Editorial

4 pages, 201 KiB

Open AccessEditorial

by Fernando Capela e Silva, Elsa Lamy and Paula Midori Castelo

Biomedicines 2022, 10(5), 952; https://doi.org/10.3390/biomedicines10050952 - 20 Apr 2022

Viewed by 1421

Oral biology is a scientific field that involves several disciplines, such as anatomy, cellular and molecular biology, genetics, microbiology, immunology, biochemistry, pharmacology, physiology and pathology [...] Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

Research

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19 pages, 2920 KiB

Open AccessArticle

Prognostic Relevance of CD4⁺, CD8⁺ and FOXP3⁺ TILs in Oral Squamous Cell Carcinoma and Correlations with PD-L1 and Cancer Stem Cell Markers

by Paloma Lequerica-Fernández, Julián Suárez-Canto, Tania Rodriguez-Santamarta, Juan Pablo Rodrigo, Faustino Julián Suárez-Sánchez, Verónica Blanco-Lorenzo, Francisco Domínguez-Iglesias, Juana María García-Pedrero and Juan Carlos de Vicente

Biomedicines 2021, 9(6), 653; https://doi.org/10.3390/biomedicines9060653 - 08 Jun 2021

Cited by 19 | Viewed by 2808

Abstract

This study investigates the relevance of tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis of stromal/tumoral CD4⁺, CD8⁺ and FOXP3⁺ TILs is performed in 125 OSCC patients. Potential relationships with the expression of tumoral PD-L1 and [...] Read more.

This study investigates the relevance of tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis of stromal/tumoral CD4⁺, CD8⁺ and FOXP3⁺ TILs is performed in 125 OSCC patients. Potential relationships with the expression of tumoral PD-L1 and cancer stem cell (CSC) markers (NANOG, SOX2, OCT4, Nestin and Podoplanin (PDPN)) are assessed. CD4⁺ and CD8⁺ TILs are significantly associated with smoking and alcohol habits. CD4⁺ and CD8⁺ TILs show an inverse relationship with NANOG and SOX2 expression, and FOXP3⁺ TILs is significantly correlated with Nestin and PDPN expression. High infiltration of CD4⁺ and CD8⁺ TILs and a high tumoral CD8⁺/FOXP3⁺ ratio are significantly associated with tumors harboring positive PD-L1 expression. Infiltration of stromal/tumoral FOXP3⁺ TILs and a low stromal CD8⁺/FOXP3⁺ ratio are significantly associated with better disease-specific survival. Multivariate analysis reveals that the stromal CD8⁺/FOXP3⁺ TILs ratio is a significant independent prognostic factor. Regarding OSCC patient survival, the CD8⁺/FOXP3⁺ TILs ratio is an independent prognostic factor. TILs may act as biomarkers and potential therapeutic targets for OSCC. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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25 pages, 19829 KiB

Open AccessEditor’s ChoiceArticle

Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia

by Jutta Ries, Abbas Agaimy, Falk Wehrhan, Christoph Baran, Stella Bolze, Eva Danzer, Silke Frey, Jonathan Jantsch, Tobias Möst, Maike Büttner-Herold, Claudia Wickenhauser, Marco Kesting and Manuel Weber

Biomedicines 2021, 9(2), 194; https://doi.org/10.3390/biomedicines9020194 - 16 Feb 2021

Cited by 24 | Viewed by 3085

Abstract

Background: The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells. [...] Read more.

Background: The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells. PD-1/PD-L1 overexpression in oral squamous cell carcinoma (OSCC) compared to healthy oral mucosa (NOM) has already been demonstrated. However, little is known about its expression in oral precancerous lesions like oral leukoplakia (OLP). The aim of the study was to investigate whether an increased expression of PD-1/PD-L1 already exists in OLP and whether it is associated with malignant transformation. Material and Methods: PD-1 and PD-L1 expression was immunohistologically analyzed separately in the epithelium (E) and the subepithelium (S) of OLP that had undergone malignant transformation within 5 years (T-OLP), in OLP without malignant transformation (N-OLP), in corresponding OSCC and in NOM. Additionally, RT-qPCR analysis for PD-L1 expression was done in the entire tissues. Additionally, the association between overexpression and malignant transformation, dysplasia and inflammation were examined. Results: Compared to N-OLP, there were increased levels of PD-1 protein in the epithelial and subepithelial layers of T-OLP (p_E = 0.001; p_S = 0.005). There was no significant difference in PD-L1 mRNA expression between T-OLP and N-OLP (p = 0.128), but the fold-change increase between these groups was significant (Relative Quantification (RQ) = 3.1). In contrast to N-OLP, the PD-L1 protein levels were significantly increased in the epithelial layers of T-OLP (p = 0.007), but not in its subepithelial layers (p = 0.25). Importantly, increased PD-L1 levels were significantly associated to malignant transformation within 5 years. Conclusion: Increased levels of PD-1 and PD-L1 are related to malignant transformation in OLP and may represent a promising prognostic indicator to determine the risk of malignant progression of OLP. Increased PD-L1 levels might establish an immunosuppressive microenvironment, which could favor immune escape and thereby contribute to malignant transformation. Hence, checkpoint inhibitors could counteract tumor development in OLP and may serve as efficient therapeutic strategy in patients with high-risk precancerous lesions. Full article

