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1.
FASEB J ; 36(1): e22082, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34918389

RESUMO

Vitamin D deficiency is associated with risk of several common cancers, including colorectal cancer (CRC). Here we have utilized patient derived epithelial organoids (ex vivo) and CRC cell lines (in vitro) to show that calcitriol (1,25OHD) increased the expression of the CRC tumor suppressor gene, CDH1, at both the transcript and protein level. Whole genome expression analysis demonstrated significant differential expression of a further six genes after 1,25OHD treatment, including genes with established links to carcinogenesis GADD45, EFTUD1 and KIAA1199. Furthermore, gene ontologies relevant to carcinogenesis were enriched by 1,25OHD treatment (e.g., 'regulation of Wnt signaling pathway', 'regulation of cell death'), with common enriched processes across in vitro and ex vivo cultures including 'negative regulation of cell proliferation', 'regulation of cell migration' and 'regulation of cell differentiation'. Our results identify genes and pathways that are modifiable by calcitriol that have links to CRC tumorigenesis. Hence the findings provide potential mechanism to the epidemiological and clinical trial data indicating a causal association between vitamin D and CRC. We suggest there is strong rationale for further well-designed trials of vitamin D supplementation as a novel CRC chemopreventive and chemotherapeutic agent.


Assuntos
Antineoplásicos/farmacologia , Carcinogênese/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Neoplasias/biossíntese , Neoplasias/metabolismo , Transcriptoma/efeitos dos fármacos , Vitamina D/análogos & derivados , Células CACO-2 , Células HCT116 , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Vitamina D/farmacologia
2.
Nutrients ; 13(12)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34960016

RESUMO

BACKGROUND: Inadequate vitamin D levels may increase the risk of caries during childhood. The purpose of this study was to investigate the association between 25-hydroxyvitamin D (25(OH)D) status and severe early childhood caries (S-ECC) in preschool children. METHODS: Data were obtained from children <72 months of age in two case-control studies in Winnipeg, Manitoba and Richmond, Virginia. Serum analysis assessed 25(OH)D, calcium and parathyroid concentrations. Data on demographics, dental history and oral hygiene were obtained via questionnaires. Bivariate and multiple logistic regression analyses were performed to assess the relationships between demographic and biological variables and S-ECC. A p-value of ≤0.05 was significant. RESULTS: Data were available for 200 children with S-ECC and 144 caries-free controls. Children with S-ECC had significantly lower 25(OH)D levels than those who were caries-free (p < 0.001), and children with deficient 25(OH)D levels were 10 times more likely to have S-ECC (p < 0.001). Multiple logistic regression revealed that having higher 25(OH)D and calcium concentrations (p = 0.019 and p < 0.0001, respectively), as well as being breastfed in infancy (p < 0.001), were significantly and independently associated with lower odds of S-ECC, while dental insurance (p = 0.006) was associated with higher odds of S-ECC. CONCLUSIONS: This study provides additional evidence of an association between nutritional status, specifically vitamin D and calcium levels, and S-ECC.


Assuntos
Cárie Dentária/epidemiologia , Cárie Dentária/prevenção & controle , Suplementos Nutricionais , Vitamina D/análogos & derivados , Vitamina D/farmacologia , Vitaminas/farmacologia , Canadá/epidemiologia , Pré-Escolar , Humanos , Estados Unidos/epidemiologia , Vitamina D/sangue
3.
Nutrients ; 13(12)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34960022

RESUMO

Clinical research results of vitamin D supplementation in the improvement of prediabetes remain controversial. Accordingly, a literature search was conducted of PubMed, Embase (Ovid), and Web of Science prior to 9 November 2021. Randomized controlled studies reported that the following indicators were included: body mass index (BMI), fasting blood glucose (FBG), 2 h oral glucose tolerance test plasma glucose (2h-PG), hemoglobin A1c (HbA1c), insulin resistance by homeostasis model assessment (HOMA-IR), homeostasis model assessment of ß-cell function (HOMA-B), and fasting insulin (FINS). Twenty-nine articles (N = 3792) were included in the present meta-analysis. Intriguingly, vitamin D supplementation resulted in a vast improvement in FBG (standardized mean difference (SMD) = -0.38; 95%CI: -0.59, -0.16), HbA1c (SMD = -0.14; 95%CI: -0.22, -0.06) and FINS (SMD = 0.18; 95%CI: -0.26, -0.09), but not in other outcomes. However, preferred changes were observed in subgroups, as follows: Asia (SMD2h-PG = -0.25, 95%CI: -0.45, -0.04), study duration ≥1 year (SMDHOMA-IR = -0.44, 95%CI: -0.81, -0.06) (SMDHOMA-B = 0.34, 95%CI: 0.01, 0.66), baseline 25(OH)D < 50 nmol/L (SMD2h-PG = -0.23, 95%CI: -0.39, -0.06), and baseline 25(OH)D ≥ 50 nmol/L (SMDHOMA-IR = -0.50, 95%CI: -0.96, -0.03). In conclusion, oral supplementation of vitamin D has shown better effects in improving FBG, HbA1c, and FINS compared with controls among prediabetics; long-term vitamin D supplementation could have additional effects in participants with vitamin D deficiency for 2h-PG, HOMA-IR, and HOMA-B.


