Taste and Smell Alterations (TSAs) in Cancer Patients.

Recently, smell and taste disorders have seen renewed interest, as these symptoms are frequent complications of SARS-CoV-2 infection, since approximately 60% of patients affected by COVID-19 have shown olfactory and gustatory alterations. Otolaryngology pays attention to taste and smell abnormalities (TSAs), especially when associated with oncology. TSAs are common symptoms in people affected by cancer, yet they are ignored and underestimated. The clinical outcome of TSAs in cancer evidences the importance of identifying them with chemotherapy or radiotherapy in general, and they are associated with many types of cancer. We recognize the findings of the literature on TSAs in cancer, evaluating how it is important to consider and identify these disorders concerning reduced food enjoyment or inappropriate nutrient intake, and modulating the nutritional status, quality of life, and impact of therapy. This review aims to critically evaluate and recognize the assessment and clinical perspectives of taste and smell disorders in a cancer population.

Malignant and Benign Head and Neck Tumors of the Pediatric Age: A Narrative Review.

Malignant tumors of the head and neck are rare in children, but it is important to know these lesions and identify them early in order to have a good outcome for these patients. Benign lesions of the head and neck are much more frequent and have an excellent prognosis. For this reason, it is necessary to recognize the warning signs and symptoms and understand when to refer the patient to a reference center for the treatment of these pathologies. The clinical presentation of both benign and malignant lesions in children may be similar as usually, both categories have compressive effects. This confirms the fact that the clinical diagnosis is not sufficient and always requires instrumental investigations and biopsies. In this narrative review, we analyzed both malignant lesions such as lymphoma, rhabdomyosarcoma, thyroid tumors, salivary gland tumors, neuroblastoma, and nasopharyngeal carcinoma, and benign ones such as cystic dermoid teratoma, hemangioma, juvenile angiofibroma and fibrosis dysplasia. Indeed, we set out to discuss the most common lesions of this site by evaluating their characteristics to highlight the differentiation of malignant tumors from benign lesions and their correct clinical-therapeutic management. A literature search was carried out in the PubMed and Google Scholar databases to identify all narrative reviews addressing malignant and benign head and neck tumors of the pediatric age. In conclusion, the care of children affected by head and neck benign lesions and malignancy must be combined and multidisciplinary. It is essential to recognize the diseases early in order to differentiate and intervene as soon as possible for the correct clinical-therapeutic management.

Serum Lipocalin-2 Levels as a Biomarker in Pre- and Post-Pubertal Klinefelter Syndrome Patients: A Pilot Study.

Klinefelter syndrome (KS) is a male genetic disease caused by the presence of an extra X chromosome, causing endocrine disorders mainly responsible for a high rate of infertility and metabolic disorders in adulthood. Scientific research is interested in identifying new biomarkers that can be predictive or prognostic of alterations strictly connected to KS. Lipocalin-2 (LCN-2, also known as NGAL) is a small protein initially identified within neutrophils as a protein related to innate immunity. Serum LCN-2 estimation seems to be a useful tool in predicting the metabolic complications caused by several pathological conditions. However, little is known about its potential role in infertility conditions. The present pilot study aims to investigate the presence of LCN-2 in the serum of a group of pre-pubertal and post-pubertal children affected by KS, compared to healthy controls. We demonstrated for the first time the presence of elevated levels of LCN-2 in the serum of KS patients, compared to controls. This increase was accompanied, in pre-pubertal KS patients, by the loss of correlation with LH and HDL, which instead was present in the healthy individuals. Moreover, in all KS individuals, a positive correlation between LCN-2 and inhibin B serum concentration was found. Despite the limited size of the sample analyzed, our preliminary data encourage further studies to confirm the findings and to extend the study to KS adult patients, to verify the predictive/prognostic value of LCN-2 as new biomarker for metabolic diseases and infertility associated with the pathology.

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.

Head and Neck Squamous Cell Carcinoma Vaccine: Current Landscape and Perspectives.

