Special Issue "Saliva and Oral Diseases"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Stomatology".

Deadline for manuscript submissions: closed (31 March 2020).

Special Issue Editor

Prof. Pia Lopez-Jornet
Website
Guest Editor
Oral Medicine in the Department of Stomatology, Faculty of Dentistry, University of Murcia, 30008 Murcia, Spain
Interests: oral medicine; oral disease; salivary gland

Special Issue Information

Dear Colleagues,

Saliva is a biological fluid of great interest with regard to its application in diagnosis and monitoring in many medical areas. As a result of its numerous advantages over other body fluids (obtaining samples is easy, noninvasive, and painless), the use of saliva for these purposes has grown greatly in the last decade.

As a diagnostic tool, saliva can provide important information on the oral and general health of patients. The great number of components contained in saliva may serve as biomarkers, making it possible to secure the early detection of diseases, among other applications. This expansion in the use of saliva has been accompanied by advances in salivaomics, including improved knowledge of saliva proteomics, transcriptomics, microRNA, metabolomics, and microbiomics.

Research has led to the validation of a broad range of biomarkers, with the development of increasingly reliable, sensitive, and specific protocols. The use of these advances must be carefully assessed in relation to the standardization of analytical and preanalytical variables, such as sampling and storage methods, the circadian variability of analytes, sample recovery, prevention of sample contamination, and the analytical procedures used.

Saliva-based diagnosis has a promising future in the control of oral and general health, with applications such as personalized medical care, including clinical decisions and the prediction of post-treatment outcomes.

Prof. Pia Lopez-Jornet
Guest Editor

Manuscript Submission Information

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Keywords

  • oral medicine
  • oral disease
  • salivary gland dysfunction
  • potentially malignant oral disorders
  • biomarkers
  • diagnostics

Published Papers (7 papers)

