Lipid status association with 25-hydroxy vitamin D: Cross sectional study of end stage renal disease patients

BackgroundSome observational studies indicate an association of 25-hydroxy vitamin D (25(OH)D) insufficiency and atherogenic cholesterol concentrations. The aim of this study was to investigate relationship between 25(OH)D concentrations and lipid parameters in end stage renal disease (ESRD) patients, separately for predialysis, hemodialysis and peritoneal dialysis patients.MethodsWe have adjusted 25(OH)D concentrations for seasonal variability with cosinor analysis, and performed all further analysis using these corrected 25(OH)D concentrations. Concentrations of 25(OH)D and the lipid parameters were determined in 214 ESRD patients and 50 control group participants. The analysis included the measurement of 25(OH)D by HPLC, apolipoprotein (Apo) AI, ApoB and Lp(a) by nephelometry, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) by spectrophotometry and manually calculated ApoB/ApoAI and LDL-C/HDL-C ratio.ResultsESRD patients with adjusted 25(OH)D concentrations of 50 nmol/L had significantly higher TC (P = 0.005) and ApoAI (P = 0.049). Significantly higher HDLC (P = 0.011) and ApoAI (P = 0.020) were found in hemodialysis patients with the 25(OH)D concentrations of 50 nmol/L. The other analyzed lipid parameters differed significantly between predialysis, hemodialysis and peritoneal dialysis patients with 25(OH)D concentrations of < 50 nmol/L.ConclusionsOur study indicate the significant relationship between 25(OH)D repletion and optimal concentrations of lipid parameters in ESRD patients. Further research is necessary to explain whether joint evaluation of vitamin D status and lipid abnormalities could improve cardiovascular outcome in ESRD patients.     

Associations of cholesterol and vitamin D metabolites with the risk for development of high grade colorectal cancer

BackgroundVitamin D deficiency is repeatedly reported in colorectal cancer (CRC). Since cholesterol and vitamin D share common precursor 7-dehydrocholesterol (7-DHC), it would be important to explore the associations of key vitamin D metabolites and serum lipid parameters in patients with high and low grade CRC. The aim of this study was to analyze relationships between serum 25(OH)D3, 24,25(OH)2D3 and 7-DHC levels and serum lipids in patients with CRC, and to evaluate their potential for prediction of risk for development of high grade CRC.MethodsWe recruited 82 patients CRC and 77 controls. 7-DHC, 25(OH)D3 and 24,25(OH)2D3 were quantified by LC-MS/MS methods.Results7-DHC, 25(OH)D3 and vitamin D metabolic ratio (VDMR) were significantly lower in CRC patients than in control group (P<0.001, P<0.010, P<0.050 and P<0.050, respectively). 25(OH)D3 levels were higher in patients with grade I CRC when compared to grade II (P<0.050). All vitamin D metabolites positively correlated with total cholesterol (TC) concentration in CRC patients. 25(OH)D3 was significant predictor of increased CRC risk (P<0.010). After adjustment for TC concentration, 25(OH)D3 lost its predictive abilities. However, 25(OH)D3 remained significant predictor of poorly differentiated type of cancer (P<0.050).ConclusionsWe found significant positive association between vitamin D status and serum total cholesterol. Although low 25(OH)D3 was found to be a significant risk factor for CRC development, the obtained results primarily suggest profound impact of cholesterol level on vitamin D status in CRC. However, our results suggest that low 25(OH)D3 might independently contribute to development of poorly differentiated tumor.     

Chemical synthesis of 20S-hydroxyvitamin D3, which shows antiproliferative activity

