Oral Mucosal Cells Research Articles

TNFα signaling mechanism against cell necrosis due to overextended denture

Objective: Not all removable partial dentures are successful or function well. One thing that patients complain about injuries to the oral mucosal tissue. The presence of denture edges that are too long or what is often referred to as overextended can cause necrosis of oral mucosal cells which show a clinical form of ulcers. The purpose of this pa-per is to explain the process of mechanical injury due dentures overextended against cell necrosis. Methods: Con-duct a review by covering the keywords mucosal ulceration, overextended denture, TNFα signaling. Various articles that have been obtained were thoroughly reviewed according to the inclusion and exclusion criteria. Results and discussion: The literatures show that overextended dentures cause discomfort. This is due to pain caused by injury to the mucosal lining of the oral cavity. Injury due to overextended denture causes cells to release death receptors in the form of TNF-R1 receptors. TNFα signals to bind to TNFα trimer with the TNF-R1 receptor. This response then proceeds to various processes that then lead to necrotic cell death. Conclusion: Death receptors and TNFα ini-tiate cell death where this necrotic cell death depends on the formation of reactive oxygen species.

The Effect of Oral Mucosal Mesenchymal Stem Cells on Pathological and Long-Term Outcomes in Experimental Traumatic Brain Injury.

Background Neuroprotective effects of stem cells have been shown in some neurologic diseases. In this study, the effect of oral mucosal mesenchymal stem cells (OMSCs) on traumatic brain injury (TBI) was evaluated in long term. Materials and Methods TBI was induced by Marmarou's method. The number of 2 × 106 OMSCs was intravenously injected 1 and 24 h after the injury. Brain edema and pathological outcome were assessed at 24 h and 21 days after the injury. Besides, long-term neurological, motor, and cognitive outcomes were evaluated at days 3, 7, 14, and 21 after the injury. Results OMSCs administration could significantly inhibit microglia proliferation, and reduce brain edema and neuronal damage, at 24 h and 21 days after the injury. Neurological function improvement was observed in the times evaluated in OMSCs group. Cognitive and motor function dysfunction and anxiety-like behavior were prevented especially at 14 and 21 days after the injury in the treatment group. Conclusion According to the results of this study, OMSCs administration after TBI reduced brain edema and neuronal damage, improved neurologic outcome, and prevented memory and motor impairments and anxiety-like behavior in long term.

Profiling of Oral Cells Morphology by means of a novel Label-Free Method of Polarization Diffraction Imaging

Currently, all oral leukoplakias, per gold standard, should undergo microscopic examination for diagnosis, which is an invasive procedure, and many patients are resistant to it due to cost, fear, or aversion to pain. We plan to develop a non-invasive assay, by using polarization diffraction imaging flow cytometry (p-DIFC) which is a technique that renders a three-dimensional model of single cells. That acquires a cross-polarized diffraction image pair (p-DI) of the coherent light scattered by a single cell with high image contrast excited by a linearly polarized laser beam. This method of single-cell assay enables extraction of cell morphology related information from the diffraction patterns embedded in the p-DI pair for each individual cell. In addition, the team has developed an optical model of cells based on confocal imaging to simulate the coherent light scattering process of a cell and convert the spatial distribution of scattered light into calculated p-DI pairs. Objectives: We aim to develop a protocol for acquiring oral mucosal cells for confocal imaging and establishing their individual three-dimensional (3D) morphologic profiles in the form of a preliminary database. In Phase 2, we will establish correlations between diffraction patterns from calculated p-DI data and the morphologic features revealed by mi- croscopy. Methods: We are collecting and quantifying individual cells from oral mucosa, in order to set a quantitative 3D morphologic single-cell parameter by confocal microscopy, for modeling study of diffraction patterns. Phase 2 of the study will involve single-cell analysis using p-DIFC for identification of early malignant changes in cytological sampling of mucosal lesions suspicious for malignancy. Conclusions: The results of this ongoing investigation will lay the foundation for future non-invasive, label-free detection of precancerous cells during intraoral examination, by investigating the profiling of cells harvested from patients in our institutions.

Multisystem Mitochondrial Disease Associated With a Mare m.10000G>A Mitochondrial tRNA Gly (MT-TG) Variant.

