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1.
Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500616

RESUMO

INTRODUCTION: The most common forms of vitamin D in human and mouse serum are vitamin D3 and vitamin D2 and their metabolites. The aim of this study is to determine whether diet and sunlight directly affect the circulating concentrations of vitamin D metabolites in a mouse model. We investigated the serum concentrations of eight vitamin D metabolites-vitamin D (vitamin D3 + vitamin D2), 25OHD (25OHD3 + 25OHD2), 1α25(OH)2D (1α25(OH)2D2, and 1α25(OH)2D3)-including their epimer, 3-epi-25OHD (3-epi-25OHD3 and 3-epi-25OHD2), and a bile acid precursor 7alpha-hydroxy-4-cholesten-3-one (7αC4), which is known to cause interference in liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. METHOD: The LC-MS/MS method was validated according to FDA-US guidelines. The validated method was used for the analysis of mouse serum samples. Forty blood samples from mice were collected and divided into three groups. The first group, the DDD mice, were fed a vitamin D-deficient diet (25 IU VD3/kg of diet) and kept in the dark; the second group, the SDD mice, were maintained on a standard-vitamin D diet (1000 IU VD3) and kept in the dark; and the third group, SDL, were fed a standard-vitamin D diet (1000 IU VD3) but kept on a normal light/dark cycle. LC-MS/MS was used for the efficient separation and quantitation of all the analytes. RESULTS: The validated method showed good linearity and specificity. The intraday and interday precision were both <16%, and the accuracy across the assay range was within 100 ± 15%. The recoveries ranged between 75 and 95%. The stability results showed that vitamin D metabolites are not very stable when exposed to continuous freeze-thaw cycles; the variations in concentrations of vitamin D metabolites ranged between 15 and 60%. The overlapping peaks of vitamin D, its epimers, and its isobar (7αC4) were resolved using chromatographic separation. There were significant differences in the concentrations of all metabolites of vitamin D between the DDD and SDL mice. Between the groups SDD (control) and SDL, a significant difference in the concentrations of 3-epi-25OHD was noted, where C3 epimer was about 30% higher in SDL group while no significant differences were noted in the concentrations of vitamin D, 25OHD, 1α25(OH)2D, and 7αC4 between SDD and SDL group. CONCLUSIONS: A validated method, combined with a simple extraction technique, for the sensitive LC-MS/MS determination of vitamin D metabolites is described here. The method can eliminate the interferences in LC-MS/MS analysis caused by the overlapping epimer and isobar due to them having the same molecular weights as 25OHD. The validated method was applied to mouse serum samples. It was concluded that a standard-vitamin D diet causes an increase in the proportion of all the vitamin D metabolites and C3 epimers and isobar, while UV light has no pronounced effect on the concentrations of the majority of the vitamin D metabolites except 3-epi-25OHD. Further studies are required to confirm this observation in humans and to investigate the biochemical pathways related to vitamin D's metabolites and their epimers.


Assuntos
Cromatografia Líquida/métodos , Suplementos Nutricionais/análise , Espectrometria de Massas em Tandem/métodos , Vitamina D/sangue , Vitamina D/metabolismo , Animais , Dieta , Camundongos , Camundongos Endogâmicos C57BL , Raios Ultravioleta , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/metabolismo
2.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34576172

RESUMO

Global data correlate severe vitamin D deficiency with COVID-19-associated coagulopathy, further suggesting the presence of a hypercoagulable state in severe COVID-19 patients, which could promote thrombosis in the lungs and in other organs. The feedback loop between COVID-19-associated coagulopathy and vitamin D also involves platelets (PLTs), since vitamin D deficiency stimulates PLT activation and aggregation and increases fibrinolysis and thrombosis. Vitamin D and PLTs share and play specific roles not only in coagulation and thrombosis but also during inflammation, endothelial dysfunction, and immune response. Additionally, another 'fil rouge' between vitamin D and PLTs is represented by their role in mineral metabolism and bone health, since vitamin D deficiency, low PLT count, and altered PLT-related parameters are linked to abnormal bone remodeling in certain pathological conditions, such as osteoporosis (OP). Hence, it is possible to speculate that severe COVID-19 patients are characterized by the presence of several predisposing factors to bone fragility and OP that may be monitored to avoid potential complications. Here, we hypothesize different pervasive actions of vitamin D and PLT association in COVID-19, also allowing for potential preliminary information on bone health status during COVID-19 infection.


