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1.
Anticancer Res ; 40(1): 535-543, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892609

RESUMO

BACKGROUND/AIM: To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D3 Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D3/day for 6 months. Circulating parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. RESULTS: There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. CONCLUSION: These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.


Assuntos
Suplementos Nutricionais , Genômica , Metabolômica , Vitamina D/farmacologia , Adulto , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Hormônio Paratireóideo/sangue , Análise de Componente Principal , Mapas de Interação de Proteínas/efeitos dos fármacos , Vitamina D/análogos & derivados , Vitamina D/sangue
2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 300-303, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701710

RESUMO

OBJECTIVE: To investigate the effects of 1,25-dihydroxyvitamin D3 (1,25-VitD3) supplementation on cerebral injury after ischemia/reperfusion (I/R) in mice with middle cerebral artery occlusion (MCAO). METHODS: Male C57BL6 mice were randomly divided into Sham group, Vehicle group and 1,25-VitD3 group, with 10 mice in each group. Vehicle group and 1,25-VitD3 group were given MCAO for 1 hour, and then killed after reperfusion for 24 hours. Mice in 1,25-VitD3 group were treated with 1,25-VitD3 at the dose of 100 ng/(kg·d) by injected intraperitoneally for 5 days before MCAO operation. Cerebral ischemic penumbra areas of each group were collected for TTC staining, RT-PCR, TTC staining and immunohistochemistry assay. The function defect of mice was evaluated by using neurological function score. RESULTS: Compared with the sham group, the volume of cerebral infarction in Vehicle group was increased significantly, and the expressions of IL-6, IL-1beta and Gp91phox in brain tissues were increased significantly (P<0.05); compared with Vehicle group, supplementation of 1,25-VitD3 reduced the volume of cerebral infarction by about 50% in I/R mice (P<0.05), and the expressions of IL-6, IL-1beta and Gp91phox in brain tissues of 1,25-VitD3 group were decreased significantly (P<0.05). The expression of Foxp3, a T-regulatory cell marker, was significantly increased in the brain of mice (P<0.05), while the expression of Rorc, a transcription factor, was significantly decreased (P<0.05), suggesting that Th17/gamma Delta T-cell response was reduced and the number of neutrophils in the brain injury site of mice was significantly reduced (P<0.05). CONCLUSION: Vitamin D could alleviate the development of cerebral infarction after arterial occlusion (MCAO) reperfusion, and its mechanism may be through regulating the inflammatory response in mouse brain I/R.


Assuntos
Infarto da Artéria Cerebral Média/tratamento farmacológico , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Vitamina D/farmacologia , Animais , Encéfalo , Citocinas/metabolismo , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidase 2/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Linfócitos T , Células Th17
3.
Clin Exp Rheumatol ; 37 Suppl 119(4): 76-81, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587692

RESUMO

OBJECTIVES: Vitamin D status influences the risk to develop autoimmune diseases affecting the percentage and/or functions of regulatory T cells (Tregs). Since low levels of 25 (OH) D have been decreased in patients with systemic sclerosis (SSc), we aimed to study the effect of Vitamin D3 (cholecalciferol) supplementation on Tregs frequencies and functions. METHODS: Peripheral blood and sera samples were obtained from 45 SSc patients and controls (HC). A number of eighteen SSc patients had consumed Cholecalciferol (orally) at the dose of 25.000 UI/month for 6 months at the time of enrollment. 25(OH)D serum levels were measured and VDR polymorphisms, were genotyped by polymerase chain reaction (PCR). Tregs isolated from peripheral blood mononuclear cells were in vitro expanded and a suppression assay was performed. Flow cytometry analysis was then carried out. Finally, IL-10 production was assayed by ELISA. RESULTS: Low serum levels of 25(OH)D were detected in SSc patients. The percentage of Tregs in SSc patients was similar to controls, but, among SSc patients, it was higher in those patients taking cholecalciferol. Tregs capability to suppress T cell proliferation was impaired in SSc patients and not restored after in vitro pre-treatment with the active form of Vitamin D (1,25(OH)2D3); but at the same time the production of IL-10 was increased in treated samples obtained from patients. The lack of response of Tregs from SSc patients to 1,25(OH)2D3 treatment in vitro was not due to altered Vitamin D/VDR signalling. CONCLUSIONS: Altogether, our results indicate that the increased production of IL-10 by 1,25(OH)2D3 -treated Tregs could provide a "suppressive" cytokine milieu able to modulate immune response but it is not sufficient to restore the immune suppressive functions of Tregs.


