Gianfranco Peluso

Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses

Senescent cells secrete senescence-associated secretory phenotype (SASP) proteins to carry out several functions, such as sensitizing surrounding cells to senesce; immunomodulation; impairing or fostering cancer growth; and promoting tissue development. Identifying secreted factors that achieve such tasks is a challenging issue since the profile of secreted proteins depends on genotoxic stress and cell type. Currently, researchers are trying to identify common markers for SASP. The present investigation compared the secretome composition of five different senescent phenotypes in two different cell types: bone marrow and adipose mesenchymal stromal cells (MSC). We induced MSC senescence by oxidative stress, doxorubicin treatment, X-ray irradiation, and replicative exhaustion. We took advantage of LC-MS/MS proteome identification and subsequent gene ontology (GO) evaluation to perform an unbiased analysis (hypothesis free manner) of senescent secretomes. GO analysis allowed us to distribute SASP components into four classes: extracellular matrix/cytoskeleton/cell junctions; metabolic processes; ox-redox factors; and regulators of gene expression. We used Ingenuity Pathway Analysis (IPA) to determine common pathways among the different senescent phenotypes. This investigation, along with identification of eleven proteins that were exclusively expressed in all the analyzed senescent phenotypes, permitted the identification of three key signaling paths: MMP2 - TIMP2; IGFBP3 - PAI-1; and Peroxiredoxin 6 - ERP46 - PARK7 - Cathepsin D - Major vault protein. We suggest that these paths could be involved in the paracrine circuit that induces senescence in neighboring cells and may confer apoptosis resistance to senescent cells.

A Review on Extremozymes Biocatalysis: A Green Industrial Approach forBiomaterials Production

In the last few years, the industrial attention on biomaterials production has focused on designing and developing of methods and processes to minimize the use and the generation of polluting products. In this context of green chemistry, the enzymatic catalysis could be the right way to obtain high level of polymers industrial production without the use of hazardous reagent and pollution. This review focuses on the enzymatic approach to polymer synthesis, and in particular on enzymes from extremophiles. This class of enzymes is industrial attracting showing good resistance to solvents, temperature, pH, and, in general, extreme reaction conditions. Moreover, in this manuscript are reported also the future perspectives of enzyme molecular engineering to obtain new species with more industrial interesting features.

Hydrogel Nanocomposite Systems

Abstract The field of controlled drug delivery continues to be one of the key areas of research in pharmaceutics and medicine. In these studies, hydrogel nanocomposite systems (NC-HYGs) have been extensively investigated because of their unique and tailorable properties. In fact, NC-HYGs mimic the native tissue microenvironment through their porous and hydrated molecular structure. Moreover, new reinforced polymeric hydrogels incorporating nanoparticles within the hydrogel network are being produced with the aim to improve the mechanical properties of the hydrogel and provide superior functionality, such as controlled release. This chapter covers the most recent developments in the field of nanocomposite hydrogels with emphasis on biomedical and pharmaceutical applications. In particular, we will discuss definitions, synthesis, characterization, and applications of hydrogel nanocomposites as drug-delivery systems. Moreover, future directions in designing more advanced nanocomposite hydrogels for biomedical and biotechnological applications will be provided.

Hybrid complexes of high and low molecular weight hyaluronan delay in vitro replicative senescence of mesenchymal stromal cells: a pilot study for future therapeutic application.

Mesenchymal stem cells, a subpopulation of mesenchymal stromal cells (MSCs), are present in the stroma of several tissues. MSC in vitro cultivation for clinical treatments may greatly affect MSC properties. A primary handicap is replicative senescence that impairs MSC functions. Hyaluronan (HA) is present in the extracellular matrix that composes the stem cell niche environment and is under investigation as a key factor for in vitro stem cell growth. We evaluated the effect on MSC cultivation of HA hybrid cooperative complexes (HCC) that are obtained from high (H) and low (L) weight molecules (NAHYCO™). We compared this HCC with H-HA and L-HA. We investigated the effects of these HAs on proliferation, cell cycle, apoptosis, senescence, and differentiation following the addition of the polymer solutions in the culture media at concentrations that did not drastically modify the medium viscosity. Interestingly, 0,16% HCC significantly delayed the senescence compared with the controls. This occurred without alteration of the cell cycle, cytotoxicity, or apoptosis. HCCs also promoted adipogenic and chondrogenic differentiation. Our finding could suggest a potential functional role of HCC above the updated scientific reports of its effects and pave the way to optimization of MSC cultivation for therapeutic application.

Carnitine System and Tumor

Carnitine, a name derived from the Latin carnis (flesh), was isolated from meat extracts in 19051 and early its chemical formula (C7H15NO3) was proposed. Its structure, a trimethylbetaine of γ-amino-β-hydroxybutyric acid, was correctly identified and published about twenty years later.2 Initially, some circumstances led to consider carnitine as a vitamin. By about 1945, all of the important vitamins of the B group had been identified, but the interest in the discovery of still missing B-vitamins, their lack being possibly correlated with anemia, was tremendous. In those years Fraenkel and coworkers observed that the mealworm Tenebrio molitor required for normal growth and survival, in addition to at least eight of the known B-vitamins, also folic acid and a new factor contained in brewers yeast or in liver extract, which they tentatively named vitamin-BT (T for Tenebrio).3 The unfavorable properties of this factor (it was hygroscopic and extremely water soluble, thus, hard to crystallize) made its isolation difficult but, finally, the missing vitamin-BT was identified as carnitine.4 The widespread distribution of carnitine was established in microorganisms, lower animals, and in all organs of mammals, and in plants too.5