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13 pages, 4831 KiB

Open AccessArticle

Subcutaneous Implantation Assessment of New Calcium-Silicate Based Sealer for Warm Obturation

by João Miguel Santos, Carolina M. Coelho, Diana B. Sequeira, Joana A. Marques, Joana F. Pereira, Vitor Sousa, Paulo J. Palma and Ana C. Santos

Biomedicines 2021, 9(1), 24; https://doi.org/10.3390/biomedicines9010024 - 01 Jan 2021

Cited by 27 | Viewed by 3682

Abstract

Calcium silicate-based sealers were recently introduced as a new class of endodontic sealers, with potential further benefits due to their bioactivity. The aim of this study was to evaluate the biocompatibility of two new hydraulic calcium silicate-based sealers, TotalFill BC Sealer (FKG, La [...] Read more.

Calcium silicate-based sealers were recently introduced as a new class of endodontic sealers, with potential further benefits due to their bioactivity. The aim of this study was to evaluate the biocompatibility of two new hydraulic calcium silicate-based sealers, TotalFill BC Sealer (FKG, La Chaux-des-Fonds, Switzerland) and TotalFill BC Sealer HiFlow (FKG, La Chaux-des-Fonds, Switzerland) through subcutaneous implantation in connective tissue of rats. Subcutaneous implantation was performed in 16 young Wistar rats. Four polyethylene tubes were implanted in each animal, one empty to serve as a control, and three filled with tested sealers: AH Plus as reference (Dentsply DeTrey, Konstanz, Germany), TotalFill BC Sealer (BC) and TotalFill BC Sealer HiFlow (HiFlow). Eight rats were euthanized at 8 days and the remaining eight at 30 days. Hematoxylin-eosin staining was used to score the inflammatory reaction, macrophage infiltrate and to measure the thickness of the fibrous capsule. von Kossa staining was performed to evaluate the mineralization level. Kruskal–Wallis test followed by Dunn’s post hoc test was used to analyze non-parametric data. To analyze the influence of the implantation time within each material, a Mann–Whitney U test was performed. At eight days post-implantation, AH Plus induced a more intense inflammatory reaction when compared both with the control (p

\leq

0.001) and BC (p

\leq

0.01). HiFlow presented a higher score of macrophage infiltrate than control (p

\leq

0.01) and BC (p

\leq

0.05). The fibrous capsule thickness in this period was significantly higher for the BC group when compared to control (p

\leq

0.01) and AH Plus (p

\leq

0.05). The mineralization potential was higher for the HiFlow group when compared with the control (p

\leq

0.001) and AH Plus (p

\leq

0.001). At 30 days post-implantation, the score for the inflammatory reaction remained higher for the AH Plus group when compared both to control (p

\leq

0.01) and BC (p

\leq

0.001). The macrophage infiltrate of the HiFlow was significantly higher than control (p

\leq

0.001) and AH Plus groups (p

\leq

0.01), additionally, the fibrous capsule of the BC (p

\leq

0.001) and HiFlow (p

\leq

0.01) groups were both thicker than control. Mineralization potential was observed only on BC (p

\leq

0.05) and HiFlow groups (p

\leq

0.001), when compared to control). BC exhibited the best biocompatibility performance of all tested sealers and HiFlow provided the greatest induction of mineralized tissues. Both TotalFill BC Sealer and TotalFill BC Sealer HiFlow are biocompatible and show potential bioactivity when implanted in the subcutaneous tissue. Bioactivity was not found in AH Plus. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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12 pages, 1716 KiB