Assuntos
Glicemia/efeitos dos fármacos , Suplementos Nutricionais , Estado Pré-Diabético/tratamento farmacológico , Vitamina D/farmacologia , Humanos , Estado Pré-Diabético/sangue
4.
Nutrients ; 13(12)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34959907

RESUMO

This is a retrospective study of data from clinical practice to observe the effect of a high-calorie, high-protein oral nutritional supplement (ONS) with ß-hydroxy-ß-methylbutyrate (HMB) on nutritional status, body weight, and muscle-related parameters in 283 adult patients with or at risk of malnutrition under standard of care, 63% being cancer patients. They were recommended to increase physical activity and energy and protein intake from regular diet plus two servings per day of a specialized ONS enriched with HMB or standard ONS for up to 6 months. Dietary records, adherence and tolerance to ONS, nutritional status, body composition, handgrip strength, and blood analysis at the beginning and the end of the intervention were recorded. This program improved nutritional status from 100% malnourished or at risk of malnutrition at baseline to 80% well-nourished at final visit. It also increased body weight by 3.6-3.8 kg, fat-free mass by 0.9 to 1.3 kg, and handgrip strength by 4.7 to 6.2 kg. In a subgroup of patients (n = 43), phase angle (PhA), and body cell mass (BCM) increased only in the patients receiving the ONS enriched with HMB (0.95 (0.13) vs. -0.36 (0.4), and 2.98 (0.5) vs. -0.6 (1.5) kg, mean difference (SE) from baseline for PhA and BCM, respectively), suggesting the potential efficacy of this supplement on muscle health.


Assuntos
Composição Corporal/efeitos dos fármacos , Proteínas na Dieta/administração & dosagem , Suplementos Nutricionais , Ingestão de Alimentos/fisiologia , Ingestão de Energia/fisiologia , Desnutrição/metabolismo , Fenômenos Fisiológicos da Nutrição/fisiologia , Estado Nutricional/efeitos dos fármacos , Valeratos/administração & dosagem , Vitamina D/administração & dosagem , Administração Oral , Peso Corporal/efeitos dos fármacos , Feminino , Força da Mão , Humanos , Masculino , Desnutrição/dietoterapia , Desnutrição/etiologia , Pessoa de Meia-Idade , Neoplasias/complicações , Estudos Retrospectivos , Fatores de Tempo , Valeratos/farmacologia , Vitamina D/farmacologia
5.
Biomolecules ; 11(12)2021 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-34944509

RESUMO

Psoriasis is an autoimmune and inflammatory skin disease. Psoriatic patients express higher levels of plasma homocysteine (Hcy) concentration and pro-inflammatory mediators than healthy people; this is frequently associated with vitamin D deficiency. The aim of this clinical study was to investigate the effects of high doses of vitamin D supplementation on the parameters of Hcy metabolism and cytokines in sera of psoriatic patients. This prospective study was conducted on 40 psoriatic patients who had the vitamin D deficiency. All patients received vitamin D 5000 IU/day for three months. Clinical and biochemical measurements were taken at baseline and at follow up (3 months). The results showed that the severity of clinical features, measured by the psoriasis area severity index (PASI) score, were considerably improved in patients after vitamin D supplementation. After vitamin D supplementation, most of the patients (n = 25 or 62.5%) had mild clinical form (p < 0.001). After twelve weeks of intervention period, there were significant increases in vitamin D and B12 serum levels in comparison to the levels that had been measured at the beginning of the study (56.77 ± 14.66 nmol/L and 301.08 ± 95.02 pg/mL vs. 103.85 ± 32.20 nmol/L and 362.81 ± 118.56 pg/mL, respectively; p < 0.001). Moreover, serum levels of Hcy and folate were significantly lower at the end of the study in comparison with the initial levels (12.45 ± 1.92 µmol/L and 8.01 ± 3.88 mg/mL vs. 10.38 ± 1.66 µmol/L and 6.27 ± 2.60 mg/mL, respectively). High doses of vitamin D supplementation led to a significant decrease in pro-inflammatory cytokines (IFN-ɤ, TNF-α, IL-1ß, IL-6, IL-8, and IL-17) and high-sensitivity C-reactive protein (hsCRP), whereas the production of anti-inflammatory cytokines (IL-10, IL-5) was up-regulated. In conclusion, supplementation with high doses of vitamin D could be one of the possible preventive and therapeutic measures to reduce systemic inflammation in psoriatic patients.


