Prevention of SARS-CoV-2 transmission during a large, live, indoor gathering (SPRING): a non-inferiority, randomised, controlled trial.

BACKGROUND: Mass indoor gatherings were banned in early 2020 to prevent the spread of SARS-CoV-2. We aimed to assess, under controlled conditions, whether infection rates among attendees at a large, indoor gathering event would be similar to those in non-attendees, given implementation of a comprehensive prevention strategy including antigen-screening within 3 days, medical mask wearing, and optimised ventilation. METHODS: The non-inferiority, prospective, open-label, randomised, controlled SPRING trial was done on attendees at a live indoor concert held in the Accor Arena on May 29, 2021 in Paris, France. Participants, aged 18-45 years, recruited via a dedicated website, had no comorbidities, COVID-19 symptoms, or recent case contact, and had had a negative rapid antigen diagnostic test within 3 days before the concert. Participants were randomly allocated in a 2:1 ratio to the experimental group (attendees) or to the control group (non-attendees). The allocation sequence was computer-generated by means of permuted blocks of sizes three, six, or nine, with no stratification. The primary outcome measure was the number of patients who were SARS-CoV-2-positive by RT-PCR test on self-collected saliva 7 days post-gathering in the per-protocol population (non-inferiority margin <0·35%). This trial is registered with ClinicalTrials.gov, NCT04872075. FINDINGS: Between May 11 and 25, 2021, 18 845 individuals registered on the dedicated website, and 10 953 were randomly selected for a pre-enrolment on-site visit. Among 6968 who kept the appointment and were screened, 6678 participants were randomly assigned (4451 were assigned to be attendees and 2227 to be non-attendees; median age 28 years; 59% women); 88% (3917) of attendees and 87% (1947) of non-attendees complied with follow-up requirements. The day 7 RT-PCR was positive for eight of the 3917 attendees (observed incidence, 0·20%; 95% CI 0·09-0·40) and three of the 1947 non-attendees (0·15%; 0·03-0·45; absolute difference, 95% CI -0·26% to 0·28%), findings that met the non-inferiority criterion for the primary endpoint. INTERPRETATION: Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2-transmission risk, provided a comprehensive preventive intervention was implemented. FUNDING: French Ministry of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Graphene-Based Biosensors with High Sensitivity for Detection of Ovarian Cancer Cells.

Ovarian cancer has the highest mortality rate in the world. Therefore, it is urgent but still challenging to develop an efficient circulating tumor cell (CTC) detection method to sensitively detect ovarian cancer. To address such issues, herein, for the first time, we present a novel CTC detection method for ovarian cancer cells by designing sensitive and rapid graphene-based biosensors. This graphene-based sensor, consisting of a cell pool and two electrodes, can be prepared by a conventional chip fabrication process. It demonstrates high-sensitivity detection even for several ovarian cancer cells by comparing the electrical signal before and after adding cell solution. Moreover, the graphene-based biosensors can perform rapid detection with good repeatability. This suggests that this novel method is possible to use for the early detection of ovarian cancer with very low CTC cell concentration. This work provides a novel and quick strategy to detect ovarian cancer and further judge or predict the risk of the transfer of ovarian cancer.

Dry Mouth Caused by Facial Nerve Ischemia due to Subarachnoid Hemorrhage: An Experimental Study.

OBJECTIVE: Parasympathetic network damage results in facial nerve damage, sublingual ganglion degeneration, sublingual gland dysfunction, and dry mouth. In this study, subarachnoid hemorrhage (SAH) was considered to be the cause of dry mouth. METHODS: We assessed 23 hybrid rabbits, including 5 control (group 1, Control). One milliliter of serum saline was injected into the cisterna magna of 5 animals (group 2). SAH was induced by injecting 1 mL of autologous blood into the cisterna magna of 13 animals (group 3). The animals were killed after 3 weeks of induction. The animals' sublingual ganglion and sublingual gland were excised for histopathological examination. The number of degenerated cells in the sublingual ganglion, secretory vesicles, and secretory granules in the sublingual gland that contain salivary components were estimated using Sequential Window Acquisition of All Theoretical Mass Spectra data analysis. The values were compared by the Mann-Whitney U-test. RESULTS: The numbers of secretory vesicles in the sublingual gland were 5.3 ± 1.1 × 103 (group 1), 4.23 ± 0.45 × 103 (group 2), and 1.56 ± 0.22 × 103 (group 3); the numbers of secretory vesicles containing saliva in the sublingual gland were 324 ± 12.18 (group 1), 263 ± 36.23 (group 2), and 114 ± 23.14 (group 3); and the numbers of degenerated cells in the sublingual ganglion were 11 ± 3/mm3 (group 1), 98.43 ± 15.54/mm3 (group 2), and 346 ± 12.28/mm3 (group 3) (P < 0.05). CONCLUSIONS: Clinical findings in infection and diseases such as Sjögren syndrome, aseptic meningitis, and SAH are similar. However, until now, SAH has not been demonstrated experimentally to cause dry mouth. Discovering that SAH might cause dry mouth might prevent unnecessary use of antibiotics and decrease morbidity due to the wrong or late diagnosis.

