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.
AIM: To study the mechanism and the preventive role of 1,25-dihydroxyvitamin D3 in acute rejection following orthotopic liver transplantation.METHODS: Rats were randomly divided as donors or recipients for orthotopic ...AIM: To study the mechanism and the preventive role of 1,25-dihydroxyvitamin D3 in acute rejection following orthotopic liver transplantation.METHODS: Rats were randomly divided as donors or recipients for orthotopic liver allotransplantation model. Four groups were designed in the study, Group Ⅰ: syngenic control (Wistar to Wistar); Group Ⅱ: acute rejection (SD to Wistar);Group Ⅲ: acute rejection treated with cyclosporine A, and Group Ⅳ: acute rejection treated with 1,25-(OH)2D3. Liver function, rejection activity index and mRNA of IFN-γ, IL-10intragraft in recipients were measured on day t, 5, 7, 15,30 posttransplant for assessing graft function, severity of acute rejection and immune state of recipients.RESULTS: Survival time of recipients in Group Ⅳ was significantly prolonged (4/6 recipients survived for over 100days. vs Group Ⅱ, P＜0.001; vs Group Ⅲ, P＞0.05). After treatment with 1,25-(OH)2 D3, mean value of all the assay tested on each experimental time was compared, liver function in group Ⅳ was significantly improved (AST 127±41U/L-360±104 U/L, BIL 13±5 mmol/1-38±11 mmol/l; vs Group Ⅱ, P＜0.05; vs Group Ⅲ, P＞0.05. Rejection activity index was significantly decreased (0-3.3±1.6; vsGroup Ⅱ, P＜0.05;vsGroup Ⅲ, P＞0.05). Level of hepatic IFN-γ, mRNA in group Ⅳ was decreased, while level of hepatic IL-10 mRNA was increased (vs Group Ⅱ, P＜0.05; vs Group Ⅲ, P＞0.05).CONCLUSION: Our results indicated that 1,25-(OH)2D3induced the secretion of cytokine toward to Th2 type, which would alleviate acute rejection, protect liver function and prolong survival of recipient after orthotopic liver transplantation.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
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
目的研究脑微出血(cerebral microbleeds,CMBs)患者1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25-(OH)2D3],可溶性低密度脂蛋白受体相关蛋白1(soluble low density lipoprotein receptor related protein 1,sLRP1)水平与头颅SWI微...目的研究脑微出血(cerebral microbleeds,CMBs)患者1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25-(OH)2D3],可溶性低密度脂蛋白受体相关蛋白1(soluble low density lipoprotein receptor related protein 1,sLRP1)水平与头颅SWI微出血病灶数量及部位等影像学特征的相关关系。方法连续纳入2017年1月~2019年5月就诊于陕西省人民医院的CMBs患者196例(男性152例,女性44例),正常对照组99例(男性67例,女性32例),采集人口学资料及病史。对两组人群进行血浆1,25-(OH)2D3,sLRP1水平的检查。比较两组间血浆1,25-(OH)2D3和sLRP1水平的差异,并统计CMBs组各检验指标与CMBs病灶数量及部位的相关关系。结果CMBs组患者血浆1,25-(OH)2D3,sLRP1水平均低于对照组(23.32±18.91 mmol/L vs 39.60±18.58 mmol/L;237.96±70.62 ng/ml vs 312.61±62.78 ng/ml),差异均具有统计学意义(t=7.07,-9.24,均P<0.01)。CMBs患者血浆sLRP1水平与脑皮质CMBs病灶数量呈负相关(r=0.239,P=0.001),而与脑深部CMBs病灶数量无明显相关(t=-0.096,P>0.05)。结论CMBs患者的血浆1,25-(OH)2D3,sLRP1水平均低于正常人群。高表达的血浆sLRP1可能对脑皮质CMBs的发生具有一定的保护作用。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.
文摘AIM: To study the mechanism and the preventive role of 1,25-dihydroxyvitamin D3 in acute rejection following orthotopic liver transplantation.METHODS: Rats were randomly divided as donors or recipients for orthotopic liver allotransplantation model. Four groups were designed in the study, Group Ⅰ: syngenic control (Wistar to Wistar); Group Ⅱ: acute rejection (SD to Wistar);Group Ⅲ: acute rejection treated with cyclosporine A, and Group Ⅳ: acute rejection treated with 1,25-(OH)2D3. Liver function, rejection activity index and mRNA of IFN-γ, IL-10intragraft in recipients were measured on day t, 5, 7, 15,30 posttransplant for assessing graft function, severity of acute rejection and immune state of recipients.RESULTS: Survival time of recipients in Group Ⅳ was significantly prolonged (4/6 recipients survived for over 100days. vs Group Ⅱ, P＜0.001; vs Group Ⅲ, P＞0.05). After treatment with 1,25-(OH)2 D3, mean value of all the assay tested on each experimental time was compared, liver function in group Ⅳ was significantly improved (AST 127±41U/L-360±104 U/L, BIL 13±5 mmol/1-38±11 mmol/l; vs Group Ⅱ, P＜0.05; vs Group Ⅲ, P＞0.05. Rejection activity index was significantly decreased (0-3.3±1.6; vsGroup Ⅱ, P＜0.05;vsGroup Ⅲ, P＞0.05). Level of hepatic IFN-γ, mRNA in group Ⅳ was decreased, while level of hepatic IL-10 mRNA was increased (vs Group Ⅱ, P＜0.05; vs Group Ⅲ, P＞0.05).CONCLUSION: Our results indicated that 1,25-(OH)2D3induced the secretion of cytokine toward to Th2 type, which would alleviate acute rejection, protect liver function and prolong survival of recipient after orthotopic liver transplantation.
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 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.
文摘目的研究脑微出血(cerebral microbleeds,CMBs)患者1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25-(OH)2D3],可溶性低密度脂蛋白受体相关蛋白1(soluble low density lipoprotein receptor related protein 1,sLRP1)水平与头颅SWI微出血病灶数量及部位等影像学特征的相关关系。方法连续纳入2017年1月~2019年5月就诊于陕西省人民医院的CMBs患者196例(男性152例,女性44例),正常对照组99例(男性67例,女性32例),采集人口学资料及病史。对两组人群进行血浆1,25-(OH)2D3,sLRP1水平的检查。比较两组间血浆1,25-(OH)2D3和sLRP1水平的差异,并统计CMBs组各检验指标与CMBs病灶数量及部位的相关关系。结果CMBs组患者血浆1,25-(OH)2D3,sLRP1水平均低于对照组(23.32±18.91 mmol/L vs 39.60±18.58 mmol/L;237.96±70.62 ng/ml vs 312.61±62.78 ng/ml),差异均具有统计学意义(t=7.07,-9.24,均P<0.01)。CMBs患者血浆sLRP1水平与脑皮质CMBs病灶数量呈负相关(r=0.239,P=0.001),而与脑深部CMBs病灶数量无明显相关(t=-0.096,P>0.05)。结论CMBs患者的血浆1,25-(OH)2D3,sLRP1水平均低于正常人群。高表达的血浆sLRP1可能对脑皮质CMBs的发生具有一定的保护作用。