BackgroundMitochondrial diseases are clinically heterogeneous, can occur at any age, and can manifest with a wide range of clinical symptoms. They can involve any organ or tissue, characteristically involve multiple systems, typically affecting organs that are highly dependent on aerobic metabolism, and making a definitive molecular diagnosis of a mitochondrial disorder is challenging.MethodsClinical data of the proband and his family members were gathered in a retrospective study. Whole-exome sequencing and full-length sequencing of the mitochondrial genome that were performed on peripheral blood, urine, and oral mucosa cells were applied for genetic analysis.ResultsIn this study, we reported a childhood-onset mitochondrial phenotype in a 13-year-old patient. Analysis of the next-generation sequencing data of the nuclear genome and the full-length sequencing of the mitochondrial genome revealed the rare m.10000G>A variant in MT-TG that was present at variable heteroplasmy levels across tissue types: 32.7% in the blood, 56.15% in urinary epithelial cells, and 27.3% in oral mucosa cells. No variant was found in the peripheral blood of his mother and sister. No pathogenic mutation of nDNA was found.ConclusionOur results added evidence that the de novo m.10000G>A variation in the highly conserved sequence of MT-TG appears to suggest a childhood-onset mitochondrial phenotype in the 13-year-old patient, thus broadening the genotypic interpretation of mitochondrial DNA-related diseases.

Oral Mucosa Derived α-Synuclein as a Potential Diagnostic Biomarker for Parkinson's Disease.

BackgroundPathological α-synuclein (α-Syn) is not only exclusive to the central nervous system (CNS) in Parkinson’s disease (PD), but also extended to biofluids and peripheral tissues including oral cavity. Both oral mucosa and nervous system are derived from ectodermal tissue, and potentially share common disease-specific characteristics. Oral mucosal exfoliative cytology is a non-invasive technique, which is an easily acceptable for patients and ordinary people. The purpose of this study was to determine the abnormal accumulation of α-Syn in oral mucosa of PD patients and to learn the diagnostic utility of oral mucosa α-Syn for PD.MethodsThe oral mucosa samples were obtained from 57 patients with PD and 51 age-matched controls by cytological brush. Immunofluorescence analysis was used to investigate the presence and subcellular localization of α-Syn, phosphorylated α-Syn at Ser129 (pS129) and oligomeric α-Syn in the oral mucosa cells of PD patients and controls. Images taken as Z-stacks were analyzed for 3D reconstruction to visualize the α-Syn intracellular localization. Then, the concentrations of α-Syn, pS129, and oligomeric α-Syn in oral mucosa samples were measured using electrochemiluminescence assays.ResultsImmunofluorescence images revealed the increased α-Syn, pS129, and oligomeric α-Syn levels in oral mucosa cells of PD patients than age-matched controls. The intracellular distributions of α-Syn species were determine by Z-stack images with 3D reconstruction, and α-Syn was detected in both the nucleus and cytoplasm. However, pS129 was mainly located in the cytoplasm, and oligomeric α-Syn was highly expressed in the nucleus and perinuclear cytoplasm. The concentrations of three α-Syn species were significantly increased in the oral mucosa cell samples of PD patients than controls (α-Syn, p = 0.001; pS129, p = 0.002; oligomeric α-Syn, p = 0.013). In PD patients, the oral mucosa α-Syn and oligomeric α-Syn levels were significantly correlated with Hoehn-Yahr scales (α-Syn, r = 0.495, p = 0.001; oligomeric α-Syn, r = 0.324, p = 0.03). The area under curve (AUC) of ROC analysis using an integrative model including α-Syn, pS129, and oligomeric α-Syn for PD diagnosis was 0.749, with 66.7% sensitivity and 72.5% specificity.ConclusionThis study for the first time demonstrated increased expressions of α-Syn, pS129, and oligomeric α-Syn in oral mucosa cells from PD patients, which serve as useful and non-invasive PD diagnostic biomarkers.