Salivary Biomarkers of Oxidative Stress and Inflammation in Stroke Patients: From Basic Research to Clinical Practice.

Cerebral stroke is a serious worldwide health problem, as can be seen by the global epidemic of the disease. In this disorder, when the blood flow is compromised by ruptures or blocked arteries, sudden death of neurons is observed as a result of a lack of oxygen and nutrients. Numerous severe problems and frequent complications also exist in stroke patients; therefore, there is an urgent need to develop new therapeutic, diagnostic, and prognostic methods for the disease. At present, the diagnosis of stroke is based on a neurological examination, medical history, and neuroimaging, due to the fact that rapid and noninvasive diagnostic tests are unavailable. Nevertheless, oxidative stress and inflammation are considered key factors in stroke pathogenesis. Oxygen free radicals are responsible for oxidation of lipids, proteins, and DNA/RNA, which in turn contributes to oxidative damage of the brain. Toxic products of the oxidation reactions act cytostatically on the cell by damaging cell membranes and leading to neuronal death by apoptosis or necrosis. Thus, it seems that redox/inflammatory biomarkers might be used in the diagnosis of the disease. Nowadays, saliva is of increasing interest in clinical laboratory medicine. Redox biomarkers could be obtained easily, noninvasively, cheaply, and stress-free from saliva. This minireview is aimed at presenting the current knowledge concerning the use of salivary biomarkers of oxidative stress and inflammation in the diagnosis and prognosis of stroke.

Salivary leucocytes as suitable biomatrix for the comet assay in human biomonitoring studies.

Peripheral blood leucocytes (PBL) have been traditionally used to investigate DNA damage by the comet assay in population studies, but validating alternative non-invasive samples would expand the application of this assay in human biomonitoring. The objectives of this study were (i) to test the validity of salivary leucocytes as a proper biomatrix for the comet assay, (ii) to evaluate the ability of this approach to detect different types of primary and oxidative DNA damage, and (iii) to determine whether frozen salivary leucocytes are still suitable for displaying those types of DNA damage. Fresh and frozen leucocytes isolated from saliva samples (six healthy non-smoking volunteers), were exposed to four genotoxic agents inducing different types of DNA damage, both primary (methyl methanesulfonate, actinomycin-D, ultraviolet radiation) and oxidative (potassium bromate), and standard or enzyme-modified comet assay was conducted. Results were compared with those obtained from PBL. Cells exposed to the four genotoxic agents showed dose-dependent increases of primary and oxidative DNA damage, demonstrating the suitability of all these samples to detect genetic damage from different origin. When comparing baseline levels of DNA damage, just a slight significant increase in primary DNA damage was observed in frozen salivary leucocytes regarding the other biomatrices, but similar results were obtained regarding sensitivity to DNA damage induction by all agents tested. This study demonstrates that salivary leucocytes can be employed in comet assay as an alternative or complement to blood samples. Frozen salivary leucocytes were proved to be a very convenient sample in large biomonitoring studies.

Evaluation of the usefulness of saliva for mosaic loss of chromosome Y analysis.

Mosaic loss of chromosome Y (mLOY) in leukocytes has attracted much attention as an emerging biomarker of aging and aging-related diseases. We evaluated the usefulness of saliva for mLOY analysis and showed that saliva-derived mLOY is significantly associated with aging and increased physical activity, but not with smoking. While these data support the robust association between saliva-derived mLOY and aging, caution is required when comparing data from saliva-derived and blood-derived mLOY.

