CCL5's Role in Periodontal Disease: A Narrative Review.

Persistent host inflammatory and immune responses to biofilm play a critical role in the mechanisms that govern soft and hard tissue destruction in periodontal disease. Among the less explored facets of these mechanisms are chemokines, including CCL5 (C-C motif chemokine ligand 5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), a proinflammatory CC subfamily chemokine synthesized by T lymphocytes. Despite its importance, there is currently no comprehensive review of the role of CCL5 in periodontitis in the literature. Therefore, this paper aims to fill this gap by summarizing the existing knowledge on the involvement of CCL5 in the onset and progression of periodontitis. In addition, we aim to stimulate interest in this relatively overlooked factor among periodontitis researchers, potentially accelerating the development of drugs targeting CCL5 or its receptors. The review examines the association of CCL5 with periodontitis risk factors, including aging, cigarette smoking, diabetes, and obesity. It discusses the involvement of CCL5 in pathological processes during periodontitis, such as connective tissue and bone destruction. The data show that CCL5 expression is observed in affected gums and gingival crevicular fluid of periodontitis patients, with bacterial activity contributing significantly to this increase, but the reviewed studies of the association between CCL5 expression and periodontal disease have yielded inconclusive results. Although CCL5 has been implicated in the pathomechanism of periodontitis, a comprehensive understanding of its molecular mechanisms and significance remains elusive, hindering the development of drugs targeting this chemokine or its receptors.

The Washout Resistance of Bioactive Root-End Filling Materials.

Fast-setting bioactive cements were developed for the convenience of retrograde fillings during endodontic microsurgery. This in vitro study aimed to investigate the effect of irrigation on the washout of relatively fast-setting materials (Biodentine, EndoCem Zr, and MTA HP) in comparison with MTA Angelus White and IRM in an apicectomy model. Washout resistance was assessed using artificial root ends. A total of 150 samples (30 for each material) were tested. All samples were photographed using a microscope, and half of them were also scanned. The samples were irrigated and immersed in saline for 15 min. Then the models were evaluated. Rinsing and immersing the samples immediately after root-end filling and after 3 min did not disintegrate the fillings made of all tested materials except Biodentine. Root-end fillings made of Biodentine suffered significant damage both when rinsing was performed immediately and 3 min after the filling. Quantitative assessment of washed material resulted in a slight loss of IRM, EndoCem MTA Zr, and MTA HP. MTA Angelus White showed a slightly greater washout. Rinsing and immersion of Biodentine restorations resulted in their significant destruction. Under the conditions of the current study, the evaluated materials, excluding Biodentine, showed good or relatively good washout resistance.

Evaluation of Gingival Phenotype in the Early Transitional Dentition Phase in Children-Comparison of Three Non-Invasive Methods.

Gingival phenotype (GP) is determined based on the thickness and width of the gingival tissue. An evaluation of GP is essential for adequate treatment planning and outcome monitoring, including orthodontic treatments in a paediatric population. The present study aimed to compare the reliability of the visual and TRAN methods with that of the ultrasound biometer measurements in the early transitional dentition phase. One hundred ninety three generally healthy, 7-year-old children were examined. An assessment of GP was performed by a paedodontist and a periodontist. The average thickness of the gingiva was 0.76 ± 0.36 mm, which was classified as a thin GP. The agreement between a visual assessment and the biometric ultrasound measurements reached the highest (94%) level when assessing a very thin GP (Spearman's rank correlation coefficient r = 0.37, p < 0.01). Similarly, 99% agreement in the diagnosis of a thin GP was recorded for the TRAN and ultrasound methods (Spearman's rank correlation coefficient r = 0.49, p < 0.001). In total, 86% of cases diagnosed as having a thick GP using the TRAN method turned out to be thin according to the ultrasound measurements. The dentist's specialization and professional experience in the assessment of GP were irrelevant (Spearman's rank correlation coefficient r = 0.49, p < 0.001). All methods tested in the present study were proven to be easy to perform and well accepted by the children. The visual assessment and TRAN methods, despite the fact that they enabled the diagnosis of a thin GP (crucial for treatment planning), cannot be recommended during the teeth replacement period. A misdiagnosis of thick GP may deprive a young at-risk patient of special supervision, which may develop into mucogingival deformities. A biometric ultrasound, although expensive, allows for reliable assessment of the gingiva thickness when needed.

