维生素D与脑发育相关研究进展

近年来有关维生素D研究进展迅速,其中维生素D与大脑的发育之间的关系日益受到关注。维生素D是一种具有类固醇激素作用的物质,可参与调节细胞増殖、分化及凋亡,大量研究表明,维生素D除了具有促进钙磷吸收、骨骼发育及发挥免疫调节的作用,还可作为一类神经激素影响神经系统的发育和功能,本文将从大脑中的维生素D及维生素D受体、维生素D对脑发育可能的调控作用及维生素D与儿童神经精神障碍疾病的相关性等几方面进行阐述。     

Vitamin D: an overview of its role in skeletal muscle physiology in children and adolescents

Many children may have insufficient serum concentrations of vitamin D, which could prevent optimal muscle development and function. Vitamin D deficiency in animal models results in negative effects on muscle fiber structure and calcium/phosphorus handling, suggesting an integral role of vitamin D in skeletal muscle function. While there is a dearth of data in humans, the available evidence demonstrates a positive association between vitamin D status and muscle function. This review focuses on the important role of vitamin D in muscle function in children and adolescents who live in North American regions where exposure to ultraviolet B radiation is limited and who are thus at increased risk for vitamin D insufficiency. The effects of vitamin D on muscle cell proliferation and differentiation, muscle fiber structure, and calcium and phosphorus handling are discussed. Moreover, the roles of vitamin D and the vitamin D receptor and their genomic and nongenomic actions in muscle function are explored in depth. Future research should aim to establish a vitamin D status consistent with optimal musculoskeletal development and function in young children.     

维生素D与妊娠

维生素D不仅参与了钙磷代谢，与细胞分化、生长发育和免疫调节也有明显的关系。维生素D缺乏在妊娠期妇女非常普遍，并会导致先兆子痫、妊娠期糖尿病、牙周病及细菌性阴道病的发生增加，并影响胎儿宫内生长发育，增加予代患自身免疫性疾病、过敏性疾病的风险，使呼吸道抗感染能力下降。妊娠期妇女发生维生素D缺乏的风险较高，监测和补充维生素D很有必要，合适的剂量还需进一步研究。     

1,25-二羟维生素D3的免疫调节作用

1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25-(OH)2D3]是维生素D3的活性形式,是第二甾体类激素,它除了调节机体的钙和骨代谢外,还参与免疫系统的分化与调节.1,25-(OH)2D3是通过与它的特定受体--维生素D受体相互作用来实现它的大部分基因效应的,抗原呈递细胞和T细胞是它作用的靶细胞,它的作用主要是诱导产生基因耐受性树突细胞,抑制致病性T淋巴细胞,促进调节性T淋巴细胞的增生.1,25-(OH)2D3及其类似物已经在许多实验模型中被证明能够抑制自身免疫性疾病和移植排斥反应,这是一个复杂和丰富的研究领域,可能让我们发现一种新的治疗自身免疫性疾病和移植排斥反应的重要方法.     

Association between Polymorphisms in Vitamin D Pathway-Related Genes,Vitamin D Status,Muscle Mass and Function: A Systematic Review

An association between vitamin D level and muscle-related traits has been frequently reported. Vitamin D level is dependent on various factors such as sunlight exposure and nutrition. But also on genetic factors. We, therefore, hypothesize that single nucleotide polymorphisms (SNPs) within the vitamin D pathway-related genes could contribute to muscle mass and function via an impact on vitamin D level. However, the integration of studies investigating these issues is still missing. Therefore, this review aimed to systematically identify and summarize the available evidence on the association between SNPs within vitamin D pathway-related genes and vitamin D status as well as various muscle traits in healthy adults. The review has been registered on PROSPERO and was conducted following PRISMA guidelines. In total, 77 studies investigating 497 SNPs in 13 different genes were included, with significant associations being reported for 59 different SNPs. Variations in GC, CYP2R1, VDR, and CYP24A1 genes were reported most frequently, whereby especially SNPs in the GC (rs2282679, rs4588, rs1155563, rs7041) and CYP2R1 genes (rs10741657, rs10766197, rs2060793) were confirmed to be associated with vitamin D level in more than 50% of the respective studies. Various muscle traits have been investigated only in relation to four different vitamin D receptor (VDR) polymorphisms (rs7975232, rs2228570, rs1544410, and rs731236). Interestingly, all of them showed only very low confirmation rates (6–17% of the studies). In conclusion, this systematic review presents one of the most comprehensive updates of the association of SNPs in vitamin D pathway-related genes with vitamin D status and muscle traits in healthy adults. It might be used for selecting candidate SNPs for further studies, but also for personalized strategies in identifying individuals at risk for vitamin D deficiency and eventually for determining a potential response to vitamin D supplementation.     