Relationship between sputum periostin level and inflammatory asthma phenotypes in Egyptian patients.

INTRODUCTION: Asthma is a common chronic inflammatory air way disease which poses a high disease burden worldwide. Asthma is a heterogenous disease with various phenotypes and endotypes. Refractory asthma requires new and personalized approaches to manage it effectively. Periostin is a promising biomarker that may help in predicting severity, prognosis and could be a therapeutic target. We aimed in this study to investigate periostin levels in the sputum of asthmatic Egyptian patients of inflammatory phenotypes and its relation to asthma severity. SUBJECTS AND METHODS: This study included 96 adult asthmatic patients; 48 patients with mild-to-moderate bronchial asthma, 48 patients with severe bronchial asthma according to ATS criteria and 10 healthy controls. All participants were subjected to full history taking and clinical examination; pulmonary function tests; skin prick test; induced-sputum analysis for inflammatory cells and periostin. RESULTS: Sputum periostin concentrations were significantly higher in patients with asthma than in controls. Sputum periostin is strongly correlated with age and sputum TLC and inversely correlated with FEV1. It is correlated with sputum neutrophil count and sputum eosinophil percentage. Best cut off value for sputum periostin is >528.25 ng/ml to differentiate between mild-to-moderate and severe asthma. CONCLUSION: Sputum periostin levels provide a satisfying diagnostic accuracy in severe asthmatic with persistent airflow limitation than mild-to-moderate asthmatic adults. There is a modest positive correlation between sputum periostin and sputum eosinophilia.

Oral Neutrophils: Underestimated Players in Oral Cancer.

The composition of the oral milieu reflects oral health. Saliva provides an environment for multiple microorganisms, and contains soluble factors and immune cells. Neutrophils, which rapidly react on the changes in the microenvironment, are a major immune cell population in saliva and thus may serve as a biomarker for oral pathologies. This review focuses on salivary neutrophils in the oral cavity, their phenotype changes in physiological and pathological conditions, as well as on factors regulating oral neutrophil amount, activation and functionality, with special emphasis on oral cancer and its risk factors.

Free-Flow Isoelectric Focusing for Comprehensive Separation and Analysis of Human Salivary Microbiome for Lung Cancer.

Human microbiome contains billions of microorganisms that play important roles in the biological system and different diseases. Due to its complexity, conventional culture-independent technology may underestimate the value of low-abundance bacteria, which calls for a highly efficient method for its enrichment and comprehensive analysis. In this study, we developed a recycling free-flow isoelectric focusing (RFFIEF) method-based electrophoresis method to separate salivary microbiome. First, we used Escherichia coli (DH5α) as a model for RFFIEF method development, which was focused in a narrow pH range (0.38 pH unit). The recovery rate was 80.81% with 5.85% relative standard deviation (n = 5). The optimized method was then adopted to separate the human salivary microbiome into 32 fractions, followed by 16S rRNA gene sequencing and metaproteomics analysis. After RFFIEF fractionation, we identified 508 bacterial genera, which increased by 225% on average (n = 3) when compared to the results before fractionation. We further compared the compositional change of microbiome in the saliva of lung cancer group (n = 22) and control group (n = 21) through RFFIEF. Quantitative results demonstrated that six bacterial genera were upregulated dramatically in the lung cancer group, while two genera were downregulated. Through qPCR verification in an independent sample set (n = 48), we confirmed that genus Granulicatella was significantly upregulated in the lung cancer group, whereas Pseudomonas was remarkably downregulated (p < 0.001). RFFIEF is an efficient and reproducible technology to fractionate the microbiome for its comprehensive analysis, which can be further applied to the in-depth study of the complex microbiomes and contribute to the discovery of disease-associated bacteria.

Salivary exosomes: properties, medical applications, and isolation methods.

Salivary exosomes are extracellular vesicles (EVs) with abundant CD63 immunoreactivity on their surface. Based on their size and protein composition, these exosomes can be categorized into two classes of exosomes I (mean diameter of 83.5 nm) and II (mean diameter of 40.5 nm). We have attempted to review the features of these exosomes, including origin, composition, separation methods, and their application in medicine. Not only the composition of salivary exosomes is invaluable in term of diagnosis, but can also afford an understanding in roles of the contents and components of these exosomes in the fundamental pathophysiologic processes of different diseases. since these EVs can cross the epithelial barriers they may be essential for transporting of multifarious components from the blood into saliva. Thus, in comparison to other bodily fluids, salivary exosomes are probably a better and accessible tool to examine the function of exosomes in the diagnosis and treatment of disease.

