Search

Oral squamous cell carcinoma (OSCC) arises in the oral epithelium, a tissue in which immune surveillance is mediated by its primary resident leukocytes, Langerhans cells (LCs), and γδT cells. Under steady‐state conditions, LCs and γδT cells play a critical role in maintaining oral mucosal homeostasis. As antigen‐presenting cells of stratified epithelia, LCs respond to various challenges faced by the epithelium, orchestrating innate, and adaptive immune responses in order to resolve them. γδT cells also sense diverse epithelial insults and react rapidly through cytokine production and cytolytic activity. These epithelial sentinels are also considered to be the first leukocytes in the oral epithelium to encounter early carcinogenic events that have the potential of becoming OSCC. As evident in many malignancies, leukocyte populations help prevent cancer development although they also promote tumor progression. OSCC is no exception, as studies have reported both anti‐ and pro‐tumor roles of LCs and γδT cells. In this review, we summarize the ontogeny of LCs and γδT cells in the oral epithelium and discuss their role in OSCC. [ABSTRACT FROM AUTHOR]

This study compared type I and type II diabetic patients with a healthy control group using microscopic qualitative analysis of oral epithelial cytological smears in the possible early phase of diabetes. The cheek, ventral tongue mucosa, buccal, and palate smears were used for the superficial and profound cytological examination of the oral alterations. The type, duration, and consequences of diabetes were linked with cytological alterations of the oral cell population stained with PAP stain (Papanicolaou), PAS (Periodic acid-Schiff), hemotoxylin, and eosin. To detect changes, the experiment was conducted on 100 samples: 50 healthy people, 50 people with type I diabetes, and type II diabetes. They were taken from different areas, stained, and then examined with an optical microscope. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral submucous fibrosis is a progressive oral disorder categorized as a potentially malignant condition. Researchers have identified specific molecular biomarkers associated with oral submucous fibrosis. The objective of our study was to conduct an up-to-date and comprehensive review of molecular biomarkers linked to oral submucous fibrosis, as investigated in studies conducted within the last five years. We organized potential molecular biomarkers associated with oral submucous fibrosis and categorized them based on cytological characteristics and sampling methodologies. To aid in the development of practical diagnostic methods for detecting oral submucous fibrosis, our study provides fellow researchers with a coherent and informative overview of these molecular biomarkers. Oral submucous fibrosis (OSF) stands as a progressive oral ailment, designated as a potentially malignant disorder. OSF has gained widespread recognition as a significant precursor to malignant transformation. In the pursuit of dependable, straightforward, and non-invasive diagnostic measures for the early detection of oral malignant progression, research has delved into potential diagnostic biomarkers of OSF. This comprehensive review delves into current investigations that explore the correlation between various biomarkers and OSF. The molecular biomarkers of OSF are categorized based on cytology and sampling methods. Moreover, this review encompasses pertinent studies detailing how these biomarkers are acquired and processed. Within this scope, we scrutinize four potential biomarkers that hold the promise of facilitating the development of diagnostic tools for detecting early-stage OSF. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cavity and pharyngeal cancer affects 560,000 people worldwide on a yearly basis. Despite advances in treatment, the survival rate remains poor, while prognoses typically improve with early diagnosis. The epithelium of the oral cavity often exhibits abnormal cellular growth, or dysplasia, that predisposes the patient to cancer depending on severity. Our study aims to address the current lack of rigorous quantitative methods for analyzing histopathological features relevant to clinical diagnosis, such as cellular morphology and epithelial layer number. We developed a deep learning approach that segments the oral epithelium and counts epithelial layer number within H&E-stained whole slide images. Our results demonstrate the feasibility of this automated approach for segmenting oral epithelium and counting its layer number. We also show its clinical relevance by comparing oral epithelium layer numbers between dysplasia of different severities. Head and neck squamous cell carcinoma (HNSCC), specifically in the oral cavity (oral squamous cell carcinoma, OSCC), is a common, complex cancer that significantly affects patients' quality of life. Early diagnosis typically improves prognoses yet relies on pathologist examination of histology images that exhibit high inter- and intra-observer variation. The advent of deep learning has automated this analysis, notably with object segmentation. However, techniques for automated oral dysplasia diagnosis have been limited to shape or cell stain information, without addressing the diagnostic potential in counting the number of cell layers in the oral epithelium. Our study attempts to address this gap by combining the existing U-Net and HD-Staining architectures for segmenting the oral epithelium and introducing a novel algorithm that we call Onion Peeling for counting the epithelium layer number. Experimental results show a close correlation between our algorithmic and expert manual layer counts, demonstrating the feasibility of automated layer counting. We also show the clinical relevance of oral epithelial layer number to grading oral dysplasia severity through survival analysis. Overall, our study shows that automated counting of oral epithelium layers can represent a potential addition to the digital pathology toolbox. Model generalizability and accuracy could be improved further with a larger training dataset. [ABSTRACT FROM AUTHOR]