Drug-Induced Gingival Overgrowth-Molecular Aspects of Drug Actions.

Drug-induced gingival overgrowth (DIGO) is one of the side effects produced by therapeutic agents, most commonly phenytoin, nifedipine and cyclosporin A. However, the precise mechanism of DIGO is not entirely understood. A literature search of the MEDLINE/PubMed databases was conducted to identify the mechanisms involved in DIGO. The available information suggests that the pathogenesis of DIGO is multifactorial, but common pathogenic sequelae of events emerge, i.e., sodium and calcium channel antagonism or disturbed intracellular handling of calcium, which finally lead to reductions in intracellular folic acid levels. Disturbed cellular functions, mainly in keratinocytes and fibroblasts, result in increased collagen and glycosaminoglycans accumulation in the extracellular matrix. Dysregulation of collagenase activity, as well as integrins and membrane receptors, are key mechanisms of reduced degradation or excessive synthesis of connective tissue components. This manuscript describes the cellular and molecular factors involved in the epithelial-mesenchymal transition and extracellular matrix remodeling triggered by agents producing DIGO.

Covid-19 and SARS-CoV-2 infection in periodontology: A narrative review.

The present review examined the available evidence on possible involvement of gingival tissues in SARS-CoV-2 infection. Gingival tissue possess SARS-CoV-2 entry and transmission factors, among them ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane protease serine 2), which are the principal mediators of the virus cell invasion. Clinical observations reveal SARS-CoV-2 RNA in periodontal tissues and crevicular fluid, suggesting that the periodontium may act as an entry point for the virus and/or as a dissemination site. The preliminary observations prove infection potential of gingival crevicular fluid and shed epithelial cells from the periodontium. There are also findings on potential associations between periodontitis and Covid-19 (coronavirus disease 2019). PubMed and Scopus databases were used to search for suitable keywords such as: SARS-CoV-2, Covid-19, oral virus infection, gingival crevicular fluid, oral mucosa, periodontium, gingiva, ACE2, TMPRSS2, Furin, diagnosis, topical treatment, vaccine and the related words for relevant publications. Data extraction and quality valuation of articles were performed by the author. The review addressed seven major domains: periodontal structures as SARS-CoV-2 infection site, the periodontal changes under SARS-CoV-2 infection, potential associations between periodontitis and Covid-19, periodontal oral care in Covid-19, crevicular fluid as potential transmission factor and preventive measures. The search process in PubMed and Scopus was updated up to 31 March 2022. Finally 68 articles were retrieved for the final analysis, from the initial database searches. According to the inclusion criteria articles in English language without any date restriction were included. The included studies were mostly original articles, and published in 2020 and 2021 with the aim to describe Covid-19 and SARS-CoV-2 infection in periodontology. As a conclusion it can be stated that gingival tissues may play a role in SARS-CoV-2 infection.

Gingival Phenotype Changes and the Prevalence of Mucogingival Deformities during the Early Transitional Dentition Phase-A Two-Year Longitudinal Study.

Thin gingival phenotype (GPh) may contribute to periodontal tissue breakdown and recession development. Thus, the early identification of thin GPh in children can allow proper preventive care and the identification of children at risk during orthodontic treatment. The present long-term study aimed to monitor GPh changes, i.e., thickness (GT) and width of attached gingiva (AGW) during the early transitional dentition phase, as well as its potential associations with the mucogingival deformities. MATERIALS AND METHODS: 83 systematically healthy children were examined twice with an interval of 2 years. Probing depth, GT and AGW at mandibular incisors, vestibular depth, type of lower lip frenum attachment and mucogingival defects were recorded. RESULTS: 95.2% of participants at baseline and 93.9% at 2-year examination expressed thin GPh. During the transition from the deciduous to permanent dentition, GT and AGW declined, but the GT of permanent incisors already erupted at the baseline examination increased in the observation period. CONCLUSIONS: Gingival phenotype undergoes changes in the early transitional dentition phase. In spite of the thin gingival phenotype, only single pseudo-recessions and primary shallow vestibule were noticed.