Open AccessArticle

Local Vascularization during Orthodontic Tooth Movement in a Split Mouth Rat Model—A MRI Study

by Peter Proff, Agnes Schröder, Lisa Seyler, Franziska Wolf, Yüksel Korkmaz, Tobias Bäuerle, Lina Gölz and Christian Kirschneck

Biomedicines 2020, 8(12), 632; https://doi.org/10.3390/biomedicines8120632 - 19 Dec 2020

Cited by 2 | Viewed by 2335

Abstract

Orthodontic tooth movement to therapeutically align malpositioned teeth is supposed to impact blood flow in the surrounding tissues. Here, we evaluated actual vascularization in the tension area of the periodontal ligament during experimental tooth movement in rats (N = 8) with magnetic [...] Read more.

Orthodontic tooth movement to therapeutically align malpositioned teeth is supposed to impact blood flow in the surrounding tissues. Here, we evaluated actual vascularization in the tension area of the periodontal ligament during experimental tooth movement in rats (N = 8) with magnetic resonance imaging (MRI). We inserted an elastic band between the left upper first and the second rat molar; the right side was not treated and served as control. After four days of tooth movement, we recorded T1-weighted morphologic and dynamic-contrast-enhanced MRI sequences with an animal-specific 7 Tesla MRI to assess of local vascularization. Furthermore, we quantified osteoclasts and monocytes in the periodontal ligament, which are crucial for orthodontic tooth movement, root resorptions as undesirable side effects, as well as the extent of tooth movement using paraffine histology and micro-CT analysis. Data were tested for normal distribution with Shapiro–Wilk tests followed by either a two-tailed paired t-test or a Wilcoxon matched-pairs signed rank test. Significant orthodontic tooth movement was induced within the four days of treatment, as evidenced by increased osteoclast and monocyte activity in the periodontal ligament as well as by µCT analysis. Contrast enhancement was increased at the orthodontically-treated side distally of the moved upper first left molar, indicating increased vascularization at the tension side of the periodontal ligament. Accordingly, we detected reduced time-to-peak and washout rates. Our study using MRI to directly assess local vascularization thus seems to confirm the hypothesis that perfusion is enhanced in tension zones of the periodontal ligament during orthodontic tooth movement. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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16 pages, 3388 KiB

Open AccessArticle

Examination of Oral Squamous Cell Carcinoma and Precancerous Lesions Using Proximity Extension Assay and Salivary RNA Quantification

by Beáta Scholtz, Doan Vo Minh, Csongor Kiss, Ildikó Tar, Ajneesh Kumar, József Tőzsér, Éva Csősz and Ildikó Márton

Biomedicines 2020, 8(12), 610; https://doi.org/10.3390/biomedicines8120610 - 14 Dec 2020

Cited by 5 | Viewed by 2955

Abstract

Saliva is an easy-to access body fluid with high diagnostic potential. The utilization of saliva for oral cancer diagnosis can be an attractive possibility. Besides the oral cancer, it is important to better understand the precancerous lesions such as oral lichen planus (OLP) [...] Read more.

Saliva is an easy-to access body fluid with high diagnostic potential. The utilization of saliva for oral cancer diagnosis can be an attractive possibility. Besides the oral cancer, it is important to better understand the precancerous lesions such as oral lichen planus (OLP) and leukoplakia (OLK). In order to examine the changes of salivary proteins in controls, patients with oral cancer, and patients with precancerous conditions, proximity extension assay was utilized. Some proteins and functions were characteristic to the examined groups and can serve as a starting point for further biomarker studies. The different nature of OLK and OLP was demonstrated, showing the malignant transformation and the inflammation as the prominent biological processes in the OLK and OLP, respectively. The salivary level of IL6 was verified using quantitative ELISA and the mRNA level was also studied. Elevated IL6 levels could be detected in precancerous groups compared to controls. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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13 pages, 2181 KiB

Open AccessArticle

Effects of Histamine Receptor Antagonist Cetirizine on Orthodontic Tooth Movement

by Gregor Sperl, Johanna Gattner, James Deschner, Michael Wolf, Peter Proff, Agnes Schröder and Christian Kirschneck

Biomedicines 2020, 8(12), 583; https://doi.org/10.3390/biomedicines8120583 - 08 Dec 2020

Cited by 6 | Viewed by 2322

Abstract

Many patients regularly take histamine receptor antagonists, such as cetirizine, to prevent allergic reactions, but these antiallergic drugs may have inadvertent effects on orthodontic treatment. In previous studies, histamine has been shown to modulate the sterile inflammatory reaction underlying orthodontic tooth movement. Pertinent [...] Read more.