The skin and the oral mucosa represent interfaces to the environment that are constantly exposed to pathogens and harmless foreign antigens such as commensal bacteria. Both barrier organs share the presence of Langerhans cells (LC), distinctive members of the heterogeneous family of antigen‐presenting dendritic cells (DC) that have the unique ability to promote tolerogenic as well as inflammatory immune responses. While skin LC have been extensively studied in the past decades, less is known about the function of oral mucosal LC. Despite similar transcriptomic signatures, skin and oral mucosal LC differ greatly in their ontogeny and development. In this review article, we will summarize the current knowledge on LC subsets in the skin compared to the oral mucosa. We will discuss the similarities and differences in their development, homeostasis, and function in the two barrier tissues, including their interaction with the local microbiota. In addition, this review will update recent advances on the role of LC in inflammatory skin and oral mucosal diseases. [ABSTRACT FROM AUTHOR]

In humans, ankyloglossia and cleft palate are common congenital craniofacial anomalies, and these are regulated by a complex gene regulatory network. Understanding the genetic underpinnings of ankyloglossia and cleft palate will be an important step toward rational treatment of these complex anomalies. We inactivated the Sry (sex-determining region Y)-box 2 (Sox2) gene in the developing oral epithelium, including the periderm, a transient structure that prevents abnormal oral adhesions during development. This resulted in ankyloglossia and cleft palate with 100% penetrance in embryos examined after embryonic day 14.5. In Sox2 conditional knockout embryos, the oral epithelium failed to differentiate, as demonstrated by the lack of keratin 6, a marker of the periderm. Further examination revealed that the adhesion of the tongue and mandible expressed the epithelial markers E-Cad and P63. The expanded epithelia are Sox9-, Pitx2-, and Tbx1-positive cells, which are markers of the dental epithelium; thus, the dental epithelium contributes to the development of oral adhesions. Furthermore, we found that Sox2 is required for palatal shelf extension, as well as for the formation of palatal rugae, which are signaling centers that regulate palatogenesis. In conclusion, the deletion of Sox2 in oral epithelium disrupts palatal shelf extension, palatal rugae formation, tooth development, and periderm formation. The periderm is required to inhibit oral adhesions and ankyloglossia, which is regulated by Sox2. In addition, oral adhesions occur through an expanded dental epithelial layer that inhibits epithelial invagination and incisor development. This process may contribute to dental anomalies due to ankyloglossia.

Abstract Objectives The objective of this study is to confirm the developmental origin of the enamel organ and evaluate the role of E‐cadherin in tooth development by conditional deletion in the oral epithelium and its enamel organ progeny. K5‐Cre;ROSA26 compound mice were included in this study in order to confirm the oral epithelial origin of the enamel organ, as well as of the action of the K5‐Cre transgene in ablating E‐cadherin in the enamel organ. K5‐Cre;Ecadfl/fl knockout mice were included to evaluate the effects of the conditional E‐cadherin ablation onto tooth development. Material and Methods K5‐Cre transgenic mice were crossed into the ROSA26 reporter mouse to trace the cell fate of the oral epithelium and its progeny in vivo. Moreover, K5‐Cre mice were crossed into the Ecadfl/fl mice to produce K5‐Cre;Ecadfl/fl compound mouse, as well as K5‐Cre;Ecadfl/+ and Ecadfl/fl littermate controls. These litters were euthanized at postnatal day P2 to study the effects of conditional E‐cadherin ablation in vivo. Results The K5‐Cre;ROSA26 compound mouse demonstrated that the origin of the enamel organ and the structures thereof are of oral epithelial origin. Furthermore, using the K5‐Cre;Ecadfl/fl compound mouse, we determined that conditional ablation of E‐cadherin in the oral epithelium, and its progeny, results in dental anomalies involving elongation of the molar root, shrinkage of the pulp space, and alterations of the periapical area, including cementum hyperplasia. The K5‐Cre;Ecadfl/fl mice also displayed a smaller overall stature compared with heterozygotes and wild‐type littermates. Conclusions E‐cadherin is important in tooth development, including the formation of enamel, the crown, pulp space, and the roots.

Stem cells in stratified epithelia are generally believed to adhere to a non-hierarchical single-progenitor model. Using lineage tracing and genetic label-retention assays, we show that the hard palatal epithelium of the oral cavity is unique in displaying marked proliferative heterogeneity. We identify a previously uncharacterized, infrequently-dividing stem cell population that resides within a candidate niche, the junctional zone (JZ). JZ stem cells tend to self-renew by planar symmetric divisions, respond to masticatory stresses, and promote wound healing, whereas frequently-dividing cells reside outside the JZ, preferentially renew through perpendicular asymmetric divisions, and are less responsive to injury. LRIG1 is enriched in the infrequently-dividing population in homeostasis, dynamically changes expression in response to tissue stresses, and promotes quiescence, whereas Igfbp5 preferentially labels a rapidly-growing, differentiation-prone population. These studies establish the oral mucosa as an important model system to study epithelial stem cell populations and how they respond to tissue stresses.

The oral mucosa is one of the most rapidly dividing tissues in the body and serves as a barrier to physical and chemical insults from mastication, food, and microorganisms. Breakdown of this barrier can lead to significant morbidity and potentially life-threatening infections for patients. Determining the identity and organization of oral epithelial progenitor cells (OEPCs) is therefore paramount to understanding their roles in homeostasis and disease. Using lineage tracing and label retention experiments, we show that rapidly dividing OEPCs are located broadly within the basal layer of the mucosa throughout the oral cavity. Quantitative clonal analysis demonstrated that OEPCs undergo population-asymmetrical divisions following neutral drift dynamics and that they respond to chemotherapy-induced damage by altering daughter cell fates. Finally, using single-cell RNA-seq, we establish the basal layer population structure and propose a model that defines the organization of cells within the basal layer.