Saliva exosomes-derived UBE2O mRNA promotes angiogenesis in cutaneous wounds by targeting SMAD6.

BACKGROUND: Enhancing angiogenesis is critical for accelerating wound healing. Application of different types of exosomes (Exos) to promote angiogenesis represents a novel strategy for enhanced wound repair. Saliva is known to accelerate wound healing, but the underlying mechanisms remain unclear. RESULTS: Our results have demonstrated that saliva-derived exosomes (saliva-Exos) induce human umbilical vein endothelial cells (HUVEC) proliferation, migration, and angiogenesis in vitro, and promote cutaneous wound healing in vivo. Further experiments documented that Ubiquitin-conjugating enzyme E2O (UBE2O) is one of the main mRNAs of saliva-Exos, and activation of UBE2O has effects similar to those of saliva-Exos, both in vitro and in vivo. Mechanistically, UBE2O decreases the level of SMAD family member 6 (SMAD6), thereby activating bone morphogenetic protein 2 (BMP2), which, in turn, induces angiogenesis. CONCLUSIONS: The present work suggests that administration of saliva-Exos and UBE2O represents a promising strategy for enhancing wound healing through promotion of angiogenesis.

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status-A Pilot Study.

This pilot study aims to investigate whether salivary small extracellular vesicle (sEV)-associated microRNAs could act as potential biomarkers for periodontal disease status. Twenty-nine participants (10 who were healthy, nine with gingivitis, 10 with stage III/IV periodontitis) were recruited and unstimulated whole saliva samples were collected. Salivary sEVs were isolated using the size-exclusion chromatography (SEC) method and characterised by morphology, EV-protein and size distribution using transmission electron microscopy (TEM), Western Blot and Nanoparticle Tracking Analysis (NTA), respectively. Ten mature microRNAs (miRNAs) in salivary sEVs and saliva were evaluated using RT-qPCR. The discriminatory power of miRNAs as biomarkers in gingivitis and periodontitis versus healthy controls was evaluated by Receiver Operating Characteristics (ROC) curves. Salivary sEVs were comparable to sEVs morphology, mode, size distribution and particle concentration in healthy, gingivitis and periodontitis patients. Compared to miRNAs in whole saliva, three significantly increased miRNAs (hsa-miR-140-5p, hsa-miR-146a-5p and hsa-miR-628-5p) were only detected in sEVs in periodontitis when compared to that of healthy controls, with a good discriminatory power (area under the curve (AUC) = 0.96) for periodontitis diagnosis. Our study demonstrated that salivary sEVs are a non-invasive source of miRNAs for periodontitis diagnosis. Three miRNAs that are selectively enriched in sEVs, but not whole saliva, could be potential biomarkers for periodontal disease status.

Changes at global and site-specific DNA methylation of MLH1 gene promoter induced by waterpipe smoking in blood lymphocytes and oral epithelial cells.

Objective: Cigarette tobacco smoking has been shown to cause cancer through different mechanisms that include epigenetic modulation of tumor-suppressor genes. In the present study, the association between global and MLH1 gene promoter methylation and waterpipe tobacco smoking was investigated. Materials and Methods: Blood lymphocytes and oral epithelium were sampled from 150 pure waterpipe smokers and 150 never-smokers from Jordan. Methylation assessment was performed using the methylation-specific PCR technique for MLH1 gene and ELISA for global DNA methylation. Results: Significant increases were shown in global DNA methylation as measured in blood lymphocytes (p < 0.01). In addition, increases in MLH1 gene promoter methylation among waterpipe smokers compared to nonsmokers (p < 0.001) in both oral epithelium and blood lymphocytes was also observed. In addition, strong correlation was found between LWDS-10J dependence score and magnitude of promoter specific methylation of MLH1 (r2 = 0.74-0.78, p < 0.001). Moreover, the percentage of methylated MLH1 promoter was not affected by age or gender (p > 0.05). Discussion and Conclusion: Collectively, the results indicate that waterpipe tobacco use is associated with epigenetic changes that might predispose users to lung and blood cancers. The results highlight the need for actions to discourage waterpipe smoking and can be used in cessation interventions that target this type of smoking.

