Salivary Short-chain Fatty Acids (SCFAs) Are Viable Predictors of Early Changes in Systemic Health.

Short-chain fatty acids (SCFAs) are the metabolites identified in both the oral cavity and the gut. They play an important role in the triggering, development and progression of systemic diseases. SCFAs can alter the gut microbial components, intestinal epithelium and host immune system, and are also associated with cancer incidence. Salivary SCFAs, produced by the oral microbiome, are correlated with some oral diseases. The occurrence of systemic diseases associated with gut SCFAs is more clearly defined than oral SCFAs. Salivary SCFAs can enter the bloodstream directly via inflamed gingiva to cause continuous low-grade systemic inflammation. Hence, salivary SCFAs could be an indicator for the early diagnosis of systemic diseases. Furthermore, they provide a basis for understanding the oral-systemic axis driven through salivary SCFAs in the pathogenesis of several diseases.

Salivary Metabolites Produced by Oral Microbes in Oral Diseases and Oral Squamous Cell Carcinoma: A Review.

In recent years, salivary metabolome studies have provided new biological information and salivary biomarkers to diagnose different diseases at early stages. The saliva in the oral cavity is influenced by many factors that are reflected in the salivary metabolite profile. Oral microbes can alter the salivary metabolite profile and may express oral inflammation or oral diseases. The released microbial metabolites in the saliva represent the altered biochemical pathways in the oral cavity. This review highlights the oral microbial profile and microbial metabolites released in saliva and its use as a diagnostic biofluid for different oral diseases. The importance of salivary metabolites produced by oral microbes as risk factors for oral diseases and their possible relationship in oral carcinogenesis is discussed.

Salivary metabolomics in patients with oral lichen planus: a preliminary study based on NMR spectroscopy.

OBJECTIVES: The present preliminary study aimed to investigate the salivary metabolic profile in patients with asymptomatic oral lichen planus (OLP) using nuclear magnetic resonance (NMR) spectroscopy. MATERIAL AND METHODS: Stimulated whole mouth saliva (SWMS) samples were collected from 15 reticular OLP female patients and 15 from age- and sex-matched controls (HCs). A total of 23 metabolites were identified and quantified. Mann-Whitney's U test was used to compare the determined concentration salivary metabolite concentrations between OLP patients and the healthy controls. RESULTS: The concentration of acetate, methylamine, and pyruvate was elevated, whereas the concentration of tyrosine was decreased in the saliva of OLP patients compared with HCs. To identify a combination of metabolites, multivariate discrimination function analysis (DFA) was conducted. DFA analysis have shown that the most powerful discrimination between the groups was achieved when methylamine and tyrosine were considered as combined biomarkers. CONCLUSIONS: Salivary tyrosine was of particular interest and a promising finding for the screening of OLP and its progression. Further longitudinal studies are required to establish it as a reliable salivary biomarker in OLP. CLINICAL RELEVANCE: The salivary metabolic profiling can describe the pathologic characteristics of OLP on non-invasive saliva samples and NMR analysis. Salivary metabolites provide details to considered early detectors and to impact oral health of OLP patients.

Microstructural changes in the irradiated and osteoradionecrotic bone: a SEM study.

Radiation exposure is a major health concern due to bone involvement including mandible, causing deleterious effects on bone metabolism, and healing with an increasing risk of infection and osteoradionecrosis. This study aims to investigate the radiotherapy-induced microstructural changes in the human mandible by scanning electron microscopy (SEM). Mandibular cortical bone biopsies were obtained from control, irradiated, and patients with osteoradionecrosis (ORN). Bone samples were prepared for light microscopy and SEM. The SEM images were analyzed for the number of osteons, number of Haversian canal (HC), diameter of osteon (D.O), the diameter of HC (D.HC), osteonal wall thickness (O.W.Th), number of osteocytes, and number of osteocytic dendrites. The number of osteons, D.O, D.HC, O.W.Th, the number of osteocytes, and osteocytic dendrites were significantly decreased in both irradiated and ORN compared to controls (p < .05). The number of HCs decreased in irradiated and ORN bone compared to the control group. However, this was statistically not significant. The deleterious effect of radiation continues gradually altering the bone quality, structure, cellularity, and vascularity in the long term (>5 years mean radiation biopsy interval). The underlying microscopic damage in bone increases its susceptibility and contributes further to radiation-induced bone changes or even ORN.