Assuntos
Interleucina-10/biossíntese , Escleroderma Sistêmico , Linfócitos T Reguladores/efeitos dos fármacos , Vitamina D , Estudos de Casos e Controles , Suplementos Nutricionais , Feminino , Humanos , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/metabolismo , Vitamina D/farmacologia
4.
J Steroid Biochem Mol Biol ; 195: 105484, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31574299

RESUMO

Vitamin D deficiency has been associated with increased risk for aggressive prostate cancer (PCa). Prostate epithelium has a unique metabolism compared to other tissues. Normal prostate exhibits low levels of mitochondrial respiration and there is a metabolic switch to increased oxidative phosphorylation in PCa. 25-hydroxyvitamin D (25(OH)D) is the major circulating form of vitamin D and is used clinically to determine vitamin D status. Activation of 25(OH)D to the transcriptionally active form, 1,25(OH)2D occurs via a reduction-oxidation (redox) reaction within the mitochondria that is catalyzed by the P450 enzyme, CYP27B1. We sought to determine if hydroxylation of 25(OH)D by CYP27B1 contributes to non-genomic activity of vitamin D by altering the redox-dependent state of the mitochondria in benign prostate epithelial cells. Exposure to 25(OH)D produced a transient pro-oxidant effect and change in mitochondrial membrane potential that was dependent on CYP27B1. Extended exposure ultimately suppressed mitochondrial respiration, consistent with a protective effect of 25(OH)D in supporting benign prostate metabolism. To model physiologically relevant changes in vitamin D, cells were cultured in constant 25(OH)D then changed to high or deficient concentrations. This model also incurred a biphasic effect with a pro-oxidant shift after short exposure followed by decreased respiration after 16 h. Several genes involved in redox cycling and Mitochondrial Health were regulated by 25(OH)D in these cells. These results indicate a secondary non-genomic mechanism for vitamin D to contribute to prostate cell health by supporting normal mitochondrial respiration.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Mitocôndrias/efeitos dos fármacos , Próstata/citologia , Próstata/metabolismo , Vitamina D/farmacologia , Vitaminas/farmacologia , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Genômica , Humanos , Hidroxilação/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , RNA Interferente Pequeno/genética , Receptores de Calcitriol/genética
5.
Anticancer Res ; 39(9): 4795-4803, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519581

RESUMO

BACKGROUND/AIM: To determine the mechanism of vitamin D3-induced modulation of antioxidant-related factors in endometrial cancer, we investigated their role in apoptosis of human endometrial cancer cells exposed to vitamin D3 Materials and Methods: The survival rate of human endometrial cancer cells was estimated after treatment with activated vitamin D3 Reactive oxygen species (ROS) levels were measured using flow cytometry. The levels of VDR, Trx, TXNIP and apoptosis-related proteins were investigated using western blotting and immunocytochemistry in human tissues. RESULTS: Treatment with D3 induced apoptotic cell death and cell-cycle arrest by increasing ROS concentration. Vitamin D3 inhibited proliferation of human endometrial cancer cells. It regulated intracellular ROS concentration in endometrial cancer cells via increased TXNIP expression. CONCLUSION: Antioxidant regulation via TXNIP is an important cell death mechanism in human endometrial cancer, and occurs via induction by vitamin D3.


Assuntos
Antioxidantes/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias do Endométrio/metabolismo , Tiorredoxinas/metabolismo , Vitamina D/análogos & derivados , Apoptose/efeitos dos fármacos , Biomarcadores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Vitamina D/farmacologia
6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 506-511, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484613

RESUMO

To investigate the expressions of mucosal barrier proteins in colon cell line DLD-1 under hypoxic environment in vitro and its mechanism. Methods After DLD-1 cells were treated separately with hypoxia(l% O2),vitamin D(100 nmol/L),or vitamin D plus hypoxia for 48 hours,the expressions of vitamin D receptor(VDR),tight junction proteins zonula occludens-1(ZO-1),occludin,Claudin-1,and adherent junction protein(E-cadherin)were determined by Western blot.Stable VDR knock-down(Sh-VDR)DLD-1 cell line and control DLD-1 cell line were established by lentivirus package technology and the protein expressions after hypoxia treatment were detected. Results Compared with control group,the expressions of occludin,Claudin-1,and VDR increased significantly after hypoxia treatment(all P<0.001).In addition to the protein expressions of occludin,Claudin-1 and VDR,the expressions of ZO-1 and E-cadherin were also obviously higher in vitamin D plus hypoxia group than in single vitamin D treatment group(all P<0.001).After hypoxia treatment,Sh-VDR cell line showed significantly decreased expressions of ZO-1(P<0.001),occludin(P<0.05),Claudin-1(P<0.01)and E-cadherin(P<0.001)when compared with untreated Sh-VDR cell line. Conclusion VDR acts as a regulator for the expressions of intestinal mucosal barrier proteins under hypoxia environment in DLD-1 colon cell line,indicating that VDR pathway may be another important protective mechanism for gut barrier in low-oxygen environment.