Oral Pathology in COVID-19 and SARS-CoV-2 Infection-Molecular Aspects.

This review article was designed to evaluate the existing evidence related to the molecular processes of SARS-CoV-2 infection in the oral cavity. The World Health Organization stated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission is produced by respiratory droplets and aerosols from the oral cavity of infected patients. The oral cavity structures, keratinized and non-keratinized mucosa, and salivary glands' epithelia express SARS-CoV-2 entry and transmission factors, especially angiotensin converting enzyme Type 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Replication of the virus in cells leads to local and systemic infection spread, and cellular damage is associated with clinical signs and symptoms of the disease in the oral cavity. Saliva, both the cellular and acellular fractions, holds the virus particles and contributes to COVID-19 transmission. The review also presents information about the factors modifying SARS-CoV-2 infection potential and possible local pharmacotherapeutic interventions, which may confine SARS-CoV-2 virus entry and transmission in the oral cavity. The PubMed and Scopus databases were used to search for suitable keywords such as: SARS-CoV-2, COVID-19, oral virus infection, saliva, crevicular fluid, salivary gland, tongue, oral mucosa, periodontium, gingiva, dental pulp, ACE2, TMPRSS2, Furin, diagnosis, topical treatment, vaccine and related words in relevant publications up to 28 December 2021. Data extraction and quality evaluation of the articles were performed by two reviewers, and 63 articles were included in the final review.

Impact of kidney dysfunction on hepatic and intestinal drug transporters.

Emerging information suggests that pathology of the kidney may not only affect expression and function of membrane transporters in the organ, but also in the gastrointestinal tract and the liver. Transporter dysfunction may cause effects on handling of drug as well as endogenous compounds with subsequent clinical consequences. A literature search was conducted on Ovid and PubMed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of the gastrointestinal and liver localized ABC transporters and SLC carriers in kidney dysfunction or uremia states. The altered function of drug transporters in the liver and intestines in kidney failure subjects may provide compensatory activity in handling endogenous compounds (e.g. uremic toxins), which is expected to affect drug pharmacokinetics and local drug actions.

The attached gingiva thickness in the mandibular anterior region during the early transitional dentition phase.

Objectives: Adequate gingival thickness provides a stable base for appropriate oral hygiene maintenance and mucogingival lesion prevention. The study aim was to assess attached gingiva thickness in relation to its width, probing depth, crowding, and tooth position in the arch during the early transitional dentition phase. Method and materials: A cross-sectional study in 193 children aged 7 years with healthy mucogingival complex was conducted, and PIROP ultrasonic biometer measurement of gingival thickness of mandibular incisors was applied. To compare qualitative variables across different dentition groups, chi-square test or Fisher exact test were used, and for quantitative variables Kruskal-Wallis test plus post-hoc analysis (Dunn test). Spearman correlation coefficient was used to correlate gingival thickness with width of attached gingiva, as well as Kruskal-Wallis test and post-hoc analysis to assess the relationship between gingival thickness and tooth position in the arch, type of incisor, and eruption phase. Results: The mean gingival thickness value was less than 1 mm in all incisor type groups. The thinnest gingiva was noticed at permanent newly erupted incisors (0.72 ± 0.36; P < .001). Thickness of attached gingiva positively correlated with its width and with probing depth (r = 0.164, P < .001). Gingival thickness was significantly thinner at incisors positioned labially. No correlation of attached gingiva thickness with transitional crowding in mandibular incisor segment was observed. Conclusions: The results revealed thin gingiva at mandibular incisors in white children during the early transitional dentition phase. Objective, ultrasound measurements were used for the first time in a pediatric population, and the device was simple and well tolerated.

In Vitro Infrared Thermographic Assessment of Temperature Change in the Pulp Chamber during Provisionalization: Effect of Remaining Dentin Thickness.