Oral Sources of Salivary Metabolites.

The oral cavity is very diverse, wherein saliva plays an important role in maintaining oral health. The metabolism of saliva has been used to investigate oral diseases as well as general diseases, mainly to detect diagnostic biomarkers. There are many sources of salivary metabolites in the mouth. Online English language sources and the PubMed database were searched to retrieve relevant studies on oral salivary metabolites. The physiological balance of the mouth is influenced by many factors that are reflected in the salivary metabolite profile. Similarly, the dysbiosis of microbes can alter the salivary metabolite profile, which may express oral inflammation or oral diseases. This narrative review highlights the factors to be considered when examining saliva and its use as a diagnostic biofluid for different diseases. Salivary metabolites, mainly small-molecule metabolites may enter the bloodstream and cause illness elsewhere in the body. The importance of salivary metabolites produced in the oral cavity as risk factors for general diseases and their possible relationship to the body's function are also discussed.

Irradiation Alters the Expression of MUC1, CD44 and Hyaluronan in Oral Mucosal Epithelium.

Purpose: It is well established that cancer cells exploit aberrant synthesis of mucin 1 (MUC1) and hyaluronan (HA) synthesis along with HA's physiological cell surface receptor CD44. However, their role in irradiated oral tissue has not been reported previously. We, therefore, aimed to study MUC1, CD44 and HA immunohistochemically in irradiated oral mucosa and their role in the long-term effects after radiotherapy. Materials and Methods: Oral mucosal biopsies were obtained from healthy subjects as controls and from patients after radiotherapy for head and neck cancer (irradiated group) during dental implant surgery.The presence of MUC1, CD44, and HA in oral mucosa was studied by immunohistochemical methods. The differences in the localization and intensity in the oral epithelium between control and irradiated tissue were analyzed. Results: The staining intensity of MUC1 was confined to the superficial epithelial layer, whereas HA and CD44 were found in the cell membranes in the epithelial basal and intermediate layers of control specimens. In irradiated epithelium, MUC1 staining was distributed throughout all the layers of the oral epithelium, with significant staining in the basal and intermediate layers. Accordingly, HA and CD44 staining extended to involve the superficial cells of the irradiated epithelium. The staining pattern of MUC1 and CD44 showed significant changes in irradiated samples. Conclusions: Our results showed that the staining intensities of MUC1, CD44, and HA were significantly elevated in irradiated tissue compared to controls. MUC1, CD44, and HA are important markers and take part in long-term changes in the oral mucosa after radiotherapy.

Effect of smoking on MUC1 expression in oral epithelial dysplasia, oral cancer, and irradiated oral epithelium.

OBJECTIVES: The aim of this study was to assess the MUC1 expression in the oral epithelium of normal, oral epithelial dysplasia (OED), oral squamous cell carcinoma (OSCC), and irradiated oral epithelium (IROE) and its association with smoking habits in non-smokers and smokers. DESIGN: Oral mucosal biopsies from controls, OED, OSCC, and IROE groups were obtained and categorized based on the smoking history as non-smokers, smoker I (25 pack-years), and smoker II (>25 pack-years). Immunohistochemical staining of MUC1 using human milk fat globule 1 (HMFG 1) antibody was performed, and the MUC1 score was calculated. The relation between MUC1 expression and clinicopathological findings was examined. RESULTS: MUC1 staining of superficial oral epithelial cells with mild MUC1 score was detected in all control samples. The MUC1 staining extended from superficial to basal cell layer of oral epithelium with the increase in MUC1 score from moderate to strong in OED, OSCC, and IROE, and the difference was significant (p < 0.004, p < 0.002 and p < 0.004, respectively) compared to controls. A positive association between smoking and MUC1 score was observed within groups (p < 0.05). CONCLUSION: The depolarization of MUC1 protein expression is associated with smoking habits in OED and OSCC. In the IROE, the radiation causes subcellular and molecular changes, observed as altered MUC1 expression and accelerated by smoking, furthermore, complicating the oral mucosal adaptation and progress to radiation-induced lesions as a delayed effect.