Many patients regularly take histamine receptor antagonists, such as cetirizine, to prevent allergic reactions, but these antiallergic drugs may have inadvertent effects on orthodontic treatment. In previous studies, histamine has been shown to modulate the sterile inflammatory reaction underlying orthodontic tooth movement. Pertinent effects of histamine antagonization via cetirizine during orthodontic treatment, however, have not been adequately investigated. We thus treated male Fischer344 rats either with tap water (control group) or cetirizine by daily oral gavage corresponding to the clinically used human dosage adjusted to the rat metabolism (0.87 mg/kg) or to a previously published high dosage of cetirizine (3 mg/kg). Experimental anterior movement of the first upper left molar was induced by insertion of a nickel-titanium (NiTi) coil spring (0.25 N) between the molar and the upper incisors. Cone-beam computed tomography (CBCT), micro-computed tomography (µCT) images, as well as histological hematoxylin-eosin (HE), and tartrate-resistant acid phosphatase (TRAP) stainings were used to assess the extent of tooth movement, cranial growth, periodontal bone loss, root resorptions, and osteoclast activity in the periodontal ligament. Both investigated cetirizine dosages had no impact on the weight gain of the animals and, thus, animal welfare. Neither the extent of tooth movement, nor cranial growth, nor root resorption, nor periodontal bone loss were significantly influenced by the cetirizine dosages investigated. We, thus, conclude that histamine receptor antagonist cetirizine can be used during orthodontic treatment to prevent allergic reactions without clinically relevant side effects on orthodontic tooth movement. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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15 pages, 1728 KiB

Open AccessArticle

Gingival Crevicular Fluid Cytokines in Moderate and Deep Sites of Stage III Periodontitis Patients in Different Rates of Clinical Progression

by Federica Romano, Wilma Del Buono, Laura Bianco, Martina Arena, Giulia Maria Mariani, Federica Di Scipio, Giovanni Nicolao Berta and Mario Aimetti

Biomedicines 2020, 8(11), 515; https://doi.org/10.3390/biomedicines8110515 - 18 Nov 2020

Cited by 12 | Viewed by 2307

Abstract

Clinical criteria are inappropriate to measure the degree of susceptibility to progression of periodontal damage. Thus, the aim of this study was to assess whether gingival crevicular fluid (GCF) levels of cytokines could discriminate patients suffering from stage III periodontitis with moderate (Grade [...] Read more.

Clinical criteria are inappropriate to measure the degree of susceptibility to progression of periodontal damage. Thus, the aim of this study was to assess whether gingival crevicular fluid (GCF) levels of cytokines could discriminate patients suffering from stage III periodontitis with moderate (Grade B) and rapid rates of progression (Grade C) prior to and 6 months after non-surgical periodontal treatment. GCF samples were obtained from moderate and deep sites of 20 patients diagnosed as Grade B and 20 patients as grade C stage III periodontitis and analyzed for interleukin (IL)-1β, IL-9, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) using a high-sensitivity Bio-Plex Suspension Array System. At baseline, higher IL-1β but lower IL-9 GCF levels were observed in moderate sites of the grade C compared to the grade B group. In spite of comparable clinical improvement, this difference maintained after treatment, suggesting a residual pro-inflammatory state. In deep sites, no differences were observed between periodontitis groups except for VEGF levels that decreased more in Grade B periodontitis at 6 months post-therapy. A mathematical model was constructed to identify Grade C periodontitis patients based on the subjects’ GCF levels of IL-1β and IL-9, which achieved an area under the receiver-operating characteristic (ROC) curve of 0.94. This study can contribute to the early assessment of risk of future breakdown in periodontitis patients. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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14 pages, 1377 KiB

Open AccessArticle

Relative Deficiency of Anti-Inflammatory N-Acylethanolamines Compared to Prostaglandins in Oral Lichen Planus

by Linda Rankin, Sandra Gouveia-Figueira, Karin P. Danielsson and Christopher J. Fowler

Biomedicines 2020, 8(11), 481; https://doi.org/10.3390/biomedicines8110481 - 06 Nov 2020

Cited by 4 | Viewed by 1672

Abstract

Oral lichen planus (OLP) is a chronic inflammatory oromucosal disease. The N-acylethanolamines (NAEs), are a family of endogenous biologically active lipid mediators, with palmitoylethanolamide (PEA) being of particular interest here due to its anti-inflammatory and analgesic properties. In this study using oral [...] Read more.