Specialized pro-resolving mediators (SPMs) are multifunctional lipid mediators that participate in the resolution of inflammation. We have recently described that oral epithelial cells (OECs) express receptors of the SPM resolvin RvD1n-3 DPA and that cultured OECs respond to RvD1n-3 DPA addition by intracellular calcium release, nuclear receptor translocation and transcription of genes coding for antimicrobial peptides. The aim of the present study was to assess the functional outcome of RvD1n-3 DPA–signaling in OECs under inflammatory conditions. To this end, we performed transcriptomic analyses of TNF-α-stimulated cells that were subsequently treated with RvD1n-3 DPA and found significant downregulation of pro-inflammatory nuclear factor kappa B (NF-κB) target genes. Further bioinformatics analyses showed that RvD1n-3 DPA inhibited the expression of several genes involved in the NF-κB activation pathway. Confocal microscopy revealed that addition of RvD1n-3 DPA to OECs reversed TNF-α-induced nuclear translocation of NF-κB p65. Co-treatment of the cells with the exportin 1 inhibitor leptomycin B indicated that RvD1n-3 DPA increases nuclear export of p65. Taken together, our observations suggest that SPMs also have the potential to be used as a therapeutic aid when inflammation is established. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to confirm the developmental origin of the enamel organ and evaluate the role of E‐cadherin in tooth development by conditional deletion in the oral epithelium and its enamel organ progeny. K5‐Cre;ROSA26 compound mice were included in this study in order to confirm the oral epithelial origin of the enamel organ, as well as of the action of the K5‐Cre transgene in ablating E‐cadherin in the enamel organ. K5‐Cre;Ecadfl/fl knockout mice were included to evaluate the effects of the conditional E‐cadherin ablation onto tooth development. Material and Methods: K5‐Cre transgenic mice were crossed into the ROSA26 reporter mouse to trace the cell fate of the oral epithelium and its progeny in vivo. Moreover, K5‐Cre mice were crossed into the Ecadfl/fl mice to produce K5‐Cre;Ecadfl/fl compound mouse, as well as K5‐Cre;Ecadfl/+ and Ecadfl/fl littermate controls. These litters were euthanized at postnatal day P2 to study the effects of conditional E‐cadherin ablation in vivo. Results: The K5‐Cre;ROSA26 compound mouse demonstrated that the origin of the enamel organ and the structures thereof are of oral epithelial origin. Furthermore, using the K5‐Cre;Ecadfl/fl compound mouse, we determined that conditional ablation of E‐cadherin in the oral epithelium, and its progeny, results in dental anomalies involving elongation of the molar root, shrinkage of the pulp space, and alterations of the periapical area, including cementum hyperplasia. The K5‐Cre;Ecadfl/fl mice also displayed a smaller overall stature compared with heterozygotes and wild‐type littermates. Conclusions: E‐cadherin is important in tooth development, including the formation of enamel, the crown, pulp space, and the roots. [ABSTRACT FROM AUTHOR]

Abstract Objectives We set out to reprogram adult somatic oral epithelial keratinocytes into pluripotent cells for regenerative dentistry. Setting and Sample population Immortalized murine oral keratinocyte cell (IMOK) line raised from adult mouse mucosa were cultured in vitro in our studies. Materials and Methods Adult murine oral epithelial keratinocytes were chronically treated with TGF‐β1 in vitro, and the expression of Oct4, Nanog, Sox2 and Nestin, as well as specific homeobox Gata and Pax gene family members were investigated. Results We documented the induction of stem factors linked with pluripotency and/or the maintenance and regulation of stem‐cell self‐renewal in oral epithelial keratinocytes by TGFβ1. Moreover, we discovered that this TGF‐β1‐induced increase in Oct4, Nanog, Sox2 and Nestin was inhibited by SB431542, suggesting that TGF‐β1 signals via the TGF‐βRI receptor to induce pluripotency and stemness. Conclusions Adult oral epithelial keratinocytes treated chronically with TGF‐β1 acquired phenotypic characteristics consistent with pluripotent stem cells, highlighting the facileness of reprogramming adult oral keratinocytes into an unlimited supply of pluripotent stem cells.