Platycodin D Alleviates High-Glucose-Aggravated Inflammatory Responses in Oral Mucosal Cells by PI3K/mTOR Pathway

Oral mucosal diseases account for an increasing proportion of hμMan diseases. Among the many common risk factors that cause oral diseases and systemic diseases, dietary factors, especially high sugar, are particularly prominent. Exhibiting therapeutic potential in treating certain inflammation-related diseases, platycodin D (PD) has been known to possess anti-inflammatory benefits in cases of cytokine-induced inflammation, a fact that has been widely docμMented. However, there are few studies about PD in the oral mucosal disease. Investigating the effect of PD on high-glucose (HG)-induced inflammatory responses in oral mucosal cells was the endeavor of this study. The results revealed that HG induced cell mortality, promoted activity of inflammatory factor (TNF-α, IL-1β, IL-6, and IL-8), and increased ROS production in oral mucosal cells. Interestingly, PD obviously alleviated HG-induced oral mucosal cells inflammatory response. Simultaneously, the expressions of PI3K and mTOR were inhibited by PD. In addition, the activation of PI3K and mTOR decreased the protective effect of PD on oral mucosal cells. To conclude, the PI3K/mTOR signaling pathway was found to be inactivated, thereby restraining the activation of the full immune cell by inhibition of the pro-inflammatory cytokines, as revealed by the results indicating the prevention of the HG-induced inflammation response by PD.

Transplantation of cells of the oral mucosa in the treatment of limbal stem cell deficiency

The actual problem of treatment of patients with limbal cell stem deficiency is reviewed. We summarized practical experience in various fields of medicine, aimed at tissue reconstruction using cells of the buccal mucosa. In ophthalmology, an effective method has long been searched to treat patients with the limbal stem cell deficiency causing an intense opacification and vascularization of the cornea and followed by a significant decrease in visual acuity. Recent studies have shown that the transplantation of epithelial cells of oral mucosa can significantly improve the treatment of patients with this disease. Although the mechanisms of oral mucosa epithelial cells' action are still insufficiently studied, the existing positive experience of oral mucosa using for tissue repair has great interest to practitioners, giving potential possibilities of its use, therapeutic effectiveness and ease of obtaining. A brief review of the literature presents the description of the morphological features of the. buccal mucosa and the analysis of published data about the use of buccal epithelium in various branches of medicine and in ophthalmology, in particular.

Influence of clinical factors, IL4 and IL6 genes polymorphisms in functional healing in late replantation.

To investigate the genetic association in a sample of replanted teeth, it is necessary to observe the extreme phenotypes, such as, teeth that underwent functional healing and those extracted due to severe external root resorption. Thus, this study aimed to investigate the association of age of the patients, root development, storage media, and polymorphisms in the interleukin 4 (IL4) and interleukin 6 (IL6) genes with teeth that presented extreme outcomes, as functional healing or extraction, in a group whose replantation techniques did not follow the International Association of Dental Traumatology (IADT) 2012 guidelines. Forty-three avulsed and replanted teeth that did not follow IADT 2012 guidelines and underwent functional healing or were extracted were included. Periapical radiographs employed for this study were taken soon after tooth replantation and after 1 year. For genotypic IL4 and IL6 genes analysis, DNA of oral mucosa cells was extracted. Real-time- PCR performed for genotyping polymorphisms in IL4 and IL6 genes. Clinical and genetic variables were analyzed by the Chi-square test and the "Z" test. P values < .05 were considered significant. The results showed that functional healing and extraction were associated with storage media and with the rs2243268 of IL- 4 gene polymorphisms. As conclusion, the C rs2243268 allele of IL4 gene may have a positive relationship with functional healing teeth that were replanted not following the 2012 IADT guidelines. Keeping the tooth dry is associated to a fast loss of avulsed and replanted teeth after 1-year follow-up.

Two PARP13 isoforms are associated with induction of antiviral factors in oral mucosal cells.