Irradiation affects the structural, cellular and molecular components of jawbones.

PURPOSE: Emerging evidence shows that changes in the bone and its microenvironment following radiotherapy are associated with either an inhibition or a state of low bone formation. Ionizing radiation is damaging to the jawbone as it increases the complication rate due to the development of hypovascular, hypocellular, and hypoxic tissue. This review summarizes and correlates the current knowledge on the effects of irradiation on the bone with an emphasis on jawbone, as these have been a less extensively studied area. CONCLUSIONS: The stringent regulation of bone formation and bone resorption can be influenced by radiation, causing detrimental effects at structural, cellular, vascular, and molecular levels. It is also associated with a high risk of damage to surrounding healthy tissues and an increased risk of fracture. Technological advances and research on animal models as well as a few human bone tissue studies have provided novel insights into the ways in which bone can be affected by high, low and sublethal dose of radiation. The influence of radiation on bone metabolism, cellular properties, vascularity, collagen, and other factors like inflammation, reactive oxygen species are discussed.

Regulation of mucin 1 expression and its relationship with oral diseases.

OBJECTIVE: The aim of this study is to describe the polymorphic mucin 1 (MUC1), and to provide an overview of the known complex and multiple functions of MUC1 in normal oral mucosa and oral mucosal lesions in compromised situations as well as exploring the challenges associated with the heterogeneous nature of MUC1. We will review the current knowledge and provide insights into the future management possibilities of using MUC1 as a therapeutic agent. METHODS: A literature search of the electronic databases included MEDLINE (1966 -December 2019) and hand searches of cross-references were undertaken using terms related to mucins, MUC1. RESULTS: MUC1 is a large transmembrane glycoprotein expressed on the apical surface of most of epithelial cell surfaces. Not only is it involved in lubrication, cell surface hydration, and protection against degrading enzymes, MUC1 also promotes abnormal cellular signalling, angiogenesis, anti-adhesion and tumorigenesis. Aberrant glycosylation, overexpression, loss of apical constraint are characteristics of the transformation of a normal cell to a cancerous cell. This review summarizes studies of MUC1 expression and function with a special emphasis on oral epithelial cells in normal and abnormal conditions. In addition, current knowledge of MUC1 and unexplored areas of MUC1 are presented. CONCLUSION: MUC1 is an archetypical transmembrane protein, the presence of MUC1 in ectopic regions may lead to dysregulation of certain enzymes and activation of various pathways, favouring the development of inflammatory responses and tumour formation. This review examines the potential of MUC1 in the development of future therapeutics.

Disorganized histomorphology: Dentinogenic ghost cell tumor.

Calcifying odontogenic cyst (COC) is a term used broadly to define lesions which were either cystic/solid in nature. However, a new term defining dentinogenic ghost cell tumor (DGCT), as its neoplastic counterpart, histopathologically showed the presence of dentinoid-like areas, ghost cells and ameloblastomatous-like odontogenic epithelium. This possesses a great challenge to an oral pathologist in diagnosing and differentiating it from solid multicystic ameloblastoma or COCs so as to ensure the biological behavior and pathogenesis behind its multifaceted nature. The author presents an exceptional case of DGCT, with special emphasis on its pathogenesis, occurring in an 80-year-old female with facial asymmetry and unique histopathology.

Pericoronal radiolucencies with significant pathology: clinico-histopathologic evaluation.

BACKGROUND: The purpose of the study was to correlate the provisional diagnosis of pericoronal radiolucencies associated with impacted, embedded, or unerupted teeth with the histopathologic diagnosis, and also to emphasize the importance of early detection for better diagnosis and management. METHODS: This is a retrospective study involving 18 cases of pericoronal radiolucencies associated with unerupted, embedded, or impacted teeth whose data during 1-year period were retrieved, and were reviewed for clinical, radiological, and histopathologic data. Also, comparison and correlation of clinico-histopathologic diagnosis was made. RESULTS: Of the 18 cases, 11 were provisionally diagnosed as dentigerous cyst and the remaining were diagnosed as ameloblastoma, odontogenic keratocyst, adenomatoid odontogenic tumor, and calcifying epithelial odontogenic cyst. Histopathologic diagnosis of the 18 cases showed varied results, with only 10% correlating with the provisional diagnosis. CONCLUSION: Although many pathological processes may present radiographically as pericoronal radiolucencies associated with unerupted teeth, the most common is the dentigerous cyst. Hence, it is crucial for the clinician to fully investigate all teeth that fail to erupt at the expected time, and promptly initiate appropriate assessment and management of suspected cystic lesions.

