Oral Pathology and Microbiology

Burning mouth syndrome (BMS) is a chronic pain condition which affects commonly the postmenopausal women, and individuals with psychological problems. In this review, we will study the association between BMS and systemic disorders, as well try to unravel the possible pathogenic mechanisms involving potential nerve damage; which may be responsible for signs and symptoms of BMS.

Treatment planning for oral squamous cell carcinoma (OSCC) is based on the clinical TNM (Tumor, Node and Metastasis) classification. This system operates on the assumption that small tumours without clinical spread have a better prognosis than larger tumours with metastases. However, it is a well-known fact that some tumours with the same clinical staging show different growth patterns and clinical behaviour. This makes the prognosis for patients with OSCC difficult to predict on the basis of clinical staging alone. Although many histopathological characteristics of OSCC have been identified as prognostic factors, none is believed to be completely infallible. Therefore, a great need exists for more reliable prognostic markers, which will assist in treatment decisions. It is now well documented that several molecular events of significance for tumour spread, such as gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation and initiation of angiogenesis occur at the tumour-host interface or invasive front, where the deepest and presumably most aggressive cells reside. This review describes the various molecular events and interactions, which take place in the invasive front of the OSCC, and elucidates their role as prognostic markers.

The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and th...

Treatment planning for oral squamous cell carcinoma (OSCC) is based on the clinical TNM (Tumor, Node and Metastasis) classification. This system operates on the assumption that small tumours without clinical spread have a better prognosis than larger tumours with metastases. However, it is a well-known fact that some tumours with the same clinical staging show different growth patterns and clinical behaviour. This makes the prognosis for patients with OSCC difficult to predict on the basis of clinical staging alone. Although many histopathological characteristics of OSCC have been identified as prognostic factors, none is believed to be completely infallible. Therefore, a great need exists for more reliable prognostic markers, which will assist in treatment decisions. It is now well documented that several molecular events of significance for tumour spread, such as gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation and initiation of angiogenesis occur at the tumour-host interface or invasive front, where the deepest and presumably most aggressive cells reside. This review describes the various molecular events and interactions, which take place in the invasive front of the OSCC, and elucidates their role as prognostic markers.

A burning sensation on eating spicy foods purportedly supports the role of capsaicin, an active component of chili peppers, in the etiology of oral submucous fibrosis (OSF). Although the mast cell mediators and activated P2X receptors induce a constant burning sensation through an ATP-dependent mechanism, it is the activation of the transient receptor potential vanilloid 1 (TRPV-1) receptor by capsaicin that aggravates it. The molecular basis for the burning pain in OSF is thus attributable to the activation of TRPV1. There is overwhelming evidence that confirms capsaicin has more of a protective role in attenuating fibrosis and is potentially therapeutic in reversing conditions linked to collagen accumulation. The activation of TRPV-1 by capsaicin increases intracellular calcium ([Ca2+]i), upregulates AMP-activated protein kinase (AMPK) and Sirtuin-1 (SIRT-1), to enrich endothelium-dependent vasodilation via endothelial nitric oxide synthase (eNOS). The induction of vasodilation induces antifibrotic effects by alleviating hypoxia. The antifibrotic effects of capsaicin are mediated through the upregulation of antioxidant enzymes, downregulation of inflammatory genes and suppression of new collagen fibril formation. Capsaicin also demonstrates an anticarcinogenic effect by upregulating the cytotoxic T cells and downregulating regulatory T cells through the inhibition of angiogenesis and promotion of apoptosis. Judicious administration of capsaicin with an appropriate delivery mechanism may have therapeutic benefits in reducing pain sensation, rendering antifibrotic effects, and preventing the malignant transformation of OSF. This paper provides an overview of the molecular basis of capsaicin and its therapeutic application as an antifibrotic and anticarcinogenic agent for the treatment of OSF.

Keywords: anticarcinogen; antifibrotic; burning pain; capsaicin; chili; oral submucous fibrosis.

Laser capture microdissection (LCM) is a high end research and diagnostic technology that helps in obtaining pure cell populations for the purpose of cell or lesion specific genomic and proteomic analysis. Literature search on the application of LCM in oral tissues was made through PUBMED. There is ample evidence to substantiate the utility of LCM in understanding the underlying molecular mechanism involving an array of oral physiological and pathological processes, including odontogenesis, taste perception, eruptive tooth movement, oral microbes, and cancers of the mouth and jaw tumors. This review is aimed at exploring the potential application of LCM in oral tissues as a high-throughput tool for integrated oral sciences. The indispensable application of LCM in the construction of lesion specific genomic libraries with emphasis on some of the novel molecular markers thus discovered is also highlighted.

Epithelial-mesenchymal transition (EMT) is a critical process that occurs during the embryonic development, wound healing, organ fibrosis and the onset of malignancy. Emerging evidence suggests that the EMT is involved in the invasion and metastasis of cancers. The inflammatory reaction antecedent to fibrosis in the onset of oral submucous fibrosis (OSF) and the role of EMT in its malignant transformation indicates a hitherto unexplored involvement of EMT. This review focuses on the role of EMT markers which are regulators of the EMT mediated complex network of molecular mechanisms involved in the pathogenesis of OSF and OSCC. Further the gene enrichment analysis and pathway analysis supports the association of the upregulated and downregulated genes in various EMT regulating pathways.

Keywords: Epithelial-mesenchymal transition (EMT); Functional enrichment; Oral squamous cell carcinoma (OSCC); Oral submucous fibrosis (OSF); Signaling pathways in EMT; Transcription factors in EMT; Type II EMT.