Innate immune systems in the oral cavity have important roles in the host defense against viral invasion of oral mucosa. Poly(ADP‑ribose) polymerase13(PARP13), which has a strong antiviral ability, has been reported to possess two isoforms; a full‑length protein, zinc‑finger antiviral protein long (ZAPL), and a shorter protein (ZAPS). However, the expression and function of these two isoforms in oral mucosa remain unknown. In the present study, the expression levels of ZAPL and ZAPS induced by transfected double‑stranded(ds) RNA, Poly(I:C), and dsDNA, Poly(dA:dT), in immortalized oral keratinocytes and fibroblasts (RT7 and GT1 cell lines, respectively) were investigated. Subsequently, the effects of the knockdown of ZAPL and ZAPS on transfected nucleotide‑induced antiviral factors were examined. The results demonstrated constitutive expression of ZAPL and ZAPS in RT7 and GT1 cells, and their expression in both cell types was notably increased by transfection of Poly(I:C) and Poly(dA:dT) when compared with no transfection. Specific knockdown of ZAPL and ZAPS in RT7 cells decreased IFN‑β and C‑X‑C motif chemokine ligand10(CXCL10) expression induced by transfected Poly(I:C) and Poly(dA:dT). On the other hand, knockdown of ZAPL and ZAPS in GT1 cells decreased the expression of CXCL10 induced by the transfected nucleotides, whereas that had no effect on IFN‑β expression induced by Poly(dA:dT). Their knockdown was also associated with transfected nucleotides‑induced IFN regulatory factor 3 phosphorylation in both cell types. Taken together, these results indicate that ZAPL and ZAPS, isoforms of PARP13, in oral mucosal cells participate in host defense against viral infection of oral mucosa.

Phytochemical Analysis, Antioxidant, and Wound Healing Activity of Pluchea indica L. (Less) Branch Extract Nanoparticles.

Proliferation and migration of keratinocytes and fibroblasts play an important role in cutaneous wound healing, while oral mucosal squamous cell proliferation and migration are crucial for oral wound healing. In this study, the phytochemical profile of Pluchea indica branch ethanolic extract was characterized. The bioactive compound of Pluchea indica branch ethanolic extract was identified and analyzed by the validated HPLC method. The nanoparticles of P. indica branch extract were formulated by solvent displacement method to increase the solubility and the colloidal stability of the extract. The stability of the nanoparticles was investigated by using the dynamic light scattering technique. Effects of P. indica crude extract and nanoparticles on cell viability, proliferation and migration of primary epidermal keratinocytes, human dermal fibroblasts, and oral mucosal keratinocyte cells were investigated by MTT assay and scratch assay, respectively. The results showed that P. indica branch extract contained a high content of total phenolic and total flavonoids. The HPLC analysis revealed that the main compound in the extract was 4,5-O-dicaffeoylquinic acid. The cell viability of the extract and nanoparticles decreased when cells were exposed to a high concentration of extract and nanoparticles. These results demonstrate that P. indica branch extract and extract nanoparticles at specific concentrations possess in vitro wound healing activity and they may be possibly used to treat different types of wounds including dermal and oral mucosal wounds.

Clinical and cytological findings in oral cavity of young shisha smokers and non-smokers – a comparative study

Introduction: Shisha, a form of smoking tobacco is known to be detrimental to oral health. Yet, the effects of shisha on oral health is not well documented. Hence, this study was undertaken to compare the clinical and cytological findings in oral cavity of young shisha smokers as compared to non-smokers. Materials and methods: A cross-sectional analytical study was undertaken among 60 subjects including 30 young shisha smokers and 30 non-smokers. Clinical examination was carried out to record gingival status, periodontal status, oral hygiene and dental caries experience. Exfoliative cytology was used to study the cytological changes of buccal mucosal cells. Data was analysed using SPSS version 22. Student’s t-test, Fisher’s exact test and odd’s ration was used for comparison. p &lt; 0.05 was considered statistically significant. Results: No significant differences were found between the groups with respect to proportion of subjects with gingivitis (p = 0.071), erosion (p = 0.085) and dental caries experience (p = 0.329). However, shisha smokers had poorer oral hygiene and more severe gingival inflammation as compared to non-smokers with p = 0.026 and p = 0.007 respectively. The odds of having atypical cells in oral mucosa among shisha smokers was 3.76 times higher than the non-smokers. Conclusion: The findings of our study showed that young shisha smokers had more atypical cells in oral mucosa as compared to their non-smoking counterparts. However, longitudinal studies are needed to affirm the findings of this study.

