Pathogenesis Of Oral Submucous Fibrosis Research Articles

Exploring the Mechanism of tiRNA-Val-CAC-002 in the Pathogenesis of Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a chronic, progressive, and potentially malignant disease of the oral cavity. A previous study by our team found that the aberrant expression of tRNA-derived small RNA (tsRNA) was involved in the development of OSF, with tiRNA-Val-CAC-002 showing the most significant difference. This study aimed to investigate the effect of tiRNA-Val-CAC-002 on fibroblast activation and its underlying mechanisms, elucidate the pathogenesis of OSF, and explore new effective targets for OSF prevention and treatment. RT-PCR was used to detect tiRNA-Val-CAC-002 expression in OSF and arecoline-treated fibroblasts. Western blotting, MDC staining, and transmission electron microscopy validated the effects of arecoline and 002 on fibroblast autophagy. Western blotting was used to explore the signaling pathways related to tiRNA-Val-CAC-002 in OSF. Arecoline promotes fibroblast (FB) activation by upregulating tiRNA-Val-CAC-002. Arecoline stimulation and tiRNA-Val-CAC-002 overexpression activated fibroblasts by promoting autophagy. tiRNA-Val-CAC-002 regulates PI3K/AKT by mediating ITGB3 expression. Arecoline upregulates tiRNA-Val-CAC-002 expression in fibroblasts. Moreover, tiRNA-Val-CAC-002 may activate the autophagy of fibroblasts in OSF by ITGB3/PI3K/AKT pathway regulation, promoting the expression of collagen fibers.

The role of M1 (CD11c) and M2 (CD163) interplay in the pathogenesis of oral submucous fibrosis and its malignant transformation: An immunohistochemical analysis

ObjectivesThe M1/M2 macrophage framework is crucial in organ fibrosis and its progression to malignancy. This study investigated the possible role of M1/M2 macrophage interplay in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation by analysing immunohistochemical expression of CD11c (M1) and CD163 (M2) markers. MethodsImmunohistochemistry was performed using primary antibodies against CD11c and CD163 on ten formalin-fixed paraffin-embedded tissue blocks for each group: (i) Stage 1 OSF, (ii) Stage 2 OSF, (iii) Stage 3 OSF, (iv) Stage 4 OSF, (v) well-differentiated squamous cell carcinoma (WDSCC) with OSF, and (vi) WDSCC without OSF. Ten cases of healthy buccal mucosa (NOM) served as controls. ResultsEpithelial quick scores of M1 (CD11c) in NOM, Stages 1–4 OSF, and WDSCC with and without OSF were 0, 1.8, 2.9, 0.4, 0, 0, and 0, while connective tissue scores were 0, 3.2, 4.3, 2.7, 0.5, 1.2, and 2.4, respectively. Epithelial scores for M2 (CD163) were 0, 0.8, 0.8, 2.1, 0.6, 0.8, and 0.2, and connective tissue scores were 0, 1.8, 2.6, 3.9, 2.2, 5, and 4.4, respectively. Stages 3 and 4 OSF, WDSCC with and without OSF exhibited higher M2/M1 ratios compared to NOM and Stages 1–2 OSF. ConclusionThe interaction between M1 (CD11c) and M2 (CD163) macrophages, leading to M2 polarisation, plays a crucial role in the pathogenesis of OSF and its potential malignant transformation.

Mechanism of mangiferin in the treatment of oral submucous fibrosis based on Gene Expression Omnibus database chip mining combined with network pharmacology and molecular docking.

This study aims to investigate the primary target and potential mechanism of mangiferin (MF) in treating oral submucous fibrosis (OSF) through Gene Expression Omnibus (GEO) database chip mining, network pharmacology, and molecular docking techniques. Potential therapeutic targets for OSF were identified using GEO chip data. The potential targets of MF were predicted, and disease-related targets for OSF were collected from databases. A Venn diagram was created using the EVenn platform to identify overlapping targets. The protein-protein interaction (PPI) network was constructed using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID platform. Cytoscape 3.10.1 software was used to visualize a drug-target-pathway-disease network, while AutoDocktools 1.5.6 software was employed for molecular docking analysis. A total of 356 potential targets for MF and 360 disease-related targets for OSF were obtained from multiple databases. The top 15 key target proteins in the PPI network were selected as significant candidates. GO function and KEGG pathway enrichment analyses revealed that MF treatment primarily involved advanced glycation end products-receptor (AGE-RAGE), epidermal growth factor receptor (EGFR), and other signaling pathways associated with OSF pathogenesis. Molecular docking analysis demonstrated that MF exhibited a strong binding activity toward AKT serine kinase 1 (AKT1), tumor necrosis factor (TNF), and other core targets. These findings suggest that MF may exert its therapeutic effects on OSF through a multitarget approach involving various signaling pathways.

