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Objective: The study aimed to investigate the expression of hypoxia markers associated with invadopodia in glandular odontogenic cysts and to explore an association between this expression with the aggressive biological behaviour of this odontogenic cyst., Design: Immunohistochemistry was employed to assess the expression of hypoxia-inducible factor 1 alpha (HIF-1α), notch homologous protein of the neurogenic locus 1 (NOTCH-1), disintegrin and metalloproteinase-12 (ADAM-12), and heparin-binding epidermal growth factor (HB-EGF) in 17 samples of glandular odontogenic cysts, 10 samples of calcifying odontogenic cysts, and 10 samples of dental follicles., Results: The glandular odontogenic cyst samples exhibited increased expression of HIF-1α, NOTCH-1, ADAM-12 and HBEGF proteins compared with calcifying odontogenic cyst and dental follicle samples. HIF-1α demonstrated localization primarily within the nuclei of cystic epithelial cells of the glandular odontogenic cyst. NOTCH-1 and ADAM-12 exhibited expression in the cytoplasm and nuclei of epithelial and mucous cells of the glandular odontogenic cyst, of whereas HB-EGF was predominantly expressed in the cytoplasm. Weak labeling of these proteins was observed in the odontogenic epithelium of the calcifying odontogenic cyst and dental follicle samples., Conclusions: The hypoxia-related signaling proteins are overexpressed in glandular odontogenic cyst when compared with calcifying odontogenic cyst and dental follicle. The reported aggressiveness of glandular odontogenic cyst can be partially explained by the expression of these proteins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The acetylation of histones H2A on lysine 5 (H2AacK5) and H3 on lysine 27 (H3AcK27) modulate several cellular mechanisms through the p300 enzyme in pathological lesions; however, their role in odontogenic lesions has not been addressed. This study aims to evaluate the immunoexpression of p300, H2AacK5, and H3AcK27 in samples of ameloblastoma (AMB) (n = 30), odontogenic keratocyst (OK) (n = 15), adenomatoid odontogenic tumor (AOT) (n = 10), odontogenic fibroma (OF) (n = 8), calcifying odontogenic cyst (COC) (n = 8), odontogenic myxoma (MIX) (n = 10), and ameloblastic fibroma (AF) (n = 06). The percentage of p300-positive cells was higher in AOT and decreased in COC, OK, AMB, AF, OF, and MIX. H2AacK5-positive cells were higher in AF and decreased in AOT, COC, OK, OF, AMB, and MIX, whereas H3acK27-positive cells were higher in AOT and decreased in COC, OK, AF, OF, AMB, and MIX. The expression of these proteins was higher in nonaggressive lesions in comparison to aggressive lesions. There was a positive correlation between p300 and H2AacK5, and H3acK27 in AMB, MIX, and OF, whereas there was a positive correlation between p300 and H2AacK5 in AOT and COC. The histone acetylation may be involved in the biological behavior of these lesions, which could be used to improve their diagnosis and treatment., (© 2024 John Wiley & Sons A/S.)

Background: Ameloblastoma (AME) is characterized by a locally invasive growth pattern. In an attempt to justify the aggressiveness of neoplasms, the investigation of the role of stem cells has gained prominence. The SOX-2, NANOG and OCT4 proteins are important stem cell biomarkers., Methodology: To verify the expression of these proteins in tissue samples of AME, dentigerous cyst (DC) and dental follicle (DF), immunohistochemistry was performed and indirect immunofluorescence were performed on the human AME (AME-hTERT) cell line., Results: Revealed expression of SOX-2, NANOG and OCT4 in the tissue samples and AME-hTERT lineage. Greater immunostaining of the studied proteins was observed in AME compared to DC and DF ( p < 0.001)., Conclusions: The presence of biomarkers indicates a probable role of stem cells in the genesis and progression of AME., Competing Interests: Rommel Thiago Jucá Ramos is an Academic Editor for PeerJ., (© 2023 Martins Balbinot et al.)