The treatment of unresectable or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) has traditionally relied on chemotherapy or radiotherapy, yielding suboptimal outcomes. The introduction of immunotherapy has significantly improved HNSCC treatment, even if the long-term results cannot be defined as satisfactory. Its mechanism of action aims to counteract the blockade of tumor immune escape. This result can also be obtained by stimulating the immune system with vaccines. This review scope is to comprehensively gather existing evidence and summarize ongoing clinical trials focused on therapeutic vaccines for HNSCC treatment. The current landscape reveals numerous promising drugs in the early stages of experimentation, along with a multitude of trials that have been suspended or abandoned for years. Nonetheless, there are encouraging results and ongoing experiments that instill hope for potential paradigm shifts in HNSCC therapy.

Antioxidant Use after Diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC): A Systematic Review of Application during Radiotherapy and in Second Primary Cancer Prevention.

Approximately 5-20% of HNSCC patients experience second primary cancers within the first 5 years of treatment, contributing to high mortality rates. Epidemiological evidence has linked a low dietary intake of antioxidants to an increased risk of cancer, especially squamous cell carcinoma, prompting research into their potential in neoplasm chemoprevention. Cigarette smoking is the primary risk factor for HNSCC, and a diet rich in antioxidants offers protective effects against head and neck cancer. Paradoxically, smokers, who are at the highest risk, tend to consume fewer antioxidant-rich fruits and vegetables. This has led to the hypothesis that integrating antioxidants into the diet could play a role in both primary and secondary prevention for at-risk individuals. Furthermore, some HNSCC patients use antioxidant supplements during chemotherapy or radiotherapy to manage side effects, but their impact on cancer outcomes remains uncertain. This systematic review explores the evidence for the potential use of antioxidants in preventing second primary cancers in HNSCC patients. In conclusion, none of the antioxidants tested so far (α-tocopherol, ß-carotene, JP, Isotretinoin, interferon α-2a, vitamin E, retinyl palmitate, N-acetylcysteine) was effective in preventing second primary tumors in HNSCC patients, and they could only be used in reducing the side effects of radiotherapy. Further research is needed to better understand the interplay between antioxidants and cancer outcomes in this context.

Oxidative Stress in a Mother Consuming Alcohol during Pregnancy and in Her Newborn: A Case Report.

Fetal alcohol spectrum disorder (FASD) is a set of conditions resulting from prenatal alcohol exposure (PAE). FASD is estimated to affect between 2% and 5% of people in the United States and Western Europe. The exact teratogenic mechanism of alcohol on fetal development is still unclear. Ethanol (EtOH) contributes to the malfunctioning of the neurological system in children exposed in utero by decreasing glutathione peroxidase action, with an increase in the production of reactive oxygen species (ROS), which causes oxidative stress. We report a case of a mother with declared alcohol abuse and cigarette smoking during pregnancy. By analyzing the ethyl glucuronide (EtG, a metabolite of alcohol) and the nicotine/cotinine in the mother's hair and meconium, we confirmed the alcohol and smoking abuse magnitude. We also found that the mother during pregnancy was a cocaine abuser. As a result, her newborn was diagnosed with fetal alcohol syndrome (FAS). At the time of the delivery, the mother, but not the newborn, had an elevation in oxidative stress. However, the infant, a few days later, displayed marked potentiation in oxidative stress. The clinical complexity of the events involving the infant was presented and discussed, underlining also the importance that for cases of FASD, it is crucial to have more intensive hospital monitoring and controls during the initial days.

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.

Extra-Gonadal and Non-Canonical Effects of FSH in Males.

