Giovanni Messina

Short-Term Diet and Moderate Exercise in Young Overweight Men Modulate Cardiocyte and Hepatocarcinoma Survival by Oxidative Stress

The present study was designed to evaluate the effects of diet lifestyle on extending lifespan and reducing liver cancer risk. Young overweight men (n = 20), without metabolic syndrome, were placed in a 3-week residential program on a low-fat diet and moderate aerobic exercise. In each subject, pre- and postintervention fasting blood were collected for evaluating levels of serum lipids, and oxidative stress markers. Using subject sera and cardiomyocyte (H9C2) culture systems, we measured heat shock protein 27 and 90 expression, lipid accumulation, and oxidative stress marker levels. After 3-weeks of diet, significant reductions (P < 0.05) in body mass index, serum lipids and lipid ratios, and oxidative markers were recorded. In vitro, we observed that the addition of postintervention sera increased H9C2 cell number and reduced HSP27 and 90 expression, mitochondrial superoxide anion, and lipid accumulation with a parallel increase in nitric oxide (NO) production (all P < 0.01). At the same time, postintervention sera decreased human liver hepatocellular carcinoma cell line (HepG-2) proliferation, lipid accumulation, oxidative stress, and extracellular-signal-regulated kinases (ERK1/2) activity. Lifestyle modification in young overweight men, without metabolic syndrome, could ameliorate cardiocyte survival and reduce hepatocellular carcinoma cell proliferation.

The Release 6 reference sequence of the Drosophila melanogaster genome

Drosophila melanogaster plays an important role in molecular, genetic, and genomic studies of heredity, development, metabolism, behavior, and human disease. The initial reference genome sequence reported more than a decade ago had a profound impact on progress in Drosophila research, and improving the accuracy and completeness of this sequence continues to be important to further progress. We previously described improvement of the 117-Mb sequence in the euchromatic portion of the genome and 21 Mb in the heterochromatic portion, using a whole-genome shotgun assembly, BAC physical mapping, and clone-based finishing. Here, we report an improved reference sequence of the single-copy and middle-repetitive regions of the genome, produced using cytogenetic mapping to mitotic and polytene chromosomes, clone-based finishing and BAC fingerprint verification, ordering of scaffolds by alignment to cDNA sequences, incorporation of other map and sequence data, and validation by whole-genome optical restriction mapping. These data substantially improve the accuracy and completeness of the reference sequence and the order and orientation of sequence scaffolds into chromosome arm assemblies. Representation of the Y chromosome and other heterochromatic regions is particularly improved. The new 143.9-Mb reference sequence, designated Release 6, effectively exhausts clone-based technologies for mapping and sequencing. Highly repeat-rich regions, including large satellite blocks and functional elements such as the ribosomal RNA genes and the centromeres, are largely inaccessible to current sequencing and assembly methods and remain poorly represented. Further significant improvements will require sequencing technologies that do not depend on molecular cloning and that produce very long reads.

Orexin System: The Key for a Healthy Life

The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area. Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS. Orexin neurons are “multi-tasking” neurons regulating a set of vital body functions, including sleep/wake states, feeding behavior, energy homeostasis, reward systems, cognition and mood. Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions. A selective loss orexin neurons was found in narcolepsia, supporting the crucial role of orexins in maintaining wakefulness. In animal models, orexin deficiency lead to obesity even if the consume of calories is lower than wildtype counterpart. Reduced physical activity appears the main cause of weight gain in these models resulting in energy imbalance. Orexin signaling promotes obesity resistance via enhanced spontaneous physical activity and energy expenditure regulation and the deficiency/dysfunction in orexins system lead to obesity in animal models despite of lower calories intake than wildtype associated with reduced physical activity. Interestingly, orexinergic neurons show connections to regions involved in cognition and mood regulation, including hippocampus. Orexins enhance hippocampal neurogenesis and improve spatial learning and memory abilities, and mood. Conversely, orexin deficiency results in learning and memory deficits, and depression.

Exercise Modifies the Gut Microbiota with Positive Health Effects.

The human gastrointestinal tract (GIT) is inhabited by a wide cluster of microorganisms that play protective, structural, and metabolic functions for the intestinal mucosa. Gut microbiota is involved in the barrier functions and in the maintenance of its homeostasis. It provides nutrients, participates in the signaling network, regulates the epithelial development, and affects the immune system. Considering the microbiota ability to respond to homeostatic and physiological changes, some researchers proposed that it can be seen as an endocrine organ. Evidence suggests that different factors can determine changes in the gut microbiota. These changes can be both quantitative and qualitative resulting in variations of the composition and metabolic activity of the gut microbiota which, in turn, can affect health and different disease processes. Recent studies suggest that exercise can enhance the number of beneficial microbial species, enrich the microflora diversity, and improve the development of commensal bacteria. All these effects are beneficial for the host, improving its health status. In this paper, we intend to shed some light over the recent knowledge of the role played by exercise as an environmental factor in determining changes in microbial composition and how these effects could provide benefits to health and disease prevention.

Exercise increases the level of plasma orexin A in humans.

Abstract Background: The purpose of this research was to study the effects of exercise on the concentration of plasma orexin A, a peptide regulating several physiological functions. Methods: Blood samples were collected from participants (men, n=10; age: 24.4±2.93 years) 15, 0 min before the start of exercise, and 30, 45, 60 min after a cycle ergometer exercise at 75 W for 15 min. Also heart rate (HR), galvanic skin response (GSR), and rectal temperature were monitored. Results: The exercise induced a significant increase (p<0.01) in plasmatic orexin A with a peak at 30 min after the exercise bout, in association with an increase of the other three monitored variables: HR (p<0.01), GSR (p<0.05), and rectal temperature (p<0.01). Conclusions: Our findings indicate that plasmatic orexin A is involved in the reaction to physical activity.