Interim crowns and partial fixed dental prosthesis materials generate exothermic heat during polymerization. The amount of heat transmitted to the pulp chamber can be a function of several factors, including the thickness and quality of the remaining dentin after crown preparation. The aim of this in vitro study was to measure with infrared thermography the temperature changes on the adjacent surface of the chamber roof of premolar teeth extracted from young and old patients (having different thicknesses of remaining dentin after crown preparation) during fabrication of provisional resinous restorations. Twenty extracted human first and second maxillary premolar teeth (10 from young patients, with a relatively large pulp chamber, and 10 from older patients, with a relatively small pulp chamber) were used. The roots were sectioned to expose the inner side of the chamber roof, and the crowns were provisionalized after preparation for a metal-ceramic crown. Two provisional materials, Turbo Temp 2 and Luxatemp Fluorescence, were used. Temperature changes on the inner side of the chamber roof were measured at 2-second intervals using an infrared thermal imaging camera. After completion of the temperature recordings, the teeth were sectioned and the remaining dentin thickness was determined. The older group (mean thickness: 2.82 mm) and younger group (mean thickness: 1.9 mm) differed significantly in dentin thickness (P < 0.014). The mean greatest temperature increases recorded on the chamber roof of teeth with less remaining dentin were 4.07°C for Turbo Temp 2 and 3.94°C for Luxatemp Fluorescence, while increases in the premolars with greater dentin thickness were 1.69°C for Turbo Temp 2 and 1.64°C for Luxatemp Fluorescence. Significant interactions were found between tooth groups (P < 0.000001for Turbo Temp 2 and for Luxatemp Fluorescence). No significant differences were found between assessed materials regardless of the thickness of the remaining dentin (P > 0.38for the older group and P > 0.29 for the younger group). Dentin had a significant effect in limiting the temperature increase generated during polymerization of provisional materials, indicating good thermal insulating properties of this tissue. A remaining dentin thickness of 1.9 mm or more is sufficient to protect the pulp from any temperature increase during provisionalization using tested materials.

Extrahepatic Drug Transporters in Liver Failure: Focus on Kidney and Gastrointestinal Tract.

Emerging information suggests that liver pathological states may affect the expression and function of membrane transporters in the gastrointestinal tract and the kidney. Altered status of the transporters could affect drug as well as endogenous compounds handling with subsequent clinical consequences. It seems that changes in intestinal and kidney transporter functions provide the compensatory activity of eliminating endogenous compounds (e.g., bile acids) generated and accumulated due to liver dysfunction. A literature search was conducted on the Ovid and PubMed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of the gastrointestinal and kidney operating ABC (ATP-binding cassette) transporters and SLC (solute carriers) carriers. The accumulated data suggest that liver failure-associated transporter alterations in the gastrointestinal tract and kidney may affect drug pharmacokinetics. The altered status of drug transporters in those organs in liver dysfunction conditions may provide compensatory activity in handling endogenous compounds, affecting local drug actions as well as drug pharmacokinetics.

Effect of nano-hydroxyapatite and ozone on approximal initial caries: a randomized clinical trial.

The aim of the study was to assess the efficacy of three methods of enamel remineralization on initial approximal caries: (1) a nano-hydroxyapatite gel, (2) gaseous ozone therapy, (3) combination of a nano-hydroxyapatite gel and ozone. Patients (n = 92, age 20-30 years) with initial approximal enamel lesions on premolar and molar teeth (n = 546) were randomly allocated to three groups subjected to a 6-months treatment: Group I: domestic nano-hydroxyapatite remineralizing gel, group II: in-office ozone therapy, group III: both domestic remineralizing gel and ozone therapy. Caries lesions were assessed on bitewing radiographs at baseline, after 1 year and after 2 years. At one-year follow-up, the smallest rate of lesions with remineralisation (36.5%) was found in group I, and the highest (69.3%)-in group III. In group III a significant remineralisation was noticed in after 1 year and then a demineralisation after 2 years. Thus nano-hydroxyapatite gel and ozone therapy exert some capacities to remineralize approximal enamel and dentine subsurface lesions of premolar and molar teeth. Moreover, the combination of both methods produces the best effect compared to nano-hydroxyapatite or ozone therapy applied alone. However, the treatment should be continued for a long time in order to achieve nonrestorative recovery of caries.