Assuntos
Citocinas/sangue , Homocisteína/sangue , Psoríase/tratamento farmacológico , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/administração & dosagem , Adulto , Idoso , Biomarcadores/sangue , Citocinas/efeitos dos fármacos , Suplementos Nutricionais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Homocisteína/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Estudos Prospectivos , Psoríase/sangue , Vitamina B 12/sangue , Vitamina D/farmacologia , Deficiência de Vitamina D/sangue
6.
Cells ; 10(12)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34943890

RESUMO

Patients with chronic kidney disease (CKD) often have low serum concentrations of 25(OH)D3 and 1,25(OH)2D3. We investigated the differential effects of 25(OH)D3 versus 1,25(OH)2D3 repletion in mice with surgically induced CKD. Intraperitoneal supplementation of 25(OH)D3 (75 µg/kg/day) or 1,25(OH)2D3 (60 ng/kg/day) for 6 weeks normalized serum 25(OH)D3 or 1,25(OH)2D3 concentrations in CKD mice, respectively. Repletion of 25(OH)D3 normalized appetite, significantly improved weight gain, increased fat and lean mass content and in vivo muscle function, as well as attenuated elevated resting metabolic rate relative to repletion of 1,25(OH)2D3 in CKD mice. Repletion of 25(OH)D3 in CKD mice attenuated adipose tissue browning as well as ameliorated perturbations of energy homeostasis in adipose tissue and skeletal muscle, whereas repletion of 1,25(OH)2D3 did not. Significant improvement of muscle fiber size and normalization of fat infiltration of gastrocnemius was apparent with repletion of 25(OH)D3 but not with 1,25(OH)2D3 in CKD mice. This was accompanied by attenuation of the aberrant gene expression of muscle mass regulatory signaling, molecular pathways related to muscle fibrosis as well as muscle expression profile associated with skeletal muscle wasting in CKD mice. Our findings provide evidence that repletion of 25(OH)D3 exerts metabolic advantages over repletion of 1,25(OH)2D3 by attenuating adipose tissue browning and muscle wasting in CKD mice.


Assuntos
Tecido Adiposo Marrom/patologia , Caquexia/complicações , Calcifediol/farmacologia , Insuficiência Renal Crônica/complicações , Vitamina D/análogos & derivados , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Caquexia/sangue , Ingestão de Energia , Metabolismo Energético/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Insuficiência Renal Crônica/sangue , Transdução de Sinais/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Termogênese/genética , Vitamina D/farmacologia , Síndrome de Emaciação/complicações , Ganho de Peso/efeitos dos fármacos
7.
Medicina (Kaunas) ; 57(11)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34833489

RESUMO

Background and Objectives: Vitamin D is a bone modulator widely used in regenerative medicine. This study aimed to analyze the effects of vitamin D on the osteogenic differentiation and mineralization of human mesenchymal stem cells. Materials and Methods: Spheroids were fabricated using human bone marrow-derived stem cells, and were cultured in the presence of vitamin D at concentrations of 0, 0.1, 1, 10, and 100 nM. Stem cell spheroids were fabricated and the morphological evaluation was conducted on days 1, 3, 7 and 14. Determination of qualitative cellular viability was performed with Live/Dead Kit assay on days 1 and 7. Quantitative cellular viability was evaluated with Cell Counting Kit-8 on days 1, 3, 7, and 14. To analyze the osteogenic differentiation of cell spheroids, alkaline phosphatase activity assays were performed with commercially available kit on days 7 and 14. Real-time polymerase chain reaction was used to determine the expression levels of RUNX2, BSP, OCN, and COL1A1 on days 7 and 14. Results: The stem cells produced well-formed spheroids, and addition of vitamin D did not result in any noticeable changes in the shape. The addition of vitamin D did not significantly change the diameter of the spheroids at 0, 0.1, 1, 10, or 100 nM concentrations. Quantitative cell viability results from days 1, 3, 7 and 14 showed no significant difference between groups (p > 0.05). There was significantly higher alkaline phosphatase activity in the 0.1 nM group when compared with the control group on day 14 (p < 0.05). Real-time polymerase chain reaction results demonstrated that the mRNA expression levels of RUNX2, OCN, and COL1A1 were significantly increased when vitamin D was added to the culture. Conclusions: Based on these findings, we concluded that vitamin D could be applied to the increased osteogenicity of stem cell spheroids.


