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
Objective To investigate the correlation between regulatory T （Treg） cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25（OH）2D3] in relation to Treg cells. Metho...Objective To investigate the correlation between regulatory T （Treg） cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25（OH）2D3] in relation to Treg cells. Methods Fifty female BALB/c mice were randomly divided into five groups： the basal control （BAS）, Sham, ovariectomy （OVX）, OVX＋diethylstilbestrol （OVX＋DES）, and OVX＋I,2S（OH）2D3. Tibias were harvested and processed with decalcification for quantitative bone histomorphometry. Femurs were stained by immunohistochemistry to detect Foxp3 protein expression. Spleens were used to detect Treg and Foxp3 gene expression by flow cy：ometry and quantitative RT-PCR, respectively. Results In comparison with the Sham group, a significant decrease was found in the OV~ group in such indices as trabecular bone volume/tc,tal tissue area （BV/TV）, trabecular number （Tb.N） and trabecular thickness （Tb.Th）. 1,25（OH）2D3 and DES partly prevented the decrease in BV/TV, Tb.N, Tb.Th in OVX mice. Treg cell number, Foxp3 mRI~：A expression in spleen and Foxp3 protein expression in femur significantly decreased in the OVX-tr^ated group compared with those in the sham group. 1,25（OH）2D3 and DES significantly increased Treg cell number and Foxp3 expression. Treg cells and Foxp3 gene expression were related to bone histomorphometric parameters. Conclusion The decrease in Treg cell numbers is relevant to the postmenopausal osteoporosis. The antiosteoporosis of 1,25（OH）2D3 is related to regulatory T cells.展开更多
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 chemo...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.
In the present study, we examine the effects of the treatment with 1,25-dihydroxyvitamin D3 [150 IU/Kg (3.75 μg/Kg) once a day, for 15 days] to non-diabetic and streptozotocin-induced diabetic rats. The results indic...In the present study, we examine the effects of the treatment with 1,25-dihydroxyvitamin D3 [150 IU/Kg (3.75 μg/Kg) once a day, for 15 days] to non-diabetic and streptozotocin-induced diabetic rats. The results indicate that treatment with 1,25-dihydroxyvitamin D3 had minor effects in non-diabetic rats. The same treatment in streptozotocin-induced diabetic rats, although it did not correct the hyperglycemia and hypoinsulinemia induced by the diabetes, caused other actions that could mean beneficial effects on the amelioration of diabetes e.g., it avoided body weight loss, increased calcium and phosphorus plasma levels, and corrected the over-expression of the insulin receptor mRNA species of 9.5 and 7.5 Kb present in the hind limb muscle and heart of these animals. These genomic 1,25-dihydroxyvitamin D3 effects could involve transcriptional mechanisms of repression mediated by vitamin D response elements in the rat insulin receptor gene promoter. Using computer analysis of this promoter, we propose the -249/-235 bp VDRE (5’GGGTGACCCGGGGTT3’) with a pyrimidine (T) in the (+7) position of the3’half-site as the best candidate for negative control by 1,25-dihydroxy-vitamin D3. In addition, posttranscriptional mechanisms of regulation could also be implicated. Thus, computer inspection of the5’untranslated region of the rat insulin receptor pre-mRNA indicated the presence of a virtual internal ribosome entry segment whereas the computer inspection of the3’untranslated region localized various destabilizing sequences, including various AU-rich elements. We propose that through these virtual cis-regulatory sequences, 1,25-dihydroxyvitamin D3 could control the translation and stability of insulin receptor mRNA species in the hind limb muscle and heart of diabetic rats.展开更多
The effect of 1,25-dihydroxyvitamin D<sub>3</sub> [1,25（OH）<sub>2</sub>D<sub>3</sub>] and13-cis-retinoic acid（RA）on the proliferation of a novel human megakaryoblasticleukemia c...The effect of 1,25-dihydroxyvitamin D<sub>3</sub> [1,25（OH）<sub>2</sub>D<sub>3</sub>] and13-cis-retinoic acid（RA）on the proliferation of a novel human megakaryoblasticleukemia cell line（HIMeg）was investigated.At the concentration of 10<sup>9</sup> 10<sup>6</sup>mol/L,1,25（OH）<sub>2</sub>D<sub>3</sub> and RA showed significant inhibition of the proliferation of themegakaryoblastic leukemic cells,which was demonstrated by the count of survival cells,incorporation of<sup>3</sup>H-TdR and<sup>3</sup>H-UR,and cloning efficiency in dose-dependent and time-dependent manners.The results can further explain the mechanism of differentiation-inducing agents and the effect of 1 ,25（OH）<sub>2</sub>D<sub>3</sub> on myelofibrosis.It is possible for1,25（OH）<sub>2</sub>D<sub>3</sub> and RA to be used to treat malignant megakaryocytic diseases.展开更多