Assuntos
Plaquetas/imunologia , COVID-19/complicações , Osteoporose/imunologia , Trombose/imunologia , Deficiência de Vitamina D/imunologia , Vitamina D/metabolismo , Plaquetas/metabolismo , Remodelação Óssea/imunologia , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Retroalimentação Fisiológica , Humanos , Osteoporose/sangue , Ativação Plaquetária/imunologia , Contagem de Plaquetas , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Trombose/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações
3.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360529

RESUMO

Nowadays, type II diabetes mellitus, more specifically ensuing diabetic nephropathy, and severe COVID-19 disease are known to be closely associated. The exact mechanisms behind this association are less known. An implication for the angiotensin-converting enzyme 2 remains controversial. Some researchers have started looking into other potential actors, such as neuropilin-1, mitochondrial glutathione, vitamin D, and DPP4. In particular, neuropilin-1 seems to play an important role in the underlying mechanism linking COVID-19 and diabetic nephropathy. We suggest, based on the findings in this review, that its up-regulation in the diabetic kidney facilitates viral entry in this tissue, and that the engagement of both processes leads to a depletion of neuropilin-1, which was demonstrated to be strongly associated with the pathogenesis of DN. More studies are needed to confirm this hypothesis, and research should be directed towards elucidating the potential roles of all these suggested actors and eventually discovering new therapeutic strategies that could reduce the burden of COVID-19 in patients with diabetic nephropathy.


Assuntos
COVID-19/complicações , COVID-19/imunologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Dipeptidil Peptidase 4/metabolismo , Glutationa/metabolismo , Humanos , Neuropilina-1/metabolismo , Vírus da SARS/imunologia , Vitamina D/metabolismo
4.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445530

RESUMO

Inflammation is a major contributor to the development and progression of atherosclerosis. Interleukin (IL)-33 and IL-37, members of the IL-1 family, modulate inflammation, with IL-33 having a pro-inflammatory effect and IL-37 having anti-inflammatory properties. IL-37 is constitutively expressed at low levels but upregulated in inflammatory contexts. The aim of this study was to evaluate the effect of vitamin D on the expression of IL-33, IL-37, macrophages, and caspase-1 in the neointimal tissue of coronary artery in Yucatan microswine with vitamin D deficient, sufficient, and supplemented status. The intimal injury was induced by balloon angioplasty and stenting in the coronary artery, and tissues were harvested after 6 months. The expression of various proteins of interest was evaluated by immunostaining. Increased expression of IL-33 and IL-37 in the neointimal tissue of the vitamin D deficient, as compared to the sufficient and supplemented microswine, as revealed by histological evaluation and semi-quantitative analysis, suggested the immunomodulatory effect of vitamin D on the expression of IL-33 and IL-37. The minimal expression or absence of IL-33 and IL-37 expression in stented arteries is suggestive of an attenuated inflammatory response in stented arteries, compared to balloon angioplasty. The decreased IL-33 expression in the sufficient and supplemented microswine could be a potential mechanism for controlling the inflammatory process and neointima formation leading to attenuated luminal narrowing of the coronary artery. Overall, these results support supplementation of vitamin D to attenuate inflammation, neointima formation, and restenosis.


Assuntos
Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/imunologia , Hiperlipidemias/fisiopatologia , Interleucina-1/metabolismo , Interleucina-33/metabolismo , Neointima/imunologia , Stents , Vitamina D/metabolismo , Animais , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Suplementos Nutricionais , Imunomodulação , Neointima/patologia , Neointima/terapia , Suínos
5.
Anticancer Res ; 41(7): 3683-3688, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230167

RESUMO

BACKGROUND/AIM: There are no clinically significant cutoff values of serum vitamin D levels and time points to predict the prognosis of colon cancer, particularly in patients who underwent curative surgical resection. PATIENTS AND METHODS: We retrospectively analyzed serum vitamin D levels in 795 patients with stages I to III colon cancer who underwent curative surgical resection. RESULTS: Patients with vitamin D levels below 12 ng/ml at one year after surgical resection demonstrated a significantly reduced disease-free survival (DFS) than those who did not have vitamin D deficiency (p=0.01). In the multivariate analysis, an age of 70 years or older [hazard ratio (HR)=1.992; p=0.001], pathologic stage (HR=3.739; p<0.001), and vitamin D deficiency (less than 12 ng/ml) at one year after surgery (HR=0.563; p=0.020) were factors unfavorably influencing DFS. CONCLUSION: In patients with stages I to III of colon cancer, vitamin D deficiency at one year after surgical resection was associated with increased disease relapse.