On bells, saliva, and abdominal pain or discomfort: Early aversive visceral conditioning and vulnerability for anorexia nervosa.

Gastrointestinal (GI) symptoms are common in anorexia nervosa (AN), can predate illness onset, complicate renourishment, and persist after recovery. We explore how, through processes of aversive visceral conditioning, early GI pain and discomfort may increase vulnerability to AN in some individuals. Processes include enhanced preoccupation with the gut resulting from aversive visceral memories and disruptions in the typical acquisition of self-attunement when children learn to map and interpret interoceptive sensations and develop adaptive actions. We question whether a fear of weight gain, in some cases, may be an epiphenomenon of the recapitulation of actual or perceived GI symptoms that is especially relevant during puberty, especially in girls. This conceptualization has immediate clinical implications and offers ideas for future research. We propose that GI discomfort associated with renourishment may reignite prior aversive visceral experiences. We encourage development of a formulation that organizes the individual's current experience of the body with respect to these prior aversive experiences. Our conceptualization underscores the importance of assessment of GI experiences in individuals with AN; the examination of dietary strategies that minimize GI symptoms and enhance renourishment efficacy; and strategies that attempt to alter this aversive visceral conditioning by mapping sensations to meanings and adaptive actions.

Carious Lesion Severity Induces Higher Antioxidant System Activity and Consequently Reduces Oxidative Damage in Children's Saliva.

Oxidative stress biomarkers can be found at detectable concentrations in saliva. These salivary biomarkers reflect specific oxidation pathways associated with caries and periodontitis. Our study evaluated the influence of dental caries severity (assessed using the ICCMS™ criteria) on the levels of oxidative stress biomarkers in saliva from children. Unstimulated saliva samples were collected from patients (from one to three years old) in a day care center in Birigui, SP, Brazil, two hours after fasting. Children were divided into four groups (n = 30/group), according to caries severity: caries free (group A), early carious lesions (group B), moderate carious lesions (group C), and advanced carious lesions (group D). The following salivary biomarkers were determined: total proteins (TP), measured by the Lowry method; oxidative damage, measured by the TBARS method; total antioxidant capacity (TAC); superoxide dismutase (SOD) enzymatic antioxidant activity; and uric acid (UA) non-enzymatic antioxidant activity. Data were analyzed by ANOVA, followed by the Student-Newman-Keuls test, Pearson and Spearman correlation coefficients, and multivariable linear regression (p < 0.05). TP, TAC, SOD enzymatic antioxidant activity, and UA non-enzymatic antioxidant activity increased with caries severity, consequently reducing salivary oxidative damage. It was concluded that higher caries severity increases salivary antioxidant system activity, with consequent reduction in salivary oxidative damage.

Saliva, an easily accessible fluid as diagnostic tool and potent stem cell source for Alzheimer's Disease: Present and future applications.

Alzheimer's disease (AD) is a progressive and multifactorial disease. Many scientific advances have advanced our understanding of the pathogenesis of AD. However, the clinical diagnosis of AD remains difficult, with only post-mortem assays confirming its definitive diagnosis. There is a crucial need for an early and accurate detection of AD related symptoms. To date, current diagnosis techniques are costly or invasive. Finding a peripheral biomarker that could provide a sensitive, reproducible, and accurate detection prior to the onset of the AD clinical symptoms will allow identification of "at risk" individuals, thereby facilitating early initiation of treatments that may prove more effective. Salivary glands contain stem cells, which are affected by aging, suggesting that tissue samples from these glands may reveal a stem cell biomarker of AD, but also stem cells may be harvested from these glands, with proper timing and isolation technique, for cell-based regenerative medicine. Alternatively, instead of the salivary glands, saliva may represent an attractive source for biomarkers due to minimal discomfort to the patient, non-invasive collection, and the possibility of cost-effective screening large populations, encouraging greater compliance in clinical trials and frequent testing. In addition, salivary glands contain stem cells, which are likely also present in the saliva, making these cells as potentially sensitive cellular biomarker of and a therapeutic agent for AD. The aim of this review is to critically analyze the use of saliva for the identification of circulating biological markers to help the diagnosis of early cognitive impairment associated with AD and to generate insights into the potential application of stem cells derived from salivary glands or saliva as therapeutics (i.e., stem cell transplantation) for the disease.