Recombinant follicle-stimulating hormone (FSH) is commonly used for the treatment of female infertility and is increasingly being used in males as well, as recommended by notable guidelines. FSH is composed of an α subunit, shared with other hormones, and a ß subunit, which confers specificity of biological action by interacting with its surface receptor (FSHR), predominantly located in granulosa and Sertoli cells. However, FSHRs also exist in extra-gonadal tissues, indicating potential effects beyond male fertility. Emerging evidence suggests that FSH may have extra-gonadal effects, including on bone metabolism, where it appears to stimulate bone resorption by binding to specific receptors on osteoclasts. Additionally, higher FSH levels have been associated with worse metabolic and cardiovascular outcomes, suggesting a possible impact on the cardiovascular system. FSH has also been implicated in immune response modulation, as FSHRs are expressed on immune cells and may influence inflammatory response. Furthermore, there is growing interest in the role of FSH in prostate cancer progression. This paper aims to provide a comprehensive analysis of the literature on the extra-gonadal effects of FSH in men, with a focus on the often-conflicting results reported in this field. Despite the contradictory findings, the potential for future development in this area is substantial, and further research is needed to elucidate the mechanisms underlying these effects and their clinical implications.

Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.

Programmed cell death ligand-1 (PD-L1) binds PD-1 on CD8+ lymphocytes, inhibiting their cytotoxic action. Its aberrant expression by head and neck squamous cell carcinoma (HNSCC) cells leads to immune escape. Pembrolizumab and nivolumab, two humanized monoclonal antibodies against PD-1, have been approved in HNSCC treatment, but ~60% of patients with recurrent or metastatic HNSCC fail to respond to immunotherapy and only 20 to 30% of treated patients have long-term benefits. The purpose of this review is to analyze all the fragmentary evidence present in the literature to identify what future diagnostic markers could be useful for predicting, together with PD-L1 CPS, the response to immunotherapy and its durability. We searched PubMed, Embase, and the Cochrane Register of Controlled Trials and we summarize the evidence collected in this review. We confirmed that PD-L1 CPS is a predictor of response to immunotherapy, but it should be measured across multiple biopsies and repeatedly over time. PD-L2, IFN-γ, EGFR, VEGF, TGF-ß, TMB, blood TMB, CD73, TILs, alternative splicing, tumor microenvironment, and some macroscopic and radiological features are promising predictors worthy of further studies. Studies comparing predictors appear to give greater potency to TMB and CXCR9.

Neuroinflammation and Oxidative Stress in Individuals Affected by DiGeorge Syndrome.

DiGeorge syndrome (DGS) is a rare genetic disease caused by microdeletions of the 22q11.2 region (DGS1). A haploinsufficiency at 10p level has been proposed also as a DGS cause (DGS2). Clinical manifestations are variable. The most frequent features are thymic hypoplasia or aplasia with consequent immune deficiency, cardiac malformations, hypoparathyroidism, facial and palatine abnormalities, variable degrees of cognitive impairment and psychiatric disorders. The specific aim of this descriptive report is to discuss the correlation between oxidative stress and neuroinflammation in DGS patients with microdeletions of the 22q11.2 region. The deleted chromosomic region maps various genes involved in mitochondrial metabolisms, such as DGCR8 and TXNRD2, that could lead to reactive oxygen species (ROS) increased production and antioxidant depletion. Furthermore, increased levels of ROS in mitochondria would lead to the destruction of the projection neurons in the cerebral cortex with consequent neurocognitive impairment. Finally, the increase in modified protein belonging to the family of sulfoxide compounds and hexoses, acting as inhibitors of the IV and V mitochondria complex, could result in direct ROS overproduction. Neuroinflammation in DGS individuals could be directly related to the development of the syndrome's characteristic psychiatric and cognitive disorders. In patients with psychotic disorders, the most frequent psychiatric manifestation in DGS, Th-17, Th-1 and Th-2 cells are increased with consequent elevation of proinflammatory cytokine IL-6 and IL1ß. In patients with anxiety disorders, both CD3 and CD4 are increased. Some patients with autism spectrum disorders (ASDs) have an augmented level of proinflammatory cytokines IL-12, IL-6 and IL-1ß, while IFNγ and the anti-inflammatory cytokine IL-10 seem to be reduced. Other data proposed that altered synaptic plasticity could be directly involved in DGS cognitive disorders. In conclusion, the use of antioxidants for restoring mitochondrial functionality in DGS could be a useful tool to protect cortical connectivity and cognitive behavior.

