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1.
J Frailty Aging ; 10(1): 2-9, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33331615

RESUMO

Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Evidences from various organisms suggests that several factors influence telomere length regulation, such as telomere binding proteins, telomere capping proteins, telomerase, and DNA replication enzymes. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. In this study, our main goal is investigating the relationship between telomerase enzyme and vitamin D. Findings of this study suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases. Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. Significant Low levels of telomerase activity create short telomeres, which in turn signal exit from the cell cycle resulting in cell senescence and apoptosis. In follow-up examination, the patients who remained vitamin D deficient tended to have shorter telomeres than those patients whose 25-hydroxyvitamin D levels were depleted. Increasing 25-hydroxyvitamin D levels in patients with SLE may be beneficial in maintaining telomere length and preventing cellular aging. Moreover, anti-telomere antibody levels may be a promising biomarker of SLE status and disease activity.


Assuntos
Senescência Celular/fisiologia , Telômero/metabolismo , Vitamina D/sangue , Vitamina D/metabolismo , Envelhecimento/sangue , Envelhecimento/genética , Envelhecimento/metabolismo , Envelhecimento/patologia , Humanos , Telomerase/genética , Telomerase/metabolismo , Telômero/genética
2.
Cell Biol Int ; 45(1): 54-57, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32990980

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains access to host cells by attaching to angiotensin-converting enzyme 2 (ACE2). Vitamin D (VitD) can upregulate ACE2 and has an antagonistic effect on Renin, which exerts a vasodilatation and anti-inflammatory effect against coronavirus disease (COVID-19). However, it may also facilitate viral entry by increasing ACE2 as the main SARS-CoV-2 receptor and mediates ROS production through NADPH oxidase, as a double-edged sword effect. Lung function and the immune system are also influenced by VitD through several mechanisms, including increased natural antibiotics (Defensin and Cathelicidin) and upregulated transforming growth factor-ß. A higher IgA, Th2/Th1 ratio, and T-regulatory cells are attributable to VitD effects on the immune cells, while these changes may also be a double-edged sword in COVID-19. Although VitD supplementation might be highly recommended in COVID-19, the administration's dosage and route could be challenging. Furthermore, this issue has not been mentioned in various studies so far. So, the report aimed to explain the current challenges with the application of VitD in COVID-19.


Assuntos
/metabolismo , Deficiência de Vitamina D/metabolismo , Vitamina D/administração & dosagem , Vitamina D/metabolismo , Animais , Humanos , Resultado do Tratamento , Deficiência de Vitamina D/tratamento farmacológico
3.
Curr Opin Clin Nutr Metab Care ; 24(1): 18-24, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32941186

RESUMO

PURPOSE OF REVIEW: Old age, obesity and vitamin D deficiency are considered as independent risk factors for severe courses of COVID-19. The aim of the review is to discuss common features of these risk factors and the impact of vitamin D. RECENT FINDINGS: The recently discovered relationship between vitamin D and the infection pathway of the virus via the renin--angiotensin system (RAS) and the adipokines leptin and adiponectin play an important role. The frequency of studies showing a relationship between a low vitamin D status in comorbidities and severe COVID-19 courses makes an impact of vitamin D effects likely. SUMMARY: There is a direct relationship between vitamin D, body fat and age in COVID-19 courses. With age, the ability of the skin to synthesize vitamin D decreases, and leads to vitamin D-deficits. If the skin is insufficiently exposed to sunlight, severe deficits can develop. As vitamin D plays an important role not only in the immune system but also in the RAS, and thus at the point where the virus attacks, a good vitamin D supply is an important basis for reducing the risk of severe COVID-19 processes. Treatment with vitamin D supplements should be based on severity of the vitamin D deficiency.


Assuntos
Envelhecimento , Estado Nutricional , Obesidade/epidemiologia , Índice de Gravidade de Doença , Deficiência de Vitamina D/complicações , Vitamina D , Tecido Adiposo , Idoso , /epidemiologia , Comorbidade , Suplementos Nutricionais , Humanos , Pandemias , Sistema Renina-Angiotensina , Fatores de Risco , Luz Solar , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia , Vitaminas/metabolismo , Vitaminas/uso terapêutico
4.
Cent Eur J Public Health ; 28(4): 306-312, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33338368