Intestinal drug transporters in pathological states: an overview.

Emerging information suggests that gastrointestinal and systemic pathology states may affect expression and function of membrane transporters in the gastrointestinal tract. Altered status of the transporters could affect drug as well as endogenous compounds handling with subsequent clinical consequences. It seems that in some pathologies, e.g., liver or kidney failure, changes in the intestinal transporter function provide compensatory functions, eliminating substrates excreted by dysfunctional organs. A literature search was conducted on Ovid and Pubmed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of intestinal drug transporters. The accumulated data suggest that gastrointestinal pathology (inflammatory bowel disease, celiac disease, cholestasis) as well as systemic pathologies (kidney failure, liver failure, hyperthyroidism, hyperparathyroidism, obesity, diabetes mellitus, systemic inflammation and Alzheimer disease) may affect drug transporter expression and function in the gastrointestinal tract. The altered status of drug transporters may provide compensatory activity in handling endogenous compounds, affect local drug actions in the gastrointestinal tract as well as impact drug bioavailability.

Effect of air-polishing on surface roughness of composite dental restorative material - comparison of three different air-polishing powders.

BACKGROUND: Increased composite roughness enhances bacterial adhesion and discoloration, thus increasing the risk of gingival inflammation and secondary caries. Concerns about detrimental effects of sodium bicarbonate on surface roughness influenced the development of less abrasive powders: a glycine-based powder and an erythritol-based powder, additionally - sodium bicarbonate-based powder of reduced grain size. However, there is limited evidence on effects of these materials on the surface of dental fillings. The aim of the present study was to compare the effects of three air-polishing powders (of a reduced abrasiveness) on surface roughness of microhybrid restorative composite material. MATERIAL AND METHODS: Microhybrid light-cure resin composite samples were placed on 64 plaster cubes and light-cured through polyester strips. Surface roughness was measured using laser confocal microscope (magnification 2160x). The specimens were randomly divided into three groups (n = 20, 20 and 24) and air-polished with: sodium bicarbonate (40 µm), glycine (25 µm) and erythritol (14 µm), respectively. Then surface roughness was remeasured, keeping the same field of observation. Specialized 3D analysis software was used for data processing. Parameters according to ISO 25178: Sa, Sq, Sku, Sp, Sv, Sz, Ssk were used to describe surface roughness. RESULTS: Sa, Sq, Sp, Sv, Sz increased significantly following air polishing. Ssk was significantly higher, whereas Sku was significantly lower in sodium bicarbonate and erythritol groups than before air polishing. Comparison between the three powders revealed that Sa was significantly higher in sodium bicarbonate group than in glycine group. Sku was significantly higher in glycine and erythritol groups than in sodium bicarbonate group. CONCLUSIONS: Sodium bicarbonate has a stronger detrimental effect on composite surface than glycine or erythritol. No advantage of erythritol comparing to glycine could be found.

Membrane Transporters in Human Parotid Gland-Targeted Proteomics Approach.

Salivary glands provide secretory functions, including secretion of xenobiotics and among them drugs. However, there is no published information about protein abundance of drug transporters measured using reliable protein quantification methods. Therefore, mRNA expression and absolute protein content of clinically relevant ABC (n = 6) and SLC (n = 15) family member transporters in the human parotid gland, using the qRT-PCR and liquid chromatography‒tandem mass spectrometry (LC-MS/MS) method, were studied. The abundance of nearly all measured proteins ranged between 0.04 and 0.45 pmol/mg (OCT3 > MRP1 > PEPT2 > MRP4 > MATE1 > BCRP). mRNAs of ABCB1, ABCC2, ABCC3, SLC10A1, SLC10A2, SLC22A1, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLCO1A2, SLCO1B1, SLCO1B3 and SLCO2B1 were not detected. The present study provides, for the first time, information about the protein abundance of membrane transporters in the human parotid gland, which could further be used to define salivary bidirectional transport (absorption and secretion) mechanisms of endogenous compounds and xenobiotics.