Chronic inflammatory responses can inflict permanent damage to host tissues. Specialized pro‐resolving mediators downregulate inflammation but also can have other functions. The aim of this study was to examine whether oral epithelial cells express the receptors FPR2/ALX and DRV1/GPR32, which bind RvD1n‐3 DPA, a recently described pro‐resolving mediator derived from omega‐3 docosapentaenoic acid (DPA), and whether RvD1n‐3 DPA exposure induced significant responses in these cells. Gingival biopsies were stained using antibodies to FPR2/ALX and DRV1/GPR32. Expression of FPR2/ALX and DRV1/GPR32 was examined in primary oral epithelial cells by qRT‐PCR, flow cytometry, and immunofluorescence. The effect of RvD1n‐3 DPA on intracellular calcium mobilization and transcription of beta‐defensins 1 and 2, and cathelicidin was evaluated by qRT‐PCR. FPR2/ALX and DRV1/GPR32 were expressed by gingival keratinocytes in situ. In cultured oral epithelial cells, FPR2/ALX was detected on the cell surface, whereas FPR2/ALX and DRV1/GPR32 were detected intracellularly. Exposure to RvD1n‐3 DPA induced intracellular calcium mobilization, FPR2/ALX internalization, DRV1/GPR32 translocation to the nucleus, and significantly increased expression of genes coding for beta‐defensin 1, beta‐defensin 2, and cathelicidin. This shows that the signal constituted by RvD1n‐3 DPA is recognized by oral keratinocytes and that this can strengthen the antimicrobial and regulatory potential of the oral epithelium. [ABSTRACT FROM AUTHOR]

According to the World Health Organization, corneal blindness is the fourth most common cause of blindness and visual impairment worldwide. In Russia, up to 18% of blindness is caused by corneal damage. Limbal stem cell deficiency (LSCD) is one of the causes of corneal blindness and visual impairment due to anterior epithelial replacement with fibrovascular pannus. Bilateral LSCD may develop in patients with aniridia, Steven-Jones syndrome, and severe corneal burns of both eyes, leading to severe decrease in visual acuity in both eyes and, as a consequence, physical disability associated with blindness. In such cases, cell therapy, based on autologous oral epithelial culture as an alternative to allogeneic limbus transplants, is proposed for reconstruction of the anterior corneal epithelium. This new treatment method promotes corneal reepithelization, better visual acuity, reduced nonspecific ocular complaints and improved quality of life of patients. The effectiveness and significant increase in the frequency of transparent engraftment of donor corneas after cell therapy drives huge interest in this topic all over the world. This review presents literature data on the features of histotopography and methods for obtaining a cultured autologous oral mucosal epithelium, on cell markers that are used to identify epithelial cells, and on methods for creating cell grafts for subsequent transplantation to the corneal surface in LSCD patients.

Oral cancer, predominantly squamous cell carcinoma, carries high morbidity and disease burden all over the world. Evaluation of the cellular basis of oral carcinogenesis has implied dysregulation in cytokeratins as one of the contributory factors. These intermediate filament proteins of the oral epithelium, guardian of cellular architecture, are known to maintain cellular interactions and are involved in various cell cycle regulation pathways. Oral premalignancy and neoplastic progression are often depicted by disturbed and/or haphazard expression of these cytokeratins. We present a summarized analysis of cytokeratins and explore their diagnostic potential using immunohistochemistry. CK 8/18 is a significant and reliable biomarker of oral precancer and cancer that can be utilized in addition to histopathology for early malignancy screening and intervention. Moreover, dysplastic oral lesions are attributed to downregulation and/or gradual disappearance of CK 4/13, CK 5/14, and expression of CK 17. Increasing the diagnostic strategy using immunohistochemical techniques on specific cytokeratins and extensive sample studies on premalignant lesions, dysplasia, and oral squamous cell carcinoma can open up many possibilities. Utilizing the enhanced diagnostic spectrum of specific cytokeratins can help clinicians and dental specialists diagnose early, thus timely managing and alleviating suffering associated with oral cancer. [ABSTRACT FROM AUTHOR]

Objectives: To assess the literature on (i) the relevance of the presence of a minimum dimension of keratinized peri‐implant mucosa (KPIM) to maintain the health and stability of peri‐implant tissues, and; (ii) the surgical interventions and grafting materials used for augmenting the dimensions of the KPIM when there is a minimal amount or absence of it. Material & Methods: Two systematic reviews complemented by expert opinion from workshop group participants served as the basis of the consensus statements, implications for clinical practice and future research, and were approved in plenary session by all workshop participants. Results: Thirty‐four consensus statements, eight implications for clinical practice, and 13 implications for future research were discussed and agreed upon. There is no consistent data on the incidence of peri‐implant mucositis relative to the presence or absence of KPIM. However, reduced KPIM width is associated with increased biofilm accumulation, soft‐tissue inflammation, greater patient discomfort, mucosal recession, marginal bone loss and an increased prevalence of peri‐implantitis. Free gingival autogenous grafts were considered the standard of care surgical intervention to effectively increase the width of KPIM. However, substitutes of xenogeneic origin may be an alternative to autogenous tissues, since similar results when compared to connective tissue grafts were reported. Conclusion: Presence of a minimum width of KPIM should be assessed routinely in patients with implant supported restorations, and when associated with pathological changes in the peri‐implant mucosa, its dimensions may be surgically increased using autogenous grafts or soft‐tissue substitutes with evidence of proven efficacy. [ABSTRACT FROM AUTHOR]

Mucosal barrier integrity is vital for homeostasis with commensal organisms while preventing pathogen invasion. We unexpectedly found that fungal-induced immunosurveillance enhances resistance to fungal outgrowth and tissue invasion by remodeling the oral mucosal epithelial barrier in mouse models of adult and neonatal Candida albicans colonization. Epithelial subset expansion and tissue remodeling were dependent on interleukin-22 (IL-22) and signal transducer and activator of transcription 3 (STAT3) signaling, through a non-canonical receptor complex composed of glycoprotein 130 (gp130) coupled with IL-22RA1 and IL-10RB. Immunosurveillance-induced epithelial remodeling was restricted to the oral mucosa, whereas barrier architecture was reset once fungal-specific immunity developed. Collectively, these findings identify fungal-induced transient mucosal remodeling as a critical determinant of resistance to mucosal fungal infection during early stages of microbial colonization., Competing Interests: Competing interests The authors declare no competing interests.