Assuntos
Osteogênese , Vitamina D , Células da Medula Óssea , Diferenciação Celular , Células Cultivadas , Humanos , Vitamina D/farmacologia
8.
Molecules ; 26(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34641542

RESUMO

Cancer is the second leading cause of death in the world. Chemotherapy and radiotherapy (RT) are the common cancer treatments. In addition to these limitations, the development of adverse effects from chemotherapy and RT reduces the quality of life for cancer patients. Cellular radiosensitivity, or the ability to resist and overcome cell damage caused by ionizing radiation (IR), is directly related to cancer cells' response to RT. Therefore, radiobiological research is emphasizing chemical compounds 'radiosensitization of cancer cells so that they are more reactive in the IR spectrum. Recent years researchers have seen an increase in interest in natural products that have antitumor effects with minimal side effects. Natural products, on the other hand, are easy to recover and therefore less expensive. There have been several scientific studies done based on these compounds that have tested their ability in vitro and in vivo to induce tumor radiosensitization. The role of natural products in RT, as well as their usefulness and potential applications, is the goal of this current review.


Assuntos
Produtos Biológicos/farmacologia , Radioterapia/efeitos adversos , Berberina/farmacologia , Curcumina/farmacologia , Emodina/farmacologia , Genisteína/farmacologia , Humanos , Neoplasias/radioterapia , Triterpenos Pentacíclicos/farmacologia , Protetores contra Radiação/farmacologia , Radiossensibilizantes/farmacologia , Resveratrol/farmacologia , Sesquiterpenos/farmacologia , Triterpenos/farmacologia , Vitamina D/farmacologia , Vitanolídeos/farmacologia
9.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638897

RESUMO

The novel coronavirus severe acute respiratory syndrome (SARS-CoV-2) has progressed rapidly from an outbreak to a global pandemic, with new variants rapidly emerging. Coronavirus disease 2019 (COVID-19), the disease resulting from SARS-CoV-2 infection, can lead to multiorgan damage. Due to the extremely contagious and fatal nature of the virus, it has been a priority of medical research to find effective means of treatment. Amid this search, the role of vitamin D in modulating various aspects of the innate and adaptive immune system has been discussed. This review aims to consolidate the research surrounding the role of vitamin D in the treatment and prevention of COVID-19. While there are some conflicting results reported, the consensus is that vitamin D has a host of immunomodulatory effects which may be beneficial in the context of COVID-19 and that low levels of vitamin D can result in dysfunction of crucial antimicrobial effects, potentially contributing to poor prognosis. Studies also show that the effects of low vitamin D can be mitigated via supplementation, although the benefits of vitamin D supplementation in the treatment of COVID-19 remain controversial.


Assuntos
COVID-19/prevenção & controle , Fatores Imunológicos/uso terapêutico , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Imunidade Adaptativa/efeitos dos fármacos , Animais , COVID-19/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/farmacologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Vitamina D/farmacologia , Vitaminas/farmacologia
10.
Nutrients ; 13(10)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34684379

RESUMO

Recent evidence has shown a number of extra-skeletal functions of Vitamin D (VD), primarily involving the immune system. One of these functions is mediated by the modulation of gut microbiota, whose alterations are linked to many diseases. Our purpose is to contribute to the understanding of existing evidence on the association between VD and gastrointestinal microbiota alterations. A systematic review of studies with human subjects has been conducted up to January 2021. We included publications reporting the association between gut microbiota and VD, including VD supplementation, dietary VD intake and/or level of 25(OH)D. We identified 25 studies: 14 were interventional and 11, observational. VD supplementation was found to be associated with a significant change in microbiome composition, in particular of Firmicutes, Actinobacteria and Bacteroidetes phyla. Furthermore, Firmicutes were found to be correlated with serum VD. Concerning alpha and beta diversity, a high nutritional intake of VD seems to induce a shift in bacterial composition and/or affects the species' richness. Veillonellaceae and Oscillospiraceae families, in the Firmicutes phylum, more frequently decreased with both increasing levels of 25(OH)D and vitamin D supplementation. We found evidence of an association, even though the studies are substantially heterogeneous and have some limitations, resulting sometimes in conflicting results. To further understand the role of VD on the modulation of the gastrointestinal microbiota, future research should be geared toward well-designed animal-based studies or larger randomized controlled trials (RCTs).


