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Saliva and Oral Diseases

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Dentistry, Oral Surgery and Oral Medicine".

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 46226

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Pia Lopez-Jornet

E-Mail Website
Guest Editor
Oral Medicine in the Department of Stomatology, Faculty of Dentistry, University of Murcia, 30008 Murcia, Spain
Interests: oral mucosa; oral lichen planus; leukoplakia; aphta; oral potentially malignant disorders (OPMDs); xerostomia; pain oral
Special Issues, Collections and Topics in MDPI journals

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

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Keywords

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

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Published Papers (10 papers)

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Editorial

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2 pages, 177 KiB  
Editorial
Special Issue “Saliva and Oral Diseases”
by Pia López Jornet
J. Clin. Med. 2020, 9(6), 1955; https://doi.org/10.3390/jcm9061955 - 23 Jun 2020
Cited by 2 | Viewed by 1729
Abstract
The discovery of microbial, immunological or molecular markers in saliva offers unique opportunities, and has caused our view of saliva to change drastically in recent years [...] Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)

Research

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10 pages, 249 KiB  
Article
Salivary Levels of Titanium, Nickel, Vanadium, and Arsenic in Patients Treated with Dental Implants: A Case-Control Study
by Piero Papi, Andrea Raco, Nicola Pranno, Bianca Di Murro, Pier Carmine Passarelli, Antonio D’Addona, Giorgio Pompa and Maurizio Barbieri
J. Clin. Med. 2020, 9(5), 1264; https://doi.org/10.3390/jcm9051264 - 27 Apr 2020
Cited by 9 | Viewed by 2576
Abstract
Background: Recent articles have hypothesized a possible correlation between dental implants dissolution products and peri-implantitis. The null hypothesis tested in this case-control study was that there would be no differences in salivary concentrations of titanium (Ti), vanadium (V), nickel (Ni) and arsenic (As) [...] Read more.
Background: Recent articles have hypothesized a possible correlation between dental implants dissolution products and peri-implantitis. The null hypothesis tested in this case-control study was that there would be no differences in salivary concentrations of titanium (Ti), vanadium (V), nickel (Ni) and arsenic (As) ions among patients with dental implants, healthy (Group A) or affected by peri-implantitis (Group B), compared to subjects without implants and/or metallic prosthetic restorations (Group C). Methods: Inductively coupled plasma mass spectrometry was used to analyze saliva samples. One-way repeated-measure analysis of variance (ANOVA) was used to identify statistically significant differences in the salivary level of Ti, V, Ni and As between the three groups. Results: A total of 100 patients were enrolled in the study (42 males and 58 females), distributed in three groups: 50 patients in Group C, 26 patients in Group B and 24 patients Group B. In our study, concentrations of metallic ions were higher in Group A and B, compared to the control group, with the exception of vanadium. However, there were no statistically significant differences (p > 0.05) for metallic ions concentrations between Group A and Group B. Conclusions: Based on our results, there are no differences in titanium or other metals concentrations in saliva of patients with healthy or diseased implants. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
10 pages, 1167 KiB  
Article
Salivary Biomarkers and Their Correlation with Pain and Stress in Patients with Burning Mouth Syndrome
by Pia Lopez-Jornet, Candela Castillo Felipe, Luis Pardo-Marin, Jose J. Ceron, Eduardo Pons-Fuster and Asta Tvarijonaviciute
J. Clin. Med. 2020, 9(4), 929; https://doi.org/10.3390/jcm9040929 - 28 Mar 2020
Cited by 26 | Viewed by 3764
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 as compared to 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)
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17 pages, 2204 KiB  
Article
Enhanced Inflammation and Nitrosative Stress in the Saliva and Plasma of Patients with Plaque Psoriasis
by Anna Skutnik-Radziszewska, Mateusz Maciejczyk, Iwona Flisiak, Julita Krahel, Urszula Kołodziej, Anna Kotowska-Rodziewicz, Anna Klimiuk and Anna Zalewska
J. Clin. Med. 2020, 9(3), 745; https://doi.org/10.3390/jcm9030745 - 10 Mar 2020
Cited by 42 | Viewed by 3228
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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22 pages, 3894 KiB  
Article
