Head and neck cancer (HNC) concerns more than 890,000 patients worldwide annually and is associated with the advanced stage at presentation and heavy outcomes. Alcohol drinking, together with tobacco smoking, and human papillomavirus infection are the main recognized risk factors. The tumorigenesis of HNC represents an intricate sequential process that implicates a gradual acquisition of genetic and epigenetics alterations targeting crucial pathways regulating cell growth, motility, and stromal interactions. Tumor microenvironment and growth factors also play a major role in HNC. Alcohol toxicity is caused both directly by ethanol and indirectly by its metabolic products, with the involvement of the oral microbiota and oxidative stress; alcohol might enhance the exposure of epithelial cells to carcinogens, causing epigenetic modifications, DNA damage, and inaccurate DNA repair with the formation of DNA adducts. Long-term markers of alcohol consumption, especially those detected in the hair, may provide crucial information on the real alcohol drinking of HNC patients. Strategies for prevention could include food supplements as polyphenols, and alkylating drugs as therapy that play a key role in HNC management. Indeed, polyphenols throughout their antioxidant and anti-inflammatory actions may counteract or limit the toxic effect of alcohol whereas alkylating agents inhibiting cancer cells’ growth could reduce the carcinogenic damage induced by alcohol. Despite the established association between alcohol and HNC, a concerning pattern of alcohol consumption in survivors of HNC has been shown. It is of primary importance to increase the awareness of cancer risks associated with alcohol consumption, both in oncologic patients and the general population, to provide advice for reducing HNC prevalence and complications.

Both physiological and pathological aging processes induce brain alterations especially affecting the speed of processing, working memory, conceptual reasoning and executive functions. Many therapeutic approaches to reduce the impact of brain aging on cognitive functioning have been tested; unfortunately, there are no satisfactory results as a single therapy. As aging is partly contributed by free radical reactions, it has been proposed that exogenous antioxidants could have a positive impact on both aging and its associated manifestations. The aim of this report is to provide a summary and a subsequent review of the literature evidence on the role of antioxidants in preventing and improving cognition in the aging brain. Manipulation of endogenous cellular defense mechanisms through nutritional antioxidants or pharmacological compounds represents an innovative approach to therapeutic intervention in diseases causing brain tissue damage, such as neurodegeneration. Coherently with this notion, antioxidants, especially those derived from the Mediterranean diet such as hydroxytyrosol and resveratrol, seem to be able to delay and modulate the cognitive brain aging processes and decrease the occurrence of its effects on the brain. The potential preventive activity of antioxidants should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability, able to bypass the blood-brain barrier limitation, and that are well standardized.

Nerve growth factor (NGF) plays a dual role both in inflammatory states and cancer, acting both as a pro-inflammatory and oncogenic factor and as an anti-inflammatory and pro-apoptotic mediator in a context-dependent way based on the signaling networks and its interaction with diverse cellular components within the microenvironment. This report aims to provide a summary and subsequent review of the literature on the role of NGF in regulating the inflammatory microenvironment and tumor cell growth, survival, and death. The role of NGF in inflammation and tumorigenesis as a component of the inflammatory system, its interaction with the various components of the respective microenvironments, its ability to cause epigenetic changes, and its role in the treatment of cancer have been highlighted in this paper.

: Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects of gestational alcohol use have been well documented, only recently the role of paternal preconceptual alcohol consumption (PPAC) prior to copulating has drawn specific epigenetic considerations. Solid human and animal model data demonstrated that PPAC may affect sperm function eliciting oxidative stress. In newborns, PPAC may induce changes in the behavior, cognitive functions and emotional responses. Furthermore, PPAC may elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill disruptions, hearing loss, endocrine and immune alterations, reduced physical growth, placental disruptions and metabolic alterations. Neurobiological studies on PPAC disclosed also changes in brain function and structure by the disruption of the growth factors pathways. In particular, as shown in animal model studies PPAC alters brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) synthesis and release. This review shows that the crucial topic of lifelong disabilities induced by PPAC and/or gestational alcohol drinking is quite challenging at the individual, societal, and familial levels. Since a nontoxic drinking behavior before pregnancy (for both men and women) during pregnancy and lactation cannot be established the only suggestion for couples planning pregnancies is to completely avoid the consumption of alcoholic beverages.

Neurodegenerative disorders, mental conditions, and cognitive decline represent significant challenges worldwide, with growing pieces of evidence implicating alterations in neurotrophin signaling as central to these diseases. Neurotrophins—such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)—are indispensable for neuronal survival, differentiation, and synaptic plasticity, and their dysregulation is closely associated with various neuropathological situations. Similarly, dietary plant polyphenols, abundant in vegetables, fruits, wine, tea, and extra virgin olive oil, show powerful anti-inflammatory, antioxidant, and anti-apoptotic activities. This narrative review critically addresses the evolving body of evidence that links plant polyphenols and brain neurotrophins, emphasizing several molecular mechanisms by which polyphenols regulate and modulate neurotrophin signaling. Crucial pathways include mitigation of neuroinflammatory responses, activation of intracellular cascades such as the cAMP response element-binding protein (CREB), epigenetic modulation, and the diminution of oxidative stress. Together, these effects contribute to potentiated enhanced synaptic function, neuronal integrity, and better learning and memory processes. Moreover, this narrative review examines how polyphenol-induced upregulation of neurotrophins may alleviate conditions associated not only with neurodegeneration but also with addiction and mood disorders, suggesting extensive therapeutic approaches. Findings from clinical investigations and animal models are presented to sustain the neuroprotective role of polyphenol-rich diets. Lastly, future research directions are recommended, focusing on polyphenol bioavailability optimization, considering combinatory dietary stratagems, and proposing personalized nutritional interventions. This wide-ranging perspective highlights plant polyphenols as encouraging modulators of neurotrophin pathways and supports their inclusion in approaches aimed at promoting brain health and counteracting neurodegenerative decline.

Fetal alcohol spectrum disorders (FASD) represent a continuum of lifelong impairments resulting from prenatal exposure to alcohol, with significant global impact. The “spectrum” of disorders includes a continuum of physical, cognitive, behavioral, and developmental impairments which can have profound and lasting effects on individuals throughout their lives, impacting their health, social interactions, psychological well-being, and every aspect of their lives. This narrative paper explores the intricate relationship between oxidative stress and epigenetics in FASD pathogenesis and its therapeutic implications. Oxidative stress, induced by alcohol metabolism, disrupts cellular components, particularly in the vulnerable fetal brain, leading to aberrant development. Furthermore, oxidative stress is implicated in epigenetic changes, including alterations in DNA methylation, histone modifications, and microRNA expression, which influence gene regulation in FASD patients. Moreover, mitochondrial dysfunction and neuroinflammation contribute to epigenetic changes associated with FASD. Understanding these mechanisms holds promise for targeted therapeutic interventions. This includes antioxidant supplementation and lifestyle modifications to mitigate FASD-related impairments. While preclinical studies show promise, further clinical trials are needed to validate these interventions’ efficacy in improving clinical outcomes for individuals affected by FASD. This comprehensive understanding of the role of oxidative stress in epigenetics in FASD underscores the importance of multidisciplinary approaches for diagnosis, management, and prevention strategies. Continued research in this field is crucial for advancing our knowledge and developing effective interventions to address this significant public health concern.