Assuntos
Neoplasias do Colo/patologia , Recidiva Local de Neoplasia/patologia , Deficiência de Vitamina D/patologia , Vitamina D/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias/métodos , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Deficiência de Vitamina D/metabolismo , Adulto Jovem
6.
J Steroid Biochem Mol Biol ; 212: 105949, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242778

RESUMO

BACKGROUND: Vitamin D deficiency (VDD) has been associated with adverse maternal and foetal outcomes and is determined by measuring 25 hydroxyvitamin D (25(OH)D). The 25(OH)D is catabolized to 24, 25-(OH) 2D and the ratio of 25(OH) D to 24, 25-(OH)2D, the vitamin D metabolite ratio (VMR), is thought to be a superior marker of VDD, being elevated in such states. The aims of this study were to assess the longitudinal vitamin D status of pregnant women by measuring cholecalciferol, 25(OH)D, 24, 25-(OH)2D and VMR at two time points and also to determine any association of vitamin D and metabolites with gestational age at birth, birth length and weight. METHODS: We recruited 400 pregnant black African women in their first trimester (V1) and measured weights and heights. Ultrasound scans were performed for gestational age. Blood was drawn at V1 and at about 26 weeks (V2) of gestation for cholecalciferol, 25(OH)D, 24, 25-(OH)2D, VMR and parathyroid hormone (PTH). An OGTT was performed at V2 where fasting glucose, insulin and 30-minute glucose were measured. At birth, we measured birth weight, length and gestational age. Maternal insulin, PTH and vitamin D binding protein (VDBP) were measured by immunoassay. Maternal albumin was measured colorimetrically. Maternal cholecalciferol, 25(OH)D and 24, 25-(OH)2D, were measured by mass spectrometry and free and bioavailable vitamin D were calculated. Initial gestation was determined by ultrasound. We compared analytes by visit as well as by 25(OH)D status. Vitamin D deficiency (<30 nmol/L) was defined according to the National Academy of Medicine guidelines. Linear regression analysis was used to determine associations of vitamin D molecules with maternal blood pressure, fasting and 30-minute insulin and blood glucose and neonatal parameters. RESULTS: Results are presented for participants for whom we had complete data (n = 330-346 depending on variable). The prevalence of vitamin D deficiency (VDD) was 35.8 % at V1 and 32.4 % at V2. Levels of 25(OH)D did not change significantly between visits. Levels of 24, 25(OH)2D dropped from the first to the second visit (17.64 ± 12.64 to 9.39 ± 9.07 nmol/L; p < 0.0001) while VMR increased ((3.15 (1.31; 7.67) to 7.90 (2.44; 25.98); p < 0.0001). The proportion of women with the lowest cholecalciferol concentrations increased at V2 compared to the V1 (36.1-42.8 %; p = 0.02). In multivariable regression models 25(OH)D was negatively associated with 30-minute glucose concentrations (p = 0.038) whilst 24, 25-(OH)2D was positively associated with fasting insulin (p = 0.017) and HOM A-I R (p = 0.023). There was no correlation of 25(OH)D or metabolites with infant birth weight, birth length or gestational age. CONCLUSIONS: Maternal VDD is common in pregnant black South African women. Decreased VMR suggest that catabolism of 25(OH)D is reduced in pregnancy to maintain adequate free vitamin D levels.


Assuntos
Gravidez/metabolismo , Deficiência de Vitamina D/metabolismo , Vitamina D/metabolismo , Vitaminas/metabolismo , Adulto , Grupo com Ancestrais do Continente Africano , Tamanho Corporal , Feminino , Idade Gestacional , Humanos , Gravidez/sangue , África do Sul/epidemiologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitaminas/sangue , Adulto Jovem
7.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208589

RESUMO

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor ß (TGFß), insulin-like growth factor (IGF) and Wnt-ß-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Neoplasias/etiologia , Deficiência de Vitamina D/complicações , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Biomarcadores , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Redes e Vias Metabólicas , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Neoplasias/terapia , Prognóstico , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo , Vitamina D/farmacologia , Deficiência de Vitamina D/metabolismo
8.
J Steroid Biochem Mol Biol ; 213: 105957, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34329737

RESUMO

This review examines the beneficial effects of ultraviolet radiation on systemic autoimmune diseases, including multiple sclerosis and type I diabetes, where the epidemiological evidence for the vitamin D-independent effects of sunlight is most apparent. Ultraviolet radiation, in addition to its role in the synthesis of vitamin D, stimulates anti-inflammatory pathways, alters the composition of dendritic cells, T cells, and T regulatory cells, and induces nitric oxide synthase and heme oxygenase metabolic pathways, which may directly or indirectly mitigate disease progression and susceptibility. Recent work has also explored how the immune-modulating functions of ultraviolet radiation affect type II diabetes, cancer, and the current global pandemic caused by SARS-CoV-2. These diseases are particularly important amidst global changes in lifestyle that result in unhealthy eating, increased sedentary habits, and alcohol and tobacco consumption. Compelling epidemiological data shows increased ultraviolet radiation associated with reduced rates of certain cancers, such as colorectal cancer, breast cancer, non-Hodgkins lymphoma, and ultraviolet radiation exposure correlated with susceptibility and mortality rates of COVID-19. Therefore, understanding the effects of ultraviolet radiation on both vitamin D-dependent and -independent pathways is necessary to understand how they influence the course of many human diseases.