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.

Neuroimmune Dysregulation in Prepubertal and Adolescent Individuals Affected by Klinefelter Syndrome.

BACKGROUND: The syndrome Klinefelter syndrome (KS) is a genetic disorder due to an extra X chromosome in males. Many cases remain undiagnosed until the onset of major manifestations, which include hypergonadotropic hypogonadism and infertility. This condition is associated with many comorbidities that involve the cardiovascular, endocrine, and immune systems. Last but not the least, individuals with KS show a high risk of developing psychiatric and mood disorders in adult age. OBJECTIVE: While many studies are accessible on KS in adult individuals, the neuroinflammatory condition in adolescent and prepubertal KS individuals is not fully known. METHODS: Our study aims to evaluate in prepubertal and adolescent KS individuals, for the first time, the levels of the serum of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), cytokines having subtle roles in oxidative processes, and neuroinflammation with respect to the levels of TNF-α, TGF-ß, MCP-1, IL-1α, IL-2, IL-6, IL-10, and IL-12 and oxidative stress by employing free oxygen radicals defense and free oxygen radicals test. RESULTS: We found no changes in NGF and oxidative stress parameters, but BDNF decreased compared to healthy children. Quite interestingly, our data showed reduced levels of IL-2, IL-1α, IL- 12, IL-10, and IL-6 in prepubertal KS children. CONCLUSION: The present study discloses disrupted immune system and neurotrophin pathways in KS children.

NGF and BDNF in pediatrics syndromes.

Neurotrophins (NTs) as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) play multiple roles in different settings including neuronal development, function and survival in both the peripheral and the central nervous systems from early stages. This report aims to provide a summary and subsequent review of evidences on the role of NTs in rare and non-common pediatric human diseases associated with changes in neurodevelopment. A variety of diseases has been analyzed and many have been linked to NTs neurobiological effects, including chronic granulomatous disease, hereditary sensory and autonomic neuropathy, Duchenne muscular dystrophy, Bardet-Biedl syndrome, Angelman syndrome, fragile X syndrome, trisomy 16, Williams-Beuren syndrome, Prader-Willi syndrome, WAGR syndrome, fetal alcohol spectrum disorders, Down syndrome and Klinefelter Syndrome. NTs alterations have been associated with numerous pathologic manifestations including cognitive defects, behavioral abnormalities, epilepsy, obesity, tumorigenesis as well as muscle-skeletal, immunity, bowel, pain sensibility and cilia diseases. In this report, we discuss that further studies are needed to clear a possible therapeutic role of NTs in these still often uncurable diseases.

Characteristic Hallmarks of Aging and the Impact on Carcinogenesis.

Evidence shows that there is a synergistic, bidirectional association between cancer and aging with many shared traits. Age itself is a risk factor for the onset of most cancers, while evidence suggests that cancer and its treatments might accelerate aging by causing genotoxic and cytotoxic insults. Aging has been associated with a series of alterations that can be linked to cancer: i) genomic instability caused by DNA damage or epigenetic alterations coupled with repair errors, which lead to progressive accumulation of mutations; ii) telomere attrition with possible impairment of telomerase, shelterin complex, or the trimeric complex (Cdc13, Stn1 and Ten1 - CST) activities associated with abnormalities in DNA replication and repair; iii) altered proteostasis, especially when leading to an augmented proteasome, chaperon and autophagy-lysosome activity; iv) mitochondrial dysfunction causing oxidative stress; v) cellular senescence; vi) stem cells exhaustion, intercellular altered communication and deregulated nutrient sensing which are associated with microenvironmental modifications which may facilitate the subsequential role of cancer stem cells. Nowadays, anti-growth factor agents and epigenetic therapies seem to assume an increasing role in fighting aging-related diseases, especially cancer. This report aims to discuss the impact of age on cancer growth.

