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Air pollution is well recognized as a central player in cardiovascular disease. Exhaust particulate from diesel engines (DEP) is rich in nanoparticles and may contribute to the health effects of particulate matter in the environment. Moreover, diesel soot emitted by modern engines denotes defective surfaces alongside chemically-reactive sites increasing soot cytotoxicity. We recently demonstrated that engineered nanoparticles can cross the air/blood barrier and are capable to reach the heart. We hypothesize that DEP nanoparticles are pro-arrhythmogenic by direct interaction with cardiac cells. We evaluated the internalization kinetics and the effects of DEP, collected from Euro III (DEPe3, in the absence of Diesel Particulate Filter, DPF) and Euro IV (DEPe4, in the presence of DPF) engines, on alveolar and cardiac cell lines and on in situ rat hearts following DEP tracheal instillation. We observed significant differences in DEP size, metal and organic compositions derived from both engines. DEPe4 comprised ultrafine particles (

Recently, studies on inositol supplementation during in vitro fertilization program (IVF) have gained particular importance due to the effect of this molecule on reducing insulin resistance improving ovarian function, oocyte quality, and embryo and pregnancy rates and reducing gonadotropin amount during stimulation. Inositol and its isoforms, especially myoinositol (MYO), are often used as prestimulation therapy in infertile patients undergoing IVF cycle. Inositol supplementation started three months before ovarian stimulation, resulting in significant improvements in hormonal responses, reducing the amount of FSH necessary for optimal follicle development and serum levels of 17beta-estradiol measured the day of hCG injection. As shown by growing number of trials, MYO supplementation improves oocyte quality by reducing the number of degenerated and immature oocytes, in this way increasing the quality of embryos produced. Inositol can also improve the quality of sperm parameters in those patients affected by oligoasthenoteratozoospermia.

This chapter presents an overview of the growth and optical properties (Section 10.2) and some in vitro applications of core-shell 3C-SiC-SiO2 NWs and bare SiC NWs. In Section 10.3 it was shown, by the analysis of cell proliferation, cell cycle progression, and oxidative stress, that the core-shell NWs are cytocompatible over a time of up to 10 days. They are effectively internalized by cells through the macropinocytosis mechanism (phagocytosis only in the THP-1 model) and sporadically by direct penetration. In all the cell lines, the intracellular presence of NWs induces the same molecular events: peroxidation of membrane lipids and oxidation of proteins. These effects are late and may be limited by the activation of protection systems, for instance the effect of ROS is not acute and effectively countered by the intracellular scavenger. Our results highlight that the core-shell 3C-SiC-SiO2 NWs do not elicit either midterm (72 h) or long-term (10 day) cytotoxic activity leading to irreversible cellular damages or death. In Section 10.4 it was shown that the hybrid nanosystem formed by core-shell NWs conjugated with an organic photosensitizer, a tetracarboxyphenyl porphyrin derivative, is an efficient source of singlet oxygen under 6 MV X-ray irradiation. Further, this nanosystem is effective for SLPDT tests in vitro on lung cancer cells cultured with the functionalized NWs and irradiated in a clinical linear accelerator for radiation therapy. The experimental results validate the nanosystem in view of nanomedicine applications aimed at the definition of more effective and synergic treatments of tumors deep inside the body. In Section 10.5 it was shown that core-shell 3C-SiC-SiO2 NWs and bare 3C-SiC NWs could be used as a biomimetic biomaterial for cell cultures, providing a biological interface that is biocompatible according to ISO 10993 standards. The blood compatibility of the NWs was also evaluated analyzing the interaction of the NW platforms with PRP, in agreement with ISO 10993-4 guidelines. The analysis of adhesion and activation of platelets on the NW bundles indicates that a higher platelet activation was induced by the core-shell structures compared to the bare ones. These data suggest that SiC-SiO2 NWs may be suitable for tissue regeneration, while SiC NWs may be exploited for implantable prosthetic devices.

The BCR/ABL fusion protein is a constitutively active tyrosine kinase that is responsible for the pathogenesis of chronic myelogenous leukemia (CML). Clinically, CML is characterized by a chronic phase (CP) that eventually terminates into a blast crisis (BC). BC transformation is associated with accumulation of CD34+ blasts. We investigated the expression and phosphorylation of Src-homology-2 and collagen-homology domains (SHC) [corrected] proteins in subpopulations of CML primary cells. Shc polypeptides are tyrosine kinase substrates that are constitutively tyrosine-phosphorylated in continuous cell lines of CML origin. High levels of Shc expression were found in the CD34+ cells from CML-BC, CML-CP and normal bone marrow. In contrast, CD34- fractions from CML-CP and normal bone marrow expressed low levels of p46Shc. Shc proteins were constitutively phosphorylated in the CD34+ fractions from CML cells (both CP and BC), but not in normal CD34+ cells. These data bear implications for the role of Shc in normal hemopoiesis and CML leukemogenesis: (a) dramatic changes of Shc expression during terminal differentiation of hemopoietic cells adds a further level of regulation to the signal transduction function of Shc; and (b) constitutive Shc tyrosine-phosphorylation in the rare CD34+ cells of CML-CP might contribute to the selection of this subpopulation during the blast crisis transformation of CMLs.