Assuntos
Colo/citologia , Receptores de Calcitriol/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Hipóxia Celular , Linhagem Celular , Claudina-1/metabolismo , Humanos , Ocludina/metabolismo , Junções Íntimas , Vitamina D/farmacologia , Proteína da Zônula de Oclusão-1/metabolismo
7.
J Dairy Sci ; 102(10): 8587-8603, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31400903

RESUMO

Yogurt is a good source of probiotics, calcium, and proteins, but its content of vitamin D is low. Therefore, yogurt could be a good choice for vitamin D fortification to improve the positive health outcomes associated with its consumption. The primary aim of this systematic review and meta-analysis was to investigate the effect of vitamin D-fortified yogurt compared with plain yogurt on levels of serum 25-hydroxy vitamin D (25OHD). The secondary aim was to evaluate the effect of fortified yogurt on parathyroid hormone, anthropometric parameters, blood pressure, glucose metabolism, and lipid profile. We searched PubMed, Scopus, and Google Scholar for eligible studies; that is, randomized controlled trials (RCT) that compared vitamin D-fortified yogurt with control treatment without any additional supplement. Random-effects models were used to estimate pooled effect sizes and 95% confidence intervals. Findings from 9 RCT (n = 665 participants) that lasted from 8 to 16 wk are summarized in this review. The meta-analyzed mean differences for random effects showed that vitamin D-fortified yogurt (from 400 to 2,000 IU) increased serum 25OHD by 31.00 nmol/L. In addition, vitamin D-fortified yogurt decreased parathyroid hormone by 15.47 ng/L, body weight by 0.92 kg, waist circumference by 2.01 cm, HOMA-IR by 2.18 mass units, fasting serum glucose by 22.54 mg/dL, total cholesterol by 13.38 mg/dL, and triglycerides by 30.12 mg/dL compared with the controlled treatments. No publication bias was identified. Considerable between-study heterogeneity was observed for most outcomes. Vitamin D-fortified yogurt may be beneficial in improving serum 25OHD, lipid profile, glucose metabolism, and anthropometric parameters and decreasing parathyroid hormone level in pregnant women and adult and elderly subjects with or without diabetes, prediabetes, or metabolic syndrome.


Assuntos
Alimentos Fortificados , Valor Nutritivo , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Iogurte , Suplementos Nutricionais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitamina D/farmacologia , Vitaminas/farmacocinética
8.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31455010

RESUMO

1,25-dihydroxyvitamin D3 (1,25D3) is implicated in many cellular functions, including cell proliferation and differentiation, thus exerting potential antitumor effects. A major limitation for therapeutic use of 1,25D3 are potent calcemic activities. Therefore, synthetic analogs of 1,25D3 for use in anticancer therapy should retain cell differentiating potential, with calcemic activity being reduced. To obtain this goal, the analogs should effectively activate transcription of genes responsible for cell differentiation, leaving the genes responsible for calcium homeostasis less active. In order to better understand this phenomenon, we selected a series of structurally related 19-nor analogs of 1,25D (PRI-5100, PRI-5101, PRI-5105, and PRI-5106) and tested their activities in blood cells and in cells connected to calcium homeostasis. Affinities of analogs to recombinant vitamin D receptor (VDR) protein were not correlated to their pro-differentiating activities. Moreover, the pattern of transcriptional activities of the analogs was different in cell lines originating from various vitamin D-responsive tissues. We thus hypothesized that receptors which participate in transport of the analogs to the cells might contribute to the observed differences. In order to study this hypothesis, we produced renal cells with knock-out of the megalin gene. Our results indicate that megalin has a minor effect on semi-selective activities of vitamin D analogs.


