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In dermatology, lichenoid describes lesions with a violaceous hue that is a clinical reflection of basal cell damage in the epithelium and dense mononuclear infiltrate in the sub‐epithelium. The violaceous color results from pigment incontinence due to basal cell damage and the Tyndall effect. Although classically described in lichen planus, a lichenoid hue is noted in the oral mucosa in several other disorders that often lead to diagnostic dilemmas. Early and accurate diagnosis is important for the appropriate management of the underlying condition and prognostication. Dermatologists play a central role in managing such patients since, apart from the oral mucosa findings, the cutaneous features also help to significantly differentiate various conditions. Mimickers of oral lichen planus include nicotine stomatitis, oral submucous fibrosis, oral lichenoid lesions, mucosal discoid lupus erythematosus, pemphigus vulgaris, paraneoplastic pemphigus, mucous membrane pemphigoid, fixed drug eruption, plasma cell cheilitis/gingivitis, and erythema multiforme. While a detailed history and clinical examination can help reach a diagnosis in most cases, histopathology, immunofluorescence, and other relevant investigations help establish the diagnosis. [ABSTRACT FROM AUTHOR]

Common digestive precancerous lesions, including oral potentially malignant disorders (OPMDs), gastric ulcers and colorectal adenoma, harbor high risk of cancerous transformation. Early intervention of these lesions is significant to prevent carcinogenesis and improve patients’ prognosis. Lycopene, a carotenoid predominantly accumulated in tomatoes, is clinically recommended with its cis structure; as lycopene harbors the most potent antioxidative effects among carotenoids, its chemopreventive effects on the premalignant lesions is noted. Despite several reviews have assessed lycopene’s efficacy for OPMDs, emerging studies have reported varying efficacy for digestive precancerous lesion with no comprehensive summary. Therefore, this review initially evaluates the efficacy and underlying mechanisms of lycopene for management of digestive precancerous lesions. According to the included studies, lycopene may show high promise in the management of digestive precancerous lesions, such as relieving mouth opening and burning sensation of oral submucous fibrosis (OSF), presenting potentially equivalent efficacy on managing oral lichen planus (OLP) as steroids and alleviating gastrointestinal precancers’ symptoms, meanwhile lowering colon cancer risk. Moreover, its mechanisms for managing digestive precancerous lesions are concretely summarized, including anti-oxidative stress effects, anti-inflammatory response and regulation of cell proliferation and apoptosis, especially its modifications on TLR4/TRIF/NF-κB signaling pathway and p53-dependent cell cycle control and apoptosis. More studies are warranted to confirm its long-term efficacy and preventive role against malignant transformation of digestive precancerous lesions as evidence is insufficient. [ABSTRACT FROM AUTHOR]

Introduction: Oral Submucous Fibrosis (OSMF) is a longterm condition characterised by the gradual buildup of fibrous tissue in the oral cavity, often extending to the throat and upper oesophagus. The primary symptoms include progressive limitation in mouth opening due to the formation of stiff fibrous bands in the oral mucosa, accompanied by muscle atrophy. However, the most concerning aspect of this restriction, known as trismus, is its hindrance to effective cancer monitoring. Surgical approaches typically aim to release these fibrotic bands, while medical interventions focus on managing inflammation and preventing further fibrosis. Need of the Study: A modification of the nasolabial flap has been suggested for the reconstruction of intraoral defects following ablative surgery for OSMF. The study will assess its merits in comparison to the conventional nasolabial flap. Aim: To evaluate and compare the aesthetic and functional outcomes of the rima oris between the Conventional Nasolabial Flap and the Nasolabial Flap with Fishtail Modification in patients undergoing surgical intervention for OSMF. Materials and Methods: A prospective, double-blinded, randomised controlled trial will be conducted in the Department of Oral and Maxillofacial Surgery at Acharya Vinoba Bhave Rural Hospital, associated with Jawaharlal Nehru Medical College, Wardha, Maharashtra, India, from November 2023 to November 2024. Patients older than 18 years of age diagnosed with OSMF, without any superimposing cancerous lesions, will be included in the study. They will be divided into two groups: Group A will be treated with bilateral fibrotomy, coronoidotomy and reconstruction with the conventional nasolabial flap, while Group B will undergo the same surgical intervention, except that the reconstruction will be performed using the fishtail modification of the nasolabial flap. The parameters that will be compared include interincisal mouth opening, intercommissural width, dehiscence and flap necrosis. The analysis will be conducted using the Chi-square test and Fisher's-exact test for categorical data and the independent t-test for continuous data that follow a normal distribution. These statistical tests will help evaluate the association between different demographic, clinical and etiological factors and the outcomes under consideration. A p-value of <0.05 will be considered statistically significant. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) is a condition characterized by inflammation and excessive collagen deposition, which has been identified as a potentially malignant disorder. Recently, several microRNAs (miRNAs) have been shown to be implicated in various disorders associated with fibrosis. However, how these miRNAs modulate OSF development is poorly understood. Therefore, the study aimed to identify the specific miRNAs that contribute to the progression of OSF and to investigate their molecular mechanisms in promoting fibrosis. The expression and clinical significance of potential pro-fibrosis miRNA in the OSF cohort and primary buccal mucosal fibroblasts were confirmed through RNA sequencing and qRT–PCR. Luciferase reporter activity assay, miRNA mimic or inhibitor, and short-hairpin RNA silencing were used to elucidate the molecular mechanism of miRNA. Transwell migration, collagen contraction, and reactive oxygen species (ROS) generation detection were used to investigate the effects of this mechanism on the myofibroblast phenotype and cellular pro-fibrosis capacity. This study demonstrated that miR-190a was overexpressed in fibrotic buccal mucosal fibroblasts (fBMFs). Transfecting fBMFs with miR-190a inhibitor resulted in reduced cell migration, collagen gel contraction, ROS generation, and expression of fibrotic markers. Furthermore, miR-190a exerted this pro-fibrosis property by direct binding to its target, Krüppel-like factor 15 (KLF15). The results also indicated that the aberrant upregulation of miR-190a, in turn, downregulated the expression of KLF15, which resulted in the activation of myofibroblast. Our findings demonstrated that miR-190a was involved in myofibroblast activation, suggesting that targeting the miR-190a/KLF15 axis may be a feasible approach in the therapy of OSF. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF), characterized by excessive collagen deposition by myofibroblasts, is often linked to Areca nuts consumption. Probiotics consumption has shown protective effects against fibrotic diseases, and recently, their metabolic byproducts, known as postbiotics, have demonstrated superior advantages over probiotics. However, studies on the therapeutic impact of postbiotics on OSF have been scarce. Therefore, this study aims to examine the effect of PostBio GK4, a postbiotic derived from Lactobacillus pentosus GK4 , on OSF and explore its underlying mechanisms. The cytotoxicity of GK4 in normal buccal mucosal fibroblasts (BMFs) and fibrotic BMFs (fBMFs) were assessed. Following this, we evaluated the effects of GK4 on collagen contraction, migratory, and wound healing capacities in arecoline-induced fibrotic BMFs. Next, Western blotting and ELISA were employed to assess GK4's impact on fibrosis-related proteins such as COL1A1, and α-SMA, as well as on TGF-β and Smad2/3 signaling pathway. Arecoline was shown to stimulate cell migratory, contractile and wound healing abilities as well as the expression of α-SMA and COL1A1 in BMFs. Treatment with GK4 reduced all arecoline-induced phenomena in BMFs. Moreover, GK4 diminished the increased expression of TGF-β and Smad2/3. Our findings proposed that GK4 may exert a suppressive effect on arecoline-induced myofibroblast activities via the inhibition of TGF-β and Smad2/3 signaling pathway. Therefore, GK4 holds promise as an adjunct therapeutic approach for intervening in OSF. Further in-vivo and clinical studies are warranted to validate these observations. [ABSTRACT FROM AUTHOR]

