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1.
DNA Cell Biol ; 43(2): 95-102, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38118108

RESUMEN

HeberNasvac, a therapeutic vaccine for chronic hepatitis B, is able to safely stimulate multiple Toll-like receptors, increasing antigen presentation in vitro and in a phase II clinical trial (Profira) in elderly volunteers who were household contacts of respiratory infection patients. Thus, a new indication as a postexposure prophylaxis or early therapy for respiratory infections has been proposed. In this study, we evaluated the expression of several interferon-stimulated genes (ISGs) after mucosal administration of HeberNasvac and compared this effect with the nasal delivery of interferon alpha 2b (Nasalferon). Molecular studies of blood samples of 50 subjects from the Profira clinical trial who were locally treated with HeberNasvac or Nasalferon and concurrent untreated individuals were compared based on their relative mRNA expression of OAS1, ISG15, ISG20, STAT1, STAT3, and DRB1-HLA II genes. In most cases, the gene expression induced by HeberNasvac was similar in profile and intensity to the expression induced by Nasalferon and significantly superior to that observed in untreated controls. The immune stimulatory effect of HeberNasvac on ISGs paved the way for its future use as an innate immunity stimulator in elderly persons and immunocompromised subjects or as part of Mambisa, a nasal vaccine to prevent severe acute respiratory syndrome coronavirus 2 infection.


Asunto(s)
Pandemias , Vacunas , Humanos , Anciano , Inmunidad Innata/genética , Vacunas/farmacología
2.
Hum Genet ; 131(4): 625-38, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22037902

RESUMEN

Pathogenic CAG (cytosine-adenine-guanine) expansions beyond certain thresholds in the ataxin-2 (ATXN2) gene cause spinocerebellar ataxia type 2 (SCA2) and were shown to contribute to Parkinson disease, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Regulation of ATXN2 gene expression and the function of the protein product are not known. SCA2 exhibits an inverse correlation between the size of the CAG repeat and the age at disease onset. However, a wide range of age at onset are typically observed, with CAG repeat number alone explaining only partly this variability. In this study, we explored the hypothesis that ATXN2 levels could be controlled by DNA methylation and that the derangement of this control may lead to escalation of disease severity and influencing the age at onset. We found that CpG methylation in human ATXN2 gene promoter is associated with pathogenic CAG expansions in SCA2 patients. Different levels of methylation in a SCA2 pedigree without an intergenerational CAG repeat instability caused the disease anticipation in a SCA2 family. DNA methylation also influenced the disease onset in SCA2 homozygotes and SCA3 patients. In conclusion, our study points to a novel regulatory mechanism of ATXN2 expression involving an epigenetic event resulting in differential disease course in SCA2 patients.


Asunto(s)
Metilación de ADN , Proteínas del Tejido Nervioso/genética , Regiones Promotoras Genéticas/genética , Ataxias Espinocerebelosas/genética , Adolescente , Adulto , Ataxina-3 , Ataxinas , Secuencia de Bases , Islas de CpG/genética , Epigénesis Genética , Salud de la Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas Nucleares/genética , Linaje , Reacción en Cadena de la Polimerasa , Proteínas Represoras/genética , Homología de Secuencia de Ácido Nucleico , Ataxias Espinocerebelosas/patología , Expansión de Repetición de Trinucleótido/genética
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