Assuntos
Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Receptores de Calcitriol/metabolismo , Vitamina D/farmacologia , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Concentração Inibidora 50 , Cinética , Especificidade de Órgãos/efeitos dos fármacos , Ligação Proteica , Receptores de Calcitriol/agonistas , Vitamina D/análogos & derivados , Vitamina D/química
9.
Folia Biol (Praha) ; 65(2): 70-87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464183

RESUMO

We investigated the detrimental effects of diabetes on myocardium of pregestational streptozotocin (STZ)-diabetic mother rats and their neonates via evaluations of oxidative redox, inflammatory and apoptotic pathways, also aiming to characterize whether calcitriol and/or pomegranate peel extract confer myocardial protection in hyperglycaemic dams and their foetuses via modulation of the Raf/MEK/ERK cascade. Sixty Sprague-Dawley female rats were randomized into five groups (N = 12): control, diabetic, diabetic treated with calcitriol and/or pomegranate peel extract (PPE), and mated with non-diabetic healthy males. After confirmation of pregnancy, treatments were kept until gestational day (E-18). Serum and cardiac tissues of mothers and foetuses were collected and processed for biochemical, histopathological, and molecular assessments. We observed that, compared to the control, diabetic mothers showed dramatically increased hyperglycaemia and hyperlipidaemia associated with decreased myocardial functions and disrupted maternal performance. Also, diabetic mothers and their neonates exhibited elevated levels of myocardial injury (troponin I, endothelin 1, creatine kinase-MB, lactate dehydrogenase), with increased pro-inflammatory cytokines (interleukin 1, interleukin 1ß, transforming growth factor ß) and oxidative redox. Concurrently, the MAPK pathway was significantly down-regulated with increased myocardial apoptotic activity. Furthermore, mRNA expression of angiogenic and fibrotic markers was significantly increased. Paradoxically, calcitriol and/or pomegranate peel extract alleviated these diabetic myocardial insults and normalized the aforementioned assayed parameters. Our findings hypothesized that calcitriol and/or pomegranate peel extract exerted cardioameliorative impacts due to their unique anti-oxidative and anti-inflammatory properties, and thus may be a promising treatment that directly targets the secondary myocardial complications of diabetes in dams and their offspring.


Assuntos
Apoptose , Calcitriol/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Sistema de Sinalização das MAP Quinases , Extratos Vegetais/uso terapêutico , /química , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Cardiomiopatias/complicações , Cardiomiopatias/patologia , Caspase 3/metabolismo , Citocinas/metabolismo , Dano ao DNA , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Feminino , Feto/patologia , Fibrose , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Miocárdio/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Reprodução , Espectroscopia de Infravermelho com Transformada de Fourier , Estreptozocina , Regulação para Cima/efeitos dos fármacos , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Quinases raf/metabolismo
10.
J Surg Res ; 243: 460-468, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31377485

RESUMO

INTRODUCTION: Neointimal hyperplasia (NIH) and restenosis after percutaneous transluminal coronary angioplasty (PTCA) and intravascular stenting remain a problem on a long-term basis by causing endothelial denudation and damage to the intima and media. Vascular sterile inflammation has been attributed to the formation of NIH. Cathepsin L (CTSL), a lysosome protease, is associated with diet-induced atherogenesis. Vitamin D regulates the actions and regulatory effects of proteases and protease inhibitors in different cell types. Objectives of this study are to evaluate the modulatory effect of vitamin D on CTSL activity in post-PTCA coronary arteries of atherosclerotic swine. METHODS: Yucatan microswine were fed with high-cholesterol atherosclerotic diets. The swine were stratified to receive three diets: (1) vitamin D-deficient diet, (2) vitamin D-sufficient diet, and (3) vitamin D-supplement diet. After 6 mo, PTCA was performed in the left circumflex coronary artery (LCx). After 1 y, angiography and optical coherence tomography imaging were performed, and swine was euthanized. Coronary arteries were embedded in paraffin. Tissue sections were stained with hematoxylin and eosin. Expression of Ki67 and CTSL were evaluated by immunofluorescence. RESULTS: Increased number of Ki67 + cells were observed in the postangioplasty LCx in vitamin D-deficient compared with vitamin D-sufficient or vitamin D-supplemented swine. Notably, the expression of CTSL was significantly increased in postangioplasty LCx of vitamin D-deficient swine compared with the vitamin D-sufficient or vitamin D-supplemented animal groups. CONCLUSIONS: Increased expression of CTSL correlates with the formation of NIH in the PTCA-injured coronary arteries. However, in the presence of sufficient or supplemented levels of vitamin D in the blood, CTSL expression was significantly reduced.