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Research

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Open AccessArticle
Salivary Biomarkers and Their Correlation with Pain and Stress in Patients with Burning Mouth Syndrome
J. Clin. Med. 2020, 9(4), 929; https://doi.org/10.3390/jcm9040929 (registering DOI) - 28 Mar 2020
Abstract
Objective: To evaluate a panel of salivary analytes involving biomarkers of inflammation, stress, immune system and antioxidant status in patients with burning mouth syndrome (BMS) and to study their relationship with clinical variables. Materials and Methods: A total of 51 patients with BMS [...] Read more.
Objective: To evaluate a panel of salivary analytes involving biomarkers of inflammation, stress, immune system and antioxidant status in patients with burning mouth syndrome (BMS) and to study their relationship with clinical variables. Materials and Methods: A total of 51 patients with BMS and 31 controls were consecutively enrolled in the study, with the recording of oral habits, the severity of pain using a visual analogue scale (VAS), the Hospital Anxiety and Depression (HAD) score and the Oral Health Impact Profile-14 (OHIP14) score. Resting whole saliva was collected with the drainage technique, followed by the measurement of 11 biomarkers. Results: The salivary flow was higher in patients with BMS. Among all the biomarkers studied, significantly higher levels of alpha-amylase, immunoglobulin A (IgA), and macrophage inflammatory protein-4 (MIP4) and lower levels of uric acid and ferric reducing activity of plasma (FRAP) were observed in the saliva of patients with BMS and the controls (p < 0.05 in all cases). Positive correlations were found between pain, oral quality of life and anxiety scores and salivary biomarkers. Conclusions: BMS is associated with changes in salivary biomarkers of inflammation, oxidative stress and stress, being related to the degree of pain and anxiety. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
Open AccessArticle
Enhanced Inflammation and Nitrosative Stress in the Saliva and Plasma of Patients with Plaque Psoriasis
J. Clin. Med. 2020, 9(3), 745; https://doi.org/10.3390/jcm9030745 - 10 Mar 2020
Abstract
Psoriasis is the most common inflammatory skin disease, characterized by the release of proinflammatory cytokines from lymphocytes, keratinocytes, and dendritic cells. Although psoriasis is considered an immune-mediated inflammatory disease, its effect on secretory activity of salivary glands and quantitative composition of saliva is [...] Read more.
Psoriasis is the most common inflammatory skin disease, characterized by the release of proinflammatory cytokines from lymphocytes, keratinocytes, and dendritic cells. Although psoriasis is considered an immune-mediated inflammatory disease, its effect on secretory activity of salivary glands and quantitative composition of saliva is still unknown. The aim of this study was to evaluate the secretion of saliva as well as several selected inflammation and nitrosative stress biomarkers in unstimulated and stimulated saliva as well as plasma of psoriasis patients. We demonstrated that, with progressing severity and duration of the disease, the secretory function of the parotid and submandibular salivary glands is lost, which is manifested as decreased unstimulated and stimulated saliva secretion and reduced salivary amylase activity and total protein concentration. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and interferon-gamma (INF-γ) were significantly higher, whereas interleukin-10 (IL-10) content was considerably lower in unstimulated and stimulated saliva of patients with psoriasis compared to the controls, and the changes increased with the disease duration. Similarly, we observed that the intensity of nitrosative stress in the salivary glands of psoriasis patients depended on the duration of the disease. By means of receiver operating characteristic (ROC) analysis, we showed that the evaluation of nitric oxide (NO), nitrotyrosine, and IL-2 concentration in non-stimulated saliva with high sensitivity and specificity differentiated psoriasis patients on the basis of the rate of saliva secretion (normal salivation vs. hyposalivation). In summary, the dysfunction of salivary glands in psoriasis patients is caused by inflammation and nitrosative stress. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
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Open AccessArticle
Dysfunction of Salivary Glands, Disturbances in Salivary Antioxidants and Increased Oxidative Damage in Saliva of Overweight and Obese Adolescents
J. Clin. Med. 2020, 9(2), 548; https://doi.org/10.3390/jcm9020548 - 17 Feb 2020
Cited by 1
Abstract
Obesity is inseparably connected with oxidative stress. This process may disturb the functioning of the oral cavity, although the effect of oxidative stress on salivary gland function and changes in the qualitative composition of saliva are still unknown. Our study is the first [...] Read more.
Obesity is inseparably connected with oxidative stress. This process may disturb the functioning of the oral cavity, although the effect of oxidative stress on salivary gland function and changes in the qualitative composition of saliva are still unknown. Our study is the first to evaluate salivary redox homeostasis in 40 overweight and obese adolescents and in the age- and gender-matched control group. We demonstrated strengthening of the antioxidant barrier (superoxide dismutase, catalase, peroxidase, uric acid, total antioxidant capacity (TAC)) with a simultaneous decrease in reduced glutathione concentration in saliva (non-stimulated/stimulated) in overweight and obese teenagers compared to the controls. The concentration of the products of oxidative damage to proteins (advanced glycation end products), lipids (malondialdehyde, 4-hydroxynonenal) and DNA (8-hydroxydeoxyguanosine) as well as total oxidative status were significantly higher in both non-stimulated and stimulated saliva as well as plasma of overweight and obese adolescents. Importantly, we observed more severe salivary and plasma redox alterations in obese adolescents compared to overweight individuals. In the study group, we also noted a drop in stimulated salivary secretion and a decrease in total protein content. Interestingly, dysfunction of parotid glands in overweight and obese teenagers intensified with the increase of BMI. We also showed that the measurement of salivary catalase and TAC could be used to assess the central antioxidant status of overweight and obese adolescents. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
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Open AccessArticle
Salivary Cytokine Biomarker Concentrations in Relation to Obesity and Periodontitis
J. Clin. Med. 2019, 8(12), 2152; https://doi.org/10.3390/jcm8122152 - 05 Dec 2019
Abstract
Systemic low-grade inflammation is associated with obesity. Our aim was to examine the association between obesity and salivary biomarkers of periodontitis. Salivary interleukin (IL)-1-receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α concentrations were measured from 287 non-diabetic obese (body mass [...] Read more.
Systemic low-grade inflammation is associated with obesity. Our aim was to examine the association between obesity and salivary biomarkers of periodontitis. Salivary interleukin (IL)-1-receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α concentrations were measured from 287 non-diabetic obese (body mass index (BMI) of >35 kg/m2) individuals and 293 normal-weight (BMI of 18.5–25 kg/m2) controls. Periodontal status was defined according to a diagnostic cumulative risk score (CRS) to calculate the risk of having periodontitis (CRS I, low risk; CRS II, medium risk; CRS III, high risk). In the whole population, and especially in smokers, higher IL-8 and lower IL-10 concentrations were detected in the obese group compared to the control group, while in non-smoking participants, the obese and control groups did not differ. IL-1Ra and IL-8 concentrations were higher in those with medium or high risk (CRS II and CRS III, p < 0.001) of periodontitis, whereas IL-10 and TNF-α concentrations were lower when compared to those with low risk (CRS I). In multivariate models adjusted for periodontal status, obesity did not associate with any salivary cytokine concentration. In conclusion, salivary cytokine biomarkers are not independently associated with obesity and concentrations are dependent on periodontal status. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
Open AccessArticle
Monitoring of Bactericidal Effects of Silver Nanoparticles Based on Protein Signatures and VOC Emissions from Escherichia coli and Selected Salivary Bacteria
J. Clin. Med. 2019, 8(11), 2024; https://doi.org/10.3390/jcm8112024 - 19 Nov 2019
Abstract
Escherichia coli and salivary Klebsiella oxytoca and Staphylococcus saccharolyticus were subjected to different concentrations of silver nanoparticles (AgNPs), namely: 12.5, 50, and 100 µg mL−1. Matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) spectra were acquired after specified periods: 0, 1, 4, [...] Read more.
Escherichia coli and salivary Klebsiella oxytoca and Staphylococcus saccharolyticus were subjected to different concentrations of silver nanoparticles (AgNPs), namely: 12.5, 50, and 100 µg mL−1. Matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) spectra were acquired after specified periods: 0, 1, 4, and 12 h. For study of volatile metabolites, headspace solid-phase microextraction coupled to gas chromatography/mass spectrometry (HS-SPME-GC-MS) was employed—AgNPs were added to bacteria cultures and the headspace was analyzed immediately and after 12 h of incubation. Principal components analysis provided discrimination between clusters of protein profiles belonging to different strains. Canonical correlation, network analysis, and multiple linear regression approach revealed that dimethyl disulfide, dimethyl trisulfide, 2-heptanone, and dodecanal (related to the metabolism of sulfur-containing amino acids and fatty acids synthesis) are exemplary molecular indicators, whose response variation deeply correlated to the interaction with bacteria. Therefore, such species can serve as biomarkers of the agent’s effectiveness. The present investigation pointed out that the used approaches can be useful in the monitoring of response to therapeutic treatment based on AgNPs. Furthermore, biochemical mechanisms enrolled in the bactericidal action of nanoparticles can be applied in the development of new agents with enhanced properties. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
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Open AccessArticle
Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma
J. Clin. Med. 2019, 8(11), 1958; https://doi.org/10.3390/jcm8111958 - 13 Nov 2019
Abstract
Salivary IL-6 mRNA was previously identified as a promising biomarker of oral squamous cell carcinoma (OSCC). We performed a multi-center investigation covering all geographic areas of Hungary. Saliva from 95 patients with OSCC and 80 controls, all Caucasian, were collected together with demographic [...] Read more.
Salivary IL-6 mRNA was previously identified as a promising biomarker of oral squamous cell carcinoma (OSCC). We performed a multi-center investigation covering all geographic areas of Hungary. Saliva from 95 patients with OSCC and 80 controls, all Caucasian, were collected together with demographic and clinicopathological data. Salivary IL-6 mRNA was quantified by real-time quantitative PCR. Salivary IL-6 protein concentration was measured by enzyme-linked immune-sorbent assay. IL-6 protein expression in tumor samples was investigated by immunohistochemistry. Normalized salivary IL-6 mRNA expression values were significantly higher (p < 0.001) in patients with OSCC (mean ± SE: 3.301 ± 0.885) vs. controls (mean ± SE: 0.037 ± 0.012). Differences remained significant regardless of tumor stage and grade. AUC of the ROC curve was 0.9379 (p < 0.001; 95% confidence interval: 0.8973–0.9795; sensitivity: 0.945; specificity: 0.819). Salivary IL-6 protein levels were significantly higher (p < 0.001) in patients (mean ± SE: 70.98 ± 14.06 pg/mL), than in controls (mean ± SE: 12.45 ± 3.29). Specificity and sensitivity of IL-6 protein were less favorable than that of IL-6 mRNA. Salivary IL-6 mRNA expression was significantly associated with age and dental status. IL-6 manifestation was detected in tumor cells and tumor-infiltrating leukocytes, suggesting the presence of a paracrine loop of stimulation. Salivary IL-6 mRNA is one of the best performing and clinically relevant biomarkers of OSCC. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
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Review

