential regimen to treat acute myeloid leukemia(AML)patients who are unfit for high-intensity chemotherapy.The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3(1,25-D3).Here,firstly,c Bio Portal database was used and we found out that vitamin D receptor(VDR)was highly expressed in acute monocytic leukemia(M5)and high VDR expression was associated with a poor survival of AML patients.Then,we confirmed that 1,25-D3 at clinical available concentration could induce more significant differentiation in acute monocytic leukemia cell lines(U937,MOLM-13,THP-1)and blasts from M5 patients than in non-monocytic cell lines(KG1 a and K562)and blasts from M2 patient.Finally,it was shown that the combination of 1,25-D3 and low-dose cytarabine further increased the differentiating rate,growth inhibition and G0/G1 arrest,while mild changes were found in the apoptosis in acute monocytic leukemia cell lines.Our study demonstrates that the enhanced response of acute monocytic leukemia cells to low-dose cytarabine by 1,25-D3 might indicate a novel therapeutic direction for patients with acute monocytic leukemia,especially for elderly and frail ones.
基金Financial support from the National Natural Science Foundation of China(No.29972013)is gratefully acknowledged.
文摘An optically active intermediate 5 for A-ring of 19-nor-1α,25-dihydroxyvitamin D3 2 has been synthesized in five steps, starting from readily available, inexpensive v（＋）-xylose 6 with good yield.
基金supported by Natural Science Foundation of Guangdong Province:gd291823
文摘Objective:To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell tryptase(MCT) in asthmatic guinea pigs.Methods:A total of 60 male or female healthy guinea pigs were randomly divided into control group(group A),asthmatic group(group B).and 1,25-dihydroxyvitamin D3 group(group C),with 20 cases in each group.To establish asthmatic guinea pig models,1ml peanut oil was tilled into stomach in the morning in group A and group B.and 1 ml peanut oil with 1,25-dihydroxyvitamin D3 was filled into stomach in group C.Airway resistance(Re) of asthmatic guinea pigs was detected,and the bronchoalveolar lavage fluid(BALF) cells were counted.Lung tissue with HE and MCT immunohistochemical staining were used to observe the pathological changes in lung tissue and the distribution of MCT.Results:After injection of different concentration of acetylcholine chloride,the Re in group B and group C were increased significantly compared with group A(P<0.05):compared with group B.the Re in group C were decreased significantly(t=-5.385.-5.761.-6.184.-13.574.P<0.05):the total number of BALF cells and eosinophils were increased significantly in group B and C(t=19.618.9.598.10.854.5.388.P<0.05);compared with group B.the total number of BALF cells and eosinophils in group C was decreased significantly(t=-5.555.-5.392.P<0.05):the number of tryptase positive cells in group B was increased significantly than that in group A(t=21.312,P<0.05),and in addition to the alveolar septum and submucosa,the cells were also distributed around blood vessels and outside the cells:the number of tryptase positive cells in group C was decreased significantly compared with group B.and the difference was statistically significant(t=5.043.P<0.05).Conclusions:After the asthmatic guinea pigs arc treated with 1,25-dihydroxyvitamin D3,their BALF.Re.infiltration degree of inflammatory cells in the trachea and lung tissue and airway inflammatory reaction are reduced significantly.1,25-dihydroxyvitamin D3 has a certain inhibiting effect on the activation of mast cells and the release of MCT granules.
文摘The synthesis of 14-epi-19-nor-22-oxa-1α,25（OH）2D3 5 was started from diol 8 via Fall＇s method, oxidation, epimerization, protection, coupling with the 19-nor-A-ring 7, and then deprotection of the hydroxyl functions.
基金supported by grants from the National Natural Science Foundation of China (81773800 and 81471070)the CAMS Innovation Fund for Medical Sciences (CIFMS, 2016I2M-1-010 to Xiao-wei Zhang and 2016-I2M-1-012 to Wen Jin)
文摘Vitamin D_3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D_3[1,25(OH)_2D_3], the biologically active form of vitamin D_3, significantly attenuated monosodium glutamate(MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemiceuglycemic clamp. Moreover, 1,25(OH)_2D_3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)_2D_3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied byincreased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulintargeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)_2D_3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.
文摘目的建立基于同位素稀释液相色谱串联质谱技术(liquid phase chromatography tandem mass spectrometry,LC-MS/MS)的血清25羟维生素D3[25-hydroxy vitamin D3,25(OH)D3]的候选参考测量程序。方法采用同位素标准溶液为内标,液液萃取进行前处理,正离子电喷雾模式进行监测。参照美国临床实验室标准化协会(Clinical and Laboratory Standards Institute,CLSI)C62-A和EP15-A3等文件,对方法的正确度、精密度、线性范围、定量限、检测下限、相对基质效应等进行验证。采用候选参考测量程序和质谱常规程序检测40份临床血清样本,评价两种方法的一致性。结果候选方法的分析时间为15 min,通过色谱的等度洗脱可有效分离同分异构体3-epi-25(OH)D3,特异度好。测定参考实验室室间比对(RELA)样本,偏倚低于1.5%。批内精密度和批间精密度分别为0.75%~2.31%和1.28%~2.01%。定量限和检测下限分别为0.85 ng/ml和1.84 ng/ml。在2.5~220ng/ml浓度范围内线性良好。无相对基质效应和携带污染。质谱常规程序与候选参考程序的相关性较好(r=0.982),但低浓度样本处的偏差超出卫健委临检中心室间质评的允许总误差±25%。结论成功建立了基于LC-MS/MS技术的血清25(OH)D3的候选参考测量程序,分析性能符合要求,可用于临床常规方法的量值溯源。