Expression of anti-fungal peptide, β-defensin 118 in oral fibroblasts induced by C. albicans β-glucan-containing particles

Objective:Although oral fibroblasts are thought to have the potential to enhance host defenses against Candida albicans , it is unknown whether they are able to recognize Candida cell components to increase the expression of antifungal peptides, such as defensin factors, against Candida infection.Methodology:We performed expression profiles of defensin genes induced by heat-killed C. albicans in oral immortalized fibroblasts (GT1) using cDNA microarray analysis. From those results, quantitative RT-PCR was used to examine the effects of Candida β-glucan-containing particles (β-GPs) on β-Defensin 118 (DEFB 118) expression in oral mucosal cells. Furthermore, the antifungal activities of recombinant DEFB 118 against C. albicans and C. glabrata were investigated using fungicidal assays.Results:Microarray analysis showed that DEFB118, β-Defensin 129 (DEFB129), and α-Defensin 1 (DEFA1) genes were induced by heat-killed C. albicans and that their mRNA expressions were also significantly increased by live as well as heat-killed C. albicans . Next, we focused on DEFB118, and found that GT1, primary fibroblasts, and RT7 (oral immortalized keratinocytes) constitutively expressed DEFB118 mRNA expression in RT-PCR. Furthermore, C. albicans β-GPs significantly increased the expression of DEFB118 mRNA in GT1 and primary fibroblasts. Although DEFB118 mRNA expression in RT7 was significantly induced by both live and heat-killed C. albicans, C. albicans β-GPs failed to have an effect on that expression. Finally, recombinant DEFB118 significantly decreased the survival of both strains of C. albicans in a dose-dependent manner, whereas no effects were seen for both C. glabrata strains.Conclusion:DEFB118, induced by C. albicans β-GPs from oral fibroblasts, may play an important role in oral immune responses against C. albicans infection.

Association of the estrogen receptor gene with oral health-related quality of life in patients with dentofacial deformities.

This study aimed to evaluate the associations between oral health-related quality of life (OHRQoL) and patient-associated factors and polymorphisms in the estrogen receptor 1 (ESR1) and 2 (ESR2) genes in patients with dentofacial deformities (DFD). This cross-sectional study included 234 adult individuals. Data such as age, sex, and the type of facial profile (I, II, or III), were collected, and the short-form oral health impact profile 14 (OHIP-14) questionnaire was used to assess their OHRQoL. DNA was collected from oral mucosa cells, and the polymorphisms in ESR1 (rs2234693 and rs9340799) and ESR2 (rs1256049 and rs4986938) were evaluated using real-time polymerase chain reaction. The data were subjected to statistical analysis at a significance level of 5%. Individuals over 28 years of age exhibited worse OHRQoL (p = 0.003) than individuals aged less than or equal to 28 years. Women had worse OHRQoL than men (p < 0.001). Profile II individuals had worse OHRQoL in the social disability domain than profile III individuals (p = 0.030). Genetic analysis showed that rs9340799 was associated with OHRQoL in the functional limitation domain, and GG individuals exhibited worse OHRQoL than individuals carrying the AA/AG genotypes (p < 0.030). In the social handicap domain, individuals with GG genotype in rs9340799 exhibited worse OHRQoL than AG individuals (p < 0.043). Collectively, our results reveal that factors including age, sex, and type of facial profile, are associated with OHRQoL in patients with DFD. In addition, individuals with the GG genotype in rs9340799 (ESR1) may experience a negative impact on OHRQoL in the functional limitation and social handicap domains.

As a Novel Tumor Suppressor, LHPP Promotes Apoptosis by Inhibiting the PI3K/AKT Signaling Pathway in Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) refers to the malignant tumor of the head and neck with a highest morbidity. It exhibits a poor prognosis and unsatisfactory treatment partially attributed to delayed diagnosis. As indicated from existing reports, the protein histidine phosphatase LHPP acts as a vital factor in tumorigenesis in liver, lung, bladder, breast and pancreatic tumor tissues. Thus far, the functional mechanism of LHPP in OSCC remains unclear. DGE analysis, OSCC cell lines and OSCC cases were found that LHPP was down-regulated in OSCC tissues and cells compared with that in normal oral mucosa tissues and cells, and was closely related to OSCC differentiation. Cell counting Kit 8 test, EdU proliferation test, scratches test, invasion test, monoclonal formation test, mouse xenograft tumor model, HE staining and immunohistochemistry showed that LHPP inhibited OSCC growth, proliferation and migration in vivo and in vitro. GO and KEGG enrichment analysis, LHPP transcription factor analysis and flow cytometry found that LHPP promotes the apoptosis of OSCC by decreasing the transcriptional activity of p-PI3K and p-Akt. Finally, our results suggested that LHPP inhibited the progression of OSCC through the PI3K/AKT signaling pathway, indicating that LHPP may be a new target for the treatment of OSCC.