20S-hydroxyvitamin D3 (20S-(OH)D3), an in vitro product of vitamin D3 metabolism by the cytochrome P450scc, was recently isolated, identified and shown to possess antiproliferative activity without inducing hypercalcemia. The enzymatic production of 20S-(OH)D3 is tedious, expensive, and cannot meet the requirements for extensive chemical and biological studies. Here we report for the first time the chemical synthesis of 20S-(OH)D3 which exhibited biological properties characteristic of the P450scc-generated compound. Specifically, it was hydroxylated to 20,23-dihydroxyvitamin D3 and 17,20-dihydroxyvitamin D3 by P450scc and was converted to 1α,20-dihydroxyvitamin D3 by CYP27B1. It inhibited proliferation of human epidermal keratinocytes with lower potency than 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in normal epidermal human keratinocytes, but with equal potency in immortalized HaCaT keratinocytes. It also stimulated VDR gene expression with similar potency to 1,25(OH)2D3, and stimulated involucrin (a marker of differentiation) and CYP24 gene expression, showing a lower potency for the latter gene than 1,25(OH)2D3. Testing performed with hamster melanoma cells demonstrated a dose-dependent inhibition of cell proliferation and colony forming capabilities similar or more pronounced than those of 1,25(OH)2D3. Thus, we have developed a chemical method for the synthesis of 20S-(OH)D3, which will allow the preparation of a series of 20S-(OH)D3 analogs to study structure-activity relationships to further optimize this class of compound for therapeutic use.     

25(OH)D3 and 1,25(OH)2D3 serum concentration and breast tissue expression of 1alpha-hydroxylase, 24-hydroxylase and Vitamin D receptor in women with and without breast cancer

1,25(OH)2D3 is an antiproliferative agent that may inhibit proliferation of breast cancer (BC) cells in vitro and BC development in animals. Epidemiological studies have shown a high incidence of BC in people less exposed to solar rays. To unravel the role of Vitamin D3 in BC patients, we have investigated serum levels of 25(OH)D3 and its active form 1,25(OH)2D3 as well as tissue expression of 1alpha-hydroxylase, 24-hydroxylase, and Vitamin D-receptor (VDR), determined by semiquantitative RT-PCR, in 88 Brazilian BC patients and 35 women without cancer (submitted to mammoplasties or resection of benign lesions). Median age of women with and without cancer was 51 and 46 years, respectively, and the majority of BC patients were classified as clinical stage II (67%). Although no differences in 25(OH)D3 serum concentration were found, 1,25(OH)2D3 (40+/-21 pg/ml) levels in BC patients were lower than in women without cancer (53+/-23). Our results indicate that 24-hydroxylase, VDR and 1alpha-hydroxylase mRNA tissue expression is similar in both groups and no correlation between 24-hydroxylase, 1alpha-hydroxylase, and VDR expression in breast tumors was found. A low 1,25(OH)2D3 serum concentration seems to be associated to breast cancer, however, the mechanism involved in this regulation is still unclear.     

肥胖合并高脂血症患者血清食欲素A、25-羟维生素D3、瘦素水平与胰岛素抵抗、脂代谢紊乱和肥胖评价指标的相关性分析

摘要 目的：探讨肥胖合并高脂血症患者血清食欲素A（orexin A）、25-羟维生素D3[25-(OH)D3]、瘦素（Leptin）水平与胰岛素抵抗、脂代谢紊乱和肥胖评价指标的相关性。方法：选择2019年2月至2021年12月中国医科大学附属第四医院收治的105例肥胖合并高脂血症患者为研究组,另取同期在中国医科大学附属第四医院健康体检的73例志愿者为对照组。检测并对比两组血清orexin A、25-(OH)D3、Leptin、胰岛素抵抗相关指标、脂代谢指标及肥胖评价指标水平的差异。采用Pearson相关性分析血清orexin A、25-(OH)D3、Leptin水平与胰岛素抵抗相关指标、脂代谢指标及肥胖评价指标的相关性。结果：研究组血清orexin A、25-(OH)D3水平低于对照组,而Leptin水平高于对照组（P＜0.05）。研究组空腹血糖（FPG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）水平均高于对照组（P＜0.05）。研究组总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）水平高于对照组,而高密度脂蛋白胆固醇（HDL-C）水平低于对照组（P＜0.05）。研究组体质量指数（BMI）、腰臀比、腰高比均高于对照组（P＜0.05）。肥胖合并高脂血症患者的血清orexin A、25-(OH)D3水平与FPG、FINS、HOMA-IR、TC、TG、LDL-C水平、BMI、腰臀比、腰高比均呈负相关,与HDL-C水平呈正相关（P＜0.05）;Leptin水平与FPG、FINS、HOMA-IR、TC、TG、LDL-C水平、BMI、腰臀比、腰高比均呈正相关,与HDL-C水平呈负相关（P＜0.05）。结论：肥胖合并高脂血症患者血清orexin A、25-(OH)D3水平降低,Leptin水平升高,且与胰岛素抵抗、脂代谢紊乱及肥胖指标升高有关。     