Expression of IGF-1R in oral submucous fibrosis and oral squamous cell carcinoma – An RT-PCR study

ObjectivesWith the rising number of cases of oral submucous fibrosis (OSMF) undergoing malignant transformation into oral squamous cell carcinoma (OSCC), it is needed to detect the changes at the earliest. Several molecular markers have been used for this purpose, and insulin-like growth factor receptor 1 (IGF-1R) is one of the markers in vogue for several human malignancies. Thus, we compared the expression of IGF-1R mRNA in normal oral mucosa (NOM), OSMF, and OSCC. Materials and methodsThirty biopsy tissue samples for each of the three groups, NOM, OSMF, and OSCC, were taken and analyzed histopathologically and then subjected to RT-PCR for evaluation of the expression of IGF-1R mRNA in each of them. ResultsThere was an upregulation of IGF-1R mRNA in OSMF tissue samples as compared to NOM, but a downregulation as compared to OSCC. There was a 3.24-fold upregulation of IGF-1R mRNA expression in OSMF as compared to NOM and a 1.31-fold downregulation as compared to OSCC. Likewise, there was a 4.2-fold upregulation of IGF-1R mRNA expression in OSCC as compared to NOM and 1.31-fold upregulation as compared to OSMF. Moreover, the expression was more in OSMF patients with interincisal opening (IIO) < 27 mm as compared to those with IIO >27 mm and also was found to increase with the grade of OSCC. ConclusionThe study reflected a potential role of IGF-1R in the pathogenesis of OSMF and OSCC, thus implying its possible exploitation as a diagnostic and prognostic marker and also as a therapeutic target in future.

Evaluation of possible role of fluoride in pathogenesis of oral submucous fibrosis: A pilot study.

Oral submucous fibrosis (OSMF) is a potentially malignant disorder. Although areca nut chewing is an established risk factor, its low prevalence among nut chewers indicates additional factors likely facilitates pathogenesis. We recently demonstrated high fluoride levels in smokeless tobacco products and hypothesized a potential pathological role of fluoride in OSMF. Further exploring this novel role, this study compared fluoride levels in tissue, serum, and saliva samples from OSMF patients and healthy controls. The ethically approved study included 25 clinically confirmed OSMF patients and 25 healthy matched controls. OSMF cases underwent buccal mucosal incisional biopsy, while controls had buccal mucosa tissue sampling during third molar removal. Fasting venous blood and unstimulated saliva were collected. Fluoride levels were analysed using ion chromatography and expressed as median (IQR). OSMF cases showed significantly higher fluoride concentrations compared with controls in tissue biopsies (30.1 vs. 0 mg/kg, p < 0.0001), serum (0.4 vs. 0 mg/L, p = 0.005) and saliva (1.3 vs. 0 mg/L, p < 0.0001). Majority (68%) of controls had undetectable fluoride levels across all samples. Tissue fluoride weakly correlated with OSMF severity (r = -0.158, p = 0.334). The preliminary findings demonstrated increased tissue fluoride levels in OSMF patients compared with healthy controls. Along with a previous study showing high fluoride content in smokeless tobacco products, these findings provided early evidence suggesting fluoride could play a contributory role in OSMF pathogenesis. Further large-scale investigation is warranted to definitively establish whether the association between fluoride exposure and OSMF is indicative of causation.

Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis.

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model, treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs) were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (vFAOs). Consistently, treatment with arecoline reduced the expression of CD31 in vFAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

A clinic-pathological research explored the significance of ascorbic acid and iron levels in serum and saliva in premalignant disorder patients at Kanpur, Uttar Pradesh.