Oral lichen planus (OLP) is a chronic inflammatory oromucosal disease. The N-acylethanolamines (NAEs), are a family of endogenous biologically active lipid mediators, with palmitoylethanolamide (PEA) being of particular interest here due to its anti-inflammatory and analgesic properties. In this study using oral mucosa biopsies from OLP patients and healthy controls, we investigated whether NAE synthesis was mobilized in response to the inflammation associated with OLP. PTGS2 levels, coding for cyclooxygenase-2 (COX-2), were increased approximately 4-fold in OLP compared to controls and a significant increase in the ratio of PTGS2 to NAPEPLD, the latter coding for a key enzyme in NAE synthesis, was seen. This was matched by an increased ratio of COX-2-derived prostaglandins to PEA in a second patient cohort. We conclude that there is an imbalance between prostaglandins and PEA in OLP, opening up the possibility that PEA might be a useful treatment for this disorder. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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14 pages, 3776 KiB

Open AccessArticle

Differential Gene Expression Changes in Human Primary Dental Pulp Cells Treated with Biodentine and TheraCal LC Compared to MTA

by Ok Hyung Nam, Ho Sun Lee, Jae-Hwan Kim, Yong Kwon Chae, Seoung-Jin Hong, Sang Wook Kang, Hyo-Seol Lee, Sung Chul Choi and Young Kim

Biomedicines 2020, 8(11), 445; https://doi.org/10.3390/biomedicines8110445 - 22 Oct 2020

Cited by 5 | Viewed by 2966

Abstract

This study aimed to analyze the effects of pulp capping materials on gene expression changes in primary tooth-derived dental pulp cells using next-generation sequencing. Dental pulp cells were extracted and treated with mineral trioxide aggregate (MTA), Biodentine (BD), or TheraCal LC (TC). Cell [...] Read more.

This study aimed to analyze the effects of pulp capping materials on gene expression changes in primary tooth-derived dental pulp cells using next-generation sequencing. Dental pulp cells were extracted and treated with mineral trioxide aggregate (MTA), Biodentine (BD), or TheraCal LC (TC). Cell viability assays were performed. Total RNA was extracted and analyzed through mRNA sequencing. Bioinformatic analysis of differential gene expression in dental pulp cells exposed to BD or TC versus MTA was performed. MTA, BD, and TC exposure had no significant effect on pulp cell viability (p > 0.05). Gene sets associated with inflammatory response (p = 2.94 × 10⁻⁵) and tumor necrosis factor alpha (TNF-α) signaling via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (p = 2.94 × 10⁻⁵) were enriched in all materials. In BD-treated cells, Wnt/β-catenin signaling (p = 3.15 × 10⁻⁴) gene sets were enriched, whereas enrichment of interferon gamma (IFN-γ) response (p = 3 × 10⁻³) was observed in TC-treated cells. In gene plot analysis, marked increases in receptor activator of nuclear factor kappa-Β ligand (RANKL) expression were seen in TC-treated cells over time. Despite the similar cell viabilities exhibited among MTA-, BD-, and TC-treated cells, patterns of gene networks differed, suggesting that diverse functional gene differences may be associated with treatment using these materials. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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19 pages, 3317 KiB

Open AccessArticle

Evaluation of Root-End Preparation with Two Different Endodontic Microsurgery Ultrasonic Tips

by Paulo J. Palma, Joana A. Marques, Margarida Casau, André Santos, Francisco Caramelo, Rui I. Falacho and João Miguel Santos

Biomedicines 2020, 8(10), 383; https://doi.org/10.3390/biomedicines8100383 - 28 Sep 2020

Cited by 14 | Viewed by 3800

Abstract

The aim of this study is to compare root-end preparation performed with two different ultrasonic tips—CVDentus and NSK—and respective time requirements. After root-end resection, 32 teeth were randomly divided in two groups, according to the ultrasonic tip used for root-end preparation. Preparation time [...] Read more.