Measurement and characterization of C-3 epimerization activity toward vitamin D3

Recently, epimerization of the hydroxyl group at C-3 has been identified as a unique metabolic pathway of vitamin D compounds. We measured C-3 epimerization activity in subcellular fractions prepared from cultured cells and investigated the basic properties of the enzyme responsible for the epimerization. C-3 epimerization activity was detected using a NADPH-generating system containing glucose-6-phosphate, NADP, glucose-6-phosphate dehydrogenase, and Mg(2+). The highest level of activity was observed in a microsomal fraction prepared from rat osteoblastic UMR-106 cells but activity was also observed in microsomal fractions prepared from MG-63, Caco-2, Hep G2, and HUH-7 cells. In terms of maximum velocity (V(max)) and the Michaelis constant (K(m)), 25-hydroxyvitamin D(3) [25(OH)D(3)] exhibited the highest specificity for the epimerization at C-3 among 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], 25(OH)D(3), 24,25-dihydroxyvitamin D(3) [24,25(OH)(2)D(3)], and 22-oxacalcitriol (OCT). The epimerization activity was not inhibited by various cytochrome P450 inhibitors and antiserum against NADPH cytochrome P450 reductase. Neither CYP24, CYP27A1, CYP27B1 nor 3(alpha-->beta)hydroxysteroid epimerase (HSE) catalyzed the epimerization in vitro. Based on these results, the enzyme(s) responsible for the epimerization of vitamin D(3) at C-3 are thought to be located in microsomes and different from cytochrome P450 and HSE.     

Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study

Background

Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.

Methods

We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV₁) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV₁ in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV₁ in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.

Results

We found a positive cross-sectional association between 25(OH)D and FEV₁ in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV₁ in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV₁ (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV₁ in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).

Conclusions

Serum 25(OH)D status was associated with cross-sectional FEV₁, but not longitudinal change in FEV₁. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV₁ and is a promising candidate gene for further studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users.     

Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: A randomized,double blind,placebo-controlled study

The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m²; serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n = 15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n = 14) or (3) 8000 IU (n = 17). Supplements were taken daily for 35 days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000 IU, ≈29%; 8000 IU, ≈57%) and 1,25(OH)D (4000 IU, ≈12%; 8000 IU, ≈38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n = 31) were dependent on initial levels as serum 25(OH)D (r = −0.63, p < 0.05) and 1,25(OH)D (r = −0.45, p < 0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D < 29 ng/mL) compared to sufficient (serum 25(OH)D ⩾ 30 ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D.     

Rates of insufficiency and deficiency of vitamin D levels in elite professional male and female skiers: A chronobiologic approach