A Community-Based Approach to Biospecimen Collection Among Pacific Islanders.

This study tested the feasibility of collecting saliva samples from Pacific Islanders (PIs) via a community-based participatory research approach. Collection of saliva samples were conducted by trained and trusted PI community leaders at various partner sites. A total of 214 saliva samples were donated by PIs living in Southern California, more than half of whom were females between the ages of 18 and 35 years. Donors indicated that they donated because they wanted to help science and their community. A majority of donors reported a very positive experience with the donation process and were willing to donate saliva and hair samples in the future. The positive findings of this article highlight the importance of community input and participation.

Alleviation of dry mouth by saliva substitutes improved swallowing ability and clinical nutritional status of post-radiotherapy head and neck cancer patients: a randomized controlled trial.

PURPOSE: The aim of this study is to investigate the effect of an edible saliva substitute, oral moisturizing jelly (OMJ), and a topical saliva gel (GC) on dry mouth, swallowing ability, and nutritional status in post-radiotherapy head and neck cancer patients. METHODS: Sixty-two post-radiation head and neck cancer patients with xerostomia completed a blinded randomized controlled trial. They were advised to swallow OMJ (n = 31) or apply GC orally (n = 31) for 2 months. Outcome measures were assessed at baseline, 1, and 2 months, including subjective and objective dry mouth (Challcombe) scores, subjective swallowing problem scores (EAT-10), water swallowing time, clinical nutritional status (PG-SGA), body weight, and dietary intake. RESULTS: After 1 and 2 months of interventions, subjective and objective dry mouth scores, subjective swallowing problem scores, swallowing times, and clinical nutritional status in both groups were significantly improved (p < 0.0001). Compared to GC, OMJ group had higher percent improvement in all outcome measures (p < 0.001) except swallowing time and clinical nutritional status. Interestingly, subjective dry mouth scores were significantly correlated with subjective swallowing problem scores (r = 0.5321, p < 0.0001). CONCLUSIONS: Continuous uses of saliva substitutes (OMJ or GC) for at least a month improved signs and symptoms of dry mouth and enhanced swallowing ability. An edible saliva substitute was superior to a topical saliva gel for alleviating dry mouth and swallow problems. These lead to improved clinical nutritional status. Thus, palliation of dry mouth may be critical to support nutrition of post-radiotherapy head and neck cancer patients. CLINICAL TRIAL REGISTRY: Clinicaltrials.gov NCT03035825.

Salivary Antioxidant Barrier, Redox Status, and Oxidative Damage to Proteins and Lipids in Healthy Children, Adults, and the Elderly.

Despite the proven role of oxidative stress in numerous systemic diseases and in the process of aging, little is still known about the salivary redox balance of healthy children, adults, and the elderly. Our study was the first to assess the antioxidant barrier, redox status, and oxidative damage in nonstimulated (NWS) and stimulated (SWS) saliva as well as blood samples of healthy individuals at different ages. We divided 90 generally healthy people into three equally numbered groups based on age: 2-14 (children and adolescents), 25-45 (adults), and 65-85 (elderly people). Antioxidant enzymes (salivary peroxidase (Px), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase-1 (SOD)), nonenzymatic antioxidants (reduced glutathione (GSH) and uric acid (UA)), redox status (total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), and malondialdehyde (MDA)) were evaluated in NWS and SWS as well as in erythrocyte/plasma samples. We demonstrated that salivary and blood antioxidant defense is most effective in people aged 25-45. In the elderly, we observed a progressive decrease in the efficiency of central antioxidant systems (↓GPx, ↓SOD, ↓GSH, and ↓TAC in erythrocytes and plasma vs. adults) as well as in NWS (↓Px, ↓UA, and ↓TAC vs. adults) and SWS (↓TAC vs. adults). Both local and systemic antioxidant systems were less efficient in children and adolescents than in the group of middle-aged people, which indicates age-related immaturity of antioxidant mechanisms. Oxidative damage to proteins (↑AGE, ↑AOPP) and lipids (↑MDA) was significantly higher in saliva and plasma of elderly people in comparison with adults and children/adolescents. Of all the evaluated biomarkers, only salivary oxidative damage products generally reflected their content in blood plasma. The level of salivary redox biomarkers did not vary based on gender.