The Impact of Oxidative Stress on the Epigenetics of Fetal Alcohol Spectrum Disorders.

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.

The Impact of ROS and NGF in the Gliomagenesis and their Emerging Implications in the Glioma Treatment.

Reactive oxygen species (ROS) are highly reactive molecules derived from molecular oxygen (O2). ROS sources can be endogenous, such as cellular organelles and inflammatory cells, or exogenous, such as ionizing radiation, alcohol, food, tobacco, chemotherapeutical agents and infectious agents. Oxidative stress results in damage of several cellular structures (lipids, proteins, lipoproteins, and DNA) and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging. A large body of studies showed that ROS plays an important role in carcinogenesis. Indeed, increased production of ROS causes accumulation in DNA damage leading to tumorigenesis. Various investigations demonstrated the involvement of ROS in gliomagenesis. The most common type of primary intracranial tumor in adults is represented by glioma. Furthermore, there is growing attention on the role of the Nerve Growth Factor (NGF) in brain tumor pathogenesis. NGF is a growth factor belonging to the family of neurotrophins. It is involved in neuronal differentiation, proliferation and survival. Studies were conducted to investigate NGF pathogenesis's role as a pro- or anti-tumoral factor in brain tumors. It has been observed that NGF can induce both differentiation and proliferation in cells. The involvement of NGF in the pathogenesis of brain tumors leads to the hypothesis of a possible implication of NGF in new therapeutic strategies. Recent studies have focused on the role of neurotrophin receptors as potential targets in glioma therapy. This review provides an updated overview of the role of ROS and NGF in gliomagenesis and their emerging role in glioma treatment.

The Impact of Alcohol Consumption and Oral Microbiota on Upper Aerodigestive Tract Carcinomas: A Pilot Study.

Alcohol consumption is associated with oxidative stress and an increased risk of carcinoma of the upper aero-digestive tract (UADT). Recently, it has been found that some microorganisms in the human oral cavity may locally metabolize ethanol, forming acetaldehyde, a carcinogenic metabolite of alcohol. In a cohort of patients first visited for UADT cancers, we estimated their alcohol consumption by measuring Ethyl Glucuronide/EtG (a long-lasting metabolite of ethanol) in the hair and carbohydrate-deficient transferrin/CDT (short-term index of alcohol intake) in the serum. Moreover, we analyzed, by culture-based methods, the presence of Neisseria subflava, Streptococcus mitis, Candida albicans, and glabrata (microorganisms generating acetaldehyde) in the oral cavity. According to the EtG values, we correlated drinking alcohol with endogenous oxidative stress and the investigated microorganism's presence. We found that 55% of heavy drinkers presented microorganisms generating acetaldehyde locally. Moreover, we found that the presence of oral acetaldehyde-producing bacteria correlates with increased oxidative stress compared to patients without such bacteria. As for the study of alcohol dehydrogenase gene polymorphisms (the enzyme that transforms alcohol to acetaldehyde), we found that only the "CGTCGTCCC" haplotype was more frequent in the general population than in carcinoma patients. This pilot study suggests the importance of estimating alcohol consumption (EtG), the presence of bacteria producing acetaldehyde, and oxidative stress as risk factors for the onset of oral carcinomas.

Urine Dipstick Analysis on Automated Platforms: Is a Reliable Screening Tool for Proteinuria? An Experience from Umberto I Hospital in Rome.

Urinalysis is commonly used as a screening tool for kidney disease. In many cases, the dipstick urine assay includes the assessment of albumin/protein and creatinine; consequently, the value of their ratio is available on the urine section report. Identification of albuminuria/proteinuria at early stages is an important issue to prevent or at least delay the onset of chronic kidney disease (CKD), kidney failure, and the progression of cardiovascular damage linked to the kidney's loss of function. Sensitive and specific diagnostic methods are required for the assessment of such an important biomarker: urine albumin, creatinine, and their ratio (ACR) measured with quantitative assays are considered the gold standard. Routine dipstick methods (more rapid and at a lower cost) are intended for wide population screening. The aim of our study was to verify the reliability of an automated urinalysis dipstick method by comparing the results with the quantitative test of creatinine and albumin performed on a clinical chemistry platform. The first-morning voids of 249 patients who arrived from different departments were analyzed in the Central Laboratory of the University Hospital Policlinico Umberto I in Rome. We found a good correlation between the two assays, even though we observed that the dipstick assessment tends to overestimate the ACR's value, disclosing a higher number of false positives if compared to the reference method. As an important novelty in this study, we analyzed our data considering age (starting from pediatric to geriatric patients) and sex as variables for a sub-stratification of the participants. Our results show that positive values need to be confirmed with quantitative methods, especially in women and younger people, and that from samples that resulted as diluted at the dipstick assay, the ACR's values can be obtained if they are reanalyzed with quantitative assays. Moreover, patients with microalbuminuria (ACR 30-300 mg/g) or severe albumin urinary excretion (ACR > 300 mg/g) should be reanalyzed using quantitative methods to obtain a more reliable calculation of the ACR.