BACKGROUND Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin-Goltz syndrome (GGS), is an inherited autosomal dominant disorder caused by mutations in the patched (PTCH) tumor-suppressor gene, which has high penetrance and variable phenotypic expressivity. In 1960, Gorlin and Goltz defined the condition by 3 main characteristics: multiple basal cell carcinomas, odontogenic keratocyst (OKC), and skeletal anomalies. Nowadays, many neurologic, ophthalmic, endocrine, and genital manifestations are known to be associated with this syndrome. Considering the complexity of the clinical manifestations, a multidisciplinary approach is necessary for the diagnosis and follow-up of patients with NBCCS. CASE REPORT We report the case of a 27-year-old woman who presented with multiple maxillary and mandibular OKCs, as well as mandibular dentigerous cysts, all detected by X-ray. The medical records of the patient reported other findings such as falx cerebri calcification, osteolysis in femoral bones, and focal bone alteration suggestive of simple bone cysts. Based on the presented manifestations, it was concluded that the patient had characteristics of NBCCS. A multidisciplinary approach was necessary, and odontological intervention was used in managing treatment of the jaw cysts. CONCLUSIONS In view of this combination of findings, it is of primary importance for dental surgeons and physicians to be able to recognize the signs and symptoms of NBCCS in order to achieve an early diagnosis and avoid the progression of oral cysts, the metastasis of skin lesions, and progression of other less frequent manifestations.

Objectives: To investigate the biochemical and morphological effects of ethanol (EtOH) binge drinking during pregnancy on parotid glands (PG), submandibular glands (SMG), and saliva of offspring rats., Methods: Pregnant Wistar rats (n = 8) were exposed to EtOH consumption (3 g/kg/day - 20 % w/v) for three consecutive days. The saliva of 40-day-old offspring rats was collected to determine amylase activity and total protein concentration. PG and SMG were collected to performe oxidative biochemistry, morphometric and immunohistochemistry analyses (Student's t-test, p < .05)., Results: EtOH consumption during pregnancy significantly decreased the total protein concentration and decreased amylase activity. In the PG, the EtOH group showed increased lipid peroxidation and decreased antioxidant capacity against peroxyl. In the SMG, the EtOH group showed increased lipid peroxidation and NOx metabolite levels. PG exposed to EtOH showed a decrease of acini, ducts, and total parenchymal area. SMG exposed to EtOH showed an increase in the total stromal area. The expression of CK-19 and Vimentin were found not different between groups., Conclusions: For the first time, a three-day EtOH binge-drinking protocol during pregnancy is associated with oxidative stress and morphometric alterations in the salivary glands of offspring rats and with the functional reduction of the main salivary enzyme (amylase)., Clinical Relevance: EtOH consumption during pregnancy altered the morphology and physiology of the salivary glands of offspring rats., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: This study aimed to investigate the Epstein-Barr virus (EBV) prevalence and viral load in subgingival sites of human immunodeficiency virus type 1 (HIV-1) positive (HIV+) individuals, correlating subgingival EBV load to the clinical periodontal condition, HIV systemic load, EBV systemic load, and use of antiretroviral therapy (ART)., Method and Materials: Ninety individuals were recruited and divided into three categories: those without periodontal disease (G1), with gingivitis (G2), and with periodontitis (G3). Subgingival biofilm and blood samples were analyzed by quantitative polymerase chain reactions (qPCR). A questionnaire was administered to collect general information about patients, and data regarding HIV and use of ART were accessed from their medical records., Results: EBV was detected in 85.6% of the samples. Comparing subgingival and systemic load of EBV in G1, G2, and G3, there was a statistical difference only in G3 (3.93 log10 copies/mL and 5.47 log10 copies/mL, respectively; P = .014), where EBV load was higher in periodontal pockets than in the blood. All groups had high EBV loads in subgingival sites (> 2,000 copies/mL). A positive linear correlation between systemic HIV load and EBV subgingival load was found in G1 and G2 (r = 0.647; P < .001), but not in G3. Only G1 individuals using ART had lower subgingival EBV loads than those not using it (5.03 log10 copies/mL, and 7.14 log10 copies/mL, respectively; P = .0348)., Conclusions: Subgingival sites, especially the periodontal pockets, are suggested to act as a reservoir of EBV in HIV+ individuals. Therefore, the identification of latent EBV infections in this easily accessible site might help to improve quality of life in patients with HIV by maintaining oral/periodontal health. In addition it might encourage new approaches in investigating EBV-associated disorders in HIV+ patients.

