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.
Synthesis of an optically active intermediate 4b for the A-ring of 1a,25-dihydroxyvitamin D3 analogs has been achieved in eight steps, starting from readily available, inexpensive D-(+)-xylose.
Background Human adipose tissue-derived stromal cells （hADSCs） can be induced to differentiate along an osteoblastic lineage under stimulation of dexamethasone （DEX）. Recent studies, however, have questioned the e...Background Human adipose tissue-derived stromal cells （hADSCs） can be induced to differentiate along an osteoblastic lineage under stimulation of dexamethasone （DEX）. Recent studies, however, have questioned the efficacy of glucocorticoids such as DEX in mediating the osteogenesis process of skeletal progenitor cells and processed lipoaspirate cells. Is it possible to find a substitute for DEX？ Therefore, this study was designed to investigate osteogenic capacity and regulating mechanisms for osteoblastic differentiation of hADSCs by comparing osteogenic media （OM） containing either 1, 25-dihydroxyvitamin D3 （VD） or DEX and determine if VD was an ideal substitute for DEX as an induction agent for the osteogenesis of hADSCs. Methods Osteogenic differentiation of hADSCs was induced by osteogenic medium （OM） containing either 10 nmol/L VD or 100 nmol/L DEX. Differentiation of hADSCs into osteoblastic lineage was identified by alkaline phosphatase （ALP） staining, von Kossa staining, and reverse transcription-polymerase chain reaction assays for mRNA expression of osteogenesis-related genes such as type Ⅰ collagen （COL Ⅰ）, bone sialoprotein （BSP）, osteocalcin （OC）, bone morphogenetic protein （BMP）-2, BMP-4, BMP-6, BMP-7, runt-related transcription factor 2/core binding factor α1 （Runx2/Cbfal）, osterix （Osx）, and LIM mineralization protein- 1 （LMP- 1）. Results von Kossa staining revealed that the differentiated cells induced by both VD and DEX were mineralized in vitro. They also expressed osteoblast-related markers, such as ALP, COL Ⅰ, BSP, and OC. Runx2/Cbfal, Osx, BMP-6, and LMP-1 were upregulated during VD and DEX-induced hADSC osteoblastic differentiation, but BMP-4, BMP-7 were not. BMP-2 was only expressed in VD-induced differentiated cells. Conclusions VD or DEX-induced hADSCs differentiate toward the osteoblastic lineage in vitro. Runx2/Cbfal, Osx, BMP-2, BMP-6, and LMP-1 are involved in regulating osteoblastic differentiation of hADSCs, but BMP-4, BMP-7 are not. VD, but not DEX, induces expression of BMP-2 during osteogenic induction of hADSCs. VD is an ideal substitute for DEX for osteogenic induction of hADSCs.展开更多
Background::The transforming growth factorβ1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)has been proven associated with the pathogenesis of asthmatic airway remodeling,in which the Wnt/β-catenin pathway ...Background::The transforming growth factorβ1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)has been proven associated with the pathogenesis of asthmatic airway remodeling,in which the Wnt/β-catenin pathway plays an important role,notably with regard to TGF-β1.Recent studies have shown that 1α,25-dihydroxyvitamin D 3(1α,25(OH)2D 3)inhibits TGF-β1-induced EMT,although the underlying mechanism have not yet been fully elucidated.Methods::Alveolar epithelial cells were exposed to 1α,25(OH)2D 3,ICG-001,or a combination of both,followed by stimulation with TGF-β1.The protein expression of E-cadherin,α-smooth muscle actin,fibronectin,andβ-catenin was analyzed by western blotting and immunofluorescence analysis.The mRNA transcript of Snail was analyzed using RT-qPCR,and matrix metalloproteinase 9(MMP-9)activity was analyzed by gelatin zymogram.The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results::Both 1α,25(OH)2D 3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells.In addition,the Top/Fop Flash reporters showed that 1α,25(OH)2D 3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes,including MMP-9 and Snail,in synergy with ICG-001.Conclusion::1α,25(OH)2D 3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.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
Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiolog...Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, wesummarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.展开更多
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Synthesis of an optically active intermediate 4b for the A-ring of 1a,25-dihydroxyvitamin D3 analogs has been achieved in eight steps, starting from readily available, inexpensive D-(+)-xylose.