In this study the systematic review of trials was carried out to evaluate the prevalence of oral cancer in India. The articles related to the prevalence of Oral Cancer in India were hand searched using electronic databases which includes Prospero, Grey literature, Science Direct, Lilacs, Wiley online library and PubMed. The most common site of Oral cancer in North, East, Central and West zone is Buccal mucosa while in North- east and south zone Tongue is the most affected part. Prevalence rate for Leukoplakia is 37.1%, Speckled leukoplakia is 21.7%, Oral Submucous Fibrosis is 21.1% and Lichen Planus is 19.8%. Highest prevalence can be seen in Males of East zone with 75.7%. The mean age group prevalence is 30- 50 years of age. The study observed a general increase in oral cancer incidence especially in the East Zone. This will pave the path for evidence- based interventions and policies that promote oral health and improve the overall well- being of the population. Indian Government should give importance for the prevention of Oral Cancer by implementing new schemes and providing awareness program to promote the healthy lifestyle and banning of tobacco products. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of a new drug combination in the medical management of oral submucous fibrosis (OSMF) patients. Materials and Methods: This retrospective cohort study included 89 patients who were clinically diagnosed of having OSMF (grade I, II, III). These patients had been administered the new drug combination for 6 months and clinical parameters such as burning sensation score, mouth opening and tongue protrusion were evaluated at 1 month, 3 months, 6 months and 12 months post-medication retrospectively. Results: Out of the total 89 patients included in the study, 18 patients had Grade-I, 50 patients had Grade-II and 21 patients had Grade-III OSMF. A significant improvement was observed in the mouth opening and tongue protrusion in all the three grades of OSMF from baseline to 1 month, 3 months, 6 months and 12 months after treatment (p < 0.0001) on intra- and intergroup comparison. A significant reduction in the burning sensation score from baseline to 1 month, 3 months, 6 months and 12 months after treatment was observed (p < 0.0001) in all the three grades on intra group comparison. Conclusion: This retrospective study showed that this novel drug combination is significantly effective in improving burning sensation score, mouth opening and tongue protrusion in OSMF grade I, II and III patients with results consistent after 1 year of follow-up. [ABSTRACT FROM AUTHOR]

Background: Oral Submucous fibrosis has a substantial burden on the Indian population; thus there is a substantial need for a validated questionnaire assessing QoL in Hindi. Thus, a prospective cross-sectional study was designed to translate and validate the English version of the OHR QoL-OSF questionnaire into Hindi. Methodology: We followed the guidelines suggested by the European Organisation for Research and Treatment of Cancer (EORTC) for the translation procedure and subsequently validated the translated questionnaire with reliability and validity. Results: A total of 50 patients were included in this pilot study. Cronbach's alpha for 17 items was 0.87 signifying high reliability. All questions had an I-CVI of 1.00, demonstrating complete agreement among the content experts regarding the relevance and clarity of items in the questionnaire. Convergent validity was adequately established for all factors except for factor 3 for which it was around 0.43. The intraclass coefficient was 0.803 showing good agreement between the test–retest results. Conclusion: The Hindi version of the OHR QoL questionnaire is a reliable instrument having good reliability, good content, good acceptability, and good responsiveness, and thus appears to be a valid instrument. Large studies with large sample sizes can be conducted in the future. [ABSTRACT FROM AUTHOR]