Environmental and occupational mercury exposure is considered a major public health issue. Despite being well known that MeHg exposure causes adverse effects in several physiologic functions, MeHg effects on salivary glands still not completely elucidated. Here, we investigated the cellular MeHg-induced damage in the three major salivary glands (parotid, submandibular, and sublingual) of adult rats after chronic, systemic and low doses of MeHg exposure. Rats were exposed by 0.04 mg/kg/day over 60 days. After that, animals were euthanized and all three glands were collected. We evaluated total Hg accumulation, metallothionein I/II (MT I/II), α-smooth muscle actin (α-SMA), and cytokeratin 18 (CK18) immune expression. Our results have showed that MeHg is able to disrupt gland tissue and to induce a protective mechanism by MT I/II expression. We also showed that cell MT production is not enough to protect gland tissue against cellular structural damage seen by reducing marking of cytoskeletal proteins as CK18 and α-SMA. Our data suggest that chronic MeHg exposure in low-daily doses is able to induce cellular damage in rat salivary glands.

Mercury exposure is considered to be a public health problem due to the generation of toxic effects on human health as a result of environmental and occupational conditions. The inorganic form of mercury (HgCl 2 ) can cause several biological changes in cells and tissues through its cumulative toxic potential, but little has been experimentally proven about the effects of inorganic mercury on salivary glands, an important modulator organ of oral health. This study analyzes the effects of prolonged low dose exposure to HgCl 2 on the salivary glands of rats. Adult animals received a dose of 0.375 mg kg -1 day -1 over a period of 45 days. The parotid and submandibular glands were collected for analysis of the mercury levels and evaluation of oxidative stress, histological parameters and immunomodulation for metallothionein I and II (MT-I/II). In this investigation, biochemical and tissue changes in the salivary glands were verified due to the mercury levels, causing reduction in antioxidant capacity against peroxyl radicals, with consequent cellular lipid peroxidation and an increase in nitrite levels, volumetric changes and cytoskeletal damage in the submandibular glands, with less severe damage to the parotid glands. The results also have shown the occurrence of a cytoprotection mechanism due to increased MT-I/II expression, but not enough to avoid the morphology and oxidative damage. This evidence highlights, for the first time, that inorganic mercury is able to alter the morphology and oxidative biochemistry in salivary glands when exposed for a long time in low doses.

Introduction: The objective of this study was to establish the anatomical relation between nasal septum deviation (NSD) and oropharynx volume in different facial patterns using cone beam computed tomography (CBCT)., Methods: Ninety CBCT examinations were analyzed. InVivoDental software was used to evaluate cephalometric image reconstructions in terms of facial type, determined from cephalometric measurements indicative of growth direction; the presence of NSD was also evaluated. ITK-SNAP software was employed for delimitation of the oropharynx. Intra-examiner error methods were recorded. The results were subjected to parametric and non-parametric tests using Bioestat 5.0., Results: A comparison of facial types revealed a significantly lower prevalence of NSD in the dolichofacial group compared with the brachyfacial and mesofacial groups (P = 0.0101 and 0.0149, respectively). In the total sample, there was a very strong positive relation between the presence of NSD and oropharynx space volume (P = 0.0162). The oropharynx volume was larger in all facial patterns in the presence of NSD., Conclusion: The presence of NSD was not associated with facial type, although the oropharynx volume in patients with NSD increased. Therefore, deviation of the septum influences oropharynx volume.