RESUMO

OBJECTIVE: The aim of the study was to determine the effects of age, gender and season on vitamin D status in healthy urban population at reproductive age. Also, we investigated the distribution of population into different groups regarding 25(OH)D levels. METHODS: Serum 25(OH)D levels of 21,317 participants: 5,364 men (25.1%) and 15,953 women (74.8%), aged between 18-45 years, applying to two medical centres for check-up located in the same city were retrospectively analyzed. Group I consisted of 14,720 participants (11,257 women and 3,463 men) in the first centre and Group II consisted of 6,597 participants (4,696 women and 1,901 men) in the second centre. RESULTS: The mean 25(OH)D levels did not differ between women and men in both groups: 23.4 (SD = 14.4) and 23.1 (SD = 12.6) in Group I, and 22.6 (SD = 15.9) and 23.1 (SD = 14.3) in Group II, respectively, (p > 0.05). Similar trends exhibiting lower mean 25(OH)D levels at younger ages and higher levels at later ages were observed in both groups; a seasonal variation of 25(OH)D levels was observed in both genders with the highest levels in August and September and the lowest levels from February through April; percentages of women with 25(OH)D level of < 5 ng/ml were significantly higher than of men in Group I (1.4% vs. 0.2%, respectively, p < 0.001) and in Group II (4.1% vs. 1.1%, respectively, p < 0.001). CONCLUSION: There is a slight increase in serum 25(OH)D levels from 18 through 45 years of age in healthy population. The seasonal variation of 25(OH)D levels is prominent in both genders with men having slightly lower levels in some months of winter and higher levels in summer as compared to women. The prevalence of women having 25(OH)D levels less than 5 ng/ml is higher than that of men.


Assuntos
Deficiência de Vitamina D , Adolescente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estações do Ano , População Urbana , Vitamina D/metabolismo , Deficiência de Vitamina D/epidemiologia , Adulto Jovem
5.
Med Hypotheses ; 144: 110296, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254487

RESUMO

The factors that may contribute to a COVID-19 patient remaining in the asymptomatic stage, or to the infection evolving into the more serious stages are examined. In particular, we refer to the TMPRSS2 expression profile, balance of androgen and estrogen, blood group-A and/or B, nonsynonymous mutations in ORF3, and proteins NS7b and NS8 in SARS-CoV-2. Also, we review other factors related to the susceptibility and pathogenicity of SARS-CoV-2.


Assuntos
Infecções Assintomáticas , Predisposição Genética para Doença , Serina Endopeptidases/genética , Alelos , Androgênios/metabolismo , /virologia , Exoma , Feminino , Perfilação da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , Modelos Teóricos , Mutação , Fases de Leitura Aberta , Polimorfismo de Nucleotídeo Único , Proteínas não Estruturais Virais/genética , Vitamina D/análogos & derivados , Vitamina D/metabolismo
6.
PLoS One ; 15(11): e0241976, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33211721

RESUMO

Conflicting data exists as to whether vitamin D receptor agonists (VDRa) are protective of arterial calcification. Confounding this, is the inherent physiological differences between human and animal experimental models and our current fragmented understanding of arterial vitamin D metabolism, their alterations in disease states and responses to VDRa's. Herein, the study aims to address these problems by leveraging frontiers in human arterial organ culture models. Human arteries were collected from a total of 24 patients (healthy controls, n = 12; end-stage CKD, n = 12). Cross-sectional and interventional studies were performed using arterial organ cultures treated with normal and calcifying (containing 5mmol/L CaCl2 and 5mmol/L ß-glycerophosphate) medium, ex vivo. To assess the role of VDRa therapy, arteries were treated with either calcitriol or paricalcitol. We found that human arteries express a functionally active vitamin D system, including the VDR, 1α-hydroxylase and 24-hydroxylase (24-OHase) components and these were dysregulated in CKD arteries. VDRa therapy increased VDR expression in healthy arteries (p<0.01) but not in CKD arteries. Arterial 1α-OHase (p<0.05) and 24-OHase mRNA and protein expression were modulated differentially in healthy and CKD arteries by VDRa therapy. VDRa exposure suppressed Runx2 and MMP-9 expression in CKD arteries, however only paricalcitol suppressed MMP-2. VDRa exposure did not modulate arterial calcification in all organ culture models. However, VDRa reduced expression of senescence associated ß-galactosidase (SAßG) staining in human aortic-smooth muscle cells under calcifying conditions, in vitro. In conclusion, maladaptation of arterial vitamin D signaling components occurs in CKD. VDRa exposure can exert vasculo-protective effects and seems critical for the regulation of arterial health in CKD.