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Open AccessReview
Saliva and Oral Diseases
J. Clin. Med. 2020, 9(2), 466; https://doi.org/10.3390/jcm9020466 - 08 Feb 2020
Abstract
Saliva is a fascinating biological fluid which has all the features of a perfect diagnostic tool. In fact, its collection is rapid, simple, and noninvasive. Thanks to several transport mechanisms and its intimate contact with crevicular fluid, saliva contains hundreds of proteins deriving [...] Read more.
Saliva is a fascinating biological fluid which has all the features of a perfect diagnostic tool. In fact, its collection is rapid, simple, and noninvasive. Thanks to several transport mechanisms and its intimate contact with crevicular fluid, saliva contains hundreds of proteins deriving from plasma. Advances in analytical techniques have opened a new era—called “salivaomics”—that investigates the salivary proteome, transcriptome, microRNAs, metabolome, and microbiome. In recent years, researchers have tried to find salivary biomarkers for oral and systemic diseases with various protocols and technologies. The review aspires to provide an overall perspective of salivary biomarkers concerning oral diseases such as lichen planus, oral cancer, blistering diseases, and psoriasis. Saliva has proved to be a promising substrate for the early detection of oral diseases and the evaluation of therapeutic response. However, the wide variation in sampling, processing, and measuring of salivary elements still represents a limit for the application in clinical practice. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
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