Assuntos
COVID-19/prevenção & controle , Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Esclerose Múltipla/prevenção & controle , Neoplasias/prevenção & controle , Luz Solar , Vitamina D/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Células Dendríticas/imunologia , Células Dendríticas/efeitos da radiação , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Progressão da Doença , Suscetibilidade a Doenças , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/imunologia , Humanos , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Neoplasias/imunologia , Neoplasias/patologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/imunologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/efeitos da radiação , Comportamento Sedentário , Linfócitos T/imunologia , Linfócitos T/efeitos da radiação , Vitamina D/imunologia
9.
Ann Agric Environ Med ; 28(2): 326-330, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34184518

RESUMO

INTRODUCTION: Estrogen deficiency found in postmenopausal women may lead to disturbances in the balance of bone metabolism. Study of the influence of estradiol on markers of bone turnover may help to understand the mechanisms of bone metabolism and to monitor osteoporosis therapy in postmenopausal women at high risk of fractures. The aim of the study was evaluation of the effect of estradiol on the basic markers of bone turnover in postmenopausal women. MATERIAL AND METHODS: The study was conducted in a group of 92 postmenopausal women, divided into two groups: Gr-1 with low estradiol levels ≤ 10 pg/ml and Gr-2 with reference estradiol levels ≥ 25 pg/ml). Basic markers of bone turnover were examined: Ctx (C-terminal cross-linked telopeptide of type I collagen alpha chain) and OC (osteocalcin); pro-resorptive cytokines: IL-6 and TNF-α; vitamin 25(OH)D3 and lipid profile. Women was also analyzed according to demographic and clinical data. RESULTS: A positive relationship was found between estradiol and the main bone formation marker - OC (p = 0.041, r = 0.213) and IL-6, TNF-α (p = 0.007, r = 0.281 and p = 0.018, r = 0.246, respectivly, but only in the group with a reference hormone level. Moreover, the main markers of bone turnover: Ctx and OC showed a mutual positive correlation (p = 0.013; r = 0.257) in women with reference estradiol levels. Relationships between markers of bone remodeling, pro-resorptive cytokines and vitamin D3 depending on the level of estradiol showed no statistically significant correlation. CONCLUSIONS: The study showed that only in women with the reference estradiol level (≥ 25 pg/ml) were the bone formation and resorption processes balanced.


Assuntos
Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Feminino , Humanos , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Osteocalcina/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/fisiopatologia , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo , Vitamina D/metabolismo
10.
Inflammopharmacology ; 29(4): 1017-1031, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34185200

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-COV-2) is the culprit of the Coronavirus Disease (COVID-19), which has infected approximately 173 million people and killed more than 3.73 million. At risk groups including diabetic and obese patients are more vulnerable to COVID-19-related complications and poor outcomes. Substantial evidence points to hypovitaminosis D as a risk factor for severe disease, the need for ICU, and mortality. 1,25(OH)D, a key regulator of calcium homeostasis, is believed to have various immune-regulatory roles including; promoting anti-inflammatory cytokines, down regulating pro-inflammatory cytokines, dampening entry and replication of SARS-COV-2, and the production of antimicrobial peptides. In addition, there are strong connections which suggest that dysregulated 1,25(OH)D levels play a mechanistic and pathophysiologic role in several disease processes that are shared with COVID-19 including: diabetes, obesity, acute respiratory distress syndrome (ARDS), cytokine storm, and even hypercoagulable states. With evidence continuing to grow for the case that low vitamin D status is a risk factor for COVID-19 disease and poor outcomes, there is a need now to address the public health efforts set in place to minimize infection, such as lock down orders, which may have inadvertently increased hypovitaminosis D in the general population and those already at risk (elderly, obese, and disabled). Moreover, there is a need to address the implications of this evidence and how we may apply the use of cheaply available supplementation, which has yet to overcome the near global concern of hypovitaminosis D. In our review, we exhaustively scope these shared pathophysiologic connections between COVID-19 and hypovitaminosis D.


