Valentina Di Felice

Chlamydia trachomatis infection and anti-Hsp60 immunity: the two sides of the coin.

Chlamydia trachomatis (CT) infection is one of the most common causes of reproductive tract diseases and infertility. CT-Hsp60 is synthesized during infection and is released in the bloodstream. As a consequence, immune cells will produce anti-CT-Hsp60 antibodies. Hsp60, a ubiquitous and evolutionarily conserved chaperonin, is normally sequestered inside the cell, particularly into mitochondria. However, upon cell stress, as well as during carcinogenesis, the chaperonin becomes exposed on the cell surface (sf-Hsp60) and/or is secreted from cells into the extracellular space and circulation. Reports in the literature on circulating Hsp and anti-Hsp antibodies are in many cases short on details about Hsp60 concentrations, and about the specificity spectra of the antibodies, their titers, and their true, direct, pathogenetic effects. Thus, more studies are still needed to obtain a definitive picture on these matters. Nevertheless, the information already available indicates that the concurrence of persistent CT infection and appearance of sf-Hsp60 can promote an autoimmune aggression towards stressed cells and the development of diseases such as autoimmune arthritis, multiple sclerosis, atherosclerosis, vasculitis, diabetes, and thyroiditis, among others. At the same time, immunocomplexes composed of anti-CT-Hsp60 antibodies and circulating Hsp60 (both CT and human) may form deposits in several anatomical locations, e.g., at the glomerular basal membrane. The opposite side of the coin is that pre-tumor and tumor cells with sf-Hsp60 can be destroyed with participation of the anti-Hsp60 antibody, thus stopping cancer progression before it is even noticed by the patient or physician.

Tetralogy of Fallot as a Model to Study Cardiac Progenitor Cell Migration and Differentiation During Heart Development

Tetralogy of Fallot (ToF) has long been considered a congenital disorder that occurs due to environmental alterations during gestation. Recently, several mutated genes have been discovered that are thought to be responsible for the malformations observed in ToF. These genetic mutations, which are microdeletions, are sporadic and are frequently also present in trisomy 21 patients. The ToF malformations can be lethal, but for the last 50 years, surgical repairs that place an artificial patch to repair the four features of ToF have improved the survival of patients with ToF. However, 0.5% to 6% of patients who survive after surgical repair of ToF die of sudden cardiac death caused by ventricular tachycardia. In fact, even if the septum has been repaired, the patch used to close the interventricular defect may cause deformation of the heart, altering the force lines essential for normal function of the right ventricle. In the present review, we hypothesize that mutations in the GATA binding protein 4 (GATA-4)/friend of GATA-2 transcriptional complex and NKX2.5 gene may play a role in the abnormal migration and behavior of precardiac cells during heart development in patients with ToF. An understanding of cardiac precursor cell behavior is needed in order for future research regarding therapeutic approaches to correct the defects seen in ToF without affecting cardiac hemodynamics to be successful.

Identification and characterization of the nano‐sized vesicles released by muscle cells

Several cell types secrete small membranous vesicles that contain cell‐specific collections of proteins, lipids, and genetic material. The function of these vesicles is to allow cell‐to‐cell signaling and the horizontal transfer of their cargo molecules. Here, we demonstrate that muscle cells secrete nano‐sized vesicles and that their release increases during muscle differentiation. Analysis of these nanovesicles allowed us to characterize them as exosome‐like particles and to define the potential role of the multifunctional protein Alix in their biogenesis.

Endurance exercise and conjugated linoleic acid (CLA) supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis.

A new role for fat supplements, in particular conjugated linoleic acid (CLA), has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C) supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone and an up-regulation of CYP17A1 mRNA and protein. The effect of training on CYP17A1 expression and testosterone biosynthesis was significantly higher in the trained mice supplemented with CLA compared to the placebo. The results of the present study demonstrated that CLA stimulates testosterone biosynthesis via CYP17A1, and endurance training led to the synthesis of testosterone in vivo by inducing the overexpression of CYP17A1 mRNA and protein in the Leydig cells of the testis. This effect was enhanced by CLA supplementation. Therefore, CLA-associated physical activity may be used for its steroidogenic property in different fields, such as alimentary industry, human reproductive medicine, sport science, and anti-muscle wasting.

Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer

Recent studies have correlated physical activity with a better prognosis in cachectic patients, although the underlying mechanisms are not yet understood. In order to identify the pathways involved in the physical activity-mediated rescue of skeletal muscle mass and function, we investigated the effects of voluntary exercise on cachexia in colon carcinoma (C26)-bearing mice. Voluntary exercise prevented loss of muscle mass and function, ultimately increasing survival of C26-bearing mice. We found that the autophagic flux is overloaded in skeletal muscle of both colon carcinoma murine models and patients, but not in running C26-bearing mice, thus suggesting that exercise may release the autophagic flux and ultimately rescue muscle homeostasis. Treatment of C26-bearing mice with either AICAR or rapamycin, two drugs that trigger the autophagic flux, also rescued muscle mass and prevented atrogene induction. Similar effects were reproduced on myotubes in vitro, which displayed atrophy following exposure to C26-conditioned medium, a phenomenon that was rescued by AICAR or rapamycin treatment and relies on autophagosome-lysosome fusion (inhibited by chloroquine). Since AICAR, rapamycin and exercise equally affect the autophagic system and counteract cachexia, we believe autophagy-triggering drugs may be exploited to treat cachexia in conditions in which exercise cannot be prescribed.