Objectives: We set out to reprogram adult somatic oral epithelial keratinocytes into pluripotent cells for regenerative dentistry. Setting and Sample population: Immortalized murine oral keratinocyte cell (IMOK) line raised from adult mouse mucosa were cultured in vitro in our studies. Materials and Methods: Adult murine oral epithelial keratinocytes were chronically treated with TGF‐β1 in vitro, and the expression of Oct4, Nanog, Sox2 and Nestin, as well as specific homeobox Gata and Pax gene family members were investigated. Results: We documented the induction of stem factors linked with pluripotency and/or the maintenance and regulation of stem‐cell self‐renewal in oral epithelial keratinocytes by TGFβ1. Moreover, we discovered that this TGF‐β1‐induced increase in Oct4, Nanog, Sox2 and Nestin was inhibited by SB431542, suggesting that TGF‐β1 signals via the TGF‐βRI receptor to induce pluripotency and stemness. Conclusions: Adult oral epithelial keratinocytes treated chronically with TGF‐β1 acquired phenotypic characteristics consistent with pluripotent stem cells, highlighting the facileness of reprogramming adult oral keratinocytes into an unlimited supply of pluripotent stem cells. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the role of serotonin in the development of a biomimetic enamel‐like material in vitro. Setting and Sample population: Immortalized murine oral keratinocytes raised from adult mouse mucosa were cultured in vitro. In addition, specimens incorporating molar tooth buds harvested from mice were included in our studies. Materials and Methods: We used cell‐based scaffold‐free tissue engineering to assemble three‐dimensional (3D) organoids into complex tissue constructs that closely emulate the complexity of adult enamel. We also analysed mouse molar specimens using immunohistochemistry for serotonin expression as well as its cognate receptor. Results: TGF‐β1–reprogrammed murine oral keratinocytes formed organoids that laid down an amelogenin‐rich protein matrix when grown as three‐dimensional (3D) cultures in the presence of serotonin. Following mineralization, the newly formed crystals were densified under pressure and vacuum to produce a biomimetic enamel‐like material that demonstrated parallel alignment of hydroxyapatite crystals with some interspaced residual organoid matter into enamel prism‐like structures conferring size, mechanical properties comparable to tooth enamel, including light translucency. Serotonin expression was localized by immunohistochemistry proximal to the enamel organ of developing molar buds. Moreover, serotonin HTRb2 receptor expression was localized on ameloblasts within the enamel organ proximal to the area where serotonin was immunolocalized. Conclusions: Our results demonstrate that serotonin is inductive in the development of a biomimetic enamel‐like material from reprogrammed oral epithelial keratinocytes in vitro. The facileness of harvesting adult somatic cells together with the versatility of our approach offers exciting opportunities to address regenerative challenges linked to lost enamel. [ABSTRACT FROM AUTHOR]

Epithelium attachment to the tooth or abutment surface is necessary to form a biological seal preventing pathogens and irritants from penetrating the body and reaching the underlying soft tissues and bone, which in turn can lead to inflammation and subsequent bone resorption. The present review investigated oral wound closure and the role of micro-environment, saliva, crevicular fluid and microbiota in wound healing. The importance of the junctional epithelium (peri-implant epithelium) attachment to the abutment surface was investigated. Current research focuses on macro-design, surface-topography, surface-chemistry, materials, coatings and wettability to enhance attachment, since these optimised surface properties are expected to promote keratinocyte attachment and spreading through hemi-desmosome formation. Detailed studies describing the extent of junctional epithelium attachment – e.g. barrier function, hemi-desmosomes, epithelium quality, composition of the external basement membrane or ability of the epithelium to resist microbial penetration and colonisation – are not yet reported in animals due to ethical considerations, scalability, expense, technical challenges and limited availability of antibodies. In vitro studies generally include relatively simple 2D culture models, which lack the complexity required to draw relevant conclusions. Additionally, human organotypic 3D mucosa models are being developed. The present review concluded that more research using these organotypic mucosa models may identify relevant parameters involved in soft-tissue-abutment interactions, which could be used to study different macro-shapes and surface modifications. Such studies would bridge the gap between clinical, animal and traditional in vitro cell culture studies supporting development of abutments aiming at improved clinical performance.

