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1.
Gene ; 781: 145488, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33588040

RESUMO

Oxidative stress (OS) plays an essential role in demyelination and tissue injury related to pathogenesis of multiple sclerosis (MS). On the other hand, vitamin D (VD) as an antioxidant reduces oxidative stress and has been used as adjuvant therapy in autoimmune diseases. Although VD supplementation is suggested as a protective and immunomodulation factor for MS patients, the molecular mechanisms remain unclear. Given that VD may modulate the immune system of MS patients through the DNA repair pathway, we aimed to evaluate the effects of VD supplementation in DNA repair genes expression including OGG1, MYH, MTH1, and ITPA. Transcript levels were measured using the RT-qPCR method in peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) patients before and after two months of VD supplementation. Furthermore, in silico analysis and correlation gene expression analysis was performed to find the biological binding sites and the effect of NRF2 on the regulation of DNA repair genes. Our data revealed that in MS patients, 2-month VD treatment significantly altered the expression of MYH, OGG1, MTH1, and NRF2 genes. A significant correlation was observed between DNA repair genes and NRF2 expression, which was confirmed by the presence of antioxidant response element (ARE) binding sites in the promoter of OGG1, MYH, and MTH1 genes. This study demonstrated that the impact of VD on MS patients may be mediated through the improvement of DNA repair system efficiency. This finding brought some new evidence for the involvement of DNA repair genes in the physiopathology of MS patients.


Assuntos
Reparo do DNA/genética , Expressão Gênica/efeitos dos fármacos , Esclerose Múltipla/genética , Vitamina D/farmacologia , Vitaminas/farmacologia , Adulto , Simulação por Computador , DNA Glicosilases/genética , Reparo do DNA/efeitos dos fármacos , Enzimas Reparadoras do DNA/genética , Feminino , Humanos , Masculino , Esclerose Múltipla/tratamento farmacológico , Fator 2 Relacionado a NF-E2/genética , Monoéster Fosfórico Hidrolases/genética , Reação em Cadeia da Polimerase em Tempo Real
2.
Immunology ; 153(4): 479-487, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29030863

RESUMO

Studies have revealed that dysregulation in gene expression is one of the main aspects of multiple sclerosis (MS) pathogenesis. Although the molecular pathways underlying the immunomodulatory role of vitamin D (VD) in MS is not completely elucidated, VD has more recently become a topic of interest in immune regulation and is widely administered to patients with MS as an immunomodulatory supplement. Long non-coding RNAs (lncRNAs) are known to play important roles in regulation of gene expression via different mechanisms. Given that VD-related genes are regulated by epigenetic mechanisms, here we aimed to evaluate the role of VD in combination with HOTAIR and ANRIL lncRNAs using in vivo, in vitro and in silico experiments in MS pathogenesis. Our data revealed that HOTAIR but not ANRIL lncRNA is probably involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis through an unclear mechanism and it seems that by affecting the expression, inflammation and VD can influence HOTAIR-related mechanisms, which require further study.


Assuntos
Esclerose Múltipla/genética , RNA Longo não Codificante/genética , Células Cultivadas , Epigênese Genética/genética , Epigênese Genética/imunologia , Humanos , Esclerose Múltipla/imunologia , RNA Longo não Codificante/imunologia , Vitamina D/imunologia
3.
Neurosci Lett ; 653: 258-263, 2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28576565

RESUMO

BACKGROUND AND PURPOSE: The aim of this study was to investigate the expression levels of vitamin D receptor (VDR) and NF-κB mRNAs in vitamin D (VD) supplemented multiple sclerosis (MS) patients. METHODS: RRMS patients received 50,000 IU vitamin D3/week as an intra-muscular injection for 2 months. Blood samples were obtained from 30 MS patients before and after VD supplementation and 32 healthy individuals, and then VDR and NF-κB mRNA levels were measured by real time PCR method and analyzed with independent and paired t-tests. Moreover, some correlations were performed between the expression levels of selected genes and some clinical features of MS and control groups. RESULTS: Surprisingly, the expression level of VDR mRNA significantly decreased after 2 months supplementation with VD in our selected patients and in contrast, the level of serum 25(OH) D increased after supplementation. Although, we didn't find any significant difference in the expression level of NF-κB gene before and after treatment with VD, its expression significantly decreased in untreated MS cases compared with healthy controls. CONCLUSION: In conclusion, we found some new evidences from the molecular mechanism of vitamin D effectiveness in MS treatment. Also, we need more functional studies to find the effect of VD on the expression level of VDR mRNA.


Assuntos
Colecalciferol/sangue , Colecalciferol/farmacologia , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , NF-kappa B/sangue , Receptores de Calcitriol/sangue , Adulto , Colecalciferol/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Receptores de Calcitriol/efeitos dos fármacos , Adulto Jovem
4.
Int Immunopharmacol ; 28(1): 414-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26188623

RESUMO

Vitamin D regulates gene expression and affects target cell functions. IL-6 and IL-17A are pro-inflammatory cytokines associated with MS pathogenesis. The aim of this study was to investigate the vitamin D effects on the expression level of IL-6 and IL-17A in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients. Also, we performed a correlation analysis between the gene expression and some clinical features such as serum level of vitamin D and the expanded disability status scale (EDSS). Significant up-regulation of IL-6 and IL-17A gene expression was shown under vitamin D treatment. Also, some gender specific correlations between the gene expression with vitamin D levels were detected in female RR-MS patients.


Assuntos
Interleucina-17/genética , Interleucina-6/genética , Esclerose Múltipla/genética , Vitamina D/farmacologia , Adulto , Suplementos Nutricionais , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , RNA Mensageiro/metabolismo , Regulação para Cima/efeitos dos fármacos , Vitamina D/sangue , Vitamina D/farmacocinética , Adulto Jovem
5.
Life Sci ; 134: 63-7, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26037400

RESUMO

AIM: A variety of evidence suggests that vitamin D can prevent the development of multiple sclerosis (MS). TGF-ß pathway genes also play important roles in MS. Here, we aim to study whether vitamin D affects TGF-ß pathway gene expression and Expanded Disability Status Scale (EDSS) scores in MS patients. MAIN METHODS: A randomized clinical trial was conducted on 31 relapsing-remitting (RR) MS patients. Using real-time RT-PCR, we tested the levels of TGF-ß2, TGF-ßRI and TGF-ßRII mRNAs in the RRMS patients before and after 8 weeks of supplementation with vitamin D. KEY FINDINGS: Expression of TGF-ß2 mRNA increased 2.84-fold, while TGF-ßRI and TGF-ßRII mRNA levels did not change after vitamin D treatment. In addition, these results revealed no correlation between the normalized expression of TGF-ß2, TGF-ßRI, or TGF-ßRII and EDSS scores. SIGNIFICANCE: Here, we demonstrate new evidence for the complex role of vitamin D in the pathogenesis, activity and progression of MS through the TGF-ß signaling pathway.


Assuntos
Regulação da Expressão Gênica , Esclerose Múltipla/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Receptores de Fatores de Crescimento Transformadores beta/biossíntese , Fator de Crescimento Transformador beta2/biossíntese , Vitamina D/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II
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