Assuntos
Artérias/metabolismo , Transdução de Sinais/fisiologia , Calcificação Vascular/metabolismo , Vitamina D/metabolismo , Artérias/efeitos dos fármacos , Calcitriol/uso terapêutico , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Estudos Transversais , Ergocalciferóis/uso terapêutico , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Receptores de Calcitriol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Calcificação Vascular/tratamento farmacológico , Vitamina D3 24-Hidroxilase/metabolismo , beta-Galactosidase/metabolismo
8.
Free Radic Biol Med ; 161: 84-91, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33038530

RESUMO

There is a marked variation in mortality risk associated with COVID-19 infection in the general population. Low socioeconomic status and other social determinants have been discussed as possible causes for the higher burden in African American communities compared with white communities. Beyond the social determinants, the biochemical mechanism that predisposes individual subjects or communities to the development of excess and serious complications associated with COVID-19 infection is not clear. Virus infection triggers massive ROS production and oxidative damage. Glutathione (GSH) is essential and protects the body from the harmful effects of oxidative damage from excess reactive oxygen radicals. GSH is also required to maintain the VD-metabolism genes and circulating levels of 25-hydroxyvitamin D (25(OH)VD). Glucose-6-phosphate dehydrogenase (G6PD) is necessary to prevent the exhaustion and depletion of cellular GSH. X-linked genetic G6PD deficiency is common in the AA population and predominantly in males. Acquired deficiency of G6PD has been widely reported in subjects with conditions of obesity and diabetes. This suggests that individuals with G6PD deficiency are vulnerable to excess oxidative stress and at a higher risk for inadequacy or deficiency of 25(OH)VD, leaving the body unable to protect its 'oxidative immune-metabolic' physiological functions from the insults of COVID-19. An association between subclinical interstitial lung disease with 25(OH)VD deficiencies and GSH deficiencies has been previously reported. We hypothesize that the overproduction of ROS and excess oxidative damage is responsible for the impaired immunity, secretion of the cytokine storm, and onset of pulmonary dysfunction in response to the COVID-19 infection. The co-optimization of impaired glutathione redox status and excess 25(OH)VD deficiencies has the potential to reduce oxidative stress, boost immunity, and reduce the adverse clinical effects of COVID-19 infection in the AA population.


Assuntos
/patologia , Deficiência de Glucosefosfato Desidrogenase/genética , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Deficiência de Vitamina D/genética , Afro-Americanos/estatística & dados numéricos , Síndrome da Liberação de Citocina/patologia , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Glutationa/metabolismo , Humanos , Vitamina D/análogos & derivados , Vitamina D/metabolismo
9.
J Steroid Biochem Mol Biol ; 204: 105771, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33065275

RESUMO

Vitamin D may be a central biological determinant of COVID-19 outcomes. The objective of this quasi-experimental study was to determine whether bolus vitamin D3 supplementation taken during or just before COVID-19 was effective in improving survival among frail elderly nursing-home residents with COVID-19. Sixty-six residents with COVID-19 from a French nursing-home were included in this quasi-experimental study. The "Intervention group" was defined as those having received bolus vitamin D3 supplementation during COVID-19 or in the preceding month, and the "Comparator group" corresponded to all other participants. The primary and secondary outcomes were COVID-19 mortality and Ordinal Scale for Clinical Improvement (OSCI) score in acute phase, respectively. Age, gender, number of drugs daily taken, functional abilities, albuminemia, use of corticosteroids and/or hydroxychloroquine and/or antibiotics (i.e., azithromycin or rovamycin), and hospitalization for COVID-19 were used as potential confounders. The Intervention (n = 57; mean ± SD, 87.7 ± 9.3years; 79 %women) and Comparator (n = 9; mean, 87.4 ± 7.2years; 67 %women) groups were comparable at baseline, as were the COVID-19 severity and the use of dedicated COVID-19 drugs. The mean follow-up time was 36 ± 17 days. 82.5 % of participants in the Intervention group survived COVID-19, compared to only 44.4 % in the Comparator group (P = 0.023). The full-adjusted hazard ratio for mortality according to vitamin D3 supplementation was HR = 0.11 [95 %CI:0.03;0.48], P = 0.003. Kaplan-Meier distributions showed that Intervention group had longer survival time than Comparator group (log-rank P = 0.002). Finally, vitamin D3 supplementation was inversely associated with OSCI score for COVID-19 (ß=-3.84 [95 %CI:-6.07;-1.62], P = 0.001). In conclusion, bolus vitamin D3 supplementation during or just before COVID-19 was associated in frail elderly with less severe COVID-19 and better survival rate.


