Background: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and are strongly influenced by dietary habits. Beyond caloric intake, nutrients act as molecular signals that regulate cardiac metabolism, mitochondrial function, inflammation, and epigenetic remodeling. Objectives: This review aims to synthesize current evidence on how dietary patterns and specific nutritional interventions regulate cardiac metabolism and function through interconnected molecular and epigenetic mechanisms, highlighting their relevance for cardiovascular disease prevention. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science, focusing on studies published between 2006 and 2025. Experimental, translational, and clinical studies addressing diet-induced modulation of cardiac metabolic pathways, oxidative and inflammatory signaling, epigenetic regulation, and gut microbiota-derived metabolites were included. Results: The analyzed literature consistently shows that unbalanced diets rich in saturated fats and refined carbohydrates impair cardiac metabolic flexibility by disrupting key nutrient-sensing pathways, including AMP-activated protein kinase (AMPK), proliferator-activated receptor alpha (PPARα), mammalian target of rapamycin (mTOR), and sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1/PGC-1α), leading to mitochondrial dysfunction, oxidative stress, chronic inflammation, and maladaptive remodeling. In contrast, cardioprotective dietary patterns, such as caloric restriction (CR), intermittent fasting (IF), and Mediterranean and plant-based diets, enhance mitochondrial efficiency, redox balance, and metabolic adaptability. These effects are mediated by coordinated activation of AMPK-SIRT1 signaling, suppression of mTOR over-activation, modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, and favorable epigenetic remodeling involving DNA methylation, histone modifications, and non-coding RNAs. Emerging evidence also highlights the central role of gut microbiota-derived metabolites, particularly short-chain fatty acids, in linking diet to epigenetic and metabolic regulation of cardiac function. Conclusions: Diet quality emerges as a key determinant of cardiac metabolic health, acting through integrated molecular, epigenetic, and microbiota-mediated mechanisms. Targeted nutritional strategies can induce long-lasting cardioprotective metabolic and epigenetic adaptations, supporting the concept of diet as a modifiable molecular intervention. These findings provide a mechanistic rationale for integrating personalized nutrition into cardiovascular prevention and precision cardiology, complementing standard pharmacological therapies.

The intrinsically disordered protein (IDP) c-Myc plays a crucial role in regulating cell growth, proliferation, and apoptosis, making it a significant target for cancer therapy. Herein, we report an integrated approach combining computational and biological methods to uncover key c-Myc structural aspects aimed at identifying modulators of this protein. A virtual screening campaign starting from commercially available libraries was performed, leading to the selection of 11 promising c-Myc binders. Preliminary biophysical and biological analysis, including Surface Plasmon Resonance (SPR) and MTT [(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)] assays, highlighted three new potential c-Myc/Max heterodimerization inhibitors. Among them, 11 emerged as the most active one, displaying promising dissociation costant (K_D) values on c-Myc (~ 60 μM), only slightly higher than the known binder 10058-F4 (with a K_D ~ 40 μM) and on Max (with a K_D ~ 80 μM). Notably, 11 showed significant antiproliferative effects on three different malignant cell lines (i.e., U937, HCT-116, and HT-29, as models of acute myeloid leukemia and colorectal cancer cell lines, respectively) in a dose- and cell-dependent manner. Importantly, a significant decrease in c-Myc levels was observed, especially in U937 leukemia cells with an 85 % reduction. Finally, molecular dynamics simulations and proteomic studies were performed to identify its binding site and key interacting residues. In summary, this work presents a robust research strategy and offers valuable insights for identifying new c-Myc/Max disruptors.

MYC gene has become one of the most investigated oncogenes for regulating programmed cell death and tumor growth. MYC is a transcription factor that regulates the expression of numerous genes involved in critical cellular processes, such as metabolism, stress response, and proliferation. However, its dysfunction, often caused by gene amplifications or translocations, makes it a potent oncogenic driver, contributing to uncontrolled growth, angiogenesis, invasiveness, and metastasis. Paradoxically, MYC can promote both tumor cell survival and elimination through the activation of apoptotic mechanisms, creating a delicate balance between cell survival and death. This chapter explores the dual role of MYC as a regulator of cell life and death, analyzing the molecular mechanisms that determine its activity in different biological contexts. The main apoptotic pathways controlled by MYC, its contribution to tumor plasticity, and its interactions with other oncogenes and tumor suppressors will be discussed. Finally, emerging therapeutic strategies aimed at targeting MYC or its regulatory networks will be reviewed, along with the challenges of translating this knowledge into clinical interventions. A thorough understanding of MYC biology is crucial to develop innovative therapies and improve the treatment of aggressive and resistant tumors.