Vitamin D is essential for the maintenance and promotion of musculoskeletal health, for the functioning of the immune, cardiovascular and reproductive systems, and its main action is to keep calcium and phosphate plasmatic physiological concentrations at intestinal, renal and bony level. Vitamin D affects several parameters related to physical performance too and a particularly high percentage of vitamin D insufficiency and deficiency in professional athletes has been observed. Several variables are able to impair the synthesis of 25(OH)D in athletes, specifically both genetic and environmental factors, but the most probable explanation for the deficient/insufficient vitamin D levels is the insufficient ultraviolet B light (UVB) exposure during winter. To confirm this, the existence of a circannual rhythm of vitamin D in professional soccer players, highlighting a peak in summer and lowest values in winter regardless the period of the season, has been documented. Nonetheless, from what we are aware of, no other study adopted a chronobiologic approach to better understand and describe the circannual variations of serum 25(OH)D in other sport disciplines. Therefore, we studied serum vitamin D in a cohort of top-level professional skiers, during a period of three consecutive competitive seasons (2015, 2016 and 2017), in order to evaluate, with a rhythmometric approach, the vitamin D behavior along the year. The study population was composed by 152 professional Italian alpine skiers of FISI (Winter Sport Italian Federation), 63 females and 89 males (mean age: 24.1 ± 3.2 years) and a total of 298 blood drawings were carried out to determine plasma 25(OH)D. Vitamin D data were compared between genders and then processed with the population mean cosinor tests to evaluate the presence of a circannual rhythm, both for female and male athletes. In total, 77 skiers (50.7%) showed, at least once during the three competitive seasons, an insufficient level of 25(OH)D and other 45 subjects (29.6%) showed a deficient status; no differences were observed between genders (mean for females: 26.9 ± 8.1 ng/mL; mean for males: 27.4 ± 7.6 ng/mL). In addition, the rhythmometric analysis highlighted the existence of a significant circannual rhythm for both female and male professional skiers; the acrophases (Φ) occurred in July and both MESOR (M) and amplitude (A) were comparable between the two groups. Our data indicate that, despite the physical effort spent, vitamin D follows a classical season-associated rhythm with a peak in summer and a nadir in winter. Moreover, the percentage of insufficiency and deficiency is in line with that of the general population. In conclusion, our findings reinforce the hypothesis that there is no direct effect of physical activity on vitamin D metabolism and that the factors involved in the determination of vitamin D levels in the general population are valid also for athletes.     

Vitamin D and overall mortality

Vitamin D is a steroid molecule, mainly produced in the skin that regulates the expression of a large number of genes. Several meta‐analyses of epidemiological studies support the evidence that low vitamin D serum level, which is highly prevalent worldwide, could be a ‘new’ risk factor for many chronic diseases including cancer, and for all‐cause mortality. A meta‐analysis in healthy subjects suggested that current doses of vitamin D supplements could be associated with decrease in total mortality rates. However, these associations are insufficient to establish causality between vitamin D and all‐cause mortality. Furthermore, long‐term health effects of high doses of vitamin D, that is, prolonged supplementation and association with different baseline vitamin D levels, remain to be investigated. Several trials are ongoing but population‐based, placebo‐controlled randomized trials with total mortality as the main endpoint should be planned to confirm a real beneficial effect of vitamin D for non‐skeletal diseases and to prove causality.     

Vitamin D Promotes Odontogenic Differentiation of Human Dental Pulp Cells via ERK Activation

The active metabolite of vitamin D such as 1α,25-dihydroxyvitamin D₃ (1α,25(OH)₂D₃) is a well-known key regulatory factor in bone metabolism. However, little is known about the potential of vitamin D as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro. The purpose of this study was to evaluate the effect of vitamin D₃ metabolite, 1α,25(OH)₂D₃, on odontoblastic differentiation in HDPCs. HDPCs extracted from maxillary supernumerary incisors and third molars were directly cultured with 1α,25(OH)₂D₃ in the absence of differentiation-inducing factors. Treatment of HDPCs with 1α,25(OH)₂D₃ at a concentration of 10 nM or 100 nM significantly upregulated the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein1 (DMP1), the odontogenesis-related genes. Also, 1α,25(OH)₂D₃ enhanced the alkaline phosphatase (ALP) activity and mineralization in HDPCs. In addition, 1α,25(OH)₂D₃ induced activation of extracellular signal-regulated kinases (ERKs), whereas the ERK inhibitor U0126 ameliorated the upregulation of DSPP and DMP1 and reduced the mineralization enhanced by 1α,25(OH)₂D₃. These results demonstrated that 1α,25(OH)₂D₃ promoted odontoblastic differentiation of HDPCs via modulating ERK activation.     