Assuntos
Colecalciferol/administração & dosagem , Infecções por Coronavirus/genética , Pneumonia Viral/genética , Vitamina D/genética , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Taxa de Sobrevida , Vitamina D/metabolismo
10.
J Fr Ophtalmol ; 43(10): 1009-1019, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33004198

RESUMO

PURPOSE: To clarify the association between serum vitamin D levels and its receptor polymorphisms with glaucoma risk. METHODS: A meta-analysis was performed from available studies investigating serum vitamin D levels and vitamin D receptor (VDR) polymorphisms in glaucoma patients and controls. RESULTS: Twelve studies in total, including 130,676 and 476 subjects, were analysed for the association between serum vitamin D levels and VDR polymorphisms with glaucoma, respectively. Collectively, it was found that glaucoma patients have lower levels of vitamin D compared to controls (SMD=-1.16, 95% CI=-1.56--0.76, P<0.00001). In parallel, the pooled results showed a significant association between glaucoma and allelic (b vs. B, OR=1.84, 95% CI=1.37-2.46, P=0.00001) and recessive (bb vs. Bb+BB, OR=3.16, 95% CI=1.30-7.66, P=0.001) models of VDR BsmI (rs1544410) polymorphism, but not with VDR TaqI (rs731236) or FokI (rs2228570) polymorphisms. CONCLUSION: This meta-analysis suggests that patients with glaucoma may have vitamin D deficiency. In addition, the vitamin D signalling cascade may be a contributing factor in developing glaucoma, which is supported by the evidence that b allele carriers of VDR BsmI exhibited an increase in the risk of glaucoma. Thus, dietary supplementation of vitamin D may become an important approach as an additional treatment for glaucoma.


Assuntos
Glaucoma/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Vitamina D/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Glaucoma/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/genética , Receptores de Calcitriol/metabolismo , Fatores de Risco , Vitamina D/metabolismo
11.
PLoS Med ; 17(10): e1003394, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33064751

RESUMO

BACKGROUND: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. METHODS AND FINDINGS: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. CONCLUSIONS: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Vitamina D/análogos & derivados , Adulto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Suplementos Nutricionais , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Vitamina D/análise , Vitamina D/sangue , Vitamina D/metabolismo
12.
J Steroid Biochem Mol Biol ; 204: 105754, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32946925

RESUMO

OBJECTIVES AND METHODS: A total of 41 GDM and 40 normal glucose tolerance subjects were recruited. Through detecting the level of Serum vitamin D with electrochemical luminescence and vitamin D receptor (VDR) with Enzyme-linked immunosorbent assay (ELISA) in maternal and cord blood, the expression leves of CYP24A1, CYP27B1, VDR protein and mRNA in placenta and umbilical cord with western blotting and RT-PCR, and the DNA methylation levels of CYP24A1 and CYP27B1 gene in placenta with methylation-specific PCR (MSP) and direct bisulfite sequencing (BSP) analysis to explore the potential role of the vitamin D and its related genes in gestational diabetes mellitus (GDM). RESULTS: Serum vitamin D concentrations were significantly higher in normal pregnant than women with GDM in maternal blood (P < 0.01) and cord blood (P = 0.014). Compared to the control group, the expression levels of CYP24A1 protein (P < 0.01) and mRNA (P = 0.021) and VDR protein (P = 0.026) and mRNA (P = 0.023) in the GDM group were significantly higher in placenta and umbilical cord tissues (P = 0.015, P < 0.01, P = 0.028, P < 0.01, respectively), while that of CYP27B1 protein (P < 0.01) and mRNA (P = 0.042) was significantly lower (P = 0.022, P = 0.032, respectively). Moreover, partial DNA methylation of CYP24A1 and CYP27B1 genes was observed in both GDM and control groups. CONCLUSIONS: Vitamin D deficiency participates in the pathogenesis of GDM, and changes in the expression of genes related to the vitamin D metabolic pathway are closely related to vitamin D levels in the pregnancy and fetus. However, DNA methylation of CYP24A1 and CYP27B1 might not be involved in the pathogenesis of GDM.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase , Diabetes Gestacional , Placenta/metabolismo , Receptores de Calcitriol , Vitamina D3 24-Hidroxilase , Vitamina D/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Adulto , Metilação de DNA , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Feminino , Sangue Fetal/metabolismo , Expressão Gênica , Humanos , Gravidez , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Vitamina D/sangue , Vitamina D3 24-Hidroxilase/genética , Vitamina D3 24-Hidroxilase/metabolismo
13.
PLoS Pathog ; 16(9): e1008874, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32946517