Background/Purpose: Lichen planus is a T-cell-mediated mucocutaneous disorder characterized histopathologically by a band of chronic inflammatory cells in the subepithelial zone and degeneration of basal layer. The present study was aimed to evaluate the distribution and quantitative assessment of cluster of differentiation 1a (CD1a)-positive Langerhans cells (LCs) in oral lichen planus (OLP), thus to determine the role of LCs pertaining to the changes occurring in OLP. Materials and Methods: Five cases of normal oral mucosa and 20 cases of OLP were immunostained with CD1a antibody; the positive cells were counted manually in the photomicrographs and statistically analyzed using t-test, Mann–Whitney test, and Wilcoxon signed-rank test. Results: The average percentage of CD1a-positive LCs in normal subjects was 0.9%, and in the OLP cases higher percentage was observed (3.93%). The statistical comparison of these two parameters was significant (P =0.018). The degree of basal cell degeneration and density of subepithelial infiltrate on statistical comparison with the concentration of CD1a-positive LCs showed significant results. Conclusion: LCs play a pivotal role in the recruitment of CD4+ and CD8+ cells to the subepithelial region and basal keratinocytes apoptosis. A small number of study subjects, assessment of only CD1a molecule and LCs in the epidermis only were a few of the drawbacks of the study.

Objectives: Evaluating structural changes in oral epithelium can assist with the diagnosis of cancerous lesions. Two-dimensional (2D) non-invasive optical coherence tomography (OCT) is an established technique for this purpose. The objective of this study was to develop and test the diagnostic accuracy of a three-dimensional (3D) evaluation method. Methods: The oral lip mucosa of 10 healthy volunteers was scanned using an 870-nm spectral-domain OCT device (SD-OCT) with enhanced depth imaging (EDI). Four raters semi-automatically segmented the epithelial layer twice. Thus, eighty 3D datasets were created and analyzed for epithelial thickness. To provide a reference standard for comparison, the raters took cross-sectional 2D measurements at representative sites. The correlation between the 2D and 3D measurements, as well as intra- and inter-rater reliability, were analyzed using intraclass correlation coefficients (ICC). Results: Mean epithelial thickness was 280 ± 64μm (range 178–500 μm) and 268 ± 49μm (range 163–425 μm) for the 2D and 3D analysis, respectively. The inter-modality correlation of the thickness values was good (ICC: 0.76 [0.626–0.846]), indicating that 3D analysis of epithelial thickness provides valid results. Intra-rater and inter-rater reliability were good (3D analysis) and excellent (2D analysis), suggesting high reproducibility. Conclusions: Diagnostic accuracy was high for the developed 3D analysis of oral epithelia using non-invasive, radiation-free OCT imaging. Clinical significance: This new 3D technique could potentially be used to improve time-efficiency and quality in the diagnosis of epithelial lesions compared with the 2D reference standard.

Aim: To evaluate the similarities and differences in barrier function of a peri‐implant epithelium (PIE) versus a native junctional epithelium (JE). Materials and methods: A mouse model was used wherein titanium implants were placed sub‐occlusally in healed extraction sites. The PIE was examined at multiple timepoints after implant placement, to capture and understand the temporal nature of its assembly and homeostatic status. Mitotic activity, hemidesmosomal attachment apparatus, and inflammatory responses in the PIE were compared against a JE. Additionally, we evaluated whether the PIE developed a Wnt‐responsive stem cell niche like a JE. Results: The PIE developed from oral epithelium (OE) that had, by the time of implant placement, lost all characteristics of a JE. Compared with a JE, an established PIE had more proliferating cells, exhibited lower expression of attachment proteins, and had significantly more inflammatory cells in the underlying connective tissue. Wnt‐responsive cells in the OE contributed to an initial PIE, but Wnt‐responsive cells and their descendants were lost as the PIE matured. Conclusions: Although histologically similar, the PIE lacked a Wnt‐responsive stem cell niche and exhibited characteristics of a chronically inflamed tissue. Both features contributed to suboptimal barrier functions of the PIE compared with a native JE. [ABSTRACT FROM AUTHOR]

The aim of this study is to understand the association of HPV infection and wnt-β-catenin self-renewal pathway in development of head and neck squamous cell carcinoma (HNSCC). For this reason, the molecular profiles (methylation/deletion/expression) of antagonists (SFRP1/2 and DKK1), agonists (FZD7 and LRP6) and effector protein β-catenin of the pathway were analyzed in HPV positive/negative oral epithelium at first, followed by its changes during development of the tumor along with correlations with different clinico-pathological parameters. HPV infection alone or in combination with tobacco habit could activate p- β-catenin expression in basal/parabasal layers of oral epithelium through high expression of FZD7 and significant down regulation of SFRP1/2 through promoter hypermethylation due to over expression of DNMT1 with ubiquitous down regulation of DKK1 and up-regulation of LRP6. This phenomenon has been seen in respective HPV positive and negative HNSCC tumors with additional deletion/microsatellite size alterations in the antagonists. Overall alterations (methylation/deletion) of SFRP1/2, DKK1 gradually increased from Group I (HPV-/Tobacco-) to Group IV(HPV+/Tobacco+) tumors, leading to the worst prognosis of the patients. Thus, the transmission of differentially activated wnt-β-catenin pathway from HPV positive/negative basal/parabasal layers of oral epithelium to HNSCC tumors determines differences in molecular pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Background: Silver, especially oxidized silver, has been used as a medicine considered to have bactericidal properties. In the present day, ionic silver (Ag+) is also used in the manufacture of cosmetics, socks, food containers, detergents, sprays and other products to prevent the spread of germs. Unfortunately, ionic silver is assumed to be toxic not only to bacteria, but also to humans and the environment. Therefore, it is essential to identify the optimum dosage of ionic silver considered safe by investigating the effects of ionic silver concentration on cell death through activation of mutant p-53 expression by caspase 3 in the oral epithelium. Purpose: This research aimed to analyze the effects of concentrated liquid ionic silver (Ag+) on caspase-3 and mutant p53 expression in the oral mucosal epithelium. Methods: This research constituted a laboratory-based experimental study with posttest-only design. The research subjects consisted of 28 Wistar rats, divided into four treatment groups, namely; KK (with Aquadest), KP 1 (with 5% liquid ionic silver), KP 2 (with 10% liquid ionic silver) and KP 3 (with 15% liquid ionic silver). Each rat was then treated orally with 0.5ml of liquid ionic silver at fixed concentrations twice a day for seven days. The Wistar rats were then terminated and their tissue samples processed by means of histopathological and immunohistochemical staining examination. The monoclonal Caspase-3 and mutant p53 expressions in each group were evaluated with the data being tabulated and analyzed statistically. Results: Mutant p53 expression was also found in the control group. Moreover, the higher the concentration of liquid ionic silver, the greater the elevated Caspase-3 and mutant p53 expressions. Conclusion: The concentration of liquid ionic silver plays an important role in elevating Caspase-3 and mutant p53 expressions.