Assuntos
Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , Vitamina D/farmacologia , Vitaminas/farmacologia , Humanos , Vitamina D/sangue , Vitaminas/sangue
11.
Nutrients ; 13(10)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34684572

RESUMO

To date, vitamin D seems to have a significant role in affecting the prevention and immunomodulation in COVID-19 disease. Nevertheless, it is important to highlight that this pro-hormone has other several activities, such as affecting drug concentrations, since it regulates the expression of cytochrome P450 (CYP) genes. Efavirenz (EFV) pharmacokinetics is influenced by CYPs, but no data are available in the literature concerning the association among vitamin D levels, seasonality (which affects vitamin D concentrations) and EFV plasma levels. For this reason, the aim of this study was to evaluate the effect of 25-hydroxy vitamin D (25(OH)D3) levels on EFV plasma concentrations in different seasons. We quantified 25(OH)D3 by using chemiluminescence immunoassay, whereas EFV plasma concentrations were quantified with the HPLC-PDA method. A total of 316 patients were enrolled in Turin and Rome. Overall, 25(OH)D3levels resulted in being inversely correlated with EFV concentrations. Some patients with EFV levels higher than 4000 ng/mL showed a deficient 25(OH)D3 concentration in Turin and Rome cohorts and together. EFV concentrations were different in patients without vitamin D supplementation, whereas, for vitamin D-administered individuals, no difference in EFV exposure was present. Concerning seasonality, EFV concentrations were associated with 25(OH)D3 deficiency only in winter and in spring, whereas a significant influence was highlighted for 25(OH)D3 stratification for deficient, insufficient and sufficient values in winter, spring and summer. A strong and inverse association between 25(OH)D3and EFV plasma concentrations was suggested. These data suggest that vitamin D is able to affect drug exposure in different seasons; thus, the achievement of the clinical outcome could be improved by also considering this pro-hormone.


Assuntos
Alcinos/sangue , Alcinos/uso terapêutico , Benzoxazinas/sangue , Benzoxazinas/uso terapêutico , Ciclopropanos/sangue , Ciclopropanos/uso terapêutico , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Vitamina D/farmacologia , Vitaminas/farmacologia , Adulto , Estudos de Coortes , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/sangue , Inibidores da Transcriptase Reversa/uso terapêutico , Estações do Ano , Resultado do Tratamento , Vitamina D/sangue , Vitaminas/sangue
12.
Nutrients ; 13(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34684492

RESUMO

Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extra-skeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association.


Assuntos
Resistência à Insulina/fisiologia , Estado Nutricional/fisiologia , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Vitamina D/farmacologia , Feminino , Humanos , Masculino , Vitamina D/sangue
13.
Int J Mol Sci ; 22(17)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34502422

RESUMO

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Available drugs aim to suppress gut inflammation. These drugs have significantly delayed disease progression and improved patients' quality of life. However, the disease continues to progress, underscoring the need to develop novel therapies. Aside from chronic gut inflammation, IBD patients also experience a leaky gut problem due to damage to the intestinal epithelial layer. In this regard, epithelial regeneration and repair are mediated by intestinal stem cells. However, no therapies are available to directly enhance the intestinal stem cells' regenerative and repair function. Recently, it was shown that active vitamin D, i.e., 1,25-dihydroxyvitamin D or 1,25(OH)2D, was necessary to maintain Lgr5+ intestinal stem cells, actively cycling under physiological conditions. In this study, we used two strategies to investigate the role of 1,25(OH)2D in intestinal stem cells' regenerative function. First, to avoid the side effects of systemic high 1,25(OH)2D conditions, we used our recently developed novel strategy to deliver locally high 1,25(OH)2D concentrations specifically to inflamed intestines. Second, because of the Lgr5+ intestinal stem cells' active cycling status, we used a pulse-and-chase strategy via 5-bromo-2'-deoxyuridine (BrdU) labeling to trace the Lgr5+ stem cells through the whole epithelial regeneration process. Our data showed that locally high 1,25(OH)2D concentrations enhanced intestinal stem cell migration. Additionally, the migrated cells differentiated into mature epithelial cells. Our data, therefore, suggest that local delivery of high 1,25(OH)2D concentrations is a promising strategy to augment intestinal epithelial repair in IBD patients.