Cod liver oil. A natural Vitamin D for preserving health

Vitamin D deficiency is pandemic in industrialized countries due to life-style changes. Recent studies suggest that besides bone-metabolism, vitamin D plays a central role in basic cell function like multiplication, differentiation and metabolism. This may explain that low vitamin D levels represent a risk factor for several apparently different diseases such as infective, autoimmune, neurodegenerative and cardiovascular diseases, as well as diabetes, osteoporosis and cancer. Accumulating evidences suggest that an adequate intake of vitamin D may significantly decrease prevalence and clinical outcome of these diseases. Estimated reduction of the economic burden might reach about 10 percent through normalizing vitamin D levels for these diseases. However, high doses of vitamin D monotherapy needs precaution for potential adverse effects and it should be substituted with the recommended doses of vitamin D in combination with synergistic vitamin A and omega 3 fatty acids, such as cod liver oil.     

Vitamin D in the Context of Evolution

For at least 1.2 billion years, eukaryotes have been able to synthesize sterols and, therefore, can produce vitamin D when exposed to UV-B. Vitamin D endocrinology was established some 550 million years ago in animals, when the high-affinity nuclear receptor VDR (vitamin D receptor), transport proteins and enzymes for vitamin D metabolism evolved. This enabled vitamin D to regulate, via its target genes, physiological process, the first of which were detoxification and energy metabolism. In this way, vitamin D was enabled to modulate the energy-consuming processes of the innate immune system in its fight against microbes. In the evolving adaptive immune system, vitamin D started to act as a negative regulator of growth, which prevents overboarding reactions of T cells in the context of autoimmune diseases. When, some 400 million years ago, species left the ocean and were exposed to gravitation, vitamin D endocrinology took over the additional role as a major regulator of calcium homeostasis, being important for a stable skeleton. Homo sapiens evolved approximately 300,000 years ago in East Africa and had adapted vitamin D endocrinology to the intensive exposure of the equatorial sun. However, when some 75,000 years ago, when anatomically modern humans started to populate all continents, they also reached regions with seasonally low or no UV-B, i.e., and under these conditions vitamin D became a vitamin.     

维生素D及衍生物治疗银屑病的研究现状

银屑病是一种常见的慢性复发性炎症性皮肤病,全球大约2.5％的人群罹患此病.紫外线光疗是治疗方法之一,可促使表皮产生1,25(OH)2D.维生素D活性代谢产物1,25(OH)2D及其衍生物通过其细胞核受体即维生素D受体发挥重要的生理作用,除了经典的调节钙、磷代谢外,1,25(OH)2D及其衍生物抗增殖及促分化的免疫调节作用正在被逐渐认识.它可能通过调节皮肤局部的免疫反应、抑制角质细胞的增殖并诱导分化从而有效地治疗银屑病.因此,进一步了解维生素D及衍生物在银屑病中的作用机制,对于更有效地治疗银屑病具有重要的意义.     

The Role of Vitamin D in Hematologic Disease and Stem Cell Transplantation

Vitamin D is a steroid hormone with a broad range of biological effects ranging from the classical role as a mediator of calcium and phosphate balance to cellular differentiation and immune modulation. These effects impact normal and dysfunctional hematopoietic and immune function, which may allow an avenue for improved treatment and support of patients suffering from hematologic disorders. In this review, we will summarize the role of vitamin D in normal hematopoiesis, discuss ways in which vitamin D may improve outcomes, and discuss a potential role of vitamin D for treating hematologic disorders and modulating the immune system to improve the outcome of allogeneic stem cell transplant.     

Molecular Link between Vitamin D and Cancer Prevention

The metabolite of vitamin D, 1α,25-dihydroxyvitamin D₃ (also known as calcitriol), is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. Its molecular mode of action ranges from immediate nongenomic responses to longer term mechanisms that exert persistent genomic effects. The genomic mechanisms of vitamin D action rely on cross talk between 1α,25-dihydroxyvitamin D₃ signaling pathways and that of other growth factors or hormones that collectively regulate cell proliferation, differentiation and cell survival. In vitro and in vivo studies demonstrate a role for vitamin D (calcitriol) in modulating cellular growth and development. Vitamin D (calcitriol) acts as an antiproliferative agent in many tissues and significantly slows malignant cellular growth. Moreover, epidemiological studies have suggested that ultraviolet-B exposure can help reduce cancer risk and prevalence, indicating a potential role for vitamin D as a feasible agent to prevent cancer incidence and recurrence. With the preventive potential of this biologically active agent, we suggest that countries where cancer is on the rise—yet where sunlight and, hence, vitamin D may be easily acquired—adopt awareness, education and implementation strategies to increase supplementation with vitamin D in all age groups as a preventive measure to reduce cancer risk and prevalence.     

