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
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
Objective:To investigate the essential biochemical indices like 1-hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them.Methods:A total of 120 SPF grade Wist...Objective:To investigate the essential biochemical indices like 1-hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them.Methods:A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups:sham group(SO group) and severe acute pancreatitis group(SAP group).Then they were divided into 1 h,3 h,6 h,and 12 h subgroups according to the killing lime.The severe acute pancreatitis model was established by retrograde injection of 5%sodium taurocholate.Serum calcium,serum creatinine,serum urea nitrogen and serum amylase were measured at different time.Serum 1,25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay.The expression of 1-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location.The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope.Results:Compared with the SO group,rats in the SAP group showed continuous pathological injury as time went by.There was significant increase in serum creatinine,serum urea nitrogen and serum amylase in SAP group compared with the SO group 1,3,6,12 hours after the operation(P<0.05).There was significant decrease in serum calcium and 1,25 dihydroxy vitamin D3 3.6,12 hours after the operation(P<0.05).It also showed that the expression of the 1-hydroxylase protein in kidney tissues was upregulated at 1 h.3 h and decreased at 6h,12 h compared with the SO group.The serum calcium,1,25 dihydroxy vitamin D3 and the expression of the 1-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease.Western blotting showed positive correlation between the 1-hydroxylase expression and serum calcium at 3 h.6 h and 12 h(r=0.976,P<0.001;r=0.948.P<0.001;r=0.742,P=0.001) and also positive correlation between the 1-hydroxylase expression and serum1,25 dihydroxy vitamin D3 at 1 h,3 h,6 h and 12 h(r=0.935,P<0.001;r=0.952,P<0.001;r=0.917.P<0.001:r=0.874,P<0.001).Conclusions:At the early stage of the kidney injury,the expression of 1-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.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
Vitamin D is a fat soluble vitamin that is foundin a variety of forms , amongwhich 1,25-（0H） 2D3 is themain active form. It not only exhibits a major physiological function to regulate the metabolism of calcium and ...Vitamin D is a fat soluble vitamin that is foundin a variety of forms , amongwhich 1,25-（0H） 2D3 is themain active form. It not only exhibits a major physiological function to regulate the metabolism of calcium and phosphorus, but also relates to the prevention and treatment of a variety of diseases such as lung diseases, cancers, diabetes, tuberculosis, lupus erythematosus, autoimmune diseases and liver damage. In this paper, the latest research progresses of the physiological function of vitamin D were summarized and discussed, aiming at providing the solid basis for utilization and application of vitamin D.展开更多
Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, foo...Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, food habits, and physical activities. Some studies have focused on the association between vitamin D and colorectal cancer. Today, there is growing evidence that high vitamin D intake and a plasma level of 25(OH)D3 reduce the incidence of colorectal cancer by modifying cancer angiogenesis, cell apoptosis, differentiation, and proliferation. Taken together, these results suggest that vitamin D supplementation alone, or in combination with anti-cancer agents, might reduce the incidence of colorectal cancer. In this review, we discuss the function and mechanism of vitamin D including the effect of vitamin D on colorectal cancer.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.
基金supported by Natural Science And Technology Fund of Sichuan Province(sc2812345)
文摘Objective:To investigate the essential biochemical indices like 1-hydroxylase and hypocalcaemia in the rats with severe acute pancreatitis and explore the correlation between them.Methods:A total of 120 SPF grade Wistar male rats which were in similar physiological status were selected and randomly divided into two groups:sham group(SO group) and severe acute pancreatitis group(SAP group).Then they were divided into 1 h,3 h,6 h,and 12 h subgroups according to the killing lime.The severe acute pancreatitis model was established by retrograde injection of 5%sodium taurocholate.Serum calcium,serum creatinine,serum urea nitrogen and serum amylase were measured at different time.Serum 1,25 dihydroxy vitamin D3 level was determined by enzyme linked immunosorbentassay.The expression of 1-hydroxylase protein in the kidney tissue was determined with Western blotting and immunohistochemistry to observe its location.The pathologic features of the kidney tissue section was observed under light microscope and submicroscopic structure of the proximal convoluted tubule epithelial cell was observed under transmission electron microscope.Results:Compared with the SO group,rats in the SAP group showed continuous pathological injury as time went by.There was significant increase in serum creatinine,serum urea nitrogen and serum amylase in SAP group compared with the SO group 1,3,6,12 hours after the operation(P<0.05).There was significant decrease in serum calcium and 1,25 dihydroxy vitamin D3 3.6,12 hours after the operation(P<0.05).It also showed that the expression of the 1-hydroxylase protein in kidney tissues was upregulated at 1 h.3 h and decreased at 6h,12 h compared with the SO group.The serum calcium,1,25 dihydroxy vitamin D3 and the expression of the 1-hydroxylase protein in kidney tissues of the SAP group showed sustaining decrease.Western blotting showed positive correlation between the 1-hydroxylase expression and serum calcium at 3 h.6 h and 12 h(r=0.976,P<0.001;r=0.948.P<0.001;r=0.742,P=0.001) and also positive correlation between the 1-hydroxylase expression and serum1,25 dihydroxy vitamin D3 at 1 h,3 h,6 h and 12 h(r=0.935,P<0.001;r=0.952,P<0.001;r=0.917.P<0.001:r=0.874,P<0.001).Conclusions:At the early stage of the kidney injury,the expression of 1-hydroxylase in the kidney tissue is reduced with the progress of the disease and the decrease in its activity has a correlation with the hypocalcaemia.
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Vitamin D is a fat soluble vitamin that is foundin a variety of forms , amongwhich 1,25-（0H） 2D3 is themain active form. It not only exhibits a major physiological function to regulate the metabolism of calcium and phosphorus, but also relates to the prevention and treatment of a variety of diseases such as lung diseases, cancers, diabetes, tuberculosis, lupus erythematosus, autoimmune diseases and liver damage. In this paper, the latest research progresses of the physiological function of vitamin D were summarized and discussed, aiming at providing the solid basis for utilization and application of vitamin D.
文摘Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, food habits, and physical activities. Some studies have focused on the association between vitamin D and colorectal cancer. Today, there is growing evidence that high vitamin D intake and a plasma level of 25(OH)D3 reduce the incidence of colorectal cancer by modifying cancer angiogenesis, cell apoptosis, differentiation, and proliferation. Taken together, these results suggest that vitamin D supplementation alone, or in combination with anti-cancer agents, might reduce the incidence of colorectal cancer. In this review, we discuss the function and mechanism of vitamin D including the effect of vitamin D on colorectal cancer.