Assuntos
Movimento Celular/efeitos dos fármacos , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Células-Tronco/metabolismo , Vitamina D/análogos & derivados , Animais , Rastreamento de Células , Inflamação/metabolismo , Inflamação/patologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos BALB C , Células-Tronco/patologia , Vitamina D/farmacologia
14.
Int J Mol Sci ; 22(17)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34502510

RESUMO

Vitamin D showed a protective effect on intervertebral disc degeneration (IDD) although conflicting evidence is reported. An explanation could be due to the presence of the FokI functional variant in the vitamin D receptor (VDR), observed as associated with spine pathologies. The present study was aimed at investigating-through high-throughput gene and protein analysis-the response of human disc cells to vitamin D, depending on the VDR FokI variants. The presence of FokI VDR polymorphism was determined in disc cells from patients with discopathy. 1,25(OH)2D3 was administered to the cells with or without interleukin 1 beta (IL-1ß). Microarray, protein arrays, and multiplex protein analysis were performed. In both FokI genotypes (FF and Ff), vitamin D upregulated metabolic genes of collagen. In FF cells, the hormone promoted the matrix proteins synthesis and a downregulation of enzymes involved in matrix catabolism, whereas Ff cells behaved oppositely. In FF cells, inflammation seems to hamper the synthetic activity mediated by vitamin D. Angiogenic markers were upregulated in FF cells, along with hypertrophic markers, some of them upregulated also in Ff cells after vitamin D treatment. Higher inflammatory protein modulation after vitamin D treatment was observed in inflammatory condition. These findings would help to clarify the clinical potential of vitamin D supplementation in patients affected by IDD.


Assuntos
Disco Intervertebral/efeitos dos fármacos , Receptores de Calcitriol/genética , Vitamina D/farmacologia , Adulto , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Proteômica/métodos , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , Vitaminas/farmacologia
15.
Nutrients ; 13(9)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34578802

RESUMO

It is urgent to seek new potential targets for the prevention or relief of gastrointestinal syndrome in clinical radiation therapy for cancers. Vitamin D, mediated through the vitamin D receptor (VDR), has been identified as a protective nutrient against ionizing radiation (IR)-induced damage. This study investigated whether VDR could inhibit IR-induced intestinal injury and explored underlying mechanism. We first found that vitamin D induced VDR expression and inhibited IR-induced DNA damage and apoptosis in vitro. VDR was highly expressed in intestinal crypts and was critical for crypt stem/progenitor cell proliferation under physiological conditions. Next, VDR-deficient mice exposed to IR significantly increased DNA damage and crypt stem/progenitor cell apoptosis, leading to impaired intestinal regeneration as well as shorter survival time. Furthermore, VDR deficiency activated the Pmaip1-mediated apoptotic pathway of intestinal crypt stem/progenitor cells in IR-treated mice, whereas inhibition of Pmaip1 expression by siRNA transfection protected against IR-induced cell apoptosis. Therefore, VDR protects against IR-induced intestinal injury through inhibition of crypt stem/progenitor cell apoptosis via the Pmaip1-mediated pathway. Our results reveal the importance of VDR level in clinical radiation therapy, and targeting VDR may be a useful strategy for treatment of gastrointestinal syndrome.


Assuntos
Apoptose/efeitos dos fármacos , Intestinos/efeitos da radiação , Lesões Experimentais por Radiação/prevenção & controle , Receptores de Calcitriol/metabolismo , Células-Tronco/metabolismo , Vitamina D/farmacologia , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Lesões Experimentais por Radiação/patologia , Protetores contra Radiação/farmacologia , Ratos
16.
Nutrients ; 13(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34578863

