Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux

BACKGROUND: Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. METHODS: We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber's diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. RESULTS: UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber's diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. CONCLUSIONS: Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.

Interferencia de la información léxica sobre la identificación de fonemas durante una tarea de decisión fonológica / Lexical information interference in phonemic recognition during a phonological decision task

A partir de estudios con potenciales relacionados a eventos en tareas de decisión fonológica (DF) o léxica (DL), se ha propuesto que el procesamiento auditivo del lenguaje es de tipo serial con interacciones tardías entre los módulos fonológico, sintáctico y semántico. Este trabajo intentó valorar si existía una interferencia entre el procesamiento fonológico y semántico durante la DL y DF de sintagmas nominales utilizando un artículo definido en concordancia con un sustantivo. A fin de examinar esto, se presentaron 180 estímulos auditivos a un grupo de participantes, y se les pidió que realizaran una tarea de DL y una de decisión DF; 60 estímulos utilizaron palabras de la lengua, 60 con una vocal alterada en el sustantivo que generaba una pseudopalabra (PSP1), y 60 con una sílaba traslocada en el sustantivo para generar otro tipo de pseudopalabra (PSP2). Se registraron 10 participantes hispanohablantes adultos sin padecimientos neurológicos ni psiquiátricos. Se encontró que los participantes se equivocaron más al identificar las PSP1 que las PSP2 en la tarea de DL. No se encontraron diferencias en el componente N400 durante DL. En la tarea de DF, se encontró que el N100 incrementó su amplitud ante la presentación de palabras. Estos hallazgos apuntan a que la información léxica interfiere con la fase de procesamiento fonológico y cuestiona el modelo de procesamiento serial del lenguaje.

Experiments using event-related potentials during phonological decision (PD) and lexical decision (LD) tasks have suggested that auditory language processing occurs in a serial fashion, with late interactions amongst the phonological, syntactic and semantic modules. This paper sought to assess the existence of interference between phonological and semantic processing during LD and PD in nominal phrases, by using a definite article to match a noun. In order to examine this, 180 auditory stimuli were presented to a group of participants, and they were asked to perform a LD and a PD task. Sixty auditory stimuli included a noun that generated a pseudo-word (PSP1), and 60 others included a misplaced syllable within the noun so as to generate another type of pseudo-word (PSP2). Ten adult Spanish speakers without any neurological or psychiatric disorders volunteered to take part in the experiment. Participants were found to make more mistakes when identifying PSP1 than PSP2 during the LD task. There were no significant differences in the N400 component during LD. As for the PD task, it was found that N100 increased in amplitude when words were presented. These findings go to show that lexical information interferes with the phonological processing phase, and questions the serial model of language processing.

Cultivo de blastocitos con medios secuenciales / Human blastocysts culture with sequential media

Son bien conocidas las ventajas de cultivar preembriones humanos hasta etapa de blastocisto. Esto no es nuevo, lo que es reciente es el empleo de medios de cultivo secuenciales sin el apoyo de células somáticas. El objetivo fue cultivar preembriones humanos hasta etapa de blastocisto para determinar las tasas de recuperación, tasa de implantación y tasa de embarazo en pacientes sometidas a FIVT/TE o ICSI. Una vez obtenidos los óvulos de las pacientes, fueron inseminados/inyectados para posteriormente ser cultivados por 72 horas. usando medio P1 al 10 por ciento de SSS bajo aceite mineral para posteriormente ser transferidos a un medio complejo para cultivo de blastocistos por 48 horas. y finalmente ser transferidos. Se incluyeron 13 pacientes (9 de FIV y 4 de ICSI) obteniendo 205 óvulos, fertilizaron 143 y 131 tuvieron división celular. Se cultivaron 121 preembriones a etapa de blastocisto de los cuales 53 alcanzaron esa etapa (43.8 por ciento), transfiriendo 28 y congelando 25. En promedio se transfirieron 2.1 blastocistos por paciente. Se presentaron cuatro embarazos y un recién nacido vivo a término para una tasa de implantación de 14.2 por ciento y una tasa de embarazo de 30 por ciento. El estudio muestra nuestra experiencia inicial, la cual demostró una aceptable tasa de recuperación de blastocistos y de embarazo.