C-25 hydroxylation of 1alpha,24(R)-dihydroxyvitamin D3 is catalyzed by 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1): metabolism studies with human keratinocytes and rat recombinant CYP24A1

Recently, 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) has been shown to catalyze not only hydroxylation at C-24 but also hydroxylations at C-23 and C-26 of the secosteroid hormone 1alpha, 25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). It remains to be determined whether CYP24A1 has the ability to hydroxylate vitamin D3 compounds at C-25. 1alpha,24(R)-dihydroxyvitamin D3 (1alpha,24(R)(OH)2D3) is a non-25-hydroxylated synthetic vitamin D3 analog that is presently being used as an antipsoriatic drug. In the present study, we investigated the metabolism of 1alpha,24(R)(OH)2D3 in human keratinocytes in order to examine the ability of CYP24A1 to hydroxylate 1alpha,24(R)(OH)2D3 at C-25. The results indicated that keratinocytes metabolize 1alpha,24(R)(OH)2D3 into several previously known both 25-hydroxylated and non-25-hydroxylated metabolites along with two new metabolites, namely 1alpha,23,24(OH)3D3 and 1alpha,24(OH)2-23-oxo-D3. Production of the metabolites including the 25-hydroxylated ones was detectable only when CYP24A1 activity was induced in keratinocytes 1alpha,25(OH)2D3. This finding provided indirect evidence to indicate that CYP24A1 catalyzes C-25 hydroxylation of 1alpha,24(R)(OH)2D3. The final proof for this finding was obtained through our metabolism studies using highly purified recombinant rat CYP24A1 in a reconstituted system. Incubation of this system with 1alpha,24(R)(OH)2D3 resulted in the production of both 25-hydroxylated and non-25-hydroxylated metabolites. Thus, in our present study, we identified CYP24A1 as the main enzyme responsible for the metabolism of 1alpha,24(R)(OH)2D3 in human keratinocytes, and provided unequivocal evidence to indicate that the multicatalytic enzyme CYP24A1 has the ability to hydroxylate 1alpha,24(R)(OH)2D3 at C-25.     

Caffeine decreases vitamin D receptor protein expression and 1,25(OH)2D3 stimulated alkaline phosphatase activity in human osteoblast cells

Of the various risk factors contributing to osteoporosis, dietary/lifestyle factors are important. In a clinical study we reported that women with caffeine intakes >300 mg/day had higher bone loss and women with vitamin D receptor (VDR) variant, tt were at a greater risk for this deleterious effect of caffeine. However, the mechanism of how caffeine effects bone metabolism is not clear. 1,25-Dihydroxy vitamin D₃ (1,25(OH)₂D₃) plays a critical role in regulating bone metabolism. The receptor for 1,25(OH)₂D₃, VDR has been demonstrated in osteoblast cells and it belongs to the superfamily of nuclear hormone receptors. To understand the molecular mechanism of the role of caffeine in relation to bone, we tested the effect of caffeine on VDR expression and 1,25(OH)₂D₃ mediated actions in bone. We therefore examined the effect of different doses of caffeine (0.2, 0.5, 1.0 and 10 mM) on 1,25(OH)₂D₃ induced VDR protein expression in human osteoblast cells. We also tested the effect of different doses of caffeine on 1,25(OH)₂D₃ induced alkaline phosphatase (ALP) activity, a widely used marker of osteoblastic activity. Caffeine dose dependently decreased the 1,25(OH)₂D₃ induced VDR expression and at concentrations of 1 and 10 mM, VDR expression was decreased by about 50–70%, respectively. In addition, the 1,25(OH)₂D₃ induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)₂D₃ stimulated VDR protein expression and 1,25(OH)₂D₃ mediated actions in human osteoblast cells.     

Autoradiographic studies with 3H 1,25 (OH)2 vitamin D3 and 3H 25 (OH) vitamin D3 in rat parathyroid glands

Summary After injection of radiolabeled 1,25 (OH)₂ vitamin D₃, nuclear concentration of radioactivity is observed in parenchymal cells of the parathyroid gland in pregnant, adult male, and 10-day male neonatal rats. In competition studies with unlabeled 1,25 (OH)₂ vitamin D₃, but not with 25 (OH) vitamin D₃, nuclear uptake is prevented. Experiments with ³H 25 (OH) vitamin D₃, in contrast to ³H 1,25 (OH)₂ vitamin D₃, do not show nuclear concentration in cells of the parathyroid. The results of the autoradiographic studies suggest the presence of receptors for a direct effect of 1,25 (OH)₂ vitamin D₃ on the parathyroid gland for modulation of parathyroid hormone secretion.     