In this study the systematic review of trials was carried out to evaluate the prevalence of oral cancer in India. The articles related to the prevalence of Oral Cancer in India were hand searched using electronic databases which includes Prospero, Grey literature, Science Direct, Lilacs, Wiley online library and PubMed. The most common site of Oral cancer in North, East, Central and West zone is Buccal mucosa while in North- east and south zone Tongue is the most affected part. Prevalence rate for Leukoplakia is 37.1%, Speckled leukoplakia is 21.7%, Oral Submucous Fibrosis is 21.1% and Lichen Planus is 19.8%. Highest prevalence can be seen in Males of East zone with 75.7%. The mean age group prevalence is 30- 50 years of age. The study observed a general increase in oral cancer incidence especially in the East Zone. This will pave the path for evidence- based interventions and policies that promote oral health and improve the overall well- being of the population. Indian Government should give importance for the prevention of Oral Cancer by implementing new schemes and providing awareness program to promote the healthy lifestyle and banning of tobacco products. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) is a precancerous condition in the oral cavity, which is closely related to the myofibroblast conversion of buccal mucosal fibroblasts (BMFs) after chronic consumption of areca nut. Emerging evidence suggests pyroptosis, a form of programmed cell death that is mediated by inflammasome, is implicated in persistent myofibroblast activation and fibrosis. Besides, numerous studies have demonstrated the effects of non‐coding RNAs on pyroptosis and myofibroblast activities. Herein, we aimed to target key long non‐coding RNA PVT1 with natural compound, carvacrol, to alleviate pyroptosis and myofibroblast activation in OSF. We first identified PVT1 was downregulated in the carvacrol‐treated fBMFs and then demonstrated that myofibroblast features and expression of pyroptosis makers were all reduced in response to carvacrol treatment. Subsequently, we analysed the expression of PVT1 and found that PVT1 was aberrantly upregulated in OSF specimens and positively correlated with several fibrosis markers. After revealing the suppressive effects of carvacrol on myofibroblast characterisitcs and pyroptosis were mediated by repression of PVT1, we then explored the potential mechanisms. Our data showed that PVT1 may serve as a sponge of microRNA(miR)‐20a to mitigate the myofibroblast activation and pyroptosis. Altogether, these findings indicated that the anti‐fibrosis effects of carvacrol merit consideration and may be due to the attenuation of pyroptosis and myofibroblast activation by targeting the PVT1/miR‐20a axis. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma arising from oral submucous fibrosis is recognized as a clinicopathologically distinct disease. This study aims to summarize and compare the population and clinicopathologic characteristics of OSCC-OSF with other OSCC in Hunan Province, China. The objective is to formulate treatment strategies more in line with regional characteristics. Methods: A retrospective review of OSCC cases recruited from the Second Xiangya Hospital from 2010 to 2020 was conducted. A total of 1,413 OSCC patients were selected, including 481 patients with OSCC-OSF and 932 were other OSCC. Population characteristics, risk factors and clinicopathological manifestations were explored in OSCC-OSF and other OSCC, as well as thinprep cytologic test and DNA quantification. Results: We found that OSCC-OSF patients were younger than those with other OSCC. Both types of disease were predominantly observed in males compared to females. Tumor biopsy analysis indicated that tumor cells within OSCC-OSF patients were more likely to be well differentiated and showed a higher frequency of lymph node metastases. Clinicopathological factors, such as the chewing betel nuts habit and smoking, were more prevalent in OSCC-OSF patients in contrast to other OSCC. DNA quantification revealed that the number of DNA aneuploid cells was higher in OSCC-OSF compared to other OSCCs. Conclusion: In this study, OSCC-OSF is considered a clinicopathologically distinct disease. Compared with other OSCC, OSCC-OSF patients have a higher incidence of nodal metastases, an early clinical TNM stage, and a lower three-year survival rate. Therefore, early diagnosis and treatment are crucial to improving the prognosis of OSCC-OSF. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Key Points Plain Language Summary Betel leaf chewing habit has been studied extensively, as it has been an ancient practice in many Asian countries. Although betel leaf has been reported to have potential beneficial properties, it has also been shown to have a strong association with oral diseases, including periodontitis. This case series addresses the presentation of periodontitis among betel quid users, to help clinicians identify and manage such patients when they are encountered in settings outside the countries and territories where betel quid use is common.Four patients of Asian ethnicity were referred to The Ohio State University College of Dentistry Graduate Periodontology clinic for periodontal treatment. Targeted questioning resulted in all four patients reporting a past and current betel leaf chewing habit, established at a young age, typically in a family setting, and long before their immigration from their native country.All four patients exhibited similar reddish‐brown staining on the teeth and generalized radiographic bone loss. Notably, the patients disclosed the betel chewing habit only after different vernacular names for betel quid were used during questioning, which complicated history taking. Severe periodontitis (stage III/IV, grade C) was diagnosed in all four patients, who were given appropriate periodontal treatment plans.Betel leaf chewing, prevalent in many Asian countries, is associated with periodontitis and may present with extensive tooth staining. Oral healthcare providers should consider this cultural habit and pursue thorough assessment and history taking for their patients originating from countries where the habit is common practice. Clinicians should be aware of the clinical presentation and oral findings in betel quid users. Given the increasing diversity of the patient pool that clinicians are encountering, knowledge of vernacular names for betel quid usage can prove valuable in history taking. A protocol for betel quid cessation should be incorporated into the management strategy for these patients in clinical practice. Clinicians should be aware of the clinical presentation and oral findings in betel quid users.Given the increasing diversity of the patient pool that clinicians are encountering, knowledge of vernacular names for betel quid usage can prove valuable in history taking.A protocol for betel quid cessation should be incorporated into the management strategy for these patients in clinical practice.Betel quid (paan) chewing is a widespread cultural habit, especially in Asia. The chewing of betel quid, whether alone or with tobacco, has been strongly associated with periodontitis and other oral conditions, such as leukoplakia, oral cancer, and oral submucous fibrosis. This report illustrates the typical presentation of periodontitis patients who habitually chew betel quid, highlights the associated clinical features, such as reddish‐brown tooth staining and severe bone loss, and underlines the challenge of obtaining a complete history because of the very many vernacular names used for betel quid in different countries and the fact that for many of the patients, this is considered a routine cultural tradition. It is unusual to encounter patients chewing betel quid in this country because the practice is not common. However, immigrants from countries where betel quid chewing is commonplace may continue the habit after they move to the United States. Oral healthcare providers should be aware of this possibility and elicit the relevant information from the patients. This will help practitioners to properly address this underlying factor and to provide appropriate care to these patients, including cessation advice and support, and establishment of routine oral screenings and regular periodontal maintenance. [ABSTRACT FROM AUTHOR]

Objectives Subjects and Methods Results Conclusions The renin‐angiotensin system (RAS) plays essential roles in cardiovascular and renal function regulation. Recent studies have shown that the RAS components are widely expressed in oral tissues, but their roles in oral diseases remain underexplored. This review aims to summarize the effects of the RAS in select oral diseases including oral squamous cells carcinoma (OSCC), periodontitis, oral submucous fibrosis (OSF), and ageusia/dysgeusia.Data searches were performed using PubMed, Web of Science and Scopus through July 2024. A narrative overview of current literature was undertaken to synthesize the contexts with elaboration and summary.In OSCC, ACE/Ang II/AT1R promotes OSCC by inducing angiogenesis, cell proliferation and invasiveness. Conversely, ACE/Ang II/AT2R and ACE2/Ang (1–7)/MasR inhibit OSCC progressions. In periodontitis, ACE/Ang II/AT1R upregulates inflammatory cytokines and promotes osteoclast differentiation factor RANKL, whereas ACE2/Ang (1–7)/MasR exerts opposite effects by preventing inflammation and alveolar bone loss. In OSF, Ang (1–7) counters the profibrotic and proinflammatory action of Ang II. In dysgeusia, Ang II suppresses salt taste responses and enhances sweet taste sensitivities, while Ang (1–7) exhibits opposite effects.The RAS cascade plays crucial roles in OSCC, periodontitis, OSF and ageusia/dysgeusia. The imbalanced RAS may aggravate the progression of these diseases. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of Kangfuxin liquid combined with triamcinolone acetonide in the treatment of oral submucous fibrous degeneration. Methods: A total of 140 patients with oral submucosal fibrous degeneration admitted to the outpatient clinic of Haiyan County Stomatological Hospital, China from June 2020 to June 2023 were divided equally into study and control groups. The study group received Kangfuxin liquid in addition to 1 mL triamcinolone acetonide (40 mg/mL) while the control group received 1 mL triamcinolone acetonide; therapeutic effects were compared after 4 weeks of treatment. Visual analogue scale (VAS) score, serum transforming growth factor (TGF-ß1), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) levels were determined. Also, whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR), and incidence of adverse reactions were evaluated. Result: The study group showed significantly reduced pain levels compared to the control group, as well as lower mucosal damage areas and improved mouth opening after 4 weeks of treatment compared to control group (p < 0.05). Also, the study group showed significantly lower TGF-ß1, TNF-a and IL-6 compared to control group after treatment (p < 0.05). It showed significantly lower WBV, PV, and ESR compared to control group (p < 0.05). Furthermore, the study group showed significantly lower incidence of adverse reactions than the control group (p < 0.05). Conclusion: Kangfuxin liquid, when combined with triamcinolone acetonide, lowers pain, reduces the levels of STGF-ß1, improves hemorheology, and produces minimal adverse effects compared to triamcinolone alone. Future studies should focus on long-term outcomes to better assess the therapeutic potential of this combined regimen. [ABSTRACT FROM AUTHOR]