RESUMO

Considering the role of bone metabolism in understanding the pathogenesis of osteoporosis, the aim of the present study was to examine the effects of vitamin D-enriched cheese on the serum concentrations of the parathyroid hormone (PTH) and certain bone remodeling biomarkers in postmenopausal women in Greece. In a randomised, controlled dietary intervention, 79 postmenopausal women (55-75 years old) were randomly allocated either to a control (CG: n = 39) or an intervention group (IG: n = 40), consuming 60 g of either non-enriched or vitamin D3-enriched Gouda-type cheese (5.7 µg of vitamin D3), respectively, daily and for eight weeks during the winter. The serum concentrations of 25-hydroxy vitamin D (25(OH)D), PTH, bone formation (i.e., osteocalcin, P1NP) and bone resorption (i.e., TRAP-5b) biomarkers were measured. Consumption of the vitamin D-enriched cheese led to higher serum 25(OH)D concentrations of 23.4 ± 6.39 (p = 0.022) and 13.4 ± 1.35 (p < 0.001) nmol/L in vitamin D-insufficient women being at menopause for less and more than 5 years, respectively. In vitamin D-insufficient women that were less than 5 years at menopause, consumption of vitamin D-enriched cheese was also associated with lower serum PTH (Beta -0.63 ± 1.11; p < 0.001) and TRAP-5b (Beta -0.65 ± 0.23; p = 0.004) levels at follow-up, compared with the CG. The present study showed that daily intake of 5.7 µg of vitamin D through enriched cheese increased serum 25(OH)D concentrations, prevented PTH increase and reduced bone resorption in vitamin D-insufficient early postmenopausal women, thus reflecting a potential food-based solution for reducing the risk of bone loss occurring after menopause.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Reabsorção Óssea/prevenção & controle , Queijo , Alimentos Fortificados , Osteoporose Pós-Menopausa/prevenção & controle , Vitamina D/farmacologia , Idoso , Biomarcadores/sangue , Reabsorção Óssea/sangue , Feminino , Grécia , Humanos , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose Pós-Menopausa/sangue , Hormônio Paratireóideo/sangue , Pós-Menopausa , Método Simples-Cego , Fatores Socioeconômicos , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitaminas/administração & dosagem , Vitaminas/sangue , Vitaminas/farmacologia
17.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445577

RESUMO

Infections by the zoonotic foodborne bacterium Campylobacter jejuni (C. jejuni) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during C. jejuni infection, using intestinal epithelial cells and mouse models focused on the interaction of C. jejuni with the VD signaling pathway and VD treatment to improve C. jejuni-induced barrier dysfunction. Our RNA-Seq data from campylobacteriosis patients demonstrate inhibition of VD receptor (VDR) downstream targets, consistent with suppression of immune function. Barrier-preserving effects of VD addition were identified in C. jejuni-infected epithelial cells and IL-10-/- mice. Furthermore, interference of C. jejuni with the VDR pathway was shown via VDR/retinoid X receptor (RXR) interaction. Paracellular leakiness of infected epithelia correlated with tight junction (TJ) protein redistribution off the TJ domain and apoptosis induction. Supplementation with VD reversed barrier impairment and prevented inhibition of the VDR pathway, as shown by restoration of transepithelial electrical resistance and fluorescein (332 Da) permeability. We conclude that VD treatment restores gut epithelial barrier functionality and decreases bacterial transmigration and might, therefore, be a promising compound for C. jejuni treatment in humans and animals.


Assuntos
Infecções por Campylobacter/complicações , Permeabilidade da Membrana Celular , Células Epiteliais/efeitos dos fármacos , Interleucina-10/fisiologia , Mucosa Intestinal/efeitos dos fármacos , Vitamina D/farmacologia , Animais , Infecções por Campylobacter/microbiologia , Campylobacter jejuni/isolamento & purificação , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas de Junções Íntimas/metabolismo , Vitaminas/farmacologia
18.
Mech Ageing Dev ; 199: 111551, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34358533

RESUMO

Polyphenols are chemopreventive through the induction of nuclear factor erythroid 2 related factor 2 (Nrf2)-mediated proteins and anti-inflammatory pathways. These pathways, encoding cytoprotective vitagenes, include heat shock proteins, such as heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1), as well as glutathione redox system to protect against cancer initiation and progression. Phytochemicals exhibit biphasic dose responses on cancer cells, activating at low dose, signaling pathways resulting in upregulation of vitagenes, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol (HT) or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Here, the importance of vitagenes in redox stress response and autophagy mechanisms, as well as the potential use of dietary antioxidants in the prevention and treatment of multiple types of cancer are discussed. We also discuss the possible relationship between SARS-CoV-2, inflammation and cancer, exploiting innovative therapeutic approaches with HT-rich aqueous olive pulp extract (Hidrox®), a natural polyphenolic formulation, as well as the rationale of Vitamin D supplementation. Finally, we describe innovative approaches with organoids technology to study human carcinogenesis in preclinical models from basic cancer research to clinical practice, suggesting patient-derived organoids as an innovative tool to test drug toxicity and drive personalized therapy.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Desenvolvimento de Medicamentos , Fator 2 Relacionado a NF-E2/metabolismo , Organoides/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Vitamina D/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , COVID-19/tratamento farmacológico , COVID-19/genética , COVID-19/metabolismo , COVID-19/virologia , Humanos , Fator 2 Relacionado a NF-E2/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Organoides/metabolismo , Oxirredução , Estresse Oxidativo/genética
19.
Nutrients ; 13(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34371846