Caffeine decreases vitamin D receptor protein expression and 1,25(OH)2D3 stimulated alkaline phosphatase activity in human osteoblast cells

Of the various risk factors contributing to osteoporosis, dietary/lifestyle factors are important. In a clinical study we reported that women with caffeine intakes >300 mg/day had higher bone loss and women with vitamin D receptor (VDR) variant, tt were at a greater risk for this deleterious effect of caffeine. However, the mechanism of how caffeine effects bone metabolism is not clear. 1,25-Dihydroxy vitamin D₃ (1,25(OH)₂D₃) plays a critical role in regulating bone metabolism. The receptor for 1,25(OH)₂D₃, VDR has been demonstrated in osteoblast cells and it belongs to the superfamily of nuclear hormone receptors. To understand the molecular mechanism of the role of caffeine in relation to bone, we tested the effect of caffeine on VDR expression and 1,25(OH)₂D₃ mediated actions in bone. We therefore examined the effect of different doses of caffeine (0.2, 0.5, 1.0 and 10 mM) on 1,25(OH)₂D₃ induced VDR protein expression in human osteoblast cells. We also tested the effect of different doses of caffeine on 1,25(OH)₂D₃ induced alkaline phosphatase (ALP) activity, a widely used marker of osteoblastic activity. Caffeine dose dependently decreased the 1,25(OH)₂D₃ induced VDR expression and at concentrations of 1 and 10 mM, VDR expression was decreased by about 50–70%, respectively. In addition, the 1,25(OH)₂D₃ induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)₂D₃ stimulated VDR protein expression and 1,25(OH)₂D₃ mediated actions in human osteoblast cells.     

绝经后女性血清25(OH)D水平与高血压的相关性分析

目的:探讨绝经后女性血清25羟维生素D[25(OH)D]与高血压的相关性。方法:选取456例绝经后女性为研究对象,按照是否存在高血压分为高血压组(n=102例)和非高血压组(n=354例),测定所有患者的血清25(OH)D水平;血清25(OH)D水平分为四组:即25(OH)D≥30 ng/m L组(n=50例)、21~29 ng/m L组(n=110例)、10~20 ng/m L组(n=240例)、25(OH)D10 ng/m L组(n=56例);比较各组相关指标的差异。并利用Logistic回归方程分析血清25(OH)D与高血压发生的关系。结果:高血压组与非高血压组在体质指数(BMI)、收缩压(SBP)、舒张压(SDP)、雌激素、高敏C反应蛋白(hs-CRP)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)方面存在统计学差异(P0.05);高血压组血清25(OH)D[14.56±3.21(ng/ml)]低于非高血压组[19.89±4.75(ng/ml)](t=10.649,P0.001);在血清25(OH)D10 ng/m L组中,SBP和SDP值、高血压发生率均高于25(OH)D≥30 ng/m L组、21~29ng/m L组(n=110例)、10~20 ng/m L组(P0.05);血清25(OH)D水平与绝经后女性发生高血压呈现负相关(P0.05)。在血清25(OH)D不同分组中,从25(OH)D≥30 ng/m L组到25(OH)D10 ng/m L组发生高血压的风险值依次增加。结论:血清25(OH)D水平与绝经后高血压的发生密切相关,随着血清25(OH)D水平的逐渐降低,高血压发生的风险亦逐渐增大。     

Vitamin D and multiple sclerosis

Vitamin D is a principal regulator of calcium homeostasis. However, recent evidence has indicated that vitamin D can have numerous other physiological functions including inhibition of proliferation of a number of malignant cells including breast and prostate cancer cells and protection against certain immune mediated disorders including multiple sclerosis (MS). The geographic incidence of MS indicates an increase in MS with a decrease in sunlight exposure. Since vitamin D is produced in the skin by solar or UV irradiation and high serum levels of 25-hydroxyvitamin D (25(OH)D) have been reported to correlate with a reduced risk of MS, a protective role of vitamin D is suggested. Mechanisms whereby the active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) may act to mediate this protective effect are reviewed. Due to its immunosuppressive actions, it has been suggested that 1,25(OH)(2)D(3) may prevent the induction of MS.