Role of orexin system in obesity

Obesity is a public health disease and its incidence is steadily increasing both in adults and in children especially in the Western World. It is important to understand the underlying mechanisms of obesity and possible treatments as the orexin system with its receptors, which are involved in different physiological processes. In fact, the aim of this mini-review is to consider the importance of the orexin system and the role that orexin plays in the regulation of obesity and physical activity. Furthermore to demonstrate how the orexin and its receptors fit within a network distributed in multiple brain areas, each with specific actions, whose activation and interconnection has been seen to lead to a lower propensity for increase of fat mass, it could thus constitute an important future target for prevention and treatment of obesity

Neuroprotective Effects of Physical Activity: Evidence from Human and Animal Studies

In the present article, we provide a review of current knowledge regarding the role played by physical activity (PA) in preventing age-related cognitive decline and reducing risk of dementia. The cognitive benefits of PA are highlighted by epidemiological, neuroimaging and behavioral studies. Epidemiological studies identified PA as an influential lifestyle factor in predicting rates of cognitive decline. Individuals physically active from midlife show a reduced later risk of cognitive impairment. Neuroimaging studies documented attenuation of age-related brain atrophy, and also increase of gray matter and white matter of brain areas, including frontal and temporal lobes. These structural changes are often associated with improved cognitive performance. Importantly, the brain regions that benefit from PA are also those regions that are often reported to be severely affected in dementia. Animal model studies provided significant information about biomechanisms that support exercise-enhanced neuroplasticity, such as angiogenesis and upregulation of growth factors. Among the growth factors, the brain-derived neurotrophic factor seems to play a significant role. Another putative factor that might contribute to beneficial effects of exercise is the neuropeptide orexin-A. The beneficial effects of PA may represent an important resource to hinder the cognitive decline associated with aging.

Functional assessment of corticospinal system excitability in karate athletes

Objectives To investigate the involvement of the primary motor cortex (M1) in the coordination performance of karate athletes through transcranial magnetic stimulation (TMS). Methods Thirteen right-handed male karate athletes (25.0±5.0 years) and 13 matched non-athlete controls (26.7±6.2 years) were enrolled. A single-pulse TMS was applied using a figure-eight coil stimulator. Resting motor threshold (rMT) was determined. Surface electromyography was recorded from the first dorsal interosseous muscle. Motor evoked potential (MEP) latencies and amplitudes at rMT, 110%, and 120% of rMT were considered. Functional assessment of the coordination performance was assessed by in-phase (IP) and anti-phase (AP) homolateral hand and foot coordination tasks performed at 80, 120, and 180 bpm. Results Compared to controls, athletes showed lower rMT (p<0.01), shorter MEP latency (p<0.01) and higher MEP amplitude (p<0.01), with a significant correlation (r = 0.50, p<0.01) between rMT and MEP latency. Coordination decreased with increasing velocity, and better IP performances emerged compared to AP ones (p<0.001). In general, a high correlation between rMT and coordination tasks was found for both IP and AP conditions. Conclusion With respect to controls, karate athletes present a higher corticospinal excitability indicating the presence of an activity-dependent alteration in the balance and interactions between inhibitory and facilitatory circuits determining the final output from the M1. Furthermore, the high correlation between corticospinal excitability and coordination performance could support sport-specific neurophysiological arrangements.

Heart Rate Variability as predictive factor for Sudden Cardiac Death

Sudden cardiac death (SCD) represents about 25% of deaths in clinical cardiology. The identification of risk factors for SCD is the philosophers stone of cardiology and the identification of non-invasive markers of risk of SCD remains one of the most important goals for the scientific community. The aim of this review is to analyze the state of the art around the heart rate variability (HRV) as a predictor factor for SCD. HRV is probably the most analyzed index in cardiovascular risk stratification technical literature, therefore an important number of models and methods have been developed. Nowadays, low HRV has been shown to be independently predictive of increased mortality in post- myocardial infarction patients, heart failure patients, in contrast with the data of the general population. Contrariwise, the relationship between HRV and SCD has received scarce attention in low-risk cohorts. Furthermore, in general population the attributable risk is modest and the cost/benefit ratio is not always convenient. The HRV evaluation could become an important tool for health status in risks population, even though the use of HRV alone for risk stratification of SCD is limited and further studies are needed.

Yeti, an essential Drosophila melanogaster gene, encodes a protein required for chromatin organization

ABSTRACT The evolutionarily conserved family of Bucentaur (BCNT) proteins exhibits a widespread distribution in animal and plants, yet its biological role remains largely unknown. Using Drosophila melanogaster as a model organism, we investigated the in vivo role of the Drosophila BCNT member called YETI. We report that loss of YETI causes lethality before pupation and defects in higher-order chromatin organization, as evidenced by severe impairment in the association of histone H2A.V, nucleosomal histones and epigenetic marks with polytene chromosomes. We also find that YETI binds to polytene chromosomes through its conserved BCNT domain and interacts with the histone variant H2A.V, HP1a and Domino-A (DOM-A), the ATPase subunit of the DOM/Tip60 chromatin remodeling complex. Furthermore, we identify YETI as a downstream target of the Drosophila DOM-A. On the basis of these results, we propose that YETI interacts with H2A.V-exchanging machinery, as a chaperone or as a new subunit of the DOM/Tip60 remodeling complex, and acts to regulate the accumulation of H2A.V at chromatin sites. Overall, our findings suggest an unanticipated role of YETI protein in chromatin organization and provide, for the first time, mechanistic clues on how BCNT proteins control development in multicellular organisms.