Oral submucous fibrosis (OSMF), or OSMF, is a well-known, potentially premalignant condition of the oral cavity. Monitoring OSMF widespread effects necessitate interventions in at-risk individuals, ideally before the disease becomes aggressive. Ascorbic acid and iron, for instance, are significant micronutrients in the pathogenesis of OSMF. This study aimed to investigate the significance of ascorbic acid and iron levels in serum and saliva in patients with premalignant disorder (OSMF) and to correlate variations in ascorbic acid and iron levels with histopathological grading. The present study was conducted on 195 patients over a period of 10 months. These patients were divided into two groups, Group I (n = 88, Control), Group II (n = 107, clinically diagnosed and histopathologically confirmed cases of OSMF). Serum and salivary ascorbic acid were analyzed by the dintrophenyl hydrazine method, whereas serum and salivary iron were analyzed by the dipyridyl method. Paired t-test and Fisher test were used to compare between the mean and to find the level of significance P value. The serum and salivary ascorbic acid levels consistently decreased with the progression of histopathological grading of OSMF. Serum and salivary iron levels were also decreased in OSMF patients, and it came as significant. Excess collagen synthesis during OSMF may have been promoted with ascorbic acid and iron. As a reason, serum and salivary monitoring may be significant in detecting and diagnosing OSMF early on.

37. Evaluation of possible role of fluoride in the pathogenesis of Oral Submucous Fibrosis: a pilot study

37. Evaluation of possible role of fluoride in the pathogenesis of Oral Submucous Fibrosis: a pilot study

Fluoride as a potential contributory factor in pathogenesis of oral submucous fibrosis: A novel hypothesis

Oral submucous fibrosis (OSMF) is a chronic premalignant condition of the oral cavity characterized by progressive submucosal fibrosis and high malignant transformation risk. Areca nut chewing is an established aetiological factor, but OSMF's sporadic incidence in nut users indicates other contributing cofactors. This paper propose a novel hypothesis on the potential role of fluoride exposure in OSMF pathogenesis. Evidence in the literature demonstrates fluoride readily accumulates in oral tissues upon topical exposure and can elicit oxidative stress, chronic inflammation, collagen changes, and muscle degeneration through various mechanisms. We hypothesize chronic topical fluoride exposure from gutkha, areca nut or other smokeless tobacco products, along with other aetiologic factors, may induce an aberrant microenvironment in the oral mucosa, initiating and propagating submucosal fibrosis. Resultant repetitive injury coupled with fluoride's interference in collagen metabolism and wound healing may culminate in OSMF pathogenesis. We further speculate that chronic ingestion of dietary fluoride especially from drinking water and food may predispose individuals to OSMF when it interacts synergistically with direct contact of gutkha or other smokeless products. In addition, it is also speculated that the cellular effects of fluoride in a dose-dependent manner, could contribute to dysplastic changes and malignant transformation in severe OSMF cases. Further research should systematically investigate fluoride levels in OSMF cohorts and correlate with disease severity and malignant transformation rates. Confirming the aetiopathologic role of fluoride as a promoting factor would highlight public health efforts to limit its topical exposure from oral habits and diet to combat this oral potentially malignant disorder.

Interplay of Transforming Growth Factor-Beta 1 and 3 in the Pathogenesis of Oral Submucous Fibrosis and Its Malignant Transformation: An Immunohistochemical Study.