Aim: To identify the molecular mechanisms mediating the persistent defensive functions of the self‐renewing junctional epithelium (JE). Materials and methods: Two strains of Wnt reporter mice, Axin2CreErt2/+;R26RmTmG/+ and Axin2LacZ/+, were employed, along with three clinically relevant experimental scenarios where the function of the JE is disrupted: after tooth extraction, after a partial gingivectomy, and after a complete circumferential gingivectomy. Results: Using transgenic Wnt reporter strains of mice, we established the JE is a Wnt‐responsive epithelium beginning at the time of its formation and that it maintains this status into adulthood. After tooth extraction, progeny of the initial Wnt‐responsive JE population directly contributed to healing and ultimately adopted an oral epithelium (OE) phenotype. In the traditional partial gingivectomy model, the JE completely regenerated and did so via progeny of the original Wnt‐responsive population. However, following circumferential gingivectomy, the OE was incapable of re‐establishing a functional JE. Conclusions: A Wnt‐responsive niche at the interface between tooth and oral epithelia is required for a functional JE. [ABSTRACT FROM AUTHOR]

The use of mobile phones is based on radiofrequency (RF) waves, and the devices act as transmitters and receivers of non-ionizing energy. The micronucleus test was developed to identify increases in the occurrence of mutations in cells exposed to various agents. This systematic review with meta-analysis adhered to the following protocol: defining the objective, outlining the search method (PICO model), conducting the search, identifying literature, selecting articles, and extracting data. The study aimed to answer the following research question: Does non-ionizing radiation emitted by mobile phones have genotoxic and/or cytotoxic effects on the oral epithelium? The search for evidence published 2009-2019 was conducted in the MEDLINE, PubMed, Scopus, LILACS, Google Scholar, PROSPERO, and Cochrane Library databases. The following inclusion criteria were defined: investigations of effects on the oral mucosa related to RF; investigations of cytotoxic and/or genotoxic effects; investigations involving humans; and investigations using cells exfoliated from the oral epithelium. Investigations related to the parotid gland were excluded. The search strategy found 464 articles; after application of the eligibility criteria, 358 abstracts were analyzed and 351 abstracts excluded. After 7 full texts were reviewed, 1 study was excluded. The 6 included studies were classified as level 5 quality of evidence (observational studies). The meta-analysis included 2 studies that compared the frequency of micronuclei on the side exposed to RF electromagnetic fields (RF-EMFs) to that on the unexposed side. The studies evaluated presented a low degree of evidence, but the meta-analysis indicated that no genotoxic effects are associated with mobile phone use. However, observations of other nuclear abnormalities in some studies suggest the occurrence of cytotoxic effects caused by exposure to the RF-EMFs emitted by mobile phones. More studies are necessary to prove or refute this association. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to demonstrate the localization of transmembrane mucin MUC1 on the outer layer of oral mucosal cells and the involvement of apical cell surface microplicae (MPL) in bioadhesion of MUC1. Tissue samples of six healthy subjects were obtained. First, the presence of MUC1 was examined with an immunohistochemical method using a monoclonal MUC1 antigen called HFMG1. Second, the localization of MUC1 was examined with immuno-scanning electron microscopy. Immunohistochemically, high intense staining for MUC1 (antigen HFMG1) was detected in the epithelial superficial layers. In the superficial layer, intense MUC1 expression was seen predominantly on the apical cell surface. On the apical epithelial cells, MUC1 was associated predominantly with MPL towards the oral cavity. The novelty of the results of the present study is that MPL serves a harbor of MUC1 in superficial epithelial cells towards the oral cavity. It is speculated that the transmembrane MUC1 is one component of the "oral mucosal barrier complex" representing a signaling pathway between saliva and mucosal cells. Abbreviations: MUC1: mucin1; MAM: membrane-anchored mucin; OMBC: oral mucosal barrier complex; LM: light microscopy; TEM: transmission electron microscopy; SEM: scanning electron microscopy; iSEM: immuno-scanning electron microscopy; MPL: microplicae [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Highlights • The frequency of MNC correlated with the accumulated radiation dose. • Buccal MNC are sensitive biological dosimeters for low doses of ionizing radiation. • Exposure to low doses of ionizing radiation is a risk factor for DNA damage. Abstract We have evaluated buccal epithelial cell micronucleus formation as a biomarker of genotoxic damage following occupational exposure to low doses of ionizing radiation. Buccal epithelial cells were collected from 42 occupationally exposed medical personnel and 39 non-exposed individuals (reference group). Each individual in the exposed group was routinely monitored with a personal radiation badge. The frequency of micronucleated cells (MNC) was significantly higher in the exposed group (5.26 vs. 1.33 MNC/2000 cells) and correlated strongly with accumulated radiation dose (Annual Deep Dose, mSv). Occupational exposure to low doses of ionizing radiation was associated with an 80% relative increase in the frequency of MNC (MRR = 1.8; 95% CI: 1.1–2.8), suggesting that such exposures cause DNA damage. This non-invasive biomonitoring method should be generally applicable to studies of workers who are exposed occupationally to low doses of IR. [ABSTRACT FROM AUTHOR]