This study investigates morphological and biochemistry effects of binge ethanol consumption in parotid (PG) and submandibular (SG) salivary glands of rats from adolescence to adulthood. Female Wistar rats (n = 26) received ethanol at 3 g/kg/day (20% w/v) for 3 consecutive days/week from the 35th until the 62nd day of life. Animals were treated in two periods: 1 week (G1) and 4 weeks (G2), with a control (treated with distilled water) and an ethanol group to each period. In morphological analysis, morphometric and immunohistochemistry evaluation for smooth muscle actin (αSMA), cytokeratin-18 (CK-18), and vimentin (VIM) were made. Biochemical changes were analyzed by concentration of nitrites and levels of malondialdehyde (MDA). The difference between groups in each analysis was evaluated by Mann-Whitney U test or Student's t-test (p ≤ 0.05). PG showed, at one week of ethanol exposure, lower CK-18 and α-SMA expression, as well as MDA levels. After four weeks, lower CK-18 and higher MDA levels were observed in PG exposed to ethanol, in comparison to control group. SG showed lower α-SMA expression after 1 and 4 weeks of ethanol exposure as well as higher MDA levels after 1 week. Ethanol binge consumption during adolescence promotes tissue and biochemical changes with only one-week binge in acinar and myoepithelial PG cells.

Alcoholism in humans is a chronic and progressive disease, characterized by loss of ethanol consumption control. Previous studies have reported that prolonged exposure to ethanol was responsible for alterations in glandular tissues of human and rodents. However, the interrelationship between ethanol and the glandular system is still the subject of numerous investigations, including the possible resistance of the submandibular gland (SG). In the present study, we investigated whether chronic ethanol exposure during adolescence may affect the parotid gland (PG) and SG in female rats. Female rats (n=16) were treated with distilled water or ethanol (dose of 6.5 g/kg/day, 22.5% w/v) through gavage for 55 days. Glands were collected, weighed and submitted to histological processing. Morphometric analysis was assessed by parenchymal and stromal area measurements. Smooth muscle actin (α-SMA), cytokeratin-19 (CK19) and apoptotic caspase-3 (CAS) were measured using ImageJ® software. Chronic ethanol administration did not alter the body weight of rats after treatment, although it increased glandular weight (p<0.001), reduced the parenchyma area (p<0.001) and decreased CK19 and α-SMA immunostainning in the PG. Besides, ethanol induced CK19 and CAS overexpression, and the occurrence of duct-like structures in SG. These results suggest that ethanol induces histological and morphometric changes in salivary glands of female rats intoxicated with ethanol during adolescence. Furthermore, the mechanism underlying these alterations needs to be investigated but may be not related to the inflammatory process.

Objective: To identify and describe the morphology and location of the canalis sinuosus (CS) and make correlations with gender, age, and distance of this canal to important adjacent structures on the region, thus mapping the anatomy of this structure., Methodology: A total of 100 cone beam computed tomography (CBCT) examinations were collected from the files of a dental clinic in the Municipality of Belém, Pará, Brazil, and analyzed to identify the site of bifurcation, the diameter of CS right after such bifurcation and in its terminal portion as well as the direction of its course and the distance to the alveolar bone crest region. The anatomical views were evaluated using InVivoDental software on sagittal, axial, and coronal sections, and the results were submitted to Fisher's exact test, Kendall correlation coefficients, Mann-Whitney tests, and T tests., Results: CS was present in 88 % of the sample. There were no statistically significant changes in the presence of CS regarding gender, age and direction of course. A strong positive correlation between CS's diameter on its initial and terminal portions was observed (p < 0.0001). There was a statistically significant change in the distance to alveolar bone crest related to gender, which is higher in men (p = 0.0303)., Conclusion: In the sample, CS was frequent and similar in both genders, with course distance to the alveolar bone crest and termination in different locations that ought to be analyzed on CBCT prior to surgical procedures.

The association between fibrous dysplasia (FD) and fractures is very rare. This paper reports the case of a zygomaticomaxillary complex fracture in a bone affected by FD, a 29-year-old man who was involved in a bicycle accident and who subsequently presented with a zygomaticomaxillary complex fracture. Computed tomography revealed multiple fractures of the left zygomaticomaxillary complex with dysplastic bone alterations. Fracture lines occurred near transitional areas between the lesion and healthy bone. The patient was treated through an intraoral approach by an open reduction and internal fixation procedure, using a titanium miniplate and screws. An incisional biopsy was performed through the maxillary sinus to confirm the diagnosis of FD. After 12 months of follow-up, there were no postoperative complications. This paper reports a rare association thought to be caused by irregular trabecular bone deposition, which increases bone thickness/resiliency and thus increases its clinical fracture resistance.