Assuntos
COVID-19/metabolismo , Síndrome da Liberação de Citocina/metabolismo , Trombofilia/metabolismo , Deficiência de Vitamina D/metabolismo , Vitamina D/administração & dosagem , Vitamina D/metabolismo , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/fisiopatologia , Humanos , Obesidade/epidemiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Fatores de Risco , Trombofilia/tratamento farmacológico , Trombofilia/fisiopatologia , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/fisiopatologia
11.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063169

RESUMO

Polycystic ovarian syndrome (PCOS) is the most prevalent endocrinopathy of reproductive years. Salient features in presentation of patients PCOS include menstrual dysfunction, hyperandrogenism and/or polycystic appearance of ovaries on ultrasound. While the diagnosis of PCOS depends on presence of specified criteria, misdiagnoses are common. Despite years of extensive research, the exact aetiology of PCOS remains largely unknown. In the past decade, apart from insulin resistance and hyperandrogenemia, anti-mullerian hormone (AMH), an important marker of ovarian reserve, and vascular endothelial growth factor (VEGF), a crucial factor in angiogenesis, have been examined as plausible players of causative relevance for PCOS. Vitamin D, a sex-steroid hormone that is universally known for its relevance for skeletal health, has received increasing attention due to growing evidence supporting its pivotal in reproductive physiology and in PCOS. In this review we summarize our current understanding of the mechanisms relevant to the pathophysiology of PCOS and examine the role of vitamin D signalling in this context.


Assuntos
Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Vitamina D/metabolismo , Hormônio Antimülleriano/metabolismo , Feminino , Humanos , Modelos Biológicos , Síndrome do Ovário Policístico/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Calcitriol/metabolismo
12.
J Cell Mol Med ; 25(16): 7825-7839, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34159729

RESUMO

The new coronavirus pandemic started in China in 2019. The intensity of the disease can range from mild to severe, leading to death in many cases. Despite extensive research in this area, the exact molecular nature of virus is not fully recognized; however, according to pieces of evidence, one of the mechanisms of virus pathogenesis is through the function of viral miRNAs. So, we hypothesized that SARS-CoV-2 pathogenesis may be due to targeting important genes in the host with its miRNAs, which involved in the respiratory system, immune pathways and vitamin D pathways, thus possibly contributing to disease progression and virus survival. Potential miRNA precursors and mature miRNA were predicted and confirmed based on the virus genome. The next step was to predict and identify their target genes and perform functional enrichment analysis to recognize the biological processes connected with these genes in the three pathways mentioned above through several comprehensive databases. Finally, cis-acting regulatory elements in 5' regulatory regions were analysed, and the analysis of available RNAseq data determined the expression level of genes. We revealed that thirty-nine mature miRNAs could theoretically derive from the SARS-CoV-2 genome. Functional enrichment analysis elucidated three highlighted pathways involved in SARS-CoV-2 pathogenesis: vitamin D, immune system and respiratory system. Our finding highlighted genes' involvement in three crucial molecular pathways and may help develop new therapeutic targets related to SARS-CoV-2.


Assuntos
COVID-19/imunologia , Interações Hospedeiro-Patógeno/fisiologia , MicroRNAs , SARS-CoV-2/genética , Vitamina D/metabolismo , COVID-19/genética , COVID-19/virologia , Regulação da Expressão Gênica , Humanos , Sistema Imunitário/virologia , Anotação de Sequência Molecular , Regiões Promotoras Genéticas , RNA Viral , Sistema Respiratório/virologia , SARS-CoV-2/patogenicidade
13.
Am J Physiol Gastrointest Liver Physiol ; 321(2): G171-G184, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34159811

RESUMO

Vitamin D deficiency is an environmental factor involved in the pathogenesis of inflammatory bowel disease (IBD); however, the mechanisms surrounding its role remain unclear. Previous studies conducted in an intestinal epithelial-specific vitamin D receptor (VDR) knockout model suggest that a lack of vitamin D signaling causes a reduction in intestinal autophagy. A potential link between vitamin D deficiency and dysregulated autophagy is microRNA (miR)-142-3p, which suppresses autophagy. In this study, we found that wild-type C57BL/6 mice fed a vitamin D-deficient diet for 5 wk had increased miR-142-3p expression in ileal tissues compared with mice that were fed a matched control diet. Interestingly, there was no difference in expression of key autophagy markers ATG16L1 and LC3II in the ileum whole tissue. However, Paneth cells of vitamin D-deficient mice were morphologically abnormal and had an accumulation of the autophagy adaptor protein p62, which was not present in the total crypt epithelium. These findings suggest that Paneth cells exhibit early markers of autophagy dysregulation within the intestinal epithelium in response to vitamin D deficiency and enhanced miR-142-3p expression. Finally, we demonstrated that treatment-naïve IBD patients with low levels of vitamin D have an increase in miR-142-3p expression in colonic tissues procured from "involved" areas of the disease. Taken together, our findings demonstrate that insufficient vitamin D levels alter expression of autophagy-regulating miR-142-3p in intestinal tissues of mice and patients with IBD, providing insight into the mechanisms by which vitamin D deficiency modulates IBD pathogenesis.NEW & NOTEWORTHY Vitamin D deficiency has a role in IBD pathogenesis, and although the mechanisms surrounding its role remain unclear, it has been suggested that autophagy dysregulation is involved. Here, we show increased ileal expression of autophagy-suppressing miR-142-3p in mice that were fed a vitamin D-deficient diet and in "involved" colonic biopsies from pediatric IBD patients with low vitamin D. miR-142-3p serves as a potential mechanism mediating vitamin D deficiency and reduced autophagy.