Cardiac Stem Cell Research: An Elephant in the Room?

Heart disease is the leading cause of death in the industrialized world, and stem cell therapy seems to be a promising treatment for injured cardiac tissue. To reach this goal, the scientific community needs to find a good source of stem cells that can be used to obtain new myocardium in a very period range of time. Since there are many ethical and technical problems with using embryonic stem cells as a source of cells with cardiogenic potential, many laboratories have attempted to isolate potential cardiac stem cells from several tissues. The best candidates seem to be cardiac “progenitor” and/or “stem” cells, which can be isolated from subendocardial biopsies from the same patient or from embryonic and/or fetal myocardium. Regardless of the technique used to isolate and characterize these cells, it appears that the different cells isolated from adult myocardium to date are all phenotypic variations of a unique cell type that expresses several markers, such as c‐Kit, CD34, MDR‐1, Sca‐1, CD45, nestin, or Isl‐1, in various combinations. Anat Rec, 292:449–454, 2009.

Cancer as a "Mitochondriopathy"

Mitochondria are subcellular organelles, whose well-known function is to produce ATP through the oxidative phosphorylation system. Alterations in respiratory activity and mitochondrial DNA (mtDNA) appear to be a general feature of malignant cells. The presence of mtDNA mutations has been reported in various cancer cells, and the abundance of mtDNA damage is consistent with the intrinsic susceptibility to constitutive oxidative stress. Research about the functional aspects of mtDNA mutations in cancer development and therapeutic response is likely to be fruitful and to have significant clinical and prognostic impact. Although many studies to date have been focused on the identification and characterization of altered mtDNA, it is not clear if these accumulated mutations are the cause or the consequence of the carcinogenic process. This article provides a brief summary of our current understanding of mitochondrial pathobiology in cancer development.

Do fat supplements increase physical performance

Fish oil and conjugated linoleic acid (CLA) belong to a popular class of food supplements known as “fat supplements”, which are claimed to reduce muscle glycogen breakdown, reduce body mass, as well as reduce muscle damage and inflammatory responses. Sport athletes consume fish oil and CLA mainly to increase lean body mass and reduce body fat. Recent evidence indicates that this kind of supplementation may have other side-effects and a new role has been identified in steroidogenensis. Preliminary findings demonstrate that fish oil and CLA may induce a physiological increase in testosterone synthesis. The aim of this review is to describe the effects of fish oil and CLA on physical performance (endurance and resistance exercise), and highlight the new results on the effects on testosterone biosynthesis. In view of these new data, we can hypothesize that fat supplements may improve the anabolic effect of exercise.

Effect of conjugated linoleic acid on testosterone levels in vitro and in vivo after an acute bout of resistance exercise

Abstract Macaluso, F, Morici, G, Catanese, P, Ardizzone, NM, Marino Gammazza, A, Bonsignore, G, Giudice, GL, Stampone, T, Barone, R, Farina, F, and Di Felice, V. Effect of conjugated linoleic acid on testosterone levels in vitro and in vivo after an acute bout of resistance exercise. J Strength Cond Res 26(6): 1667–1674, 2012—The purposes of the present study were to investigate the effect of conjugated linoleic acid (CLA) supplementation on testosterone levels in vitro on a cell line derived from Leydig cells (R2C) and in vivo in the blood of physically active subjects before and after a resistance exercise bout. In vitro R2C cells were treated with different CLA concentrations (0–30 &mgr;M) for 24 and 48 hours. After treatment, supernatant media were tested to determine testosterone secretion. The CLA increased the testosterone secretion only after 48 hours. In vivo, 10 resistance-trained male subjects, in a double-blind placebo-controlled and crossover study design were randomized for 3 weeks of either 6 g·d−1 CLA or placebo. Blood was drawn pre and post each resistance exercise bout to determine the total testosterone and sex hormone–binding globulin (SHBG) levels. No significant differences were observed for total testosterone or SHBG pre and post each resistance exercise bout; although after the resistance exercise bouts, total testosterone increased moderately (effect size = moderate), whereas after CLA supplementation, there was a large increase in total testosterone (effect size = large). CLA supplementation induced an increase in testosterone levels in Leydig cells in vitro after 48 hours but not in vivo before and after a resistance exercise bout. These findings suggest that CLA supplementation may promote testosterone synthesis through a molecular pathway that should be investigated in the future, although this effect did not have an anabolic relevance in our in vivo model.

Soccer players have a better standing balance in nondominant one-legged stance.

The purpose of this study was to analyze the differences in standing balance during dominant and nondominant one-legged stance among athletes of different sports and sedentary subjects. The right-footed subjects of four groups (sedentary, n = 20; soccer, n = 20; basketball, n = 20; windsurfer n = 20) underwent 5-sec unipedal (left and right foot) stabilometric analysis with open eyes and closed eyes to measure center of pressure (COP) sway path and COP velocity (mean value, anteroposterior, and laterolateral in millimeters per second). The soccer group showed better standing balance on the left leg than the sedentary group (P < 0.05). No other significant differences were observed within and amongst groups. The soccer players have a better standing balance on the nondominant leg because of soccer activity.