El sistema pHLIP como vehículo de microRNA en el riñón / The pHLIP system as a vehicle for microRNAs in the kidney

Los microRNA (miRNA) son ARN endógenos de pequeño tamaño que regulan la expresión génica a través de la represión postranscripcional de sus ARN mensajeros diana. El estudio de los cambios en la expresión de ciertos miRNA en el riñón ha proporcionado evidencias sobre su papel patogénico y potencial terapéutico en nefrología. En esta revisión proponemos un abordaje de nanotecnología basado en la unión de análogos o inhibidores de miRNA formados por ácidos peptidonucleicos (PNA) a péptidos con una estructura transmembrana que es sensible a pH bajo, denominada pHLIP (del inglés pH [low] insertion peptide), apoyándonos en el concepto de que el pH acídico del microambiente tubular renal puede facilitar la concentración y la distribución del complejo pHLIP-PNA en este órgano. En este contexto hemos demostrado por primera vez que la administración dirigida de inhibidores de miR-33 con el sistema pHLIP previene eficazmente del desarrollo de fibrosis renal, abriendo las puertas de esta tecnología a nuevas estrategias de diagnóstico y tratamiento de enfermedades renales

MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene expression through post-transcriptional repression of their target messenger RNAs. A study of changes in expression of certain miRNAs in the kidney has supplied evidence on their pathogenic role and therapeutic potential in nephrology. This review proposes a nanotechnology approach based on the binding of analogs or inhibitors of miRNAs formed by peptide nucleic acids (PNAs) to peptides with a transmembrane structure sensitive to a low pH, called pHLIPs (pH [low] insertion peptides). The review draws on the concept that an acidic pH in the microenvironment of the renal tubule may facilitate concentration and distribution of the pHLIP-PNA complex in this organ. In this context, we have demonstrated for the first time that targeted administration of miR-33 inhibitors with the pHLIP system effectively prevents the development of renal fibrosis, thus opening up this technology to new strategies for diagnosis and treatment of kidney diseases

Independent AMP and NAD signaling regulates C2C12 differentiation and metabolic adaptation

The balance of ATP production and consumption is reflected in adenosine monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) content and has been associated with phenotypic plasticity in striated muscle. Some studies have suggested that AMPK-dependent plasticity may be an indirect consequence of increased NAD synthesis and SIRT1 activity. The primary goal of this study was to assess the interaction of AMP- and NAD-dependent signaling in adaptation of C2C12 myotubes. Changes in myotube developmental and metabolic gene expression were compared following incubation with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and nicotinamide mononucleotide (NMN) to activate AMPK- and NAD-related signaling. AICAR showed no effect on NAD pool or nampt expression but significantly reduced histone H3 acetylation and GLUT1, cytochrome C oxidase subunit 2 (COX2), and MYH3 expression. In contrast, NMN supplementation for 24 h increased NAD pool by 45 % but did not reduce histone H3 acetylation nor promote mitochondrial gene expression. The combination of AMP and NAD signaling did not induce further metabolic adaptation, but NMN ameliorated AICAR-induced myotube reduction. We interpret these results as indication that AMP and NAD contribute to C2C12 differentiation and metabolic adaptation independently (AU)

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Enfermedad tromboembólica: dímero D sí, dímero D no / Thromboembolic disease. D dimer: yes or not?

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