Luigi Rizzuto

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.

Embryonic and foetal Islet-1 positive cells in human hearts are also positive to c-Kit

During embryogenesis, the mammalian heart develops from a primitive heart tube originating from two bilateral primary heart fields located in the lateral plate mesoderm. Cells belongings to the pre-cardiac mesoderm will differentiate into early cardiac progenitors, which express early transcription factors which are also common to the Isl-1 positive cardiac progenitor cells isolated from the developing pharyngeal mesoderm and the foetal and post-natal mice hearts. A second population of cardiac progenitor cells positive to c-Kit has been abundantly isolated from adult hearts. Until now, these two populations have been considered two different sets of progenitor cells present in the heart in different stages of an individual life. In the present study we collected embryonic, foetal and infant hearts, and we tested the hypotheses that c-Kit positive cells, usually isolated from the adult heart, are also present in the intra-uterine life and persist in the adult heart after birth, and that foetal Isl-1 positive cells are also positive to c-Kit. Using immunohistochemistry we studied the temporal distribution of Isl-1 positive and c-Kit/CD105 double positive cells, and by immunofluorescence and confocal analysis we studied the co-localization of c-Kit and Isl-1 positive cells. The results indicated that cardiomyocytes and interstitial cells were positive for c-Kit from the 9th to the 19h gestational week, that cells positive for both c-Kit and CD105 appeared in the interstitium at the 17h gestational week and persisted in the postnatal age, and that the Isl-1 positive cells were a subset of the c-Kit positive population.

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.

Silk fibroin scaffolds enhance cell commitment of adult rat cardiac progenitor cells

The use of three‐dimensional (3D) cultures may induce cardiac progenitor cells to synthesize their own extracellular matrix (ECM) and sarcomeric proteins to initiate cardiac differentiation. 3D cultures grown on synthetic scaffolds may favour the implantation and survival of stem cells for cell therapy when pharmacological therapies are not efficient in curing cardiovascular diseases and when organ transplantation remains the only treatment able to rescue the patients life. Silk fibroin‐based scaffolds may be used to increase cell affinity to biomaterials and may be chemically modified to improve cell adhesion. In the present study, porous, partially orientated and electrospun nanometric nets were used. Cardiac progenitor cells isolated from adult rats were seeded by capillarity in the 3D structures and cultured inside inserts for 21 days. Under this condition, the cells expressed a high level of sarcomeric and cardiac proteins and synthesized a great quantity of ECM. In particular, partially orientated scaffolds induced the synthesis of titin, which is a fundamental protein in sarcomere assembly. Copyright

Stem Cell Populations and Regenerative Potential in Chronic Inflammatory Lung Diseases

Several acute and chronic inflammatory pathologies of the lung are accompanied by structural modifications of airway mucosa that vary depending on the severity, duration and type of the disease. These morphological changes, that determine organ dysfunction, are not always reversible. Indeed, the cycle of injury and repair, influencing airway wall re- generation, may sometimes break off and an exacerbation of the pathology may occur. The mechanisms at the base of airway remodelling during inflammation have been widely studied and numerous evidences indicate that the molecular dialogue among the cells of the mucosa has an essential role in orchestrating cell differentiation and tissue repair. In this review, we revise old notions on pulmonary morphology at the light of some of the most recent discoveries concerning stem cell differentiation, tissue homeostasis and organ regeneration of the lung.

Silybin enhances mitochondrial function and inhibits NFkB activation in murine nonalcoholic fatty liver disease

background & Aims Non Alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease with possible cirrhotic and tumorigenic evolution. Despite a number of treatment has been proposed for NAFLD, none of these is really satisfying. Silybin, a flavonolignan extracted from milk thistle, showed marked liver protecting action in a variety of liver injury and is used as hepatoprotectant. We aimed to clarify the putative therapeutic significance of silybin and to identify the molecular pathways of silybinmediated hepatoprotection in a murine model of NAFLD. Methods We explored the effect of a 4-week daily (20mg/kg i.p.) administration of silybin in 6-week-old db/db mice feeding a methionine-choline deficient (MCD) diet. We examined liver histology, hepatic lipid homeostasis, mitochondrial function, oxidative-nitrosative stress and NFkB activation in silybin-treated mice compared with untreated animals. Results Silybin markedly decreased serum ALT and liver triglycerides content. Steatosis was less severe in grade and distribution, and lobular inflammation was almost absent in silybin-treated mice. At the molecular level, silybin promoted the gene expression of key enzymes involved in free fatty acids elongation and β-oxidation and completely restores mitochondrial respiratory chain activity. Furthermore, silybin markedly decreased oxidative-nitrosative stress and inhibited NFkB p65 and p50 subunits binding activity. Conclusions In the current study we showed that silybin displayed a marked antisteatotic and anti-inflammatory effect in the db/db + MCD murine model of NAFLD. In our opinion, these findings provide the rationale for the use of silybin in the clinical management of patients with NAFLD, which will require well-designed clinical trials.

Effects of antioxidants on CSE-induced cell death in human asthmatic primary bronchial epithelial cells

The link between cigarette smoke (CS) and lung inflammation is quite strong, however relatively little is still known on the effects of CS on human bronchial epithelial cells survival during asthma. In this study we focused our attention on the apoptotic effects of CS on healthy (HC) and asthmatic (AS) primary bronchial epithelial cells (PBEC) and on the role of antioxidants to protect epithelial cells from CSE-induced apoptosis. Twenty subjects (10 HC and 10 AS) were recruited for this study and PBEC were obtained by bronchoscopy. PBEC were treated with oxidants (H2O), anti-oxidants (GSH and AA) and cigarette smoke extracts (CSE). Early apoptosis (EA) and necrosis were measured by flow cytometry using Annexin-V and propidium iodide. After treatment with CSE 20%, AS showed an increased susceptibility to the CSE treatment compared to HC (24.34+/-9.61 vs 48.45+/-11.91, p=0.003). Similarly, when EA was taken into consideration, there was a significant increase of EA cells in the AS group treated with CSE compared to HC (33.12+/-10.38 vs 16.73+/-6.92, p<0.05). AA failed to protect both HS and AS PBEC from CSE-induced cell death. GSH instead was able to protect significantly both HS and AS from CSE-induced cell death. In particular, the association between GSH and CSE 20% determined a significant (p=0.005 in HC and p=0.003 in AS) increase of viability when compared to CSE alone and at the same time EA levels dropped considerably (p<0.05 in HC and p=0.003 in AS) down in the presence of this antioxidant Moreover, GSH treatment determined a significantly bigger (p=0.002) overall increase in viability in the AS group when compared to the HC group. In view of this data it could be possible to hypothesise that the typical imbalance in oxidants-antioxidants levels of asthmatic bronchial epithelial cells might be responsible for their increased susceptibility to oxidative stress.