Background: Melanoma, one of the most aggressive forms of skin cancer, has seen significant therapeutic advances with immune checkpoint inhibitors (ICIs). However, many patients fail to respond or develop resistance, creating the need for adjunct strategies. Objective: The objective of this study is to critically evaluate how specific dietary patterns and nutrient-derived metabolites modulate melanoma metabolism and immunotherapy outcomes, emphasizing translational implications. Methods: We performed an integrative review of preclinical and clinical studies investigating dietary interventions in melanoma models and ICI-treated patients. Mechanistic insights were extracted from studies on nutrient transport, immunometabolism, and microbiome–immune interactions, including data from ongoing nutritional clinical trials. Results: Diets rich in fermentable fibers, plant polyphenols, and unsaturated lipids, such as Mediterranean and ketogenic diets, seem to contribute to the reprogramming of tumor metabolism and enhance CD8+ T-cell activity. Fasting-mimicking and methionine-restricted diets modulate T-cell fitness and tumor vulnerability via nutrient stress sensors (e.g., UPR, mTOR). High fiber intake correlates with favorable gut microbiota and improved ICI efficacy, while excess protein, methionine, or refined carbohydrates impair immune surveillance via lactate accumulation and immunosuppressive myeloid recruitment. Several dietary molecules act as network-level modulators of host and microbial proteins, with parallels to known drug scaffolds. Conclusions: Integrating dietary interventions into melanoma immunotherapy can significantly influence metabolic reprogramming by targeting metabolic vulnerabilities and reshaping the tumor–immune–microbiome axis. When combined with AI-driven nutrient–protein interaction mapping, this approach offers a precision nutrition paradigm that supports both physicians and patients, emerging as a novel layer to enhance and consolidate existing therapeutic strategies.

Mitochondrial tRNA genes are critical hotspots for pathogenic mutations and several mitochondrial diseases. They account for approximately 70–75% of disease-causing mtDNA variants despite comprising only 5–10% of the mitochondrial genome. These mutations interfere with mitochondrial translation and affect oxidative phosphorylation, resulting in remarkably heterogeneous multisystem disorders. Under this light, we systematically reviewed PubMed, Scopus, and MITOMAP databases through October 2025, indexing all clinically relevant pathogenic mt-tRNA mutations classified by affected organ systems and underlying molecular mechanisms. Approximately 500 distinct pathogenic variants were identified across all 22 mt-tRNA genes. Beyond typical syndromes like MELAS, MERRF, Leigh syndrome, and Kearns–Sayre syndrome that are linked to mt-tRNA mutations, they increasingly implicate cardiovascular diseases (cardiomyopathy, hypertension), neuromuscular disorders (myopathies, encephalopathies), sensory impairment (hearing loss, optic neuropathy), metabolic dysfunction (diabetes, polycystic ovary syndrome), renal disease, neuropsychiatric conditions, and cancer. Beyond sequence mutations, defects in post-transcriptional modification systems emerge as critical disease mechanisms affecting mt-tRNA function and stability. The mutations on tRNA genes described herein represent potential targets for emerging genome editing therapies, although several translational challenges remain. However, targeted correction of pathogenic mt-tRNA mutations holds transformative potential for precision intervention on mitochondrial diseases.

Background: Atopic dermatitis (AD), allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP) represent interconnected conditions within the spectrum of type 2 inflammatory diseases. While these conditions share common genetic and epigenetic pathways, the precise molecular mechanisms remain underexplored. Methods: This review integrates the latest insights on the genetic and epigenetic factors linking AD, AR, and CRSwNP, focusing on genome-wide association studies, DNA methylation patterns, histone modifications, and microRNA regulation. Results: In all three conditions, epigenetic modifications, including DNA methylation (Me) and histone acetylation (Ac) and methylation, regulate inflammatory and barrier-related genes, influencing disease severity. Notably, miRNAs such as miR-146a and miR-155 play pivotal roles in modulating inflammation across all three diseases, while disease-specific miRNAs contribute to airway remodeling (miR-125b and miR-21 in AR and CRSwNP). Emerging evidence underscores the role of microbiome-driven inflammasome activation and matrix metalloproteinases (MMP-2, MMP-9, and MMP-12) in perpetuating chronic inflammation and remodeling. Conclusions: The interplay between genetic predispositions, epigenetic modifications, and exposomal factors underscores the systemic nature of type 2 inflammation. A deeper understanding of these interconnected mechanisms could lead to transformative, personalized diagnostic and therapeutic advancements.