RESUMO

Coronavirus Disease 2019 (COVID-19) pandemic remains a major public health threat in most countries. The causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can lead to acute respiratory distress syndrome and result in mortality in COVID-19 patients. Vitamin D is an immunomodulator hormone with established effectiveness against various upper respiratory infections. Vitamin D can stall hyper-inflammatory responses and expedite healing process of the affected areas, primarily in the lung tissue. Thus, there are ecological and mechanistic reasons to promote exploration of vitamin D action in COVID-19 patients. As no curative drugs are available currently for COVID-19, we feel that the potential of vitamin D to alter the course of disease severity needs to be investigated. Clinical studies may be undertaken to address the value of vitamin D supplementation in deficient, high-risk COVID-19 patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Deficiência de Vitamina D/epidemiologia , Vitamina D/metabolismo , Suplementos Nutricionais , Humanos , /etiologia
14.
Adv Exp Med Biol ; 1268: 257-283, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918223

RESUMO

Nonmelanoma skin cancers including basal and squamous cell carcinomas (SCC and BCC) represent a significant clinical problem due to their relatively high incidence, imposing an economic burden to healthcare systems around the world. It is accepted that ultraviolet radiation (UVR: λ = 290-400 nm) plays a crucial role in the initiation and promotion of BCC and SCC with UVB (λ = 290-320 nm) having a central role in this process. On the other hand, UVB is required for vitamin D3 (D3) production in the skin, which supplies >90% of the body's requirement for this prohormone. Prolonged exposure to UVB can also generate tachysterol and lumisterol. Vitamin D3 itself and its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 hydroxyderivatives show photoprotective functions in the skin. These include regulation of keratinocyte proliferation and differentiation, induction of anti-oxidative responses, inhibition of DNA damage and induction of DNA repair mechanisms, and anti-inflammatory activities. Studies in animals have demonstrated that D3 hydroxyderivatives can attenuate UVB or chemically induced epidermal cancerogenesis and inhibit growth of SCC and BCC. Genomic and non-genomic mechanisms of action have been suggested. In addition, vitamin D3 itself inhibits hedgehog signaling pathways which have been implicated in many cancers. Silencing of the vitamin D receptor leads to increased propensity to develop UVB or chemically induced epidermal cancers. Other targets for vitamin D compounds include 1,25D3-MARRS, retinoic orphan receptors α and γ, aryl hydrocarbon receptor, and Wnt signaling. Most recently, photoprotective effects of lumisterol hydroxyderivatives have been identified. Clinical trials demonstrated a beneficial role of vitamin D compounds in the treatment of actinic keratosis. In summary, recent advances in vitamin D biology and pharmacology open new exciting opportunities in chemoprevention and treatment of skin cancers.


Assuntos
Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Vitamina D/química , Animais , Progressão da Doença , Humanos , Receptores de Calcitriol/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Raios Ultravioleta/efeitos adversos , Vitamina D/metabolismo , Vitamina D/farmacologia , Vitaminas/química , Vitaminas/metabolismo , Vitaminas/farmacologia
15.
Bratisl Lek Listy ; 121(9): 675-679, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32990017

RESUMO

AIM: To evaluate vitamin D levels in patients with chronic spontaneous urticaria (CSU), depression and both of them, thus to find out whether vitamin D may be a common causative factor of CSU and depression. METHODS: Thirty patients with CSU, 30 patients with depression, 30 patients with both CSU and depression and 30 healthy volunteers as control group were involved in the study. Serum 25-hydroxyvitamin D (25(OH)D) levels of these groups were measured and compared. Correlations between 25(OH)D levels and the activity of CSU and depression were analyzed. RESULTS: Healthy controls' 25(OH)D levels (17.2±8.8 ng/mL) were higher than patients with CSU (9.1±5.1 ng/mL), depression (8.9±6.1 ng/mL) and CSU with depression (7.7±4.7 ng/mL) (p<0.001, p<0.001 and p<0.001, respectively). There were no differences in 25(OH)D levels between CSU patients with and without depression, between depression patients and CSU patients with and without depression (p=0.43, p=0.82 and p=0.92, respectively). There were no correlations between 25(OH)D levels and the activity of CSU or depression (p=0.99 and p=0.76, respectively). CONCLUSION: Lower 25(OH)D levels in CSU and/or depression may appear as a secondary phenomenon, which means being result of these diseases rather than the cause (Tab. 1, Fig. 2, Ref. 41). Text in PDFwww.elis.sk Keywords: vitamin D, vitamin D deficiency, chronic urticaria, depression.