The aim of this study is to compare root-end preparation performed with two different ultrasonic tips—CVDentus and NSK—and respective time requirements. After root-end resection, 32 teeth were randomly divided in two groups, according to the ultrasonic tip used for root-end preparation. Preparation time was recorded. Photomicrographs were taken to assess the following parameters: root surface microcracking, marginal integrity and presence of debris. One ultrasonic tip from each group was analyzed through scanning electron microscopy before and after root-end preparation. The significance level was set at α = 0.05. Incidence of microcracks in both groups was 12.5%. Solely intracanal microcracking was found, consistently positioned within the widest side of the remaining dentine. No statistically significant differences were verified between both experimental groups regarding marginal integrity (p = 0.102) and preparation time (p = 0.780), whereas statistical differences (p = 0.003) were found concerning the presence of debris (the minimum registered score was mostly verified in CVDentus group). NSK tips showed major morphological changes, with extensive surface wear and noticeable loss of particles, which was not verified on CVDentus tips. Our findings suggest significant differences regarding root-end preparation walls quality, with CVDentus tips showing better results. Concerning microcracking, as well as preparation time and marginal integrity, both ultrasonic tips showed similar results. Qualitative analysis exposed NSK tips major morphological changes and wear after use, which was not verified on CVDentus tips. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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14 pages, 758 KiB

Open AccessArticle

ICP-Mass-Spectrometry Ionic Profile of Whole Saliva in Patients with Untreated and Treated Periodontitis

by Federica Romano, Alexandra Castiblanco, Francesca Spadotto, Federica Di Scipio, Mery Malandrino, Giovanni Nicolao Berta and Mario Aimetti

Biomedicines 2020, 8(9), 354; https://doi.org/10.3390/biomedicines8090354 - 15 Sep 2020

Cited by 18 | Viewed by 2588

Abstract

Over the past decade, there has been growing interest in the association between macro and trace minerals in body fluids and systemic diseases related to chronic inflammation and oxidative stress. Due to the paucity of data in the literature on periodontitis, the aim [...] Read more.

Over the past decade, there has been growing interest in the association between macro and trace minerals in body fluids and systemic diseases related to chronic inflammation and oxidative stress. Due to the paucity of data in the literature on periodontitis, the aim of this cross-sectional study was to assess the relationship between mineral elements in saliva and periodontal status in patients with untreated and treated periodontitis compared to periodontally healthy controls. Salivary samples from 66 nonsmoker healthy patients (20 periodontally healthy, 24 untreated severe periodontitis and 22 treated severe periodontitis) were analyzed by using inductively coupled plasma mass-spectrometry (ICP-MS). Significant increases in copper (Cu), sodium (Na), iron (Fe) and manganese (Mn) concentrations occurred in saliva of severe periodontitis subjects compared to periodontally healthy controls. No differences were detected between healthy controls and treated periodontitis patients apart from levels of zinc (Zn) and lithium (Li) that were found to be increased and reduced, respectively, in periodontitis group. Most subjects were correctly separated by cluster analysis into active periodontitis and periodontally healthy individuals. Treated periodontitis individuals were classified as healthy subjects. Based on these preliminary results, the assessment of salivary concentration of mineral elements might be useful in discriminating periodontal health and disease. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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16 pages, 2451 KiB

Open AccessArticle

An In Vitro Barrier Model of the Human Submandibular Salivary Gland Epithelium Based on a Single Cell Clone of Cell Line HTB-41: Establishment and Application for Biomarker Transport Studies

by Grace C. Lin, Merima Smajlhodzic, Anna-Maria Bandian, Heinz-Peter Friedl, Tamara Leitgeb, Sabrina Oerter, Kerstin Stadler, Ulrich Giese, Johannes R. Peham, Lynne Bingle and Winfried Neuhaus

Biomedicines 2020, 8(9), 302; https://doi.org/10.3390/biomedicines8090302 - 23 Aug 2020

Cited by 6 | Viewed by 3641

Abstract

The blood–saliva barrier (BSB) consists of the sum of the epithelial cell layers of the oral mucosa and salivary glands. In vitro models of the BSB are inevitable to investigate and understand the transport of salivary biomarkers from blood to saliva. Up to [...] Read more.