Background/Purpose: Lichen planus is a T-cell-mediated mucocutaneous disorder characterized histopathologically by a band of chronic inflammatory cells in the subepithelial zone and degeneration of basal layer. The present study was aimed to evaluate the distribution and quantitative assessment of cluster of differentiation 1a (CD1a)-positive Langerhans cells (LCs) in oral lichen planus (OLP), thus to determine the role of LCs pertaining to the changes occurring in OLP. Materials and Methods: Five cases of normal oral mucosa and 20 cases of OLP were immunostained with CD1a antibody; the positive cells were counted manually in the photomicrographs and statistically analyzed using t-test, Mann–Whitney test, and Wilcoxon signed-rank test. Results: The average percentage of CD1a-positive LCs in normal subjects was 0.9%, and in the OLP cases higher percentage was observed (3.93%). The statistical comparison of these two parameters was significant (P =0.018). The degree of basal cell degeneration and density of subepithelial infiltrate on statistical comparison with the concentration of CD1a-positive LCs showed significant results. Conclusion: LCs play a pivotal role in the recruitment of CD4+ and CD8+ cells to the subepithelial region and basal keratinocytes apoptosis. A small number of study subjects, assessment of only CD1a molecule and LCs in the epidermis only were a few of the drawbacks of the study. [ABSTRACT FROM AUTHOR]

This in vitro study attempts to delineate the role of extracellular matrix (ECM) constituents at the epithelial tissue-implant interface. To know which ECM constituents have a beneficial influence on the behavior of epithelial cells, the attachment, proliferation, morphologic pattern, and differentiation or cytoskeletal organization of human oral epithelial cells on ECM-coated (type IV collagen, fibronectin, type I collagen, laminin, and vitronectin) and noncoated titanium surface have been evaluated and compared. In each experiment comparing commercially pure titanium and oxygen plasma-cleaned titanium, the same ECM constituents were used. In this study, type IV collagen could provide an excellent substratum for epithelial cell attachment on titanium surface, but vitronectin-coated titanium revealed lower effectiveness for attachment of epithelial cells than noncoated titanium. These results suggested that type IV collagen could be used as a means for obtaining good epithelial seal, whereas vitronectin could be used to restrain the attachment of epithelium to dental implants. [ABSTRACT FROM AUTHOR]

Fungal infections are a global threat; yet, there are no licensed vaccines to any fungal pathogens. Th17 cells mediate immunity to Candida albicans , particularly oropharyngeal candidiasis (OPC), but essential downstream mechanisms remain unclear. In the murine model of OPC, IκBζ (Nfkbiz , a non-canonical NF-κB transcription factor) was upregulated in an interleukin (IL)-17-dependent manner and was essential to prevent candidiasis. Deletion of Nfkbiz rendered mice highly susceptible to OPC. IκBζ was dispensable in hematopoietic cells and acted partially in the suprabasal oral epithelium to control OPC. One prominent IκBζ-dependent gene target was β-defensin 3 (BD3) (Defb3), an essential antimicrobial peptide. Human oral epithelial cells required IκBζ for IL-17-mediated induction of BD2 (DEFB4A , human ortholog of mouse Defb3) through binding to the DEFB4A promoter. Unexpectedly, IκBζ regulated the transcription factor Egr3, which was essential for C. albicans induction of BD2/ DEFB4A. Accordingly, IκBζ and Egr3 comprise an antifungal signaling hub mediating mucosal defense against oral candidiasis. [Display omitted] • During candidiasis, IκBζ (Nfkbiz) is upregulated in the oral mucosa via IL-17 • Deletion of Nfkbiz renders mice highly susceptible to oropharyngeal candidiasis • IκBζ acts partially in the suprabasal oral epithelium • IκBζ and EGR3 regulate β-defensins, non-redundant antifungal effectors Fungal pathogens are of increasing medical concern. Oropharyngeal candidiasis (OPC) is the most common fungal infection in humans, but tissue-specific correlates of oral immunity are poorly understood. Taylor et al. show that IL-17 prevents OPC through the non-canonical transcription factor, IκBζ, which regulates essential antimicrobial peptide effectors. [ABSTRACT FROM AUTHOR]