Introduction: The estimation of serum bioelements for the identification of oral premalignant and malignant lesions has been extensively studied. Higher amounts of copper have been found in all smoking and Smokeless Tobacco (SLT) products, which are responsible for the higher incidence of premalignant and malignant lesions in the oral cavity. Limited studies have shown the significance and role of salivary bioelements in premalignant lesions, such as Oral Submucous Fibrosis (OSMF) and oral leukoplakia, and malignant lesions like Squamous Cell Carcinoma (SCC) of the oral cavity. Aim: To estimate salivary copper levels in premalignant and malignant lesions of the oral cavity. Materials and Methods: The preent cross-sectional study was undertaken in Tagore Dental College and Hospital in Chennai, Tamil Nadu, India for a period of 6 months, from March 2022 to August 2022. A total of 50 patients were recruited and divided into five groups of 10 patients each: Group I- control group; Group II- SLT chewing habit without any oral lesion; Group III- 10 patients with Tobacco Pouch Keratosis (TPK); Group IV- 10 patients with OSMF; and Group V- 10 patients with oral SCC. About 5 mL of salivary samples were collected and centrifuged at 3000 rpm to obtain the supernatant saliva for analysis. The levels of copper were estimated using photo calorimetry. Statistical analysis was done using One-way Analysis of Variance (ANOVA) followed by a Post-hoc test. Results: A total of 50 patients with a mean age of 40±20 years were included in present study, comprising 46% females and 54% males. There was a statistically significant difference (p <0.05) between the mean salivary copper levels in the premalignant lesions of the oral cavity. Within the premalignant group, copper levels were found to be more in OSMF (Group IV: 296.64±56.08) compared to the other groups (Group II: 202.95±125.14; Group III: 229.25±73.35). In the oral cancer patients, no significant difference (p-value=0.174; not less than 0.001) obtained in salivary copper levels. Conclusion: Compared to the control group, salivary copper levels were significantly higher in cases of OSMF, followed by cases of TPK and non lesional cases. [ABSTRACT FROM AUTHOR]

Objective: The limited understanding of the molecular mechanism for oral submucosal fibrosis (OSF) poses challenges to the development of effective prevention and treatment strategies. The lack of suitable animal models is a major hindrance. Therefore, this study aimed to address this issue by comparing commonly used arecoline‐induced water drinking and injection mouse models. Materials and Methods: The mice were subjected to two protocols: receiving 2 mg/mL arecoline in drinking water and 4 mg/mL arecoline saline solution injections every other day. Tissues were collected at regular 4‐week intervals, with a final time point of 20 weeks. Stereo microscopy and histomorphological analysis were performed on live and harvested tissues, respectively. Results: During arecoline treatment, collagen deposition and myofibroblast proliferation progressively increased in both models. Changes in the collagen I/III ratio indicated that both models exhibited characteristics of the early and intermediate stages of OSF after 20 weeks of arecoline induction. The water‐drinking model also demonstrated multi‐organ fibrosis involving the tongue, lungs, and small intestine. Conclusion: Both the water drinking and injection mouse models effectively induced OSF, but the water‐drinking model better mirrored the observed pathogenesis in patients with OSF. These models provide valuable tools for investigating the mechanisms underlying OSF. [ABSTRACT FROM AUTHOR]

This manuscript critically examines the current classification of oral potentially malignant disorders, questioning the practicality and implications of labeling such a large population as precancerous, given that the actual progression to oral cancer is significantly low for most disorders. The paper advocates for a revised classification system that accurately reflects the varying malignancy risks associated with different disorders. It suggests a reassessment of the diagnostic and management approaches to mitigate overdiagnosis and alleviate patient burdens. We propose categorizing diseases with oral malignant potential as follows: Oral Precancerous Diseases, encompassing high‐risk lesions and conditions like erythroplakia, non‐homogeneous leukoplakia, proliferative leukoplakia, and actinic keratosis; Oral Potentially Premalignant Diseases, covering lesions, conditions, and systemic diseases with distinct oral manifestations harboring a limited or undefined risk of transformation, such as homogeneous leukoplakia, oral submucous fibrosis, oral lichenoid diseases, chronic hyperplastic candidosis, keratosis of known aetiology (smokeless tobacco, khat), palatal lesions in reverse smokers, and dyskeratosis congenita; and Systemic Conditions with Oral Malignant Potential including Fanconi's anemia, xeroderma pigmentosum, and chronic immunosuppression (including patients post‐bone marrow transplantation), which are associated with an increased risk of oral cancer without preceding precursor lesions. We provide illustrative examples to demonstrate how this framework offers practical guidance for research, policy‐making, and clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Background Oral Submucous Fibrosis (OSMF) is an oral potentially malignant disorder (OPMD) that commonly occurs in the South Asian population as there is high usage of areca nut. There has been extensive research on the pathogenesis and treatment of this condition. It is well-established in the scientific literature that mast cells (MC) have a definitive role in several inflammatory disorders. OSMF being a chronic inflammatory disorder, is also expected to have increased MCs. Hence, this review aims to evaluate the role of MCs in the pathogenesis of OSMF. Methods A systematic search of articles was performed by two of the authors independently in PubMed, Scopus, Embase, Web of Science, and Google Scholar using the appropriate keywords and Boolean terms. The risk of bias was assessed using the Modified Newcastle-Ottawa Scale. The meta-analysis was performed with R studio software (Version: 4.4.0, Year: 2024, Company: The R foundation for statistical computing). Results The search retrieved 36 studies, of which 16 were suitable for the review. There is evidence for a marked increase in the number of MCs in OSMF than the normal mucosa upon analyzing the retrieved articles. However, when comparing the grades of OSMF, there are variations in the reports. As all the retrieved articles were case-control studies, the risk of bias was analyzed using the Modified New Castle Ottawa Scale. All the studies scored in the good category (Score 6–9). The pooled effect size shows the Standard Mean Deviation (SMD) to be 0.09, 95% confidence interval (CI) [-0.18;0.37] to lie on either side of no effect. Hence the role of MCs in OSMF has not been established because of homogeneity and consistent sampling error. Conclusion Our systematic review does suggest a definitive role of mast cells in the progression of OSMF. However, there is a lack of methodological rigor in the included studies. This may contribute to diluting the results.