Dysfunction of Salivary Glands, Disturbances in Salivary Antioxidants and Increased Oxidative Damage in Saliva of Overweight and Obese Adolescents
by Anna Zalewska, Agnieszka Kossakowska, Katarzyna Taranta-Janusz, Sara Zięba, Katarzyna Fejfer, Małgorzata Salamonowicz, Paula Kostecka-Sochoń, Anna Wasilewska and Mateusz Maciejczyk
J. Clin. Med. 2020, 9(2), 548; https://doi.org/10.3390/jcm9020548 - 17 Feb 2020
Cited by 40 | Viewed by 4027
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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9 pages, 226 KiB  
Article
Salivary Cytokine Biomarker Concentrations in Relation to Obesity and Periodontitis
by Sanna Syrjäläinen, Ulvi Kahraman Gursoy, Mervi Gursoy, Pirkko Pussinen, Milla Pietiäinen, Antti Jula, Veikko Salomaa, Pekka Jousilahti and Eija Könönen
J. Clin. Med. 2019, 8(12), 2152; https://doi.org/10.3390/jcm8122152 - 5 Dec 2019
Cited by 21 | Viewed by 3665
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)
23 pages, 10355 KiB  
Article
Monitoring of Bactericidal Effects of Silver Nanoparticles Based on Protein Signatures and VOC Emissions from Escherichia coli and Selected Salivary Bacteria
by Fernanda Monedeiro, Paweł Pomastowski, Maciej Milanowski, Tomasz Ligor and Bogusław Buszewski
J. Clin. Med. 2019, 8(11), 2024; https://doi.org/10.3390/jcm8112024 - 19 Nov 2019
Cited by 14 | Viewed by 4507
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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12 pages, 1046 KiB  
Article
Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma
by Ildikó Judit Márton, József Horváth, Péter Lábiscsák, Bernadett Márkus, Balázs Dezső, Adrienn Szabó, Ildikó Tar, József Piffkó, Petra Jakus, József Barabás, Péter Barabás, Lajos Olasz, Zsanett Kövér, József Tőzsér, János Sándor, Éva Csősz, Beáta Scholtz and Csongor Kiss
J. Clin. Med. 2019, 8(11), 1958; https://doi.org/10.3390/jcm8111958 - 13 Nov 2019
Cited by 28 | Viewed by 8790
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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18 pages, 3837 KiB  
Review
Association of Salivary Human Papillomavirus Infection and Oral and Oropharyngeal Cancer: A Meta-Analysis
by Óscar Rapado-González, Cristina Martínez-Reglero, Ángel Salgado-Barreira, Almudena Rodríguez-Fernández, Santiago Aguín-Losada, Luis León-Mateos, Laura Muinelo-Romay, Rafael López-López and María Mercedes Suarez-Cunqueiro
J. Clin. Med. 2020, 9(5), 1305; https://doi.org/10.3390/jcm9051305 - 1 May 2020
Cited by 17 | Viewed by 4876
Abstract
Background. Human papillomavirus (HPV) infection has been recognized as an important risk factor in cancer. The purpose of this systematic review and meta-analysis was to determine the prevalence and effect size of association between salivary HPV DNA and the risk of developing oral [...] Read more.
Background. Human papillomavirus (HPV) infection has been recognized as an important risk factor in cancer. The purpose of this systematic review and meta-analysis was to determine the prevalence and effect size of association between salivary HPV DNA and the risk of developing oral and oropharyngeal cancer. Methods. A systematic literature search of PubMed, EMBASE, Web of Science, LILACS, Scopus and the Cochrane Library was performed, without language restrictions or specified start date. Pooled data were analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Quality assessment was performed using the Newcastle–Ottawa Scale (NOS). Results. A total of 1672 studies were screened and 14 met inclusion criteria for the meta-analysis. The overall prevalence of salivary HPV DNA for oral and oropharyngeal carcinoma was 43.2%, and the prevalence of salivary HPV16 genotype was 27.5%. Pooled results showed a significant association between salivary HPV and oral and oropharyngeal cancer (OR = 4.94; 2.82−8.67), oral cancer (OR = 2.58; 1.67−3.99) and oropharyngeal cancer (OR = 17.71; 6.42−48.84). Significant associations were also found between salivary HPV16 and oral and oropharyngeal cancer (OR = 10.07; 3.65−27.82), oral cancer (OR = 2.95; 1.23−7.08) and oropharyngeal cancer (OR = 38.50; 22.43−66.07). Conclusions. Our meta-analysis demonstrated the association between salivary HPV infection and the incidence of oral and oropharyngeal cancer indicating its value as a predictive indicator. Full article
(This article belongs to the Special Issue Saliva and Oral Diseases)
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15 pages, 274 KiB  
Review
Saliva and Oral Diseases
by Emanuela Martina, Anna Campanati, Federico Diotallevi and Annamaria Offidani
J. Clin. Med. 2020, 9(2), 466; https://doi.org/10.3390/jcm9020466 - 8 Feb 2020
Cited by 46 | Viewed by 7546
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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