The blood–saliva barrier (BSB) consists of the sum of the epithelial cell layers of the oral mucosa and salivary glands. In vitro models of the BSB are inevitable to investigate and understand the transport of salivary biomarkers from blood to saliva. Up to now, standardized, cell line-based models of the epithelium of the submandibular salivary gland are still missing for this purpose. Therefore, we established epithelial barrier models of the submandibular gland derived from human cell line HTB-41 (A-253). Single clone isolation resulted in five different clones (B2, B4, B9, D3, and F11). Clones were compared to the parental cell line HTB-41 using measurements of the transepithelial electrical resistance (TEER), paracellular marker permeability assays and analysis of marker expression for acinar, ductal, and myoepithelial cells. Two clones (B9, D3) were characterized to be of acinar origin, one clone (F11) to be of myoepithelial origin and one isolation (B4) derived from two cells, to be presumably a mixture of acinar and ductal origin. Clone B2, presumably of ductal origin, showed a significantly higher paracellular barrier compared to other clones and parental HTB-41. The distinct molecular identity of clone B2 was confirmed by immunofluorescent staining, qPCR, and flow cytometry. Experiments with ferritin, a biomarker for iron storage, demonstrated the applicability of the selected model based on clone B2 for transport studies. In conclusion, five different clones originating from the submandibular gland cell line HTB-41 were successfully characterized and established as epithelial barrier models. Studies with the model based on the tightest clone B2 confirmed its suitability for transport studies in biomarker research. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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12 pages, 635 KiB

Open AccessArticle

Drug-Induced Gingival Overgrowth: The Effect of Cyclosporin A and Mycophenolate Mophetil on Human Gingival Fibroblasts

by Dorina Lauritano, Giulia Moreo, Luisa Limongelli, Annalisa Palmieri and Francesco Carinci

Biomedicines 2020, 8(7), 221; https://doi.org/10.3390/biomedicines8070221 - 17 Jul 2020

Cited by 54 | Viewed by 3296

Abstract

Drug-induced gingival overgrowth may occur after a chronic administration of three classes of systemic drugs: Anticonvulsants, immunosuppressants, and calcium channel blockers. This study aimed to investigate how cyclosporin A and mycophenolate mophetil (immunosuppressive drugs) could interfere with human gingival fibroblasts functions, leading to [...] Read more.

Drug-induced gingival overgrowth may occur after a chronic administration of three classes of systemic drugs: Anticonvulsants, immunosuppressants, and calcium channel blockers. This study aimed to investigate how cyclosporin A and mycophenolate mophetil (immunosuppressive drugs) could interfere with human gingival fibroblasts functions, leading to gingival enlargement. Human gingival fibroblasts derived from the tissue of a 60-year-old female were cultured in a DMEME medium. A stock solution with 1 mg/mL of mycophenolate and 1 mg/mL of cyclosporine were prepared and dissolved in a DMEM medium to prepare a serial dilution at the concentrations of 5000, 2000, 1000, 500, and 100 ng/mL, for both treatments. Cell viability was measured using the PrestoBlue™ Reagent Protocol. Quantitative real-time RT-PCR was performed in order to analyze the expression of 57 genes coding for gingival fibroblasts “Extracellular Matrix and Adhesion Molecules”. Mycophenolate and cyclosporine had no effect on fibroblast cell viability at 1000 ng/mL. Both the treatments showed similar effects on the expression profiling of treated cells: Downregulation of most extracellular matrix metalloproteases genes (MMP8, MMP11, MMP15, MMP16, MMP24) was assessed, while CDH1, ITGA2, ITGA7, LAMB3, MMP12, and MMP13 were recorded to be upregulated in fibroblasts treated with immunosuppressive drugs. It has been demonstrated that gingival overgrowth can be caused by the chronic administration of cyclosporin A and mycophenolate mophetil. However, given the contrasting data of literature, further investigations are needed, making clear the possible effects of immunosuppressive drugs on fibroblasts. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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14 pages, 1918 KiB

Open AccessArticle

Distribution of Helicobacter pylori and Periodontopathic Bacterial Species in the Oral Cavity

by Tamami Kadota, Masakazu Hamada, Ryota Nomura, Yuko Ogaya, Rena Okawa, Narikazu Uzawa and Kazuhiko Nakano

Biomedicines 2020, 8(6), 161; https://doi.org/10.3390/biomedicines8060161 - 15 Jun 2020

Cited by 20 | Viewed by 2846

Abstract

The oral cavity may serve as a reservoir of Helicobacter pylori. However, the factors required for H. pylori colonization are unknown. Here, we analyzed the relationship between the presence of H. pylori in the oral cavity and that of major periodontopathic bacterial [...] Read more.