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 30200319).
文摘Background Human adipose tissue-derived stromal cells （hADSCs） can be induced to differentiate along an osteoblastic lineage under stimulation of dexamethasone （DEX）. Recent studies, however, have questioned the efficacy of glucocorticoids such as DEX in mediating the osteogenesis process of skeletal progenitor cells and processed lipoaspirate cells. Is it possible to find a substitute for DEX？ Therefore, this study was designed to investigate osteogenic capacity and regulating mechanisms for osteoblastic differentiation of hADSCs by comparing osteogenic media （OM） containing either 1, 25-dihydroxyvitamin D3 （VD） or DEX and determine if VD was an ideal substitute for DEX as an induction agent for the osteogenesis of hADSCs. Methods Osteogenic differentiation of hADSCs was induced by osteogenic medium （OM） containing either 10 nmol/L VD or 100 nmol/L DEX. Differentiation of hADSCs into osteoblastic lineage was identified by alkaline phosphatase （ALP） staining, von Kossa staining, and reverse transcription-polymerase chain reaction assays for mRNA expression of osteogenesis-related genes such as type Ⅰ collagen （COL Ⅰ）, bone sialoprotein （BSP）, osteocalcin （OC）, bone morphogenetic protein （BMP）-2, BMP-4, BMP-6, BMP-7, runt-related transcription factor 2/core binding factor α1 （Runx2/Cbfal）, osterix （Osx）, and LIM mineralization protein- 1 （LMP- 1）. Results von Kossa staining revealed that the differentiated cells induced by both VD and DEX were mineralized in vitro. They also expressed osteoblast-related markers, such as ALP, COL Ⅰ, BSP, and OC. Runx2/Cbfal, Osx, BMP-6, and LMP-1 were upregulated during VD and DEX-induced hADSC osteoblastic differentiation, but BMP-4, BMP-7 were not. BMP-2 was only expressed in VD-induced differentiated cells. Conclusions VD or DEX-induced hADSCs differentiate toward the osteoblastic lineage in vitro. Runx2/Cbfal, Osx, BMP-2, BMP-6, and LMP-1 are involved in regulating osteoblastic differentiation of hADSCs, but BMP-4, BMP-7 are not. VD, but not DEX, induces expression of BMP-2 during osteogenic induction of hADSCs. VD is an ideal substitute for DEX for osteogenic induction of hADSCs.
基金This work was supported by the Natural Science Foundation of Shanxi Province of China[2013011055-1]Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in China{2016[366]}+1 种基金Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province{[2017]144}Key Research and Development Program(International Scientific and Technological cooperation)of Shanxi Province.
文摘Background::The transforming growth factorβ1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)has been proven associated with the pathogenesis of asthmatic airway remodeling,in which the Wnt/β-catenin pathway plays an important role,notably with regard to TGF-β1.Recent studies have shown that 1α,25-dihydroxyvitamin D 3(1α,25(OH)2D 3)inhibits TGF-β1-induced EMT,although the underlying mechanism have not yet been fully elucidated.Methods::Alveolar epithelial cells were exposed to 1α,25(OH)2D 3,ICG-001,or a combination of both,followed by stimulation with TGF-β1.The protein expression of E-cadherin,α-smooth muscle actin,fibronectin,andβ-catenin was analyzed by western blotting and immunofluorescence analysis.The mRNA transcript of Snail was analyzed using RT-qPCR,and matrix metalloproteinase 9(MMP-9)activity was analyzed by gelatin zymogram.The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results::Both 1α,25(OH)2D 3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells.In addition,the Top/Fop Flash reporters showed that 1α,25(OH)2D 3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes,including MMP-9 and Snail,in synergy with ICG-001.Conclusion::1α,25(OH)2D 3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.
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 the National Natural Science Foundation of China(Nos.81770562,81602166 and 81703807)grants from the Science and Technology Planning Project of Luzhou,Sichuan Province,China(Nos.2016LZXNYD-Z04 and 2017LZXNYD-J02)
文摘Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, wesummarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.