Introduction Oral submucous fibrosis (OSF) is a chronic and potentially malignant oral condition that poses a significant public health issue due to its insidious nature. Transforming growth factor-beta (TGF-β) is a key player in the pathogenesis of OSF and is responsible for fibrosis. This study aims to investigate the relationship between the expression of TGF-β1 and TGF-β3 in OSF and its malignant transformation by using immunohistochemistry. Materials and method The present study comprised of 120 formalin-fixed paraffin-embedded tissue samples, which included 20 normal oral mucosa (NOM), 80 OSF (20 each of stage 1- 4), and 20 oral squamous cell carcinoma (OSCC) (10 each of OSCC with and without OSF), and were stained for TGF-β1 and TGF-β3 by immunohistochemistry. Data were analyzed using R software version 4.1.2, GraphPad Prism 9.3.1 (GraphPad Software,San Diego, CA, USA) and Excel (Microsoft Corp., Redmond, WA). Results TGF-β1 immunoexpression was negative in NOM with no significant difference among OSF and OSCC (with or without OSF). TGF-β3 was significantly higher in OSCC (with or without OSF) than in OSF, and no significant difference was noted between OSF and NOM and between OSCC and NOM. A significant increase was seen in TGF-β3 compared to TGF-β1 in NOM, OSF (stage 1- 4), and OSCC with and without OSF. Conclusion TGF-β3 has higher immunoexpression levels than TGF-β1 in NOM, OSF, and OSCC. We speculate that quantitative or qualitative TGF- β3 may be inadequate to prevent or attenuate fibrosis in OSF patients. There is also a modicum of probability that TGF-β3 has a preventive rather than causative role in OSF pathogenesis. The role of TGF-β3 in OSF needs further clarification.

A Review of the Transition of Oral Keratinocytes from an Epithelial to a Mesenchymal State in Oral Submucous Fibrosis and the Potential Function of Apamin in Reversing This Transition

Epithelial–mesenchymal transition (EMT) causes polarized and cohesive epithelial cells to become motile and join the extracellular matrix (ECM). Embryonic development, wound healing, and tissue repair need it. Interestingly, the same mechanism may cause cancer, organ fibrosis, scarring, and organ failure. WNT, Notch, Hedgehog, and RTK signaling impact EMT. This process also includes nontranscriptional changes due to growth hormones, cytokines, hypoxia, and ECM interaction. The reason for the development of oral submucous fibrosis (OSF) is believed to be multifaceted; nevertheless, there is substantial evidence supporting the notion that it arises from dysregulation of collagen. EMT is a prominent phenomenon in the development of OSF, whereby myofibroblasts and keratinocytes are the cells most affected. The role of EMTs is crucial in both physiological and pathological processes. The significance of EMT involvement in the pathogenesis of OSF and the preceding inflammatory response suggests a promising avenue for further investigation. Transforming growth factor-1 (TGF-1) plays a crucial role in the EMT of oral keratinocytes that initiates the pathogenesis of OSF. The objective of this review is to analyze the events of EMT in OSF, along with the processes and molecular routes that regulate alterations in gene expression within the oral cavity. The potential for cancerous transformation is linked to OSF, prompting an examination of the involvement of apamin in the advancement of EMT triggered by TGF-1 in oral keratinocytes.

Salivary transforming growth factor beta in oral submucous fibrosis: A diagnostic and predictive marker.

Growth factors and cytokines like transforming growth factor beta (TGF-β) play a key role in the pathogenesis of oral submucous fibrosis. To elucidate the role of Salivary TGF-β isoforms as a predictive and diagnostic marker for oral submucous fibrosis. A total of 30 OSMF and 10 control patients were included in this study, and their clinic-epidemiological data was recorded. The expression of TGF-β genes-TGF-β1, TGF-β2, TGF-β3-was studied by a real-time polymerase chain reaction in tissue and saliva. Patients were given medicinal intervention for 12 weeks along with jaw-opening exercises. Expression of salivary TGF-β genes was studied at 12 weeks. SPSS software version 20. Expression of salivary TGF beta isoforms in OSMF was more than in the control group. There was an increase in salivary TGF-β1, β2, β3 expressions with increasing clinical grades of OSMF and advancing the stage of the disease. Expression of all the TGF beta isoforms was decreased after treatment with statistically significant results. Statistically significant correlations were found between the mean difference of TGF-β1 and the mean difference between mouth opening and tongue protrusion. Salivary TGF-β isoforms may be used in diagnosis, risk assessment, and screening of the entire population at risk of OSMF after its clinical validation. However, adequate sample size and segmental assessment of the expression of TGF-β isoforms are needed for further evaluation.