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
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 Natural Science Foundation of Guangdong Province(10152402301000000)Science and Technology Planning Project of Dongguan(2011108102019)Science&Technology Innovation Fund of Guangdong Medical College(STIF201104)
文摘Objective To investigate the correlation between regulatory T （Treg） cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25（OH）2D3] in relation to Treg cells. Methods Fifty female BALB/c mice were randomly divided into five groups： the basal control （BAS）, Sham, ovariectomy （OVX）, OVX＋diethylstilbestrol （OVX＋DES）, and OVX＋I,2S（OH）2D3. Tibias were harvested and processed with decalcification for quantitative bone histomorphometry. Femurs were stained by immunohistochemistry to detect Foxp3 protein expression. Spleens were used to detect Treg and Foxp3 gene expression by flow cy：ometry and quantitative RT-PCR, respectively. Results In comparison with the Sham group, a significant decrease was found in the OV~ group in such indices as trabecular bone volume/tc,tal tissue area （BV/TV）, trabecular number （Tb.N） and trabecular thickness （Tb.Th）. 1,25（OH）2D3 and DES partly prevented the decrease in BV/TV, Tb.N, Tb.Th in OVX mice. Treg cell number, Foxp3 mRI~：A expression in spleen and Foxp3 protein expression in femur significantly decreased in the OVX-tr^ated group compared with those in the sham group. 1,25（OH）2D3 and DES significantly increased Treg cell number and Foxp3 expression. Treg cells and Foxp3 gene expression were related to bone histomorphometric parameters. Conclusion The decrease in Treg cell numbers is relevant to the postmenopausal osteoporosis. The antiosteoporosis of 1,25（OH）2D3 is related to regulatory T cells.
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This work was supported by research Funds from the Ministerio de Ciencia e Innovación(SAF2009-12671).
文摘In the present study, we examine the effects of the treatment with 1,25-dihydroxyvitamin D3 [150 IU/Kg (3.75 μg/Kg) once a day, for 15 days] to non-diabetic and streptozotocin-induced diabetic rats. The results indicate that treatment with 1,25-dihydroxyvitamin D3 had minor effects in non-diabetic rats. The same treatment in streptozotocin-induced diabetic rats, although it did not correct the hyperglycemia and hypoinsulinemia induced by the diabetes, caused other actions that could mean beneficial effects on the amelioration of diabetes e.g., it avoided body weight loss, increased calcium and phosphorus plasma levels, and corrected the over-expression of the insulin receptor mRNA species of 9.5 and 7.5 Kb present in the hind limb muscle and heart of these animals. These genomic 1,25-dihydroxyvitamin D3 effects could involve transcriptional mechanisms of repression mediated by vitamin D response elements in the rat insulin receptor gene promoter. Using computer analysis of this promoter, we propose the -249/-235 bp VDRE (5’GGGTGACCCGGGGTT3’) with a pyrimidine (T) in the (+7) position of the3’half-site as the best candidate for negative control by 1,25-dihydroxy-vitamin D3. In addition, posttranscriptional mechanisms of regulation could also be implicated. Thus, computer inspection of the5’untranslated region of the rat insulin receptor pre-mRNA indicated the presence of a virtual internal ribosome entry segment whereas the computer inspection of the3’untranslated region localized various destabilizing sequences, including various AU-rich elements. We propose that through these virtual cis-regulatory sequences, 1,25-dihydroxyvitamin D3 could control the translation and stability of insulin receptor mRNA species in the hind limb muscle and heart of diabetic rats.
文摘The effect of 1,25-dihydroxyvitamin D<sub>3</sub> [1,25（OH）<sub>2</sub>D<sub>3</sub>] and13-cis-retinoic acid（RA）on the proliferation of a novel human megakaryoblasticleukemia cell line（HIMeg）was investigated.At the concentration of 10<sup>9</sup> 10<sup>6</sup>mol/L,1,25（OH）<sub>2</sub>D<sub>3</sub> and RA showed significant inhibition of the proliferation of themegakaryoblastic leukemic cells,which was demonstrated by the count of survival cells,incorporation of<sup>3</sup>H-TdR and<sup>3</sup>H-UR,and cloning efficiency in dose-dependent and time-dependent manners.The results can further explain the mechanism of differentiation-inducing agents and the effect of 1 ,25（OH）<sub>2</sub>D<sub>3</sub> on myelofibrosis.It is possible for1,25（OH）<sub>2</sub>D<sub>3</sub> and RA to be used to treat malignant megakaryocytic diseases.
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.