Comparison of the bite mark pattern and intercanine distance between humans and dogs.

BACKGROUND: Bite marks show uniqueness due to specific characteristics and arrangement of teeth, but when it comes to bite mark analysis, it is complicated by numerous factors such as animal bite, abuse etc., Humans and pet animals (dog) bite marks analysis is by far the most demanding and complicated part of forensic dentistry. AIM: To analyze and compare bite marks of humans and the pet animals (dog) using indirect method, so as to assess its usefulness and application in forensic odontology. MATERIALS AND METHODS: 40 samples including 20 humans (10 males and 10 females) and 20 dogs of different breed were included in the study. Bite registration of all the samples were obtained on modeling wax and intercanine distance were measured. Data were analyzed and results were tabulated. RESULTS: Arch size and intercanine distance showed variable differences among humans and on average dogs showed more intercanine distance and arch size. Among dog breeds larger dogs showed larger variables when compared to smaller dogs. CONCLUSION: Assessment of bite marks evidences made by animals needs further investigation so that it can be a tool to assist the justice system to answer crucial questions.

Computer assisted histomorphologic comparision and the expression of AgNORs in the central and peripheral giant cell lesions of the oral cavity and giant cell tumor of the long bone.

OBJECTIVE: Computer-assisted image analysis was attempted to ascertain, if any of the previously described histologic features along with argyrophilic nucleolar organizer regions (AgNORs) could be used to determine the aggressiveness of the central giant cell granuloma of the jaws (CGCG), peripheral giant cell granuloma of the oral cavity (PGCG) and giant cell tumor of the long bones (GCT). STUDY DESIGN: The study consisted of 20 cases of CGCG, 20 cases of PGCG and 5 cases of GCT. The histological features included were number of giant cells, number of nuclei in each giant cell, number of blood vessels, fractional surface area (FSA) and relative size index (RSI) of giant cells. The histologic parameters were measured using Motic image plus analyzer and AgNORs were evaluated using silver stain. RESULTS: The statistical analysis showed significant differences among various histological parameters between CGCG, PGCG and GCT. A statistically significant difference was noted for the mean number of nuclei, FSA and RSI when GCT was compared with CGCG and PGCG. FSA of histologically aggressive central giant cell granuloma (HA-CGCG) was more compared to histologically non-aggressive central giant cell granuloma (HNA-CGCG). No statistical correlation was observed for AgNORs of multinucleated giant cells and mononuclear cells among CGCG, PGCG and GCT. CONCLUSION: Based on the present study findings, CGCG and GCT are distinct and separate entities and not a continuum of a single disease process. Histological parameters alone have a little implication on predicting clinical behavior of CGCG. AgNORs alone as a proliferative marker has a limited value in assessing the proliferation potential of giant cell lesions.

Use of microwave in diagnostic pathology.

Conventional tissue fixation and processing is as old as 100 years and still remains the gold standard against which all new technologies and methods need to be assessed. Tissue processing is one of the important steps for obtaining good thin sections without artifacts. Though conventional tissue-processing methods are most commonly followed, they are well-known as very laborious and tedious procedures. Microwaves a form of electromagnetic wave-induced heat, when applied in histotechnology, reproducibly yields histolologic material of similar or superior quality to that provided by conventional processing methods, making it more popular in the recent years. A laboratory microwave offers features like maximum output of 2000-3000 watts, an in-built source of adjustable temperature probe, facility for ventilation of hazardous fumes, but is expensive. Considering the usefulness of microwave in histotechnology, i.e., reducing the time required for the diagnosis, replacing the conventional equipments of laboratories by microwave-guided ones is a remarkable and an acceptable change.

Latent lip print development and its role in suspect identification.