Assuntos
Íleo/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , MicroRNAs/genética , Deficiência de Vitamina D/metabolismo , Vitamina D/metabolismo , Adolescente , Animais , Autofagia , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Células Cultivadas , Criança , Células HCT116 , Células HeLa , Humanos , Íleo/patologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Celulas de Paneth/metabolismo , Celulas de Paneth/patologia , Deficiência de Vitamina D/complicações
14.
Eur Rev Med Pharmacol Sci ; 25(10): 3923-3932, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34109607

RESUMO

Angiotensin converting enzyme 2 (ACE2) has potentially conflicting roles in health and disease. COVID-19 coronavirus binds to human cells via ACE2 receptor, which is expressed on almost all body organs. Boosting the ACE2 receptor levels on heart and lung cells may provide more cellular enter to virus thereby worsening the infection. Therefore, among the drug targets, ACE2 is suggested as a vital target of COVID-19 therapy. This hypothesis is based on the protective role of the drugs acting on ACE2. Therefore, this review discusses the impact and challenges of using ACE2 as a target in the current therapy of COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Antivirais/química , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/química , Alanina/metabolismo , Alanina/uso terapêutico , Enzima de Conversão de Angiotensina 2/metabolismo , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/metabolismo , Antivirais/uso terapêutico , Azitromicina/química , Azitromicina/metabolismo , Azitromicina/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Humanos , Hidroxicloroquina/química , Hidroxicloroquina/metabolismo , Hidroxicloroquina/uso terapêutico , SARS-CoV-2/isolamento & purificação , Vitamina D/química , Vitamina D/metabolismo , Vitamina D/uso terapêutico
15.
Int J Mol Sci ; 22(10)2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34065735

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still an ongoing global health crisis. Immediately after the inhalation of SARS-CoV-2 viral particles, alveolar type II epithelial cells harbor and initiate local innate immunity. These particles can infect circulating macrophages, which then present the coronavirus antigens to T cells. Subsequently, the activation and differentiation of various types of T cells, as well as uncontrollable cytokine release (also known as cytokine storms), result in tissue destruction and amplification of the immune response. Vitamin D enhances the innate immunity required for combating COVID-19 by activating toll-like receptor 2. It also enhances antimicrobial peptide synthesis, such as through the promotion of the expression and secretion of cathelicidin and ß-defensin; promotes autophagy through autophagosome formation; and increases the synthesis of lysosomal degradation enzymes within macrophages. Regarding adaptive immunity, vitamin D enhances CD4+ T cells, suppresses T helper 17 cells, and promotes the production of virus-specific antibodies by activating T cell-dependent B cells. Moreover, vitamin D attenuates the release of pro-inflammatory cytokines by CD4+ T cells through nuclear factor κB signaling, thereby inhibiting the development of a cytokine storm. SARS-CoV-2 enters cells after its spike proteins are bound to angiotensin-converting enzyme 2 (ACE2) receptors. Vitamin D increases the bioavailability and expression of ACE2, which may be responsible for trapping and inactivating the virus. Activation of the renin-angiotensin-aldosterone system (RAS) is responsible for tissue destruction, inflammation, and organ failure related to SARS-CoV-2. Vitamin D inhibits renin expression and serves as a negative RAS regulator. In conclusion, vitamin D defends the body against SARS-CoV-2 through a novel complex mechanism that operates through interactions between the activation of both innate and adaptive immunity, ACE2 expression, and inhibition of the RAS system. Multiple observation studies have shown that serum concentrations of 25 hydroxyvitamin D are inversely correlated with the incidence or severity of COVID-19. The evidence gathered thus far, generally meets Hill's causality criteria in a biological system, although experimental verification is not sufficient. We speculated that adequate vitamin D supplementation may be essential for mitigating the progression and severity of COVID-19. Future studies are warranted to determine the dosage and effectiveness of vitamin D supplementation among different populations of individuals with COVID-19.