Investigating Biomarkers for COVID-19 Morbidity and Mortality.

BACKGROUND AND OBJECTIVES: This retrospective study aims to disclose further early parameters of COVID-19 morbidity and mortality. METHODS: Three hundred and eighty-two COVID-19 patients, recruited between March and April 2020, were divided into three groups according to their outcome: (1) hospital ward group (patients who entered the hospital wards and survived); (2) intensive care unit (ICU) group (patients who attended the ICU and survived); (3) the deceased group (patients admitted to ICU with a fatal outcome). We investigated routine laboratory parameters such as albumin, glycemia, hemoglobin amylase, lipase, AST, ALT, GGT, LDH, CK, MGB, TnT-hs, IL-6, ferritin, CRP, PCT, WBC, RBC, PLT, PT, INR, APTT, FBG, and D-dimer. Blood withdrawal was carried out at the beginning of the hospitalization period. RESULTS: ANOVA and ROC data evidenced that the concomitant presence of alterations in albumin, lipase, AST, ALT, LDH, MGB, CK, IL-6, ferritin in women, CRP and D-dimer is an early sign of fatal outcomes. CONCLUSION: The present study confirms and extends the validity of routine laboratory biomarkers (i.e., lipase, AST, ALT, LDH, CK, IL-6, ferritin in women, CRP and D-dimer) as indicators of COVID-19 morbidity and mortality. Furthermore, the investigation suggests that both gross changes in albumin and MGB, markers of liver and heart damage, may early disclose COVID-19 fatal outcomes.

The RNA-Binding Protein SMN as a Novel Player in Laryngeal Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here, we focus on the SMN in the cancer context. We conducted a pilot study in a total of 20 patients with LSCC where the SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that the SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between the SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumors. This study proposes the SMN protein as a novel therapeutic target in LSSC and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of the SMN in human cancer.

Antioxidant Intervention to Improve Cognition in the Aging Brain: The Example of Hydroxytyrosol and Resveratrol.

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.

NGF and the Male Reproductive System: Potential Clinical Applications in Infertility.

Infertility is a worldwide health issue defined by the World Health Organization (WHO) as the inability to establish a pregnancy after 12 months or more of regular and unprotected sexual intercourse. Male infertility etiology can be related to either congenital or acquired factors. The therapeutical approach to male infertility depends on the underlying causes and includes medical and surgical treatments. In recent studies, the potential role of nerve growth factor (NGF) in male reproductive physiology has been proposed. It has been hypothesized that neurotrophins might be involved in testis morphogenesis and regulation of several aspects of spermatogenesis. Moreover, it has been shown that NGF exerts its role on gonadotropin-releasing hormone (GnRH) neurons through the activation of the PKC/p-ERK1/2/p-CREB cascade, which leads to the activation of hypothalamic cells and the consequent activation of hypothalamus-pituitary-gonadal axis (HPG) with the secretion of GnRH. Lastly, it has been shown that the physiology of mature sperm is affected by both exogenous and endogenous NGF. The NGF impact on the HPG axis and its effect on GnRH neurons might be exploited in the therapy of male hypogonadism or used as a protective strategy against gonadal dysfunction related to chemotherapeutic agents. Moreover, the improving effect of NGF on sperm motility and vitality could be useful to enhance assisted reproduction outcomes. NGF could be supplemented to cryopreserved sperm samples to counteract the oxidative stress induced by the frozen and thawing processes. Indeed, the potential clinical applications of NGF in male infertility treatment have been discussed.

Behavioral dysregulations by chronic alcohol abuse. Motivational enhancement therapy and cognitive behavioral therapy outcomes.

Patients with alcohol use disorder (AUD) do not manifest homogeneous clinical symptoms. Various studies described both cognitive impairments and psychiatric disorders among people with AUD. This disorder is one of the most frequent mental disorders in developed countries, due to excessive alcohol consumption. Alcohol is toxic as it increases the production of reactive oxygen species (ROS) and can cause dependence. This causes negative effects on brain development and cognitive functions that affect the individual's work, health, and social life. Current pharmacology treatment for alcohol addiction is based on direct action against the neurotransmitters involved in alcohol dependence. AUD patients without comorbid psychiatric disorders or severe cognitive deficits are defined as "pure alcoholics". To date, poor is known about effective treatments for this typology of AUD patients. Psychotherapy is largely used in resolving many psychiatric disorders, including substance use disorders. Motivational enhancement therapy (MET) and cognitive-behavioral therapy (CBT) are two psychotherapies used to achieve and maintain abstinence in patients affected by substance use disorders. This short review aims to describe two CBT and MET and to present the advantages and disadvantages of these two psychotherapies in the treatment of AUD.