AIMS AND OBJECTIVE: The study aims to develop latent lip prints on glass surface using fingerprint black powder and its comparison with standard lipstick prints and also determines the effectiveness of the technique. MATERIALS AND METHODS: This study included a total of 100 subjects, comprising of 50 males and 50 females with age ranging from 17 to 38 years. Latent lipprint was developed by pressing the lips against a glass slab with lips together and the print formed was developed by sprinkling the black finger print powder and transferred to a bond sheet. Subsequently, standard lipstick print was developed from the same subject. All the samples were coded and graded according to the patterns suggested in the literature. RESULTS: Out of 100 latent prints only 29 prints showed lip patterns in all four quadrants. The percentage matching with self lipstick print of good latent prints ranged from 25% to 100% and those of random prints ranged from 8% to 92%. Quadrant wise matching ranged from 52.67% to 57.67%. Statistically significant difference was observed between males and females. CONCLUSION: The study demonstrates the usefulness of latent lip print in personal identification.

Suprabasal expression of Ki-67 as a marker for the severity of oral epithelial dysplasia and oral squamous cell carcinoma.

BACKGROUND: Transition of the normal oral epithelium to dysplasia and to malignancy is featured by increased cell proliferation. To evaluate the hypothesis of distributional disturbances in proliferating and stem cells in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). AIM: To evaluate layer wise expression of Ki-67 in oral epithelial dysplasia and in OSCC. MATERIALS AND METHODS: Thirty histologically confirmed cases of oral epithelial dysplasia, fifteen cases of OSCC and five cases of normal buccal mucosa were immunohistochemically examined and nuclear expression of Ki-67 was counted according to basal, parabasal, and suprabasal layers in epithelial dysplasia and number of positive cells per 100 cells in OSCC as labeling index (LI). RESULTS: Suprabasal expression of Ki-67 increased according to the severity of epithelial dysplasia and the difference was statistically significant (P < 0.001). The mean Ki-67LI was 12.78 for low risk lesions, 28.68 for high risk lesions, 39.45 for OSCC and 13.6 for normal buccal mucosa. CONCLUSION: The results of the present study demonstrate the use of proliferative marker Ki-67 in assessing the severity of epithelial dysplasia. Suprabasal expression of Ki-67 provides an objective criteria for determining the severity of epithelial dysplasia and histological grading of OSCC.

Hair as biomarker of fluoride exposure in a fluoride endemic area and a low fluoridated area.

AIM: The aim of the present study was to determine whether hair could be used as biomarker of fluoride exposure. MATERIALS AND METHODS: The study was carried out on 30 people living in an endemically fluoridated area and a low fluoridated area. Samples of hair from the occipital were taken and subjected to fluoride analysis by a fluoride ion electrode. RESULTS: Lower fluoride levels in water supplies correlated with lower levels of fluoride in hair and more over higher fluoride levels in water correlated with higher levels of fluoride in hair. A direct relationship was evident between fluoride levels in water supplies and concentration of fluoride in hair (P < 0.01). CONCLUSIONS: The results of the present study indicate hair can be used as an indicator of fluoride exposure.

Micronuclei assay of exfoliated oral buccal cells: means to assess the nuclear abnormalities in different diseases.

The micronuclei assay (MA) in exfoliated buccal cells is an innovative genotoxicity technique, which holds promise for the study of epithelial carcinogens. Micronuclei are suitable internal dosimeters for revealing tissue-specific genotoxic damage in individuals exposed to carcinogenic mixtures. This article reviews the MN assay with respect to oral buccal mucosa, which has been used since the 1980s to demonstrate cytogenetic effects of environmental and occupational exposures, lifestyle factors, dietary deficiencies, and different diseases along with the characteristics of micronuclei and other nuclear abnormalities.

Sialadenoma papilliferum: clinical misdiagnosis with a histological decree.

Sialadenoma papilliferum is a rare salivary gland tumor clinically resembling papilloma originating probably from the excretory duct. It is characterized by a biphasic growth pattern of exophytic squamous component and endophytic glandular component. We report a rare case of sialadenoma papilliferum in the floor of the mouth with epithelial dysplasia with pertinent review of literature. The present case highlights the importance of keeping sialadenoma papilliferum as a differential diagnosis of exophytic papilliferous oral lesions and the need to explore the etiology and malignant potential of the tumor.