Programmed Cell Death-Ligand 1 in Head and Neck Squamous Cell Carcinoma: Molecular Insights, Preclinical and Clinical Data, and Therapies.

Aberrant expression of the programmed cell death protein ligand 1 (PD-L1) constitutes one of the main immune evasion mechanisms of cancer cells. The approval of drugs against the PD-1-PD-L1 axis has given new impetus to the chemo-therapy of many malignancies. We performed a literature review from 1992 to August 2022, summarizing evidence regarding molecular structures, physiological and pathological roles, mechanisms of PD-L1 overexpression, and immunotherapy evasion. Furthermore, we summarized the studies concerning head and neck squamous cell carcinomas (HNSCC) immunotherapy and the prospects for improving the associated outcomes, such as identifying treatment response biomarkers, new pharmacological combinations, and new molecules. PD-L1 overexpression can occur via four mechanisms: genetic modifications; inflammatory signaling; oncogenic pathways; microRNA or protein-level regulation. Four molecular mechanisms of resistance to immunotherapy have been identified: tumor cell adaptation; changes in T-cell function or proliferation; alterations of the tumor microenvironment; alternative immunological checkpoints. Immunotherapy was indeed shown to be superior to traditional chemotherapy in locally advanced/recurrent/metastatic HNSCC treatments.

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.

Salivary Biomarkers in Oral Squamous Cell Carcinoma: A Proteomic Overview.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most frequent cancers worldwide. Endoscopic methods may be useful in the evaluation of oral injuries even though the diagnostic gold standard is a biopsy. Targeted screenings could be considered the best way to prevent the occurrence of oral cancer. Aimed to elucidate the potential identification of specific biomarkers of OSCC, the use of saliva is convenient and noninvasive. Many studies reported more than a hundred putative saliva biomarkers for OSCC, and proteogenomic approaches were fundamental to disclosing this issue. METHODS: Relevant literature published in the last few years was systematically searched on PubMed and we focused on articles about the use and study of salivary biomarkers in the diagnostics of head and neck cancer (n = 110). Thereafter, we performed a selection focusing on diagnosis with salivary proteomics in OSCC (n = 8). RESULTS: Saliva proteomics can be a source of biomarkers for OSCC. We reviewed literature of biomarker proteins in saliva that could also be evaluated as probable targets for non-invasive screening of oral neoplasm such as cytokines, matrix metalloproteinases, and acute-phase response proteins. CONCLUSIONS: The measurement of salivary biomarkers is a highly hopeful technique for the diagnosis of OSCC. Proteogenomic approaches could permit an accurate and early diagnosis of OSCC. This review seeks to generate an up-to-date view on translational OSCC issues by raising awareness of researchers, physicians, and surgeons. Renewed clinical studies, which will validate the sensitivity and specificity of salivary biomarkers, are necessary to translate these results into possible strategies for early diagnosis of OSCC, thus improving patient outcomes.

The Impact of Oxidative Stress on Pediatrics Syndromes.

Oxidative stress is a condition determined by an imbalance between antioxidant and oxidative factors. Oxidative stress can have serious consequences on our organism. Indeed, it causes both necrosis and cell apoptosis, determining cellular aging, increased carcinogenesis, vascular stiffening, increased autoimmune diseases, and muscle decay. In the context of pediatric syndromes, oxidative stress could play a role in the first order. In fact, our review of the literature showed that in some pathologies, such as fetal alcohol spectrum disorders, oxidative stress related to the intake of ethanol during pregnancy is a main etiological factor determining the associated clinical syndrome. On the contrary, in Williams syndrome, Down syndrome, Marfan syndrome, Gaucher syndrome, ataxia-telangiectasia, autistic spectrum disorder, Fanconi's anemia, and primitive immunodeficiencies, the increase in oxidative stress is directly associated with the genetic alterations that cause the same pathologies. Although further studies are needed to better understand the relationship between oxidative stress and pediatric diseases, a better knowledge of this crucial issue encourages future therapeutic strategies.