Assuntos
Catepsina L/metabolismo , Vasos Coronários/efeitos dos fármacos , Neointima/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/uso terapêutico , Angioplastia Coronária com Balão/efeitos adversos , Animais , Aterosclerose/terapia , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Vasos Coronários/metabolismo , Suplementos Nutricionais , Feminino , Fator de Crescimento Insulin-Like I , Miócitos de Músculo Liso/metabolismo , Neointima/metabolismo , Neointima/prevenção & controle , Suínos , Tomografia de Coerência Óptica , Fator de Necrose Tumoral alfa/metabolismo , Vitamina D/farmacologia , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/prevenção & controle
11.
Curr Protein Pept Sci ; 20(10): 984-995, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389312

RESUMO

Vitamin D, as a natural medicine, is known to regulate calcium and phosphate homeostasis. But abundant research has shown that vitamin D also plays a regulatory role in autoimmunity, inflammation, angiogenesis and vascular cell activity. Since the vitamin D receptor (VDR) is widely distributed in vascular endothelial cells, vascular smooth muscle cells and cardiomyocytes, the role of vitamin D and VDR in hypertension has received extensive attention. Hypertension is a disease with high incidence and high cardiovascular risk. In recent years, both clinical trials and animal experiments have shown that vitamin D plays a regulatory role in decreasing blood pressure (BP) through inhibiting renin-angiotensin-aldosterone system activity, modulating function of vascular wall and reducing vascular oxidative stress. A growing body of data suggest that vitamin D deficiency is associated with increased cardiovascular disease risk in hypertension, even short-term vitamin D deficiency may directly raise BP and promote target organ damage. Due to the high correlation between vitamin D and hypertension, vitamin D supplementation therapy may be a new insight in the treatment of hypertension. The aim of this review will explore the mechanisms of the vitamin D and VDR in regulating the BP and protecting against the target organ damage.


Assuntos
Anti-Hipertensivos , Hipertensão/tratamento farmacológico , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , Vitamina D/farmacologia , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Humanos , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/antagonistas & inibidores , Sistema Renina-Angiotensina/efeitos dos fármacos
12.
Medicina (Kaunas) ; 55(7)2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31336940

RESUMO

Background and Objectives: The controversy about the impact of vitamin D supplementation on weight loss treatment was observed in several randomized controlled trials (RCTs). This meta-analysis investigates the effects of vitamin D supplementation (cholecalciferol or ergocalciferol) on weight loss through holistic measurements of Body Mass Index (BMI), weight and waist circumference. Materials and Methods: Google Scholar, WOS, PubMed and Scopus were explored to collect relevant studies. The selected articles focused on vitamin D supplementation in overweight and obese individuals with different conditions. Eleven RCTs were included into this meta-analysis with a total of 947 subjects, with a mean of the follow-up from 1 to 12 months and different vitamin D interventions (from 25,000 to 600,000 IU/monthly of cholecalciferol). Results: The meta-analyzed mean differences for random effects showed that cholecalciferol supplementation deceases the BMI by -0.32 kg/m2 (CI95% -0.52, -0.12 kg/m2, p = 0.002) and the waist circumference by -1.42 cm (CI95% -2.41, -0.42 cm, p = 0.005), but does not statistically affect weight loss -0.43 kg (CI95% -1.05, +0.19 kg, p = 0.17). Conclusions: This meta-analysis lays the foundation for defining the potential clinical efficacy of vitamin D supplementation as a potential therapeutic option for weight loss programs, but further studies are needed to confirm the validity of these findings and delineate potential underlying mechanisms.


Assuntos
Vitamina D/farmacologia , Perda de Peso/efeitos dos fármacos , Índice de Massa Corporal , Suplementos Nutricionais , Humanos , Obesidade/psicologia , Obesidade/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/psicologia , Programas de Redução de Peso/métodos , Programas de Redução de Peso/normas
13.
J Steroid Biochem Mol Biol ; 193: 105431, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31326626