Low-dose arecoline regulates distinct core signaling pathways in oral submucous fibrosis and oral squamous cell carcinoma

BackgroundBetel nut chewing plays a role in the pathogenesis of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC). As the major active ingredient of the betel nut, the effect of arecoline and its underlying mechanism to OSF and OSCC pathogenesis remain unclear.MethodsNext-generation sequencing-based transcriptome and dRRBS analysis were performed on OSF and OSCC cells under low-dose arecoline exposure. Functional analyses were performed to compare the different roles of arecoline during OSF and OSCC pathogenesis, and key genes were identified.ResultsIn this study, we identified that low-dose arecoline promoted cell proliferation of both NFs and OSCC cells via the acceleration of cell cycle progression, while high-dose arecoline was cytotoxic to both NFs and OSCC cells. We performed for the first time the transcriptome and methylome landscapes of NFs and OSCC cells under low-dose arecoline exposure. We found distinct transcriptome and methylome profiles mediated by low-dose arecoline in OSF and OSCC cells, as well as specific genes and signaling pathways associated with metabolic disorders induced by low-dose arecoline exposure. Additionally, low-dose arecoline displayed different functions at different stages, participating in the modulation of the extracellular matrix via Wnt signaling in NFs and epigenetic regulation in OSCC cells. After exposure to low-dose arecoline, the node roles of FMOD in NFs and histone gene clusters in OSCC cells were found. Meanwhile, some key methylated genes induced by arecoline were also identified, like PTPRM and FOXD3 in NFs, SALL3 and IRF8 in OSCC cells, indicating early molecular events mediated by arecoline during OSF and OSCC pathogenesis.ConclusionsThis study elucidated the contribution of low-dose arecoline to OSF and OSCC pathogenesis and identified key molecular events that could be targeted for further functional studies and their potential as biomarkers.

Expression of p53 as Potential Biomarker in Oral Submucous Fibrosis: An Immunohistochemical Study.

Oral submucous fibrosis (OSMF) is potentially malignant disorder known to transform into oral cancer. The malignant transformation is often associated with changes at the genetic level that in turn is reflected by the altered expression of proteins related to cell cycle, proliferation, and apoptosis. Expression of p53 tumor suppressor gene is one of the common findings in human cancers including the oral cancer. Therefore, the early detection of potentially malignant OSMF has been crucial in the inhibition of oral cancer. To determine the main pathological logical factors and expression of aberrant p53 in OSMF, oral squamous cell carcinomas (OSCC) and in normal patients, to study correlation between p53 expression with clinical staging and histological grading of OSMF. An immunohistochemical (IHC) study was performed for p53 expression on 35 cases of OSMF, 10 cases of OSCC with history of habits and 10 normal patients without any habits. The expression of p53 showed a significant difference between normal oral mucosa, OSMF and OSCC samples. The study demonstrated a high incidence of p53 over expression in OSMF and OSCC. The results indicate that p53 over expression may play a role in pathogenesis of OSMF and in the development of Oral squamous cell carcinoma. With early detection of the high-risk patients with OSMF, we can expect to develop more intensive treatment modalities, leading to the reduction in cancer transformation rate from OSMF.

Global and promoter specific hypermethylation of tumor suppressor genes P16, SOCS1, and SHP1 in oral squamous cell carcinoma and oral submucous fibrosis.

Aberrant methylation pattern leads to altered gene expression, that is, involved in the transformation of various cancers, including oral squamous cell carcinoma (OSCC). In the present study, an attempt has been made to examine the association of global and promoter-specific methylation of tumor suppressor genes in patients with OSCC and oral submucous fibrosis (OSMF). Promoter-specific methylation of tumor suppressor genes P16, SOCS1, and SHP1 had been studied earlier for their aberrant methylation patterns in other cancers; however, these studies were mainly conducted in-vitro or in animal models, and as such, only a few studies are available on human samples. In the present study evaluation of promoter-specific methylation of genes P16, SOCS1, and SHP1 in 76 patients' blood and tissue samples was done and compared with methylation of 35 healthy control samples using qPCR. Further, these samples were analyzed for global methylation patterns using ELISA. The results have shown a significant decreasing trend of promoter methylation (OSCC > OSMF > Controls); the methylation indices (MI) were significantly higher in OSCC than in the controls. The median MI of three genes for OSCC were P16MI (0.96), SHP1MI (0.79), and SOCS1 (0.80). Similarly, median MIs for OSMF were P16MI (0.18), SHP1 MI (0.19), and SOCS1 MI (0.5) against controls with MI (0) for each of the three genes. The global methylation %mC values were 1.9, 0.5, and 0.1, respectively. The values of MI and %mC were found to correlate with various risk factors such as tobacco, smoking, and alcohol consumption, which are positively involved in OSMF pathogenesis followed by oral cancer progression. Further, the methylation trend in tissue was reflected in blood samples, proving a window for methylation load to be used as a lesser invasive biomarker. The sensitivity and specificity of methylation load were also found reasonable. Therefore, the current study suggests that there may be a role of global and promoter-specific methylation load in the transition of OSMF to OSCC.