Assuntos
Urticária Crônica , Depressão , Vitamina D/análogos & derivados , Calcifediol , Estudos de Casos e Controles , Urticária Crônica/metabolismo , Depressão/metabolismo , Humanos , Vitamina D/metabolismo , Deficiência de Vitamina D
16.
Sci Rep ; 10(1): 15500, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968158

RESUMO

In this multicentre double-blind randomized clinical trial, we investigated the effects of oral cholecalciferol supplementation on serum hepcidin and parameters related to anaemia and CKD-MBD among haemodialysis patients. Participants were assigned in a 2:2:1:1 ratio to either (1) thrice-weekly 3,000-IU cholecalciferol, (2) once-monthly cholecalciferol (equivalent to 9,000 IU/week), (3) thrice-weekly placebo, or (4) once-monthly placebo. We also examined the effect modifications by selected single nucleotide polymorphisms in vitamin D-related genes. Out of 96 participants, 94 were available at Month 3, and 88 completed the 6-month study. After adjustment for baseline values, serum hepcidin levels were higher at Day 3 in the combined cholecalciferol (vs. placebo) group, but were lower at Month 6 with increased erythropoietin resistance. Cholecalciferol increased serum 1,25(OH)2D levels, resulting in a greater proportion of patients who reduced the dose of active vitamin D at Month 6 (31% vs. 10% in the placebo group). Cholecalciferol also suppressed intact PTH only among patients with severe vitamin D deficiency. In conclusion, cholecalciferol supplementation increases serum hepcidin-25 levels in the short term and may increase erythropoietin resistance in the long term among haemodialysis patients. Both thrice-weekly and once-monthly supplementation effectively increases serum 1,25(OH)2D levels, and hence, reduces active vitamin D drugs.Clinical Trial Registry: This study was registered at ClinicalTrials.gov and University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as NCT02214563 (registration date: 12/08/2014) and UMIN000011786 (registration date: 15/08/2014), respectively (please refer to the links below). ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/record/NCT02214563 . UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000017152&language=E .


Assuntos
Anemia/prevenção & controle , Colecalciferol/uso terapêutico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Hepcidinas/sangue , Diálise Renal/efeitos adversos , Idoso , Anemia/terapia , Colecalciferol/administração & dosagem , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Diálise Renal/métodos , Vitamina D/metabolismo
17.
Adv Exp Med Biol ; 1268: 227-253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918222

RESUMO

Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds.


Assuntos
Calcitriol/farmacologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Vitamina D/farmacologia , Animais , Calcitriol/química , Calcitriol/metabolismo , Humanos , Vitamina D/química , Vitamina D/metabolismo , Vitaminas/química , Vitaminas/metabolismo , Vitaminas/farmacologia
18.
Adv Exp Med Biol ; 1268: 285-306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918224

RESUMO

Cutaneous malignancies including melanomas and keratinocyte carcinomas (KC) are the most common types of cancer, occurring at a rate of over one million per year in the United States. KC, which include both basal cell carcinomas and squamous cell carcinomas, are substantially more common than melanomas and form the subject of this chapter. Ultraviolet radiation (UVR), both UVB and UVA, as occurs with sunlight exposure is generally regarded as causal for these malignancies, but UVB is also required for vitamin D synthesis in the skin. Keratinocytes are the major cell in the epidermis. These cells not only produce vitamin D but contain the enzymatic machinery to metabolize vitamin D to its active metabolite, 1,25(OH)2D, and express the receptor for this metabolite, the vitamin D receptor (VDR). This allows the cell to respond to the 1,25(OH)2D that it produces. Based on our own data and that reported in the literature, we conclude that vitamin D signaling in the skin suppresses UVR-induced epidermal tumor formation. In this chapter we focus on four mechanisms by which vitamin D signaling suppresses tumor formation. They are inhibition of proliferation/stimulation of differentiation with discussion of the roles of hedgehog, Wnt/ß-catenin, and hyaluronan/CD44 pathways in mediating vitamin D regulation of proliferation/differentiation, regulation of the balance between oncogenic and tumor suppressor long noncoding RNAs, immune regulation, and promotion of DNA damage repair (DDR).