RESUMO

Vitamin D reveals antiproliferative activity against many types of cancer cells. Calcitriol (1,25D3), the most active form of vitamin D3, acts mainly through the vitamin D receptor, regulating the expression of target genes. Cells with reasonable expression of VDR are considered to be sensitive to antiproliferative activity of 1,25D3. However, a few alleles of the VDR gene are correlated with higher or lower response to 1,25D3 treatment. The goal of our study was to establish if cells differing in EGFR, KRAS, p53 mutation status and VDR polymorphism were sensitive to antiproliferative activity of selected vitamin D derivatives (VDDs). In our search for the lead VDD against human lung cancer cells, we selected, for this study, low calcemic analogs of active forms of vitamin D2 and D3 that had previously shown anticancer potential. The selected cell lines revealed differential response to VDDs. The highest proliferation inhibition was observed for EGFR mutant cells while a weaker response was observed for KRAS and/or p53 mutant cells. 24,24-Dihomo-1,25D3 (PRI-1890) showed the highest activity on the VDD-sensitive cell lines (A549, HCC827, NCI-H1299, and NCI-H1703). Therefore, PRI-1890 was selected as the lead VDD for further structure optimization. None of the VDDs used in this study showed antiproliferative activity against A-427 and Calu-3. VDR polymorphisms correlated inversely with sensitivity to the antiproliferative activity of VDDs since we observed less transcriptionally active form of VDR in HCC827 cells sensitive to VDD, while more transcriptionally active form was observed in NCI-H358 cells that were stimulated by VDDs to proliferate. Lack of KRAS and p53 mutations in HCC827 cells may be, therefore, responsible for the higher antiproliferative activity of VDDs, while the presence of KRAS and/or p53 mutations in other cell lines might prevent antiproliferative activity even though the VDDs were transcriptionally active as assessed on increased CYP24A1 expression. VDR gene polymorphism is not directly responsible for the sensitivity of tested cells to VDDs.


Assuntos
Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Vitamina D/análogos & derivados , Vitamina D/farmacologia , Vitaminas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/metabolismo , Mutação , Polimorfismo Genético , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Vitamina D3 24-Hidroxilase/metabolismo
14.
J Steroid Biochem Mol Biol ; 193: 105428, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31323346

RESUMO

Early diagnosis of sepsis is often difficult in clinical practice, whilst it can be vital for positive patient outcomes in sepsis management. Any delay in diagnosis and treatment may lead to significant organ failure and can be associated with elevated mortality rates. Early diagnosis and effective management of sepsis can allow for prompt antibiotic therapy and a potential reduction in mortality; it can also minimize the unnecessary use of antibiotics. Furthermore, vitamin D supplementation, which is commonly used in the intensive care units to reduce mortality, may interfere with the ability to use procalcitonin (PCT) as a means of assessing clinical progression. This paper aims to explore the diagnostic and prognostic value of serum levels of PCT as an early marker of sepsis and to assess whether it can be used as a guide for using antibiotic therapy. Several serum-based biomarkers such as C-reactive protein, lactate, presepsin, and cytokines, such as interleukin-1 (IL-1), and IL-6 have been evaluated as early indicators of sepsis but none have been proven sensitive and/or specific enough to make a definitive diagnosis. Finally the potential benefits and disadvantages of using serum levels of PCT to diagnose and monitor patients with sepsis and septic shock will be briefly discussed.


Assuntos
Infecções Bacterianas/sangue , Suplementos Nutricionais , Pró-Calcitonina/sangue , Sepse/sangue , Vitamina D/farmacologia , Vitaminas/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Biomarcadores/sangue , Estado Terminal , Humanos , Prognóstico
15.
Autoimmun Rev ; 18(9): 102350, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31323357

RESUMO

Vitamin D plays a key role in in calcium homeostasis and, thus, provides an important support in bone growth by aiding in the mineralization of the collagen matrix. However, vitamin D performs various immunomodulatory, anti-inflammatory, antioxidant and anti-fibrotic actions. Autoimmune diseases result from an aberrant activation of the immune system, whereby the immune response is directed against harmless self-antigens. Does vitamin D play a role in the pathophysiology of autoimmune diseases? And, if so, what is its role? In the last decade, researchers' interest in vitamin D and its correlations with autoimmune diseases has considerably increased. We conducted a literature review, covering the period January 1, 2009 through March 30, 2019, in PubMed. We analyzed more than 130 studies in order to find a correlation between vitamin D levels and its effect upon several autoimmune diseases. The analysis demonstrated an inverse association between vitamin D and the development of several autoimmune diseases, such as SLE, thyrotoxicosis, type 1 DM, MS, iridocyclitis, Crohn's disease, ulcerative colitis, psoriasis vulgaris, seropositive RA, polymyalgia rheumatica. International multicenter study could allow us to confirm the data already present in the literature in the single clinical studies and to evaluate when to effectively supplement vitamin D in patients who do not take corticosteroids.