Background and aims. During root canal preparation, debris extruded beyond the apical foramen may result in periapical inflammation and postoperative pain. To date no root canal preparation method has been developed that extrudes no periapical debris. The purpose of this study was to identify a system leading to minimal extrusion of debris from the apical foramen. The study was conducted to comparatively evaluate the amount of apical extrusion of debris during root canal preparation using hand ProTaper and GT rotary and RaCe rotary instruments using crown-down technique. Materials and methods. Ninety freshly extracted human single-rooted mandibular premolars were equally assigned to three groups (n=30). The root canals were instrumented using hand ProTaper, GT rotary and RaCe rotary systems. Debris and irrigant extruded from the apical foramen were collected into vials. The mean weight of the remaining debris was calculated for each group and subjected to statistical analysis. Resul...

Fibrosis is a pathological state characterized by excessive deposition of the extracellular matrix components leading to impaired tissue function in the affected organ. It results in scarring of the affected tissue akin to an over-healing wound as a consequence of chronic inflammation and repair in response to injury. Persistent trauma of susceptible oral mucosa due to habitual chewing of betel quid resulting in zealous healing of the mucosal tissue is one plausible explanation for the onset of oral submucous fibrosis (OSF). The irreversibility and resistance of collagen to degradation and its high potential to undergo malignant change are a major reason for morbidity in OSF. Hence, early diagnosis and timely treatment are crucial to prevent the progression of OSF to malignancy. This review focuses on the mechanistic insight into the role of collagen cross-links in advancing fibrosis and possible therapeutic targets that bring about a reversal of fibrosis. These options may be beneficial if attempted as a specific therapeutic modality in OSF as is in organ fibrosis. The upregulation of lysyl oxidase and lysyl hydroxylase has been shown to exhibit the higher levels of the hydroxylysine aldehyde-derived cross-links in fibrosis and tumor stroma promoting the tumor cell survival, resistance, and invasion. The in silico analysis highlights the potential drugs that may target the genes regulating collagen crosslinking.

We applaud the authors for their excellent work on graft against host disease-induced oral submucous fibrosis (OSF). Their descriptions of blanching and marble-like appearance of buccal, labial, and lingual dorsal mucosa, as well as restricted movement and stiff leathery oral mucosa with palpable fibrous bands, were all reminiscent of OSF [1]. Despite having a different mechanism for development, OSF in the aforementioned report mainly affected the anterior areas [1]. Most studies, however, imply posterior to anterior progression based on the functional staging of OSF first reported by Haider et al. However, according to several studies, this pattern is uncommon [1-8]. This encouraged us to reconsider Haider et al.'s OSF staging scheme [9].

Background: Oral submucous fibrosis (OSF) is a persistent oral mucosal condition that carries an elevated risk of undergoing malignant transformation. Our objective was to elucidate the involvement of epithelial-tomesenchymal transition (EMT) in OSF and its progression to malignancy by studying a panel of EMT markers, thereby understanding the molecular mechanisms. Methods: An immunohistochemical analysis was done to detect the presence of E-cadherin, N-cadherin, pancytokeratin (PanCK), vimentin, α-SMA (alpha-smooth muscle actin), and CD44 in a total of 100 tissue samples. These samples comprised 40 cases of OSF, 20 cases of oral squamous cell carcinoma associated with OSF (OSFSCC), and 40 cases of oral squamous cell carcinoma (OSCC). A whole transcriptomic analysis was performed on a group of seven matched samples encompassing NOM, OSF, OSFSCC, and OSCC. Results: We observed significantly decreased expression of E-cadherin and PanCK, while N-cadherin, vimentin, α-SMA, and CD44 showed significantly higher expression in OSFSCC and OSCC as compared to OSF, both at protein and RNA levels. CD44 expression was noticeably higher in OSFSCC (p < 0.001) than in OSCC. Conclusion: Downregulation of epithelial markers with concomitant upregulation of mesenchymal and stem cell markers suggests the potential role of EMT and stemness in accelerating the pathogenesis and malignant transformation of OSF. The high levels of CD44 expression seen in OSFSCC indicate a high propensity for aggressiveness and acquisition of stem-like characteristics by the cells undergoing EMT.

Background: Oral submucous fibrosis (OSF) is a pathological condition characterized by excessive tissue healing resulting from physical, chemical, or mechanical trauma. Notably, areca nut consumption significantly contributes to the development of oral fibrosis. The current definition of OSF, recognizing its potential for malignant transformation, necessitates a more comprehensive understanding of its pathophysiology and etiology. Highlights: Areca nut induces fibrotic pathways by upregulating inflammatory cytokines such as TGF-β and expressing additional cytokines. Moreover, it triggers the conversion of fibroblasts to myofibroblasts, characterized by α-SMA and γSMA expression, resulting in accelerated collagen production. Arecoline, a component of areca nut, has been shown to elevate levels of reactive oxygen species, upregulate the expression of various cytokines, and activate specific signaling pathways (MEK, COX2, PI3K), all contributing to fibrosis. Therefore, we propose redefining OSF as "Areca nut-induced oral fibrosis" (AIOF) to align with current epistemology, emphasizing its distinctive association with areca nut consumption. The refined definition enhances our ability to develop targeted interventions, thus contributing to more effective prevention and treatment strategies for oral submucous fibrosis worldwide. Conclusion: Arecoline plays a crucial role as a mediator in fibrosis development, contributing to extracellular matrix accumulation in OSF. The re-evaluation of OSF as AIOF offers a more accurate representation of the condition. This nuanced perspective is essential for distinguishing AIOF from other forms of oral fibrosis and advancing our understanding of the disease's pathophysiology.