Assuntos
Receptores de Calcitriol/metabolismo , Pele/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Humanos , Queratinócitos/metabolismo , Pele/citologia , Neoplasias Cutâneas/metabolismo , Raios Ultravioleta/efeitos adversos , Vitamina D/metabolismo
19.
Adv Exp Med Biol ; 1268: 307-318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918225

RESUMO

It has now been convincingly shown that vitamin D and p53 signaling protect against spontaneous or carcinogen-induced malignant transformation of cells. The vitamin D receptor (VDR) and the p53/p63/p73 proteins (the p53 family hereafter) exert their effects as receptors/sensors that turn into transcriptional regulators upon stimulus. While the p53 clan, mostly in the nucleoplasm, responds to a large and still growing number of alterations in cellular homeostasis commonly referred to as stress, the nuclear VDR is transcriptionally activated after binding its naturally occurring biologically active ligand 1,25-dihydroxyvitamin D with high affinity. Interestingly, a crosstalk between vitamin D and p53 signaling has been demonstrated that occurs at different levels, has genome-wide implications, and is of high importance for many malignancies, including non-melanoma skin cancer. These interactions include the ability of p53 to upregulate skin pigmentation via POMC derivatives including alpha-MSH and ACTH. Increased pigmentation protects the skin against UV-induced DNA damage and skin photocarcinogenesis, but also inhibits cutaneous synthesis of vitamin D. A second level of interaction is characterized by binding of VDR and p53 protein, an observation that may be of relevance for the ability of 1,25-dihydroxyvitamin D to increase the survival of skin cells after UV irradiation. UV irradiation-surviving cells show significant reductions in thymine dimers in the presence of 1,25-dihydroxyvitamin D that are associated with increased nuclear p53 protein expression and significantly reduced NO products. A third level of interaction is documented by the ability of vitamin D compounds to regulate the expression of the murine double minute (MDM2) gene in dependence of the presence of wild-type p53. MDM2 has a well-established role as a key negative regulator of p53 activity. Finally, p53 and its family members have been implicated in the direct regulation of the VDR. This review gives an update on some of the implications of the crosstalk between vitamin D and p53 signaling for carcinogenesis in the skin and other tissues, focusing on a genome-wide perspective.


Assuntos
Neoplasias/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Vitamina D/metabolismo , Animais , Humanos , Raios Ultravioleta/efeitos adversos , Vitaminas/metabolismo
20.
Adv Exp Med Biol ; 1268: 409-419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918231

RESUMO

The biology of every species has been optimized for life in the environment in which that species evolved. Humans originated in the tropics, and while some natural selection took place in response to behaviors and environments that decreased exposure to ultraviolet light, there has never been a species-wide biological accommodation. Paleolithic nutrition advocates argue that risk of disease is higher because modern diets differ from what was consumed by early humans. Early humans were the naked ape living in the tropics, exposed to high levels of ultraviolet light and vitamin D nutrition (serum 25-hydroxyvitamin D; 25(OH)D) averaging 115 nmol/L, as compared to today's population averages that are well below 70 nmol/L. Natural selection from an available gene pool cannot compensate fully to an environmental change away from the one within which the species originally evolved. Vitamin D nutrition remains a contentious area. The epidemiological evidence consistently relates lower 25(OH)D to higher disease risk. However, evidence from double-blind clinical trials looking at preventing new disease in healthy volunteers has been disappointing. But such negative trials have been the case for all nutrients except for folic acid which lowers risk of spina bifida. The Paleolithic nutrition model is based on fundamental biological concepts, but it has overlooked the environmental effects of ultraviolet light and vitamin D nutrition. This paper presents evolutionary and Paleolithic aspects of ultraviolet light and vitamin D with the aim to support pertinent research and, ultimately, public policy regarding nutrition and light exposure.


Assuntos
Evolução Biológica , Modelos Biológicos , Política Nutricional , Raios Ultravioleta , Vitamina D/metabolismo , Suplementos Nutricionais , Humanos , Raios Ultravioleta/efeitos adversos , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Vitaminas/metabolismo
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