The oral cavity may serve as a reservoir of Helicobacter pylori. However, the factors required for H. pylori colonization are unknown. Here, we analyzed the relationship between the presence of H. pylori in the oral cavity and that of major periodontopathic bacterial species. Nested PCR was performed to detect H. pylori and these bacterial species in specimens of saliva, dental plaque, and dental pulp of 39 subjects. H. pylori was detected in seven dental plaque samples (17.9%), two saliva specimens (5.1%), and one dental pulp (2.6%) specimen. The periodontal pockets around the teeth, from which dental plaque specimens were collected, were significantly deeper in H. pylori-positive than H. pylori-negative subjects (p < 0.05). Furthermore, Porphyromonas gingivalis, a major periodontopathic pathogen, was detected at a significantly higher frequency in H. pylori-positive than in H. pylori-negative dental plaque specimens (p < 0.05). The distribution of genes encoding fimbriae (fimA), involved in the periodontal pathogenicity of P. gingivalis, differed between H. pylori-positive and H. pylori-negative subjects. We conclude that H. pylori can be present in the oral cavity along with specific periodontopathic bacterial species, although its interaction with these bacteria is not clear. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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17 pages, 1004 KiB

Open AccessArticle

New Pyrimidinone-Fused 1,4-Naphthoquinone Derivatives Inhibit the Growth of Drug Resistant Oral Bacteria

by Kyungmin Kim, Daseul Kim, Hyunjin Lee, Tae Hoon Lee, Ki-Young Kim and Hakwon Kim

Biomedicines 2020, 8(6), 160; https://doi.org/10.3390/biomedicines8060160 - 15 Jun 2020

Cited by 7 | Viewed by 2452

Abstract

Background: Dental caries is considered to be a preventable disease, and various antimicrobial agents have been developed for the prevention of dental disease. However, many bacteria show resistance to existing agents. Methods/Principal Findings: In this study, four known 1,4-naphthoquinones and newly synthesized 10 [...] Read more.

Background: Dental caries is considered to be a preventable disease, and various antimicrobial agents have been developed for the prevention of dental disease. However, many bacteria show resistance to existing agents. Methods/Principal Findings: In this study, four known 1,4-naphthoquinones and newly synthesized 10 pyrimidinone-fused 1,4-naphthoquinones, i.e. KHQ 701, 702, 711, 712, 713, 714, 715, 716, 717 and 718, were evaluated for antimicrobial activity against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Streptococcus sobrinus, Porphyromonas gingivalis, Actinomyces viscosus and Fusobacterium nucleatum. Pyrimidinone-fused 1,4-naphthoquinones were synthesized in good yields through a series of chemical reactions from a commercially available 1,4-dihydroxynaphthoic acid. MIC values of KHQ 711, 712, 713, 714, 715, 716, 717 and 718 were 6.25–50 μg/mL against E. faecalis (CCARM 5511), 6.25–25 μg/mL against E. faecium (KACC11954) and S. aureus (CCARM 3506), 1.56–25 μg/mL against S. epidermidis (KACC 13234), 3.125–100 μg/mL against S. mutans (KACC16833), 1.56–100 μg/mL against S. sobrinus (KCTC5809) and P. gingivalis (KCTC 5352), 3.125–50 μg/mL against A. viscosus (KCTC 9146) and 3.125–12.5 μg/mL against F. nucleatum (KCTC 2640) with a broth microdilution assay. A disk diffusion assay with KHQ derivatives also exhibited strong susceptibility with inhibition zones of 0.96 to 1.2 cm in size against P. gingivalis. Among the 10 compounds evaluated, KHQ 711, 712, 713, 715, 716 and 717 demonstrated strong antimicrobial activities against the 9 types of pathogenic oral bacteria. A pyrimidin-4-one moiety comprising a phenyl group at the C2 position and a benzyl group at the N3 position appears to be essential for physiological activity. Conclusion/Significance: Pyrimidinone-fused 1,4-naphthoquinones synthesized from simple starting compounds and four known 1,4-naphthoquinones were synthesized and showed strong antibacterial activity to the 9 common oral bacteria. These results suggest that these derivatives should be prospective for the treatment of dental diseases caused by oral bacteria, including drug-resistant strains. Full article

(This article belongs to the Special Issue Models for Oral Biology Research)

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