Herbal Formulations in Oral Submucous Fibrosis Treatment – A Narrative Review

ABSTRACT This narrative review provides an overview of the use of herbal formulations in the treatment of oral submucous fibrosis (OSMF). OSMF is a potentially malignant disorder characterized by progressive fibrosis of the oral mucosa, resulting in restricted mouth opening and other debilitating symptoms. Conventional treatment options for OSMF are limited, and their effectiveness varies. Herbal formulations have gained attention as alternative and complementary treatment options for OSMF due to their perceived natural origin, minimal side effects, and potential therapeutic effects. These formulations typically consist of plant-derived ingredients with bioactive compounds that possess anti-inflammatory, antioxidant, antifibrotic, and immunomodulatory properties. Various herbal ingredients, such as Aloe vera, curcumin, licorice, honey, and triphala, have been investigated for their potential efficacy in OSMF treatment. These ingredients have shown promise in targeting the underlying mechanisms involved in OSMF pathogenesis, including inflammation, fibrosis, oxidative stress, and immune dysregulation. Herbal formulations offer potential advantages in OSMF treatment. They may provide a holistic approach by addressing multiple aspects of the disease and promoting overall oral health. Herbal formulations also have the advantage of cultural acceptability and cost-effectiveness. To further advance our understanding of herbal formulations in OSMF treatment, well-designed clinical trials with standardized protocols and larger sample sizes are needed. In addition, the development of evidence-based guidelines for the use of herbal formulations in OSMF would aid health-care professionals in making informed treatment decisions. Herbal formulations have shown promise as potential treatment options for OSMF. While their efficacy and safety need further investigation, they offer a natural and holistic approach to OSMF management. Collaboration between researchers, clinicians, and regulatory bodies is essential to advance the research and ensure the safe and effective use of herbal formulations in OSMF treatment.

Is Epithelial-Mesenchymal Transition a New Roadway in the Pathogenesis of Oral Submucous Fibrosis: A Comprehensive Review.

Epithelial-mesenchymal transition (EMT) collectively refers to a series of episodes that reshape polarized, intact epithelial cells into discrete motile cells that can conquer the extracellular matrix (ECM). It performs a pivotal role in embryonic development, wound healing, and tissue repair. Surprisingly, the exact mechanism can also lead to the onset of malignancy and organ fibrosis contributing to scar formation and loss of function. transforming growth factor signaling, WNT signaling, Notch signaling, Hedgehog signaling, and receptor tyrosine kinase signaling, as well as non-transcriptional changes in response to extracellular cues, such as growth factors and cytokines, hypoxia, and contact with the surrounding ECM, are responsible for the initiation of EMT. Although the pathogenesis of oral submucous fibrosis (OSMF) is multifactorial, compelling evidence suggests that it results from collagen deregulation. EMT is one of the spotlight events in the pathogenesis of OSMF, with myofibroblasts and keratinocytes being the victim cells. EMT is an essential step in both physiological and pathological events. The importance of EMT in the malignant development of OSMF and the inflammatory reaction preceding fibrosis implies a new upcoming area of research. This review aims to focus on the EMTevents that function as a double-edged sword between wound healing and fibrosis and further discuss the mechanisms along with the molecular pathways that direct changes in gene expression essential for the same in the oral cavity. As OSMF involves a risk of malignant transformation, understanding the cellular and molecular events will open more avenues for therapeutic breakthroughs targeting EMT.