Assuntos
Imunidade Adaptativa , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/imunologia , Imunidade Inata , SARS-CoV-2/imunologia , Vitamina D/metabolismo , Vitamina D/farmacologia , COVID-19/mortalidade , COVID-19/fisiopatologia , COVID-19/virologia , Síndrome da Liberação de Citocina/complicações , Citocinas/metabolismo , Humanos , Receptores Virais/metabolismo , Sistema Renina-Angiotensina/fisiologia
16.
Gene ; 791: 145691, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33961971

RESUMO

AIMS: The study aimed to examine genetic polymorphism of vitamin D-related genes and association between those genes and vitamin D and cytokines levels in children with type 1 diabetes (T1D). MATERIALS AND METHODS: This study was conducted among 100 T1D children and 100 controls at Division of Endocrinology and Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, during 2016 to 2018. Vitamin D metabolite levels were measured by liquid chromatography-tandem mass spectrometry method, serum cytokine levels of IFN- É£, IL-10, IL-13, IL-17α, IL-2, IL-4, IL-6, and TNF-α by immunoassay, and genetic variations at VDR, CYP2R1, CYP27B1, GC, DHCR7, and CYP24A1 by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: A relationship between studied single nucleotide polymorphisms and T1D was found in CYP2R1 (rs10741657) (GA, OR: 1.83, 95% CI: 1.01-3.31; p = 0.04). VDR haplotypes were also remarkably different between T1D patients and controls. Controls had higher frequency of haplotype TACT than T1D patients (p = 0.02). Vitamin D and all cytokine levels, except for IL-17α, were significantly increased in T1D compared to controls. The polymorphism of DHCR7 (rs12785878) was positively associated with 25OHD3 and 3epi25OHD3 levels and was negatively associated with 25OHD2 level. On the other hand, polymorphism of CYP27B1 (rs4646536) was negatively associated with 3epi25OHD3 level. Polymorphisms of CYP27B1 (rs4646536) and GC (rs2282679) were positively associated with TNF-α levels. VDR variation of rs1544410, rs731236, and rs7975232 also showed negative association with IL-10 levels. In contrast, the level of IL-10 was positively associated with DHCR7 (rs12785878). CONCLUSION: Relationships between T1D and CYP2R1 polymorphism and VDR haplotype were found. Vitamin D gene-related variations were associated with vitamin D and circulating cytokine levels in children with T1D.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Receptores de Calcitriol/genética , Vitamina D/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Adolescente , Criança , Colestanotriol 26-Mono-Oxigenase/metabolismo , Família 2 do Citocromo P450/metabolismo , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/metabolismo , Vitamina D/sangue , Vitamina D/metabolismo , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/metabolismo , Adulto Jovem
17.
Am Heart J ; 239: 147-153, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34051171

RESUMO

The role of vitamin D in the cardiovascular system is complex because it regulates expression of genes involved in diverse metabolic processes. Although referred to as a vitamin, it is more accurately considered a steroid hormone, because it is produced endogenously in the presence of ultraviolet light. It occurs as a series of sequentially activated forms, here referred to as vitamin D-hormones. A little-known phenomenon, based on pre-clinical data, is that its biodistribution and potential effects on vascular disease likely depend on whether it is derived from diet or sunlight. Diet-derived vitamin D-hormones are carried in the blood, at least in part, in chylomicrons and lipoprotein particles, including low-density lipoprotein. Since low-density lipoprotein is known to accumulate in the artery wall and atherosclerotic plaque, diet-derived vitamin D-hormones may also collect there, and possibly promote the osteochondrogenic mineralization associated with plaque. Also, little known is the fact that the body stores vitamin D-hormones in adipose tissue with a half-life on the order of months, raising doubts about whether the use of the term "daily requirement" is appropriate. Cardiovascular effects of vitamin D-hormones are controversial, and risk appears to increase with both low and high blood levels. Since low serum vitamin D-hormone concentration is reportedly associated with increased cardiovascular and orthopedic risk, oral supplementation is widely used, often together with calcium supplements. However, meta-analyses show that oral vitamin D-hormone supplementation does not protect against cardiovascular events, findings that are also supported by a randomized controlled trial. These considerations suggest that prevalent recommendations for vitamin D-hormone supplementation for the purpose of cardiovascular protection should be carefully reconsidered.


