The novel 19 nor l α ,25 dihydroxy vitamin D 3 analogues possessing an ethyl at the 2 position(4 and 5), were synthesized by coupling 25 hydroxy Windaus Grundmann ketone derivative 20 with A ring syntho...The novel 19 nor l α ,25 dihydroxy vitamin D 3 analogues possessing an ethyl at the 2 position(4 and 5), were synthesized by coupling 25 hydroxy Windaus Grundmann ketone derivative 20 with A ring synthons(15 and 19) respectively. The enantioselective synthesis of substituted bicyclic hexanes structure A ring synthons, started from all cis 3,5 dihydroxy 4 ethyl 1 (methoxycarbonyl)cyclohexane via lipase catalyzd asymmetrization, was demonstrated.展开更多
AIM： To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25（OH）2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS： Caco-2 cells were incub...AIM： To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25（OH）2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS： Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 umol/L 25（OH）2D3 or with 1 umol/L 1α-25（OH）2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25（OH）2D3 or 1α-25（OH）2D3. 1α-25（OH）2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25（OH）2D3 protein. Finally, enzymatic activity was measured by ELISA. RESULTS： Both butyrate and 1α-25（OH）2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25（OH）2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25（OH）2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites. CONCLUSION： Our experimental data provide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25（OH）2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25（OH）2D3 in combination with butyrate may offer a new therapeutic approach forthe treatment of colon cancer.展开更多
目的:探讨妊娠早、中期妇女血清25-羟维生素D-3(25-OHD-3)与妊娠期糖尿病(GDM)的关系。方法:随机选取2018年1月至2021年12月在本院进行常规孕期检查的产妇作为研究对象,孕8~12周检测其空腹血糖(FBG)及糖化血红蛋白(HbAlc)水平,孕13~15...目的:探讨妊娠早、中期妇女血清25-羟维生素D-3(25-OHD-3)与妊娠期糖尿病(GDM)的关系。方法:随机选取2018年1月至2021年12月在本院进行常规孕期检查的产妇作为研究对象,孕8~12周检测其空腹血糖(FBG)及糖化血红蛋白(HbAlc)水平,孕13~15周检测其血清25-OHD-3水平,孕24~28周行75 g口服葡萄糖耐量试验(OGTT),包括FBG、餐后1 h血糖(1 h PBG)、餐后2 h血糖(2 h PBG),并在空腹、服糖水后1 h和2 h均检测血清25-OHD-3。根据OGTT筛查结果,将其分为GDM组(n=100)及对照组(n=100)。比较2组孕早期FBG、HbAlc,孕中期血清25-OHD-3及孕中后期空腹、服糖水后1、2 h的血糖及25-OHD-3等指标的差异,并分析血清25-OHD-3水平与GDM发病的关系。结果:GDM组孕早期FBG、HbAlc及OGTT中FBG、1 h PBG、2 h PBG均高于对照组(P<0.05);GDM组血清25-OHD-3水平低于对照组,差异具有统计学意义(P<0.05);两组孕妇存在孕期血清25-OHD-3不足且缺乏的情况,血清25-OHD-3指标GDM组充足率为6.00%,对照组为7.00%;GDM组不足率为30.00%,对照组为32.00%;GDM组缺乏率为64.00%,对照组为61.00%。综合比较显示,两组血清25-OHD-3充足率、不足率及缺乏率差异无统计学意义(P>0.05);GDM组中FBG正常组的25-OHD-3水平显著高于FBG异常组(P<0.05);而服糖后1 h及2 h,血糖正常组及异常组的25-OHD-3水平比较差异无统计学意义(P>0.05)。结论:随着孕龄的增加,孕妇血清25-OHD-3水平逐渐下降,而妊娠中期较低的血清25-OHD-3水平与GDM的发生存在相关性,增加了GDM发生的风险,对于高危人群需要加强早期监测,积极补充维生素D,以预防及减少GDM的发生。展开更多
文摘The novel 19 nor l α ,25 dihydroxy vitamin D 3 analogues possessing an ethyl at the 2 position(4 and 5), were synthesized by coupling 25 hydroxy Windaus Grundmann ketone derivative 20 with A ring synthons(15 and 19) respectively. The enantioselective synthesis of substituted bicyclic hexanes structure A ring synthons, started from all cis 3,5 dihydroxy 4 ethyl 1 (methoxycarbonyl)cyclohexane via lipase catalyzd asymmetrization, was demonstrated.
基金Supported by the Else Kroner-Fresenius Foundation, Bad Homburg, Germany
文摘AIM： To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25（OH）2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS： Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 umol/L 25（OH）2D3 or with 1 umol/L 1α-25（OH）2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25（OH）2D3 or 1α-25（OH）2D3. 1α-25（OH）2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25（OH）2D3 protein. Finally, enzymatic activity was measured by ELISA. RESULTS： Both butyrate and 1α-25（OH）2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25（OH）2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25（OH）2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites. CONCLUSION： Our experimental data provide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25（OH）2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25（OH）2D3 in combination with butyrate may offer a new therapeutic approach forthe treatment of colon cancer.
文摘目的:探讨妊娠早、中期妇女血清25-羟维生素D-3(25-OHD-3)与妊娠期糖尿病(GDM)的关系。方法:随机选取2018年1月至2021年12月在本院进行常规孕期检查的产妇作为研究对象,孕8~12周检测其空腹血糖(FBG)及糖化血红蛋白(HbAlc)水平,孕13~15周检测其血清25-OHD-3水平,孕24~28周行75 g口服葡萄糖耐量试验(OGTT),包括FBG、餐后1 h血糖(1 h PBG)、餐后2 h血糖(2 h PBG),并在空腹、服糖水后1 h和2 h均检测血清25-OHD-3。根据OGTT筛查结果,将其分为GDM组(n=100)及对照组(n=100)。比较2组孕早期FBG、HbAlc,孕中期血清25-OHD-3及孕中后期空腹、服糖水后1、2 h的血糖及25-OHD-3等指标的差异,并分析血清25-OHD-3水平与GDM发病的关系。结果:GDM组孕早期FBG、HbAlc及OGTT中FBG、1 h PBG、2 h PBG均高于对照组(P<0.05);GDM组血清25-OHD-3水平低于对照组,差异具有统计学意义(P<0.05);两组孕妇存在孕期血清25-OHD-3不足且缺乏的情况,血清25-OHD-3指标GDM组充足率为6.00%,对照组为7.00%;GDM组不足率为30.00%,对照组为32.00%;GDM组缺乏率为64.00%,对照组为61.00%。综合比较显示,两组血清25-OHD-3充足率、不足率及缺乏率差异无统计学意义(P>0.05);GDM组中FBG正常组的25-OHD-3水平显著高于FBG异常组(P<0.05);而服糖后1 h及2 h,血糖正常组及异常组的25-OHD-3水平比较差异无统计学意义(P>0.05)。结论:随着孕龄的增加,孕妇血清25-OHD-3水平逐渐下降,而妊娠中期较低的血清25-OHD-3水平与GDM的发生存在相关性,增加了GDM发生的风险,对于高危人群需要加强早期监测,积极补充维生素D,以预防及减少GDM的发生。