Assuntos
Doenças Autoimunes/etiologia , Doenças Autoimunes/terapia , Vitamina D/fisiologia , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Comorbidade , Suplementos Nutricionais , Prática Clínica Baseada em Evidências/tendências , Humanos , Sistema Imunitário/efeitos dos fármacos , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/imunologia
16.
Int J Mol Sci ; 20(14)2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31330869

RESUMO

(1) Background: Vitamin D (VD) plays a vital role in anti-viral innate immunity. However, the role of VD in anti-rotavirus and its mechanism is still unclear. The present study was performed to investigate whether VD alleviates rotavirus (RV) infection through a microRNA-155-5p (miR-155-5p)-mediated regulation of TANK-binding kinase 1 (TBK1)/interferon regulatory factors 3 (IRF3) signaling pathway in vivo and in vitro. (2) Methods: The efficacy of VD treatment was evaluated in DLY pig and IPEC-J2. Dual-luciferase reporter activity assay was performed to verify the role of miR-155-5p in 1α,25-dihydroxy-VD3 (1,25D3) mediating the regulation of the TBK1/IRF3 signaling pathway. (3) Results: A 5000 IU·kg-1 dietary VD3 supplementation attenuated RV-induced the decrease of the villus height and crypt depth (p < 0.05), and up-regulated TBK1, IRF3, and IFN-ß mRNA expressions in the jejunum (p < 0.05). Incubation with 1,25D3 significantly decreased the RV mRNA expression and the RV antigen concentration, and increased the TBK1 mRNA and protein levels, and the phosphoprotein IRF3 (p-IRF3) level (p < 0.05). The expression of miR-155-5p was up-regulated in response to an RV infection in vivo and in vitro (p < 0.05). 1,25D3 significantly repressed the up-regulation of miR-155-5p in vivo and in vitro (p < 0.05). Overexpression of miR-155-5p remarkably suppressed the mRNA and protein levels of TBK1 and p-IRF3 (p < 0.01), while the inhibition of miR-155-5p had an opposite effect. Luciferase activity assays confirmed that miR-155-5p regulated RV replication by directly targeting TBK1, and miR-155-5p suppressed the TBK1 protein level (p < 0.01). (4) Conclusions: These results indicate that miR-155-5p is involved in 1,25D3 mediating the regulation of the TBK1/IRF3 signaling pathway by directly targeting TBK1.


Assuntos
Fator Regulador 3 de Interferon/metabolismo , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/metabolismo , Infecções por Rotavirus/veterinária , Rotavirus/fisiologia , Transdução de Sinais/efeitos dos fármacos , Vitamina D/farmacologia , Animais , Regulação da Expressão Gênica , Rotavirus/efeitos dos fármacos , Suínos , Doenças dos Suínos/genética , Doenças dos Suínos/metabolismo , Doenças dos Suínos/virologia , Replicação Viral/efeitos dos fármacos
17.
Nutrients ; 11(7)2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31330899

RESUMO

Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals (n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels (p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insufficient subjects demonstrated a significant increase of LL-37 in the treatment group (p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units (p = 0.71), Shannon microbial diversity index (p = 0.82), or in principal component analyses (p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/terapia , HIV-1 , Fenilbutiratos/farmacologia , Vitamina D/farmacologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Microbioma Gastrointestinal , Humanos , Imunidade Inata , Masculino , Pessoa de Meia-Idade , Fenilbutiratos/administração & dosagem , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto Jovem
18.
J Steroid Biochem Mol Biol ; 193: 105423, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279004

RESUMO

The active form of Vitamin D (1,25(OH)2D), has been suggested to have a regulatory role in skeletal muscle function and metabolism, however, the effects and mechanisms of vitamin D (VitD) action in this tissue remain to be fully established. In this study, we have used primary human skeletal muscle myoblast (HSMM) cells that display typical characteristics of human skeletal muscle function and protein levels, to investigate the effects of the active form of VitD on proliferation, differentiation, protein synthesis and bioenergetics. Myoblast cells were treated with 100 nM of VitD for 24 h, 48 h, 72 h and five days (cells were differentiated into myotubes) and then analyses were performed. We report that VitD inhibits myoblast proliferation and enhances differentiation by altering the expression of myogenic regulatory factors. In addition, we found that protein synthesis signaling improved in myotubes after VitD treatment in the presence of insulin. We also report an increase in oxygen consumption rate after 24 h of treatment in myoblasts and after 5 days of treatment in myotubes after VitD exposure. VitD significantly impacted HSMM myogenesis, as well as protein synthesis in the presence of insulin.


