HDAC8 regulates canonical Wnt pathway to promote differentiation in skeletal muscles.

Histone deacetylase 8 (HDAC8) is a class 1 histone deacetylase and a member of the cohesin complex. HDAC8 is expressed in smooth muscles, but its expression in skeletal muscle has not been described. We have shown for the first time that HDAC8 is expressed in human and zebrafish skeletal muscles. Using RD/12 and RD/18 rhabdomyosarcoma cells with low and high differentiation potency, respectively, we highlighted a specific correlation with HDAC8 expression and an advanced stage of muscle differentiation. We inhibited HDAC8 activity through a specific PCI-34051 inhibitor in murine C2C12 myoblasts and zebrafish embryos, and we observed skeletal muscles differentiation impairment. We also found a positive regulation of the canonical Wnt signaling by HDAC8 that might explain muscle differentiation defects. These findings suggest a novel mechanism through which HDAC8 expression, in a specific time window of skeletal muscle development, positively regulates canonical Wnt pathway that is necessary for muscle differentiation.

Sex-Specific Transcriptome Differences in Substantia Nigra Tissue: A Meta-Analysis of Parkinson's Disease Data.

Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. Clinical and epidemiological studies indicate that sex differences, as well as genetic components and ageing, can influence the prevalence, age at onset and symptomatology of PD. This study undertook a systematic meta-analysis of substantia nigra microarray data using the Transcriptome Mapper (TRAM) software to integrate and normalize a total of 10 suitable datasets from multiple sources. Four different analyses were performed according to default parameters, to better define the segments differentially expressed between PD patients and healthy controls, when comparing men and women data sets. The results suggest a possible regulation of specific sex-biased systems in PD susceptibility. TRAM software allowed us to highlight the different activation of some genomic regions and loci involved in molecular pathways related to neurodegeneration and neuroinflammatory mechanisms.

Meta-Analysis of Parkinson's Disease Transcriptome Data Using TRAM Software: Whole Substantia Nigra Tissue and Single Dopamine Neuron Differential Gene Expression.

The understanding of the genetic basis of the Parkinson's disease (PD) and the correlation between genotype and phenotype has revolutionized our knowledge about the pathogenetic mechanisms of neurodegeneration, opening up exciting new therapeutic and neuroprotective perspectives. Genomic knowledge of PD is still in its early stages and can provide a good start for studies of the molecular mechanisms that underlie the gene expression variations and the epigenetic mechanisms that may contribute to the complex and characteristic phenotype of PD. In this study we used the software TRAM (Transcriptome Mapper) to analyse publicly available microarray data of a total of 151 PD patients and 130 healthy controls substantia nigra (SN) samples, to identify chromosomal segments and gene loci differential expression. In particular, we separately analyzed PD patients and controls data from post-mortem snap-frozen SN whole tissue and from laser microdissected midbrain dopamine (DA) neurons, to better characterize the specific DA neuronal expression profile associated with the late-stage Parkinson's condition. The default "Map" mode analysis resulted in 10 significantly over/under-expressed segments, mapping on 8 different chromosomes for SN whole tissue and in 4 segments mapping on 4 different chromosomes for DA neurons. In conclusion, TRAM software allowed us to confirm the deregulation of some genomic regions and loci involved in key molecular pathways related to neurodegeneration, as well as to provide new insights about genes and non-coding RNA transcripts not yet associated with the disease.

Compliance to MADIT and MUSTT criteria for implantable cardioverter defibrillator therapy in the pre-SCD-Heft and MADIT II era. Data from a multicenter Italian study.

The follow-up of 1440 consecutive post-MI patients (68.9 ± 10.9 years) with an LVEF ≤ 40% was analyzed in 19 Italian hospitals to evaluate how many patients with clinical nonsustained VT and inducible sustained VT or VF underwent post-discharge risk assessment (RA). During 38 (range, 4-76) months follow-up, 611 patients (42.4%) qualified for and 294 (20.4%) effectively underwent RA combining LVEF assessment and Holter monitoring, 29 (2.0%) subsequently underwent programmed electrical stimulation and 19 (1.3%) received an ICD.

Influence of Heart Rate on Doppler Aortic Regurgitant Velocity Curve: Clinical Role of Heart Rate Correction of Regurgitant Pressure Half-Time.

Because it was recently suggested that pressure half-time (PHT) of aortic regurgitant velocity curve is influenced by heart rate (HR), we retrospectively analyzed 76 patients with aortic regurgitation (AR) to determine whether PHT independently correlates with HR and whether HR correction of PHT can be clinically useful. PHT correlated significantly (P < 0.001) with color Doppler relative regurgitant jet height (r = -0.62), with angiographic grading (r = -0.65), and with HR (r = -0.54); such correlations were confirmed by multivariate analysis. Tachycardia influences aortic velocity curve more than bradycardia, and this effect is more evident in patients with milder regurgitation. Two methods of HR correction of PHT were tested: relative PHT (PHT/diastolic time x 100) and corrected PHT (PHT/ radicalRR): only corrected PHT was independently related to both relative regurgitant jet height and angiographic grading (P < 0.001). HR correction of PHT by corrected PHT was of limited clinical usefulness: in fact, in the entire study population, the accuracy of the usual cutoff (< 300 msec) in detecting relevant AR was not improved by corrected PHT. However, in patients with higher HR (>/= 85 beats/min), in whom the effect of HR on aortic velocity curve appeared to be greater, corrected PHT was superior to PHT because the cutoff value of < 300 msec showed a good specificity (100%), a moderate sensitivity (66%), and a good accuracy (80%) in detecting relevant AR. Corrected PHT can be useful to confirm AR severity when a short PHT is observed in tachycardic patients.