Vitamin D deficiency enhances the growth of MC-26 colon cancer xenografts in Balb/c mice

Vitamin D deficiency has been associated with increased risk of colon cancer in epidemiologic and prospective clinical studies. In vitro and in vivo studies demonstrated that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its analogs inhibit colon cancer cell proliferation. Few studies have evaluated the effect of vitamin D deficiency on the development and growth of colon cancer. To assess the antiproliferative effects of 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)2D3 in vitro, we cultured MC-26 (a colon cancer cell line) in the presence of 25(OH)D3 and 1,25(OH)2D3 and performed [3H]thymidine incorporation. The proliferation of MC-26 was significantly inhibited by both 25(OH)D3 and 1,25(OH)2D3. To determine the effect of vitamin D deficiency on colon cancer proliferation, Balb/c mice were rendered vitamin D deficient by feeding them a vitamin D-deficient diet for 3 mo. A group of vitamin D-sufficient mice was given the same diet with supplemental vitamin D. The mice were injected with MC-26 colon cancer cells and the tumors were measured daily for 20 d. Vitamin D-sufficient mice had 40% smaller tumors than vitamin D-deficient mice. The tumors were evaluated for mRNA expression of the vitamin D receptor (VDR) and 25-hydroxvitamin D-1alpha-hydroxylase (1alpha-OHase) by quantitative RT-PCR. The expression of the mRNA for the VDR and the 1alpha-OHase was 37- and 6-fold higher, respectively, in the vitamin D-sufficient mice compared with the vitamin D-deficient mice. We conclude that vitamin D deficiency enhances the growth of colon cancer in mice. The tumor expression of VDR and 1alpha-OHase indicates possible autocrine/paracrine cell growth regulation by vitamin D.     

Novel interactions of vitamin E and estrogen in breast cancer

The prevention of breast cancer through dietary modification is an active area of clinical and epidemiological research. It has been proposed that dietary supplementation of vitamin E may reduce a woman's risk of developing breast cancer. However, the exact mechanism remains unknown. alpha-Tocopherol is the most biologically active form of vitamin E. We investigated the effect of vitamin E (alpha-tocopherol) on breast cancer cell growth. A dose-dependent inhibition of cell proliferation was found in estrogen receptor (ER)-positive cells showing a potent suppression of growth at 100 microM vitamin E in MCF-7 (53%) and T47D (75%) cells. Vitamin E reduced significantly the response of both cell lines to estrogen (10 nM), and cell proliferation was decreased in MCF-7 and T47D cells by 69% and 84%, respectively. No growth inhibition was observed when cells were grown in the absence of estrogen. Vitamin E altered and decreased the growth inhibition induced by tamoxifen (10 microM) in MCF-7 (33%) and T47D (54%) cells. In addition, the immunostaining of ER of MCF-7 cells was reduced by 30% in the presence of vitamin E, suggesting an effect of vitamin E on the expression of ER. This provides evidence that vitamin E may inhibit ER-positive cell growth by altering the cellular response to estrogen.     

Breast cancer survivors and vitamin D: A review

Recent evidence has suggested a role for vitamin D in breast cancer prevention and survival. Studies have reported an inverse relation between vitamin D intake and the risk of breast cancer, improvements in survival after a diagnosis of breast cancer in women with higher levels of vitamin D, and vitamin D insufficiency in up to 75% of women with breast cancer. Preclinical data have indicated that vitamin D affects up to 200 genes that influence cellular proliferation, apoptosis, angiogenesis, terminal differentiation of normal and cancer cells, and macrophage function. Vitamin D receptors have been found in up to 80% of breast cancers, and vitamin D receptor polymorphisms have been associated with differences in survival. Although ongoing studies have investigated a possible link between adequate levels of vitamin D and improved cancer prognosis, breast cancer survivors may derive additional, non–cancer-related benefits from adequate vitamin D levels, including improvements in bone mineral density, quality of life, and mood. Maintaining adequate vitamin D stores is recommended for breast cancer survivors throughout their lifetime.