TRANSIENT TELOMERASE INDUCTION IN MYOGENIC PROGENITOR CELLS TO OVERCOME STEM CELL EXHAUSTION IN DUCHENNE MUSCULAR DYSTROPHY

Duchenne muscular dystrophy (DMD) is an X-linked disease marked by progressive muscle wasting, failed regeneration, and eventual cardiac or respiratory failure. Loss of dystrophin causes repeated cycles of degeneration and regeneration driven by membrane fragility and calcium overload. Over time, satellite cells—the main muscle stem cell population—lose their regenerative capacity, leading to fibrosis and fat infiltration that further impair muscle function. Although muscle can robustly regen...

Uncovering data-driven subtypes of depression based on neurobiological and environmental signatures: a machine learning approach

Mood disorders are clinically and biologically heterogeneous, with patients significantly differing in symptom profiles, clinical course, underlying neurobiology, genetic liability, and environmental exposures. This heterogeneity has long hampered the identification of reliable biomarkers and limited treatment efficacy. Recent attempts to stratify patients based on shared characteristics employed single-modality approaches and lacked external validation. Therefore, by leveraging advances in c...

BASE EDITING OF AN UPSTREAM ORF IN SCN1A ENHANCES TRANSLATION TO RESTORE GENE DOSAGE IN DRAVET SYNDROME

Voltage-gated sodium channels (VGSCs) are crucial for controlling the electrical activity of cells and mutations in SCN genes, which encode the α subunits of these channels (NaV), can lead to severe neurological and non-neurological conditions. Among these, Developmental Epileptic Encephalopathies (DEE), particularly Dravet syndrome (DS), are some of the most devastating. DS results from heterozygous mutations in the SCN1A gene, causing loss of function of NaV1.1, which is mainly expressed in...

RETE MULTIDISCIPLINARE PER IL CODICE OSA (SINDROME DELLE APNEE OSTRUTTIVE DEL SONNO): MODELLO OPERATIVO DIGITALE IN SANITÀ PUBBLICA PER UNA DIAGNOSI PRECOCE E IL MONITORAGGIO DELLA TERAPIA.

La sindrome delle apnee ostruttive del sonno (OSA) è associata a un aumento del rischio di declino cognitivo e di progressione verso forme di deterioramento come il mild cognitive impairment (MCI) e la malattia di Alzheimer (AD). Tuttavia, resta da chiarire se i dati clinici e polisonnografici raccolti al momento della diagnosi siano in grado di prevedere con affidabilità un peggioramento cognitivo nel breve termine. Questo studio ha esaminato il valore predittivo di variabili demografiche, a...

Role of tumor-associated Kupffer cells in liver metastasis seeding and growth

Colorectal cancer and pancreatic ductal adenocarcinoma are among the leading causes of cancer-related mortality. Notably, drainage from gastrointestinal tumors (GITs) into the liver exposes this immunoregulatory organ to high antigenic loads. We investigated how the liver’s immune milieu contributes to tumor progression through two interconnected approaches: the development of an in vivo gene therapy platform using lentiviral vectors (LVs), and the study of how tumor antigens (TAs) released b...

Interfering with mevalonate pathway to unleash effective antitumor response in melanoma

Immune checkpoint inhibitors (ICIs) have significantly improved survival in metastatic melanoma; however, most patients eventually experience disease progression and death. Emerging evidence suggests that statin therapy, widely prescribed for cardiovascular comorbidities, may potentiate ICIs efficacy, although the underlying mechanisms remain incompletely understood. Taking advantage of a unique clinical records of 66 patients with metastatic melanoma, including 20 receiving statin therapy c...

CONTROLLO COGNITIVO DURANTE IL SONNO: LO STRANO CASO DELL'AUTO-RISVEGLIO

Il presente progetto di dottorato esplora i meccanismi cognitivi e neurofisiologici alla base del fenomeno del self-awakening, definito come la capacità volontaria di svegliarsi a un’ora prestabilita senza stimoli esterni. Pur descritto già dal XIX secolo, tale fenomeno rimane poco studiato e raramente indagato con metodiche neurofisiologiche oggettive. Trenta adulti sani (20 non self-awakeners: 9 femmine, 11 maschi; età media 25 anni, e 10 self-awakeners: 4 femmine, 6 maschi; età media 23,5...

EXPLOITING CELLULAR IMMUNOTHERAPY STRATEGIES FOR PARKINSON’S DISEASE

Parkinson's disease (PD) is characterized by progressive neurodegeneration and chronic neuroinflammation driven by pathological -synuclein (Syn) accumulation. Regulatory T cells (Tregs) represent a promising therapeutic tool to restore immune homeostasis, however, their stability and antigen specificity are critical limitations. This study aimed to engineer Syn-specific chimeric antigen receptor (CAR) Tregs for targeted immunomodulation in PD. Initially, retroviral transduction of murine C...

Nuovi approcci della consulenza filosofica: il contributo trasformativo del pensiero religioso e dei linguaggi simbolici.