GENOTOXICITY AND CYTOTOXICITY CAUSED BY CLEAR ALIGNERS-AN INVIVO STUDY

Aim: To evaluate the possible cytotoxic damage to the oral mucosal cells in healthy patients undergoing orthodontic treatment with clear aligners. Materials &amp; Methods: 20 patients who required orthodontic treatment were chosen. The rst set of aligners were fabricated for each patient using a PETG material. Patients were instructed to wear the aligners for 22 hours a day for 15 days. Buccal mucosal cells were sampled at two time intervals T0- pre treatment and T1- after 15 days and were immediately smeared onto a clean glass slide. The smears were immediately xed in isopropyl alcohol, following which the slides were hydrated with distilled water, stained with the Papanicolaou method and subjected to cytomorphometric analysis. The two samples obtained at T0 and T1 for each patient were compared to check for an increase in number of micronucleated cells. Student Paired t Test was used to compare the mean micronuclei count between pre and post treatment. Results: The mean Micro Nuclei count in the post treatment period was signicantly higher (4.50 ± 1.96) as compared to pretreatment period (3.10 ± 1.73) with a mean difference of -1.40 at P=0.007. Conclusion: Within the experimental limits of this study the PETG material used for fabrication of aligners resulted in a change in the nature of buccal mucosal cells with an increase in the number of micronuclei which is an indicator for cytotoxicity. The PETG material may have a cytotoxic effect on the cells of the oral mucosa.

Disturbance of the Circadian System in Shift Work and Its Health Impact

The various non-standard schedules required of shift workers force abrupt changes in the timing of sleep and light-dark exposure. These changes result in disturbances of the endogenous circadian system and its misalignment with the environment. Simulated night-shift experiments and field-based studies with shift workers both indicate that the circadian system is resistant to adaptation from a day- to a night-oriented schedule, as determined by a lack of substantial phase shifts over multiple days in centrally controlled rhythms, such as those of melatonin and cortisol. There is evidence that disruption of the circadian system caused by night-shift work results not only in a misalignment between the circadian system and the external light-dark cycle, but also in a state of internal desynchronization between various levels of the circadian system. This is the case between rhythms controlled by the central circadian pacemaker and clock genes expression in tissues such as peripheral blood mononuclear cells, hair follicle cells, and oral mucosa cells. The disruptive effects of atypical work schedules extend beyond the expression profile of canonical circadian clock genes and affects other transcripts of the human genome. In general, after several days of living at night, most rhythmic transcripts in the human genome remain adjusted to a day-oriented schedule, with dampened group amplitudes. In contrast to circadian clock genes and rhythmic transcripts, metabolomics studies revealed that most metabolites shift by several hours when working nights, thus leading to their misalignment with the circadian system. Altogether, these circadian and sleep-wake disturbances emphasize the all-encompassing impact of night-shift work, and can contribute to the increased risk of various medical conditions. Here, we review the latest scientific evidence regarding the effects of atypical work schedules on the circadian system, sleep and alertness of shift-working populations, and discuss their potential clinical impacts.

Origin of langerin (CD207)-expressing antigen presenting cells in the normal oral mucosa and in oral lichen planus lesions.

The number of langerin-expressing antigen-presenting cells is higher in oral lichen planus than in normal oral mucosa. However, langerin may be expressed by several functionally different lineages of antigen presenting cells (APCs), and this has important implications for our understanding of the pathogenesis of oral lichen planus. The aim of this study was to determine the origin of the langerin-expressing APCs. To this end, we examined oral mucosal biopsies from healthy persons and patients with oral lichen planus using multicolor immunofluorescence. In normal oral mucosa, a substantial fraction of Langerhans cells expressed Ki-67, indicating that steady-state oral mucosal Langerhans cells are at least partially maintained by self-renewal. In oral lichen planus, the numbers of Langerhans cells were higher but proliferation was not altered, indicating that the higher cell numbers appeared to depend on recruited dendritic cell (DC)-precursors. Moreover, we found a markedly higher number of langerin+ APCs within the lamina propria of oral lichen planus lesions. Such cells did not display monocyte- or macrophage markers, but rather showed a phenotype compatible with tissue-elicited IRF4+ cDC2. Detailed understanding of how the oral mucosal APC network is regulated and the functional capacities of the different ontogenies may identify novel treatment targets for oral lichen planus.

