Human neural stem cell drug product, culturing and characterization of cell lines for treatment of secondary progressive multiple sclerosis

For several years, human neural stem cells (hNSCs) have been a focus of research, with recent attention to their potential as a cellular treatment for neurodegenerative disorders. The works of Weiss and Reynolds in the 1990s established methods for in vitro cultivation of hNSCs from neural tissue biopsies taken from the subventricular zone (SVZ). Subsequent characterization and development of appropriate potency and safety tests have paved the way for clinical trials exploring the use of thes...

Validation of an mRNA vaccine platform expressing eGFP and development of a recombinant Streptococcus gordonii as live vaccine vector

Thesis project involved the development of an mRNA and a recombinant Streptococcus gordonii vaccine model. The mRNA vaccine was produced starting from the design of a DNA plasmid template encoding for the enhanced Green Fluorescent Protein (eGFP) (Chapter 2). The mRNA was transcribed, modified and complexed with a delivery system. The vaccine complex obtained was evaluated for the transfection efficiency and the protein expression in two mammalian cell lines: HeLa cells and C2C12 cells. The e...

Impact of Streptococcus pyogenes prophage Φ1207.3 on bacterial host response to stress conditions

The SOS response is an inducible system activated by some bacterial species in the presence of stressful conditions and extensive DNA damage. Streptococci lack a canonical SOS response, but an SOS-like response was reported in some species. The mef(A)-msr(D)-carrying prophage Ф1207.3 of Streptococcus pyogenes contains a DNA region, spanning from orf6 to orf11, showing homology to characterized streptococcal SOS-like cassettes. In the present thesis, the impact of prophage Φ1207.3 SOS-like cas...

Three essays on the evaluation of public policies in the field of addictions

Epigenetic analyses in Autism Spectrum Disorders: gender differences and the contribution of maternal risk factors

ASD are one of the largest groups of complex neurodevelopment disorders that affect about 1-2% of the population with a greater frequency in males, in a ratio of 4.5: 1. The diagnosis of ASD is made on the basis of the clinical observation of the subject and the use of standardized assessment scales, such as ADOS and ADI-R. In recent decades, the prevalence of this disorder has increased significantly and this is thought to be due to both a better understanding of the problem and an improveme...

CRISPR/Cpf1 and suicide gene as personalized approach for patients with TP53-mutated Chronic Lymphocytic Leukemia (CLL)

Il codice F-Pn6771 (Reina): contenuto, struttura, generi

MOLECULAR MECHANISMS OF ANGIOGENESIS-RELATED OCULAR DISEASES IN PRECLINICAL MODELS

Neovascularization in the eye contributes to visual loss in several ocular diseases, including proliferative diabetic retinopathy (PDR), neovascular glaucoma (NVG) and retinopathy of prematurity (ROP). In these diseases, the neovascular mechanisms originate from the retina, but some advanced stages of PDR or nG can lead to the development of rubeosis iridis (RI), a clinical manifestation characterized by iris angiogenesis. Vascular endothelial growth factors (VEGFs) and their receptor (VEGFRs...

Function and targeting of the Hedgehog signaling in human cholangiocarcinoma and melanoma

ABSTRACT Hedgehog (HH) signaling is a conserved pathway that plays a pivotal role during embryonic development, tissue homeostasis and regeneration. Aberrant activation of the HH pathway has been reported to drive tumor progression in numerous cancers, including those of the skin, brain, lung and breast. The key signaling components of the HH signaling are the ligands, the cell membrane receptor Smoothened and the three transcription factors GLI1, GLI2 and GLI3, which upon activation of th...