Knowledge of antibiotics and antimicrobial resistance amongst final year dental students of Polish medical schools-A cross-sectional study.

INTRODUCTION: Antimicrobial resistance has been one of the biggest global concerns. Dentists constitute an important group of antibiotic prescribers, and it was shown that their therapeutic decisions are not always rational. In this paper, we present knowledge of antibiotics prescription rules and antimicrobial resistance amongst graduating dentistry students from all dentistry faculties of medical universities in Poland, who will soon join the group of antibiotics prescribers. MATERIALS AND METHODS: A questionnaire consisting of 28 questions was developed. The survey was conducted in May-June 2015. RESULTS: The study group comprised a total of 752 students. About 54% expressed the opinion that dentists overprescribe antibiotics. One-tenth thought that they can be used for the treatment of flu (7%) and common cold (11%). Respondents pointed to amoxicillin (46%) and clindamycin (44%) as the first-choice treatment of dentoalveolar abscess, if medically indicated. More than half of the students (58%) suggested using doxycycline and metronidazole in aggressive periodontitis in an individual allergic to penicillin. The vast majority of students (97%) indicated that penicillins and cephalosporins were suitable for treatment of dental infections in pregnant women. The majority of participants (82%) said that rheumatic disease, chronic immunosuppression, chronic kidney failure and a history of infective endocarditis required a prophylactic administration of antibiotics before or during endodontic treatment. CONCLUSIONS: The research showed variable levels of understanding of antibiotics use amongst dental students in medical universities in Poland. Our results emphasise the need to educate dental students further regarding antibiotics and risks related to antibiotic misuse, especially in dental practice.

Factors affecting the outcomes of direct pulp capping using Biodentine.

INTRODUCTION: This study aimed to evaluate the prognostic value of factors with regard to the treatment outcome of direct pulp capping using Biodentine (Septodont, Saint-Maur-des-Fossés, France), in permanent teeth in which the pulps were exposed during caries removal. METHODS: Between 2010 and 2014, 112 teeth with deep carious lesions underwent direct pulp capping. The patients were followed up at 2-3 months and 1-1.5 years with a routine examination on both recall visits. Periapical radiographs were taken at 1-1.5 years. Lack of patient complaints, positive reactions to cold and electric testing, no sensitivity to percussion, and no widening of the periapical ligament indicated success. The Fisher exact test was used for statistical analysis. The significance level was P = .05. RESULTS: Eighty-six teeth were available for 1-1.5 years follow-up. The overall success rate was 82.6%. Only age had a significant effect on the pulpal survival rate: the success rate was 90.9% in patients younger than 40 years and 73.8% in patients 40 years or older (P = .0480). Sex, initial or secondary caries treatment, occlusal or cervical/proximal caries, delayed placement of permanent filling, tooth position, and arch type did not influence the outcome. CONCLUSIONS: A patient's age influenced the outcome of direct pulp capping using this new calcium silicate cement. CLINICAL RELEVANCE: Asymptomatic vital permanent teeth with cariously exposed pulp can be treated successfully by direct pulp capping using Biodentine.

A Comparative Chemical Study of Calcium Silicate-Containing and Epoxy Resin-Based Root Canal Sealers.

Objective. The present study assessed the chemical elements in two novel calcium silicate-containing root canal sealers, BioRoot RCS and Well-Root ST, compared to a calcium silicate-containing root canal sealer that has been on the market for several years, MTA Fillapex, and epoxy resin-based sealer AHPlus. Material and Methods. The sealers were mixed and manipulated according to the manufacturers' instructions. Twelve cylindrical molds (inner diameter 4 mm; height 3 mm) were placed on a glass petri dish and packed with the materials. The dish was transferred to an incubator. After 72 h the molds were examined by scanning electron microscopy and energy dispersive X-ray microanalysis. Results. BioRoot RCS and Well-Root ST had high peaks of calcium, zirconium, oxygen, carbon, silicon, and chlorine. Well-Root ST also had sodium, magnesium, aluminum, and titanium peaks. MTA Fillapex and AHPlus had carbon, oxygen, calcium, titanium, and bismuth peaks. A silicon peak was also observed for MTA Fillapex, and zirconium and tungsten peaks for AHPlus. Conclusion. BioRoot RSC had the highest degree of purity. The clinical implication of metals contained in the other sealers needs to be investigated.