Background/purpose: Oral submucous fibrosis (OSF), characterized by excessive collagen deposition by myofibroblasts, is often linked to Areca nuts consumption. Probiotics consumption has shown protective effects against fibrotic diseases, and recently, their metabolic byproducts, known as postbiotics, have demonstrated superior advantages over probiotics. However, studies on the therapeutic impact of postbiotics on OSF have been scarce. Therefore, this study aims to examine the effect of PostBio GK4, a postbiotic derived from Lactobacillus pentosus GK4, on OSF and explore its underlying mechanisms. Materials and methods: The cytotoxicity of GK4 in normal buccal mucosal fibroblasts (BMFs) and fibrotic BMFs (fBMFs) were assessed. Following this, we evaluated the effects of GK4 on collagen contraction, migratory, and wound healing capacities in arecoline-induced fibrotic BMFs. Next, Western blotting and ELISA were employed to assess GK4's impact on fibrosis-related proteins such as COL1A1, and α-SMA, as well as on TGF-β and Smad2/3 signaling pathway. Results: Arecoline was shown to stimulate cell migratory, contractile and wound healing abilities as well as the expression of α-SMA and COL1A1 in BMFs. Treatment with GK4 reduced all arecoline-induced phenomena in BMFs. Moreover, GK4 diminished the increased expression of TGF-β and Smad2/3. Conclusion: Our findings proposed that GK4 may exert a suppressive effect on arecoline-induced myofibroblast activities via the inhibition of TGF-β and Smad2/3 signaling pathway. Therefore, GK4 holds promise as an adjunct therapeutic approach for intervening in OSF. Further in-vivo and clinical studies are warranted to validate these observations.

Background/purpose: Oral submucous fibrosis (OSF) is a condition characterized by inflammation and excessive collagen deposition, which has been identified as a potentially malignant disorder. Recently, several microRNAs (miRNAs) have been shown to be implicated in various disorders associated with fibrosis. However, how these miRNAs modulate OSF development is poorly understood. Therefore, the study aimed to identify the specific miRNAs that contribute to the progression of OSF and to investigate their molecular mechanisms in promoting fibrosis. Materials and methods: The expression and clinical significance of potential pro-fibrosis miRNA in the OSF cohort and primary buccal mucosal fibroblasts were confirmed through RNA sequencing and qRT–PCR. Luciferase reporter activity assay, miRNA mimic or inhibitor, and short-hairpin RNA silencing were used to elucidate the molecular mechanism of miRNA. Transwell migration, collagen contraction, and reactive oxygen species (ROS) generation detection were used to investigate the effects of this mechanism on the myofibroblast phenotype and cellular pro-fibrosis capacity. Results: This study demonstrated that miR-190a was overexpressed in fibrotic buccal mucosal fibroblasts (fBMFs). Transfecting fBMFs with miR-190a inhibitor resulted in reduced cell migration, collagen gel contraction, ROS generation, and expression of fibrotic markers. Furthermore, miR-190a exerted this pro-fibrosis property by direct binding to its target, Krüppel-like factor 15 (KLF15). The results also indicated that the aberrant upregulation of miR-190a, in turn, downregulated the expression of KLF15, which resulted in the activation of myofibroblast. Conclusion: Our findings demonstrated that miR-190a was involved in myofibroblast activation, suggesting that targeting the miR-190a/KLF15 axis may be a feasible approach in the therapy of OSF.

Abstract Background Oral squamous cell carcinoma arising from oral submucous fibrosis is recognized as a clinicopathologically distinct disease. This study aims to summarize and compare the population and clinicopathologic characteristics of OSCC-OSF with other OSCC in Hunan Province, China. The objective is to formulate treatment strategies more in line with regional characteristics. Methods A retrospective review of OSCC cases recruited from the Second Xiangya Hospital from 2010 to 2020 was conducted. A total of 1,413 OSCC patients were selected, including 481 patients with OSCC-OSF and 932 were other OSCC. Population characteristics, risk factors and clinicopathological manifestations were explored in OSCC-OSF and other OSCC, as well as thinprep cytologic test and DNA quantification. Results We found that OSCC-OSF patients were younger than those with other OSCC. Both types of disease were predominantly observed in males compared to females. Tumor biopsy analysis indicated that tumor cells within OSCC-OSF patients were more likely to be well differentiated and showed a higher frequency of lymph node metastases. Clinicopathological factors, such as the chewing betel nuts habit and smoking, were more prevalent in OSCC-OSF patients in contrast to other OSCC. DNA quantification revealed that the number of DNA aneuploid cells was higher in OSCC-OSF compared to other OSCCs. Conclusion In this study, OSCC-OSF is considered a clinicopathologically distinct disease. Compared with other OSCC, OSCC-OSF patients have a higher incidence of nodal metastases, an early clinical TNM stage, and a lower three-year survival rate. Therefore, early diagnosis and treatment are crucial to improving the prognosis of OSCC-OSF.

Introduction: The estimation of serum bioelements for the identification of oral premalignant and malignant lesions has been extensively studied. Higher amounts of copper have been found in all smoking and Smokeless Tobacco (SLT) products, which are responsible for the higher incidence of premalignant and malignant lesions in the oral cavity. Limited studies have shown the significance and role of salivary bioelements in premalignant lesions, such as Oral Submucous Fibrosis (OSMF) and oral leukoplakia, and malignant lesions like Squamous Cell Carcinoma (SCC) of the oral cavity. Aim: To estimate salivary copper levels in premalignant and malignant lesions of the oral cavity. Materials and Methods: The preent cross-sectional study was undertaken in Tagore Dental College and Hospital in Chennai, Tamil Nadu, India for a period of 6 months, from March 2022 to August 2022. A total of 50 patients were recruited and divided into five groups of 10 patients each: Group I- control group; Group II- SLT chewing habit without any oral lesion; Group III- 10 patients with Tobacco Pouch Keratosis (TPK); Group IV- 10 patients with OSMF; and Group V- 10 patients with oral SCC. About 5 mL of salivary samples were collected and centrifuged at 3000 rpm to obtain the supernatant saliva for analysis. The levels of copper were estimated using photo calorimetry. Statistical analysis was done using One-way Analysis of Variance (ANOVA) followed by a Post-hoc test. Results: A total of 50 patients with a mean age of 40±20 years were included in present study, comprising 46% females and 54% males. There was a statistically significant difference (p