Neurofibroma is a benign neoplasm derived from peripheral nerves whose etiology is still unclear. It may present as a solitary lesion or be associated with other diseases such as neurofibromatosis type I and II syndrome. This paper aims to report an extremely rare case of a solitary giant neurofibroma of the mental nerve whose etiology was related to a local trauma. A 14-year-old female patient presented an extensive left facial mass with a size of 7 × 5 × 4 cm, located between the teeth 33 and 37 in the mandible region. It has begun to grow 3 months after a local trauma. Imaging studies were suggestive of a soft-tissue lesion, with minimal bone changes and maintaining the integrity of the mandibular canal and mental foramen. Histopathological tests showed spindle cells with undulated and hyperchromatic nuclei, and sparse cytoplasm in a stroma composed of dense fibrous connective tissue. Immunohistochemistry revealed positive expression for the proteins S-100 and vimentin, confirming the diagnosis of neurofibroma. The patient underwent surgical removal of the lesion by intraoral approach and evolved with an excellent cosmetic result and no signs of recurrence after 2 years of follow up. We report a rare case of solitary giant neurofibroma whose etiology was related to a local trauma. To our knowledge, this is the first report of a mental nerve neurofibroma. Although the etiology remains unclear, we suggest the investigation of local trauma as a possible etiologic factor for solitary neurofibromas of the jaw.

Objective: The objective of this preliminary study was to evaluate the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and growth factors in keratocystic odontogenic tumors (KOTs)., Study Design: The expression of MMPs, TIMPs, growth factors, and the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway were assessed by immunohistochemistry in 15 cases of KOT and 4 cases of calcifying cystic odontogenic tumor (CCOT)., Results: KOT samples expressed significantly higher amounts of MMPs, TIMPs, growth factors, epidermal growth factor receptor (EGFR), and ERK compared with CCOT samples, with the exception of MMP-2 and TIMP-1., Conclusions: MMP-9, TIMP-2, EGF and transforming growth factor α act together and likely regulate the proliferation and aggressiveness of KOT. ERK-1/2 serves as the transducer of signals generated by these proteins, which signal through the common receptor, EGFR. This process may be related to the increased proliferation and aggressiveness observed in KOT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: A wide variety of manifestations is presented in patients with Gaucher's disease (GD), including bone, haematology and visceral disturbances. This study was conducted to ascertain the main maxillofacial abnormalities by means of clinical survey, panoramic and cone beam CT (CBCT); to compare the patient's group with an age-sex matched control group; and to correlate clinical and radiological data., Methods: Ten patients previously diagnosed with GD were submitted to clinical and radiological surveys (CBCT and panoramic radiographs). The examination consisted of anamnesis, extra- and intraoral examinations and analyses of each patient's records. Imaging data were collected from the point of view of 3 observers, and the results compared with a healthy group (20 individuals) by means of statistical analysis (Fisher's exact test)., Results: Gaucher patients had significantly more manifestations than otherwise healthy carriers. The most prevalent findings were enlarged marrow spaces, generalized osteopenia and effacement of jaw structures (mandibular canal, lamina dura and mental foramen). Here we describe a case in which thickening of the maxillary sinus mucosa was observed on CBCT rather than opacification of the sinus as seen on panoramic radiographs. Pathological fractures, root resorption and delay on tooth eruption were not observed., Conclusions: A poor relationship could be observed between clinical and radiological data. Patients showed important bone manifestations, which require careful diagnostic and surgical planning whenever necessary. Although panoramic radiographs have shown significant differences, CBCT is more effective in pointing out differences between patients and a control group, thus showing it as an important tool for evaluation of Gaucher patients.