The role of aryl hydrocarbon receptor (AhR) in the pathology of pleomorphic adenoma in parotid gland.

OBJECTIVES: Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, molecular mechanisms implicated in its development are not entirely defined. Therefore, the study aimed at definition of aryl hydrocarbon receptor (AhR) involvement in pleomorphic adenoma pathology, as the AhR controlled gene system was documented to play a role in development of various human tumors. DESIGN: The study was carried out in pleomorphic adenoma and control parotid gland tissues where gene expression of AHR, AhR nuclear translocator (ARNT), AhR repressor (AHRR), as well as AhR controlled genes: CYP1A1 and CYP1B1, at mRNA and protein (immunohistochemistry) levels were studied. Functional evaluation of AhR system was evaluated in HSY cells (human parotid gland adenocarcinoma cells) using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as AhR specific inducer. RESULTS: Pleomorphic adenoma specimens showed cytoplasmic and nuclear AhR expression in epithelial cells as well as in mesenchymal cells. In parotid gland AhR was expressed in cytoplasm of duct cells. Quantitative expression at mRNA level showed significantly higher expression of AHR, ARNT and CYP1B1, and comparable levels of CYP1A1 in pleomorphic adenoma tissue in comparison to healthy parotid gland. The HSY cell study revealed significantly higher expression level of AHRR in HSY as compared with MCF-7 cells (human breast adenocarcinoma cell line used as reference). Upon TCDD stimulation a drop in AHRR level in HSY cells and an increase in MCF-7 cells were observed. The HSY and MCF-7 cell proliferation rate (measured by WST-1 test) was not affected by TCDD. CONCLUSIONS: Summarizing both in vitro and in vivo observations it can be stated that AhR system may play a role in the pathology of pleomorphic adenoma.

The role of Nrf2 in pathology of pleomorphic adenoma in parotid gland.

BACKGROUND: Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, the processes involved in its carcinogenesis are not well defined. This study aimed to define the contribution of Nfr2 (nuclear factor (erythroid-derived 2)-like 2) to pleomorphic adenoma pathology. The Nrf2-controlled gene system is one of the most critical cytoprotective mechanisms, providing antioxidant responses. MATERIAL AND METHODS: The study was carried out in pleomorphic adenoma and control parotid gland tissues, investigating gene expression of NFE2L2, as well as KEAP1 (Kelch-like ECH-associated protein 1) and NQO1 (quinone oxidoreductase), at mRNA and protein (immunohistochemistry) levels. Functional evaluation of Nrf2 system in the parotid gland was evaluated in HSY cells (human parotid gland adenocarcinoma cells). RESULTS: Pleomorphic adenoma specimens showed cytoplasmic and nuclear Nfr2 expression in epithelial cells, as well as more variable lower Nrf2 level in mesenchymal cells. In the parotid gland, Nrf2 was expressed in cytoplasm of serous, mucous, and duct cells. Nuclear Nrf2 expression was predominantly seen in serous cells, whereas mucous and duct cells were mostly negative. Comparable mRNA levels of NFE2L2 and NQO1 genes and significantly higher expression of KEAP1 in pleomorphic adenoma were seen. HSY cell incubation with oltipraz demonstrated significant elevation of NFE2L2 after 24 and 48 hours of stimulation, whereas NQO1 was elevated, but significantly only after 24 hours, and KEAP1 expression remained unchanged. CONCLUSIONS: Summarizing both in vitro and in vivo observations, it can be stated that Nrf2 may play a role in the pathology of pleomorphic adenoma.