RESUMO

Aside from its role in bone metabolism, vitamin D is a key immunomodulatory micronutrient. The active form of vitamin D (1,25(OH)D) seems to modulate the innate immune system through different mechanisms. The vitamin is involved in the differentiation of monocytes into macrophages, increasing the phagocytic and chemotactic functions of these cells. At the same time, vitamin D enables efferocytosis and prevents immunopathology. In addition, vitamin D is involved in other processes related to immune function, such as inflammation. Regarding muscle tissue, vitamin D plays an active role in muscle inflammatory response, protein synthesis, and regulation of skeletal muscle function. Two mechanisms have been proposed: A direct role of 1,25(OH)D binding to vitamin D receptors (VDRs) in muscle cells and the modulation of calcium transport in the sarcoplasmic reticulum. This second mechanism needs additional investigation. In conclusion, vitamin D seems to be effective in cases of deficiency and/or if there is a great muscular commitment, such as in high intensity exercises.


Assuntos
Imunomodulação/efeitos dos fármacos , Músculo Esquelético/imunologia , Doenças Musculares/imunologia , Vitamina D/farmacologia , Diferenciação Celular/efeitos dos fármacos , Exercício Físico/fisiologia , Treinamento Intervalado de Alta Intensidade/efeitos adversos , Humanos , Inflamação , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Doenças Musculares/etiologia , Receptores de Calcitriol/imunologia
20.
Front Immunol ; 12: 677041, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394078

RESUMO

Background: Clear associations have been found between vitamin D deficiency and several autoimmune diseases including multiple sclerosis (MS). However, the benefits of vitamin D supplementation on disease management remain a matter of debate. Objective and Methods: Patients with MS (N=12) and neuromyelitis optica spectrum disorder (NMOSD; N=12) were enrolled along with 15 healthy controls. Changes in lymphocyte subset proportions during stimulation of their peripheral blood mononuclear cells (PBMCs) with the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and correlations with serum concentrations of the vitamin D precursor 25-hydroxyvitamin D3 (serum 25(OH)D3) were explored. The impact of 1,25(OH)2D3 stimulation on the expression of vitamin-D-responsive genes in immune cells was also investigated. Results: In both MS and NMOSD, stimulation of PBMCs with 1,25(OH)2D3 followed by steroid suppressed the proliferation of total lymphocytes and T cells. The ratio of CD19+CD27+ memory B cells (Bmem) to all B cells after stimulation with 1,25(OH)2D3 was negatively correlated with serum 25(OH)D3 in MS (Spearman's ρ=-0.594, p=0.042), but positively correlated in NMOSD (Pearson's r = 0.739, p=0.006). However, there was no relationship between the ratio of Bmem to CD19+CD24+CD38+ regulatory B cells and serum 25(OH)D3 in either MS or NMOSD. In addition, the level of 1,25(OH)2D3-induced CYP24A1 mRNA expression in PBMCs was significantly and negatively correlated with serum 25(OH)D3 (for ΔCT, r=0.744, p=0.014) in MS. Conclusion: These findings suggest a beneficial impact of stimulation of PBMCs with vitamin D followed by steroid on the T-cell population. The association between patient serum 25(OH)D3 and the proportion of Bmem under immune-cell stimulation differed between MS and NMOSD. Further investigations are warranted with larger patient populations.


Assuntos
Linfócitos B/efeitos dos fármacos , Calcifediol/sangue , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Esclerose Múltipla/sangue , Neuromielite Óptica/sangue , Linfócitos T/efeitos dos fármacos , Vitamina D/análogos & derivados , Vitaminas/farmacologia , Adulto , Linfócitos B/imunologia , Estudos de Casos e Controles , Células Cultivadas , Suplementos Nutricionais , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Vitamina D/farmacologia
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