Persistence of leader cell behaviour can lead to malignant transformation in oral submucous fibrosis

Betel quid (BQ) chewing-related oral submucous fibrosis (OSMF) is a common, potentially fatal condition in Southeast Asian countries. The literature has proved that BQ is associated with the development of micro-trauma-related injury to the oral mucosa. This is mainly attributed to the coarseness of the BQ and its abrasive action. Since, BQ chewing is a chronic habit in OSMF patients, it leads to the frequent development of micro-trauma and its repeated healing. This mechanism has been implicated in the pathogenesis of OSMF and its malignant transformation. However, the micro-trauma related mechanism for malignant transformation of OSMF is poorly understood. Leader cell formation is a well-known phenomenon in wound healing characterized by migration guidance to other cells, leading to epithelial repair. Due to repeated trauma and micro-wound formation in OSMF patients, we proposed the persistence of leader cells in the oral mucosa. This causes continuous activation of the p53-p21-CDK axis, which is an integral mechanism required for the transformation of normal epithelial cells into leader cells. We also propose that carcinogens derived from BQ chewing cause genetic and epigenetic changes in the leader cells. Overall, the persistence of leader cells in the oral epithelial population could be a major driver for malignant transformation in OSMF and a determinant of intra-tumoral heterogeneity. Strategies to curtail micro-trauma to the oral mucosa and target the leader cells hold good promise for preventing malignant transformation in OSMF.

Evaluation of Serum Urea, Uric Acid and Creatinine in OSMF Patients

Introduction: Oral submucous fibrosis (OSMF) is described as a chronic debilitating disease of the submucosal tissue. Leaching out compounds from areca nut is the main etiology for OSMF. Biochemical examinations have concentrated on demarcating changes in the blood, serum, or tissues of patients with this disease. Such examinations have given insights into the possible pathogenesis of OSMF. Aim: Estimation of serum urea, uric acid (UA), and creatinine (Cn.) in OSMF patients. Objective: To estimate the level of serum urea, UA, and Cn. in OSMF patients and compare them with habitual betel nut chewers. Materials and Methods: The purposive samples were selected from patients attending the OPD of the Oral Medicine and Radiology (OMR) Department. In total 180 patients were included and divided into three groups. Group I-Patients suffering from OSMF, Group II-Habitual control, and Group III-Healthy control. Results: The mean value of serum UA (mg/dL) in Group I was 7.82 ± 2.18, Group II was 5.83 ± 1.22, and Group III was 5.28 ± 1.10. The mean value of serum Cn. (mg/dL) in Group I was 1.05 ± 0.27, Group II was 1.15 ± 0.22, and Group III was 0.72 ± 0.21. One-way analysis of variance (ANOVA) was applied between the groups and significant differences were found for both serum UA and Cn. with P &lt; 0.0001, whereas no significant difference was found for serum urea. Conclusion: It can be concluded from this study that serum urea, UA, and Cn. of OSMF patients should be evaluated for liver and renal involvement and for overall improving the disease prognosis.

Analysis of copper and zinc levels in the mucosal tissue and serum of oral submucous fibrosis patients

Background and Objectives:Although the pathogenesis of oral submucous fibrosis (OSMF) has been studied, it remains unclear whether or not this illness might progress to malignancy. The pathogenesis of the illness may be better understood by measuring copper and zinc levels in tissue and serum from these people. Because of the widespread cultural and social usage of areca nuts in India, a research was conducted to investigate their concentrations in this population. Methods:Twenty people with OSMF and twenty people without it were studied in a case-control fashion. Copper and zinc concentrations were measured in the 40 patients' tissues and blood using colorimetry. Compared to the zinc concentration of 25.18 4.92 g/gm found in OSMF group tissues, copper concentration was 4.31 1.13 g/gm. Zinc levels were 0.92 0.18 g/ml and serum copper levels were 1.00 0.20 g/ml on average in the OSMF group. Interpretation and conclusion:OSMF group tissue zinc levels were substantially different from control group levels (p = 0.009), as were OSMF group tissue copper levels (p = 0.001). There was no statistically significant difference in serum copper (p = 0.35) or zinc (p = 0.08) between the experimental and control groups.