The Local Neuropeptide System of Keratinocytes.

Neuropeptides have been known for over 50 years as chemical signals in the brain. However, it is now well established that the synthesis of this class of peptides is not restricted to neurons. For example, human skin not only expresses several functional receptors for neuropeptides but, also, can serve as a local source of neuroactive molecules such as corticotropin-releasing hormone, melanocortins, and β-endorphin. In contrast, an equivalent of the hypothalamic-pituitary axis in the oral mucosa has not been well characterized to date. In view of the differences in the morphology and function of oral mucosal and skin cells, in this review I surveyed the existing evidence for a local synthesis of hypothalamic-pituitary, opiate, neurohypophyseal, and neuroendocrine neuropeptides in both epidermal and oral keratinocytes.

Investigations concerning the impact of consumption of hot beverages on acute cytotoxic and genotoxic effects in oral mucosa cells

Consumption of very hot beverages and foods increases the incidence of oral and esophageal cancer but the mechanisms are not known and the critical temperature is not well defined. We realized a study with exfoliated cells from the oral cavity of individuals (n = 73) that live in an area in Iran which has the highest incidence of EC worldwide. Consumption of beverages at very high temperatures is a characteristic feature of this population. We analyzed biomarkers which are (i) indicative for genetic instability (micronuclei that are formed as a consequence of chromosomal damage, nuclear buds which are a consequence of gene amplifications and binucleated cells which reflect mitotic disturbances), (ii) markers that reflect cytotoxic effects (condensed chromatin, karyorrhectic, karyolitic and pyknotic cells), (iii) furthermore, we determined the number of basal cells which is indicative for the regenerative capacity of the buccal mucosa. The impact of the drinking temperature on the frequencies of these parameters was monitored with thermometers. We found no evidence for induction of genetic damage but an increase of the cytotoxic effects with the temperature was evident. This effect was paralleled by an increase of the cell division rate of the mucosa which was observed when the temperature exceeded 60 °C. Our findings indicate that cancer in the upper digestive tract in drinkers of very hot beverages is not caused by damage of the genetic material but by an increase of the cell division rate as a consequence of cytotoxic effects which take place at temperatures over 60 °C. It is known from earlier experiments with rodents that increased cell divisions lead to tumor promotion in the esophagus. Our findings provide a mechanistic explanation and indicate that increased cancer risks can be expected when the drinking temperature of beverages exceeds 60 °C.

Human Cytomegalovirus Replication and Infection-Induced Syncytia Formation in Labial, Foreskin, and Fetal Lung Fibroblasts

Only a handful of cell types, including fibroblasts, epithelial, and endothelial cells, can support human cytomegalovirus (CMV) replication in vitro, in striking contrast to the situation in vivo. While the susceptibility of epithelial and endothelial cells to CMV infection is strongly modulated by their anatomical site of origin, multiple CMV strains have been successfully isolated and propagated on fibroblasts derived from different organs. As oral mucosal cells are likely involved in CMV acquisition, we sought to evaluate the ability of infant labial fibroblasts to support CMV replication, compared to that of commonly used foreskin and fetal lung fibroblasts. No differences were found in the proportion of cells initiating infection, or in the amounts of viral progeny produced after exposure to the fibroblast-adapted CMV strain AD169 or to the endothelial cell-adapted strain TB40/E. Syncytia formation was, however, significantly enhanced in infected labial and lung fibroblasts compared to foreskin-derived cells, and did not occur after infection with AD169. Together, these data indicate that fibroblast populations derived from different tissues are uniformly permissive to CMV infection but retain phenotypic differences of potential importance for infection-induced cell–cell fusion, and ensuing viral spread and pathogenesis in different organs.