Assuntos
Sistema Cardiovascular/metabolismo , Vitamina D , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Humanos , Resultado do Tratamento , Vitamina D/sangue , Vitamina D/metabolismo , Vitamina D/farmacologia
18.
J Steroid Biochem Mol Biol ; 211: 105903, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33933575

RESUMO

We aimed to evaluate sex differences in changes of lipid profiles in a cohort of metabolically healthy adults following Orthodox fasting (OF), as well as to assess a potential role of vitamin D status in mediating these variations. 45 individuals (24 premenopausal females, 53.3 %) with mean age 48.3 ± 9.1 years and mean Body Mass Index 28.7 ± 5.8 kg/m2 were prospectively followed for 12 weeks. Anthropometry, dietary and biochemical data regarding serum lipids, and vitamin D status were collected at baseline, 7 weeks after the implementation of OF, and 5 weeks after fasters returned to their standard dietary habits (12 weeks from baseline). According to 25-hydroxy-vitamin D [25(OH)D] measurements, participants were divided into two groups: those with concentrations above and below the median of values. Females with 25(OH)D concentrations below the median manifested a non-significant reduction by approximately 15 % in total and low-density lipoprotein cholesterol during the fasting period, followed by a significant increase 5 weeks after OF cessation (170.7 vs. 197.5 and 99.6 vs. 121.0 mg/dl respectively, p < 0.001). In contrast, males with 25(OH)D levels below the median demonstrated an inverse, non-significant trend of increase in lipid concentrations during the whole study period. Our findings suggest strikingly different inter-gender lipid responses to a dietary model of low-fat, mediated by vitamin D status. Further studies are necessary to reveal the underlying mechanisms and assess the importance of these differences with respect to cardiovascular health and the benefit of vitamin D supplementation strategies.


Assuntos
Índice de Massa Corporal , Suplementos Nutricionais , Jejum , Lipídeos/análise , Vitamina D/metabolismo , Vitaminas/metabolismo , Antropometria , Ortodoxia Oriental , Comportamento Alimentar , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais
19.
Braz J Med Biol Res ; 54(8): e11073, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34037098

RESUMO

The study evaluated the effect of the supernatant of placental explants from preeclamptic (PE) and normotensive (NT) pregnant women after tissue treatment with or without vitamin D (VD) on oxidative stress and nitric oxide (NO) bioavailability in human umbilical vein endothelial cells (HUVEC). Placental explants were prepared from eight NT and eight PE women, and supernatants were obtained after incubation with or without hydrogen peroxide (H2O2) and/or VD. HUVEC were cultured for 24 h with supernatants, and the following parameters were analyzed in HUVEC cultures: NO, nitrate (NO3-), and nitrite (NO2-) levels, lipid peroxidation, and intracellular reactive oxygen species (ROS). Results showed that the production of NO3-, NO2-, malondialdehyde (MDA), and ROS were significantly higher in HUVEC treated with explant supernatant from PE compared to NT pregnant women, while the supernatant of PE explants treated with VD led to a decrease in these parameters. A significantly high production of NO was detected in HUVEC cultured with control supernatant of NT group, and in cultures treated with supernatant of PE explants treated with VD. Taken together, these results demonstrated that cultures of placental explants from PE women with VD treatment generated a supernatant that decreased oxidative stress and increased the bioavailability of NO in endothelial cells.


Assuntos
Óxido Nítrico , Pré-Eclâmpsia , Disponibilidade Biológica , Células Cultivadas , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio , Óxido Nítrico/metabolismo , Estresse Oxidativo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Vitamina D/metabolismo
20.
Curr Opin Nephrol Hypertens ; 30(4): 387-396, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33990506

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to summarize the emerging studies analyzing the association between vitamin D and risk of COVID-19 infection and severity, as well as the early interventional studies investigating the protective effect of vitamin D supplementation against COVID-19. RECENT FINDINGS: Studies investigating the association between vitamin D levels and risk of COVID-19 infection and risk of severe disease and mortality among those infected have yielded mixed results. Thus far, the majority of studies investigating the association between vitamin D and COVID-19 have been observational and rely on vitamin D levels obtained at the time of admission, limiting causal inference. Currently, clinical trials assessing the effects of vitamin D supplementation in individuals with COVID-19 infection are extremely limited. Randomized, interventional trials may offer more clarity on the protective effects of vitamin D against COVID-19 infection and outcomes. SUMMARY: Decreased levels of vitamin D may amplify the inflammatory effects of COVID-19 infection, yet, data regarding the mortality benefits of vitamin D supplementation in COVID-19-infected individuals are still limited. Current observational data provides the impetus for future studies to including randomized controlled trials to determine whether vitamin D supplementation in COVID-19-infected individuals with kidney disease can improve mortality outcomes.


Assuntos
COVID-19/fisiopatologia , COVID-19/terapia , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/terapia , Vitamina D/metabolismo , Vitamina D/uso terapêutico , COVID-19/complicações , Suplementos Nutricionais , Humanos , Rim/fisiopatologia , Deficiência de Vitamina D/fisiopatologia , Vitaminas/farmacologia , Vitaminas/uso terapêutico
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