Assuntos
Fibras Musculares Esqueléticas/efeitos dos fármacos , Mioblastos Esqueléticos/efeitos dos fármacos , Vitamina D/farmacologia , Vitaminas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Humanos , Insulina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/metabolismo , Mioblastos Esqueléticos/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
19.
Biomed Res Int ; 2019: 9013904, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275989

RESUMO

Background: It has been documented that vitamin D supplementation showed an improvement of symptoms of diabetic nephropathy; however, the underlying mechanisms remain unknown. We here tested the hypothesis that active vitamin D is able to up-regulate AKT/UCP2 signaling to alleviate oxidative stress of renal tubular cell line HK2. Methods: There are eight groups in the present study: normal glucose, osmotic control (5.5 mmol/L D-glucose+24.5 mmol/L D-mannitol), NAC control (30 mmol/L D-glucose + 1.0 mmol/L N-Methylcysteine), high glucose, high glucose+VD, high glucose (HG)+VD+siVDR, HG+VD+AKT inhibitor (AI), and high glucose+VD+UCP2 inhibitor (Gelipin). Concentration of superoxide dismutase (SOD) and malondialdehyde (MDA) was analyzed by ELISA. Reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis were measured by flow cytometry. JC-1 was evaluated by flow cytometry. The presence of VDR, AKT, and UCP2 in HK cells was assessed using RT-PCR and western blot analyses. Results: VD administration significantly upregulated the SOD activation and downregulated MDA levels compared to HG group. siVDR, AKT inhibitor, and UCP2 inhibitor significantly suppressed the activation of SOD and increased the expression of MDA compared to VD group. ROS generation and apoptosis of HK2 cells in HG+VD group were significantly lower than those in HG, HG+VD+siVDR, HG+VD+AI, and HG+VD+Gelipin group. ΔΨm in HG+VD group was obviously higher than those in HG, HG+VD+siVDR, HG+VD+AI, and HG+VD+Gelipin group. Decreased mRNA and protein levels of VDR, p-AKT, and UCP2 were observed in HG+VD+siVDR, HG+VD+AI, and HG+VD+Gelipin group compared to those in HG+VD group. Conclusions: siVDR, AKT inhibitor, and UCP2 inhibitor elevated the ROS and apoptosis of HK2 cells while attenuating the mitochondrial membrane potential, suggesting that vitamin D protects renal tubular cell from high glucose by AKT/UCP2 signaling pathway.


Assuntos
Glucose/toxicidade , Túbulos Renais/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Calcitriol/metabolismo , Transdução de Sinais , Proteína Desacopladora 2/metabolismo , Vitamina D/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
20.
Molecules ; 24(13)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284538

RESUMO

Vitamin D deficiency or hypovitaminosis D is associated with increased risks of insulin resistance, type 2 diabetes mellitus (T2DM) and its related non-alcoholic fatty liver disease (NAFLD). Meanwhile, inappropriate over-activation of the renin-angiotensin system (RAS) in the liver leads to the hepatic dysfunction and increased risk of T2DM, such as abnormalities in lipid and glucose metabolism. Our previous findings have shown that calcitriol, an active metabolite of vitamin D, reduces hepatic triglyceride accumulation and glucose output in diabetic db/db mice and human hepatocellular cell HepG2 cells under insulin-resistant conditions. Notwithstanding the existence of this evidence, the protective action of vitamin D in the modulation of overexpressed RAS-induced metabolic abnormalities in the liver under insulin resistance remains to be elusive and investigated. Herein, we have reported the potential interaction between vitamin D and RAS; and its beneficial effects on the expression and function of the RAS components in HepG2 cells and primary hepatocytes under insulin-resistance states. Our study findings suggest that hormonal vitamin D (calcitriol) has modulatory action on the inappropriate upregulation of the hepatic RAS under insulin-resistant conditions. If confirmed, vitamin D supplementation might provide a nutraceutical potential as a cost-effective approach for the management of hepatic metabolic dysfunction as observed in T2DM and related NAFLD.


Assuntos
Vitamina D/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Glucose/metabolismo , Células Hep G2 , Humanos , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
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