This study is envisioned to assess the structural changes the muscles undergo beneath the submucosal tissues and whether these changes necessitate a novel strategy from the existing conventional modality in the treatment of oral submucous fibrosis (OSMF) medically through a systematic literature survey. Literature search was performed electronically using Medline, EMBASE and CENTRAL databases to identify published literature until the end of April 2024 in dental, oral and maxillofacial surgery, plastic surgery and otolaryngology journals containing the terms "oral submucous fibrosis", "muscles of mastication", "muscles of facial expression", "histopathologic study", "ultrasonographic study", "CT", "MRI" in either their titles, abstracts, and keywords with only English being the preferred language. The data was extracted from the selected articles and prudently studied to gather and compile the data. Descriptive data from all the carefully chosen articles were selected and analysed. Seven studies met the inclusion criteria. It was observed that the masseter muscle was the first to be involved in the disease process of OSMF among the muscles of mastication and facial expression. It was observed that the anterior temporalis and orbicularis oris muscles remained unaffected. However, the buccinator muscle which lies in utmost vicinity is not evaluated in the included studies. The degree of muscle degeneration and the degree of disease progression were directly related to the duration of the habit. The restricted mouth opening noticed in OSMF is not only governed by the subepithelial fibrosis but also on the extent of muscle degeneration. The changes the surrounding muscles undergo could be a manifestation of the disease, atrophy as a sequalae to the limited functional activity of the muscles which is brought about by fibrosis or it could be an essential part of the disease itself. [ABSTRACT FROM AUTHOR]

Background and Aim: Oxidative stress markers have been firmly established as elevated in oral squamous cell carcinomas (OSCCs). These markers play a crucial role in the pathogenic mechanism underlying the accumulation of advanced glycation end products (AGEs) and their respective receptors. The primary objective of this study is to discern and compare the levels of receptors of AGEs (RAGEs) within tissue samples from patients diagnosed with oral submucous fibrosis (OSMF) at varying stages, oral leukoplakia at various stages, and OSCC. Materials and Methods: A cross-sectional investigation was conducted, enrolling a total of 49 patients, distributed across three distinct groups. Tissue samples were meticulously collected from the aforementioned patient groups. Subsequently, these samples underwent a process of homogenization and centrifugation. The supernatant obtained was subjected to enzyme-linked immunosorbent assay analysis to precisely determine the concentration of RAGE. Results: The concentration of RAGEs was found to be significantly higher at various stages of OSMF when compared to the reference group of OSCC (P < 0.05). This difference was statistically significant, indicating a substantial association. In contrast, the levels of RAGE in patients with hyperkeratosis accompanied by epithelial dysplasia at various stages were observed to be lower than those in the OSCC group, with the difference in concentration being statistically insignificant (P > 0.05). Conclusion: This comprehensive study has provided compelling evidence demonstrating the heightened levels of RAGE in OSMF when compared to OSCC. These findings collectively suggest the potential utility of anti-RAGE interventions as a promising avenue for novel therapeutic strategies in potentially malignant disorders such as OSMF.

Background/purpose: Persistent activation of myofibroblasts is attributed to various dysregulated biological events conferring multiple types of fibrosis diseases, including oral submucous fibrosis (OSF). Although the significance of non-coding RNAs (ncRNAs) in the occurrence of fibrosis has been appreciated, the detailed mechanisms still have not been fully elucidated. The aim of this study was to identify key dysregulated ncRNAs and elucidate their pro-fibrotic mechanisms in promoting myofibroblast activation and the pathological development of OSF. Materials and methods: Expression of non-coding RNAs and mRNAs in OSF cohort was determined using RNA sequencing and qRT-PCR. The molecular axis of pro-fibrotic ncRNAs were exploited via luciferase reporter activity assay and RNA expression rescue experiments. Functional assays, including collagen gel contraction, wound healing ability, cell migration, and reactive oxygen species (ROS) production, were conducted to assess the changes in the myofibroblastic phenotypes of primary human buccal mucosal fibroblasts. Results: Herein, we found that long non-coding RNA MetaLnc9 was upregulated in OSF specimens and positively associated with several fibrosis markers. Silencing of MetaLnc9 diminished the features of activated myofibroblasts and the production of ROS. We not only showed that MetaLnc9 functioned as a competitive endogenous RNA of microRNA (miR)-143, but also demonstrated that the pro-fibrosis effect of MetaLnc9 on myofibroblast activities was mediated by suppression of miR-143. Moreover, our data showed that fascin actin-bundling protein 1 (FSCN1) was a direct target of miR-143 and positively related to MetaLnc9. Conclusion: Upregulation of MetaLnc9 may enhance the activation of myofibroblasts by sponging miR-143 and titrating its inhibitory property on FSCN1.

Background/purpose: Oral submucous fibrosis (OSF) affecting populations is considered a public health issue in South/Southeast Asia. The purpose of this study was to analyze the scientometric characteristics and research trends of OSF. Materials and methods: All the papers on OSF were comprehensively retrieved from the Scopus database. Regional comparison (India versus outside of India) and chronological comparison (before 2015 versus after 2015) were performed. Results: Among all the 1357 papers on OSF, 930 (68.5%) were from India. In India, biology research on antioxidant, oxidative stress, angiogenesis, and extracellular matrix were distinctive keywords. Risk factors of smokeless tobacco and gutkha and the roles of saliva and blood sampling were also distinctive keywords in India. In outside of India, biology research on myofibroblast, alpha smooth muscle actin, microRNA, long untranslated RNA, and protein p53 were distinctive keywords. The trend of biology research on connective tissue, genotype, genetic predisposition, messenger RNA, and cytology before 2015 has changed to research on myofibroblast, biological marker, microRNA, epithelial mesenchymal transition, extracellular matrix, and oxidative stress after 2015. The trend of clinical aspects of surgery and mouth hygiene before 2015 has changed to the aspects of adverse event/effects, complication, and quality of life after 2015. Conclusion: This scientometric study elucidated the current scenario and research trends of OSF, and would help in improving in reciprocal collaboration and communication for this disease control in South/Southeast Asia.

Background: Oral submucous fibrosis (OSMF) is an insidious chronic inflammatory progressive disease and one of the potentially malignant disorders, predominantly affecting the oral cavity. Objective: The current study aimed to compare the efficacy of curcumin and aloe vera along with ultrasound in the management of OSMF. Materials and Methods: In this intervention study, 40 participants with OSMF were allocated into two groups. Group A included 20 patients who received curcumin (curenext) oral gel for 3 months along with ultrasound therapy. Group B included 20 patients who received aloe vera gel (forever living gel) along with ultrasound therapy. Results: Following therapies, patients in the group A showed clinically significant improvements when compared to group B. Conclusion: The combined therapy of curcumin and ultrasound shows potential in managing OSMF by effectively alleviating clinical symptoms without any reported side effects. It is advised that future studies employ larger samples and longer treatment follow-up.

Abstract Oral submucous fibrosis (OSF) is a chronic, progressive condition affecting the oral mucosa associated with areca nut consumption. It leads to restricted tongue movement, loss of papillae, blanching and stiffening of the mucosa, difficulty in opening the mouth, and challenges in eating due to inflammation and fibrosis. This report presents a rare case of oropharyngeal stenosis secondary to OSF in a 43-year-old male with a history of chewing betel nut. A surgical procedure similar to Uvulopalatopharyngoplasty was performed to excise the submucous oropharyngeal stenosis and to reconstruct the uvula, palatoglossal arch, and palatopharyngeal arch. At 8 years postoperatively, the patient exhibited a normal mouth opening and oropharyngeal aperture.

Introduction: Oral submucous fibrosis (OSMF) is a chronic, mild, possibly malignant condition (OPMD) that primarily affects South Asian people, affecting the oral cavity and oropharynx. Clinically, trismus, restricted tongue protrusion, burning mouth, marble-like oral mucosa appearance, xerostomia, recurrent ulceration, atrophy of the tongue papillae, and palpable fibrous bands are among the symptoms and indicators of OSMF. The present study was undertaken to determine the salivary levels of oxidative stress biomarkers malondialdehyde, 8-hydroxy-2-deoxyguanosine and 8-isoprostane levels and antioxidants glutathione peroxidase and superoxide dismutase in patients with different grades of OSMF. Methodology: The observational cross-sectional study was conducted in the department of Biochemistry NIMS&R, Jaipur in association with Oral Diagnosis and Radiology at College of Dental Sciences and Research Centre, Manipur, Ahmedabad (Gujarat) after obtaining institutional ethical committee clearance. The Study population consisted of Clinically diagnosed oral submucous fibrosis patients of age 18-45 years. Unstimulated Saliva was allowed to accumulate in the floor Of mouth and collected by drooling method in a test tube. Saliva samples will be stored at -20 °C until use. Malondialdehyde was estimated by thiobarbituric acid reaction using spectrophotometer, 8-hydroxy-2-deoxyguanosine was analysed by sandwich ELISA, Glutathione peroxidase and Superoxide dismutase were analysed by spectrophotometer and 8-Isoprostane was estimated by ELISA. Results: The present study included a total of 92 patients clinically diagnosed with oral submucosal fibrosis. It is seen that out of 92 patients, 53 were males and 39 were females accounting for 57.6% and 42.39% respectively. The mean age in years in males and females were 28.97±5.80 and 32.39±3.77 years respectively. The mean levels of oxidative stress markers were significantly increased and antioxidant levels were significantly decreased as OSMF advances. Pairwise comparison of mean values of salivary oxidative stress and antioxidant biomarkers were performed using post hoc analysis by Tukey test. Table 4 displays an almost highly significant (P<0.001) difference between the mean values of all the salivary biomarkers when compared pairwise. However, a significant difference (P=0.001) was found between Grade 2 vs Grade 3 for 8-Isoprostane. The mean difference between pair Grade 3 vs Grade 4 was found to be not significant for salivary Glutathione Peroxidise and salivary 8- isoprostane having P values of 0.52 and 0.41, respectively. Conclusion: The results of our study showed that the concentration of MDA, isoprostane, 8- Hydroxydeoxy-guanosine levels were increased significantly as the clinical stage and histopathological grade of OSMF advances suggesting these biomarkers can be used as a reliable biochemical marker and also a prognostic marker to assess the extent of oxidative damage in OSMF. The concentration of antioxidant enzymes showed progressive decline as OSMF advances, indicating the potential role of supplementation of antioxidants in these patients to decrease the progression of the disease. [ABSTRACT FROM AUTHOR]

Background: Pathogenesis and malignant potential of Oral submucous fibrosis(OSMF) have always been a topic of interest among the researchers. Despite OSMF being a collagen metabolic disorder, the alterations occurring in the connective tissue stroma affects the atrophic surface epithelium in later stages and progresses to malignant phenotypes. The present review aims to summarize the role of stem cells in the pathogenesis and malignant transformation of oral submucous fibrosis. Materials and Methods: A literature search was carried out using data banks like Medline and Embase, google scholar and manual method with no time frame, pertinent to the role of mucosal stem cells in OSMF and its malignisation. The relevant literature was reviewed, critically appraised by all the authors and compiled in this narrative review. Results: Critical appraisal and evaluation of the data extracted from the selected articles were compiled in this review. The collated results highlighted the upregulation and downregulation of various stem cell markers during the progression and malignisation of OSMF were depicted in a descriptive and detail manner in the present review. Conclusion: We highlight the potential of mucosal stem cells in the regulation and malignisation of OSMF. However, future large-scale clinical studies will be needed to support whether manipulation of this stem cells at molecular level will be sufficient for the treatment and preventing the malignant transformation of OSMF. [ABSTRACT FROM AUTHOR]

Background: circRNAs have been shown to participate in diverse diseases; however, their role in oral submucous fibrosis (OSF), a potentially malignant disorder, remains obscure. Our preliminary experiments detected the expression of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF tissues (n = 20) and normal mucosa tissues (n = 20) collected from Hunan Xiangya Stomatological Hospital, and a significant decrease of circMTO1 expression was showed in OSF tissues. Therefore, we further explored circMTO1 expression in OSF. Methods: Target molecule expression was detected using RT‐qPCR and western blotting. The migration and invasion of buccal mucosal fibroblasts (BMFs) were assessed using wound healing and Transwell assays. The interaction between miR‐30c‐5p, circMTO1, and SOCS3 was evaluated using dual luciferase, RNA immunoprecipitation (RIP), and RNA pull‐down assays. The colocalisation of circMTO1 and miR‐30c‐5p was observed using fluorescence in situ hybridisation (FISH). Results: circMTO1 and SOCS3 expression decreased, whereas miR‐30c‐5p expression increased in patients with OSF and arecoline‐stimulated BMFs. Overexpression of circMTO1 effectively restrained the fibroblast–myofibroblast transition (FMT), as evidenced by the increase in expression of Coll I, α‐SMA, Vimentin, and the weakened migration and invasion functions in BMFs. Mechanistic studies have shown that circMTO1 suppresses FMT by enhancing SOCS3 expression by sponging miR‐30c‐5p and subsequently inactivating the FAK/PI3K/AKT pathway. FMT induced by SOCS3 silencing was reversed by the FAK inhibitor TAE226 or the PI3K inhibitor LY294002. Conclusion: circMTO1/miR‐30c‐5p/SOCS3 axis regulates FMT in arecoline‐treated BMFs via the FAK/PI3K/AKT pathway. Expanding the sample size and in vivo validation could further elucidate their potential as therapeutic targets for OSF. [ABSTRACT FROM AUTHOR]

Aim: To estimate and compare the level of serum immunoglobulin A in patients of oral submucous fibrosis (OSMF), leukoplakia, and control group. Introduction: OSMF is a well‑recognized potentially malignant condition in the oral cavity, and a transformation rate as high as 7.6% over a period of 10 years has been reported from India. Leukoplakia has evolved as a clinico‑pathologic concept over many years, with the current clinical designation being accepted worldwide. Materials and Methods: Quantia IgA is a turbidometric immunoassay for the detection of IgA in human serum and is based on the principle of agglutination reaction. The test specimen is mixed with the activation buffer (R1) and then with antihuman IgA reagent (R2) and allowed to react. For the estimation of serum IgA, 500 μl of Quantia IgA activation buffer R1 is taken in a clean test tube. Serum sample is diluted in the ratio of 1:5 with normal saline. Ten microliters of diluted serum sample are added to R1. After incubation for 10 min, 50 μl of R2 is added, which is Quantia IgA antihuman IgA reagent to the sample, and the reading is recorded at wavelength 340 nm at 37°C. The level of IgA will be estimated by a semi‑automatic biochemical analyzer machine and then data analysis will be done. Results: The immunologic alterations observed by us in OSMF and leukoplakia are almost similar or nearer to the alterations observed in oral cancer, so it is reasonable to assume that OSMF and leukoplakia can be an intermediate stage in the transformation process of a normal cell to oral malignancy. Conclusion: Prevention and early detection is the best way to reduce the incidence and mortality of premalignant disorders and oral cancer. There are many ways and methods of early detection of premalignant disorders and oral cancer, and the immunological method is one of them. [ABSTRACT FROM AUTHOR]

Habitual consumption of areca/betel nut in Southeast Asia has been associated with oral submucous fibrosis (OSMF) and its malignant transformation to oral squamous cell carcinoma. The current study aimed to assess the molecular alterations in fibroblast cell lines after treatment with areca nut. Areca nut extract (ANE) was prepared and characterized for its active ingredient, arecoline. ANE‐treated cells were subjected to cell viability, proliferation, migration, morphologic changes, and transcript of OSMF genes (col1a1, col1a2, hsp47, timp1, timp2, timp3, and timp4). Further, liquid chromatography–mass spectrometry (LCMS) of cell lysate and Raman microspectroscopy (RMS) of fixed cells were performed for metabolomics/lipidomics and biomolecular alterations in the nucleus and periphery of ANE‐treated cells. We compared and integrated the data from both techniques and observed that the cells treated with ANE mimicked OSMF and could be used as an in vitro model. LCMS showed a significant alteration in 17 metabolites and 165 lipid molecules in the cells treated with ANE. Further, 40 molecules in the nucleus and 29 in the periphery were found to be altered in these cells when subjected to RMS. Molecules associated with pathways such as the transfer of acetyl groups into mitochondria, amino sugar metabolism, and the Warburg effect were modulated the most upon ANE treatment. Acetyl CoA was found to be common in most of the altered pathways. Besides, the pathways affecting carbohydrate metabolism were also altered significantly. Targeting these molecules and pathways can help to prevent the malignant transformation of OSMF. [ABSTRACT FROM AUTHOR]

A condition called Oral Submucous Fibrosis (OSMF) primarily affects the Indian subcontinent. It is characterised by abnormal collagen deposition and fibrosis of submucosal tissue that progresses over time. Chewing betel nut is the most prevalent behaviour among Oral Submucous Fibrosis (OSMF) patients, with a 6.3% prevalence rate. Symptoms include ulceration, burning sensation, xerostomia, and limited mouth opening. According to the Brihatrayi (three main classical books), OSMF is associated with sarvasaramukharoga, or disorders of the oral cavity. Tobacco, lime, chilies, betel nuts, and other substances act as irritants and can damage the oral mucosa. Treatment methods include Gandusha (oil pulling), Pittashamaka, yoga, Nasya (nasal drops), Pratisarana (rubbing), etc. The present review was conducted to assess and evaluate the potential efficacy of Tulsi-turmeric oil pulling as a complementary or alternative therapy in managing OSMF. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) affecting populations is considered a public health issue in South/Southeast Asia. The purpose of this study was to analyze the scientometric characteristics and research trends of OSF. All the papers on OSF were comprehensively retrieved from the Scopus database. Regional comparison (India versus outside of India) and chronological comparison (before 2015 versus after 2015) were performed. Among all the 1357 papers on OSF, 930 (68.5%) were from India. In India, biology research on antioxidant, oxidative stress, angiogenesis, and extracellular matrix were distinctive keywords. Risk factors of smokeless tobacco and gutkha and the roles of saliva and blood sampling were also distinctive keywords in India. In outside of India, biology research on myofibroblast, alpha smooth muscle actin, microRNA, long untranslated RNA, and protein p53 were distinctive keywords. The trend of biology research on connective tissue, genotype, genetic predisposition, messenger RNA, and cytology before 2015 has changed to research on myofibroblast, biological marker, microRNA, epithelial mesenchymal transition, extracellular matrix, and oxidative stress after 2015. The trend of clinical aspects of surgery and mouth hygiene before 2015 has changed to the aspects of adverse event/effects, complication, and quality of life after 2015. This scientometric study elucidated the current scenario and research trends of OSF, and would help in improving in reciprocal collaboration and communication for this disease control in South/Southeast Asia. [ABSTRACT FROM AUTHOR]

Persistent activation of myofibroblasts is attributed to various dysregulated biological events conferring multiple types of fibrosis diseases, including oral submucous fibrosis (OSF). Although the significance of non-coding RNAs (ncRNAs) in the occurrence of fibrosis has been appreciated, the detailed mechanisms still have not been fully elucidated. The aim of this study was to identify key dysregulated ncRNAs and elucidate their pro-fibrotic mechanisms in promoting myofibroblast activation and the pathological development of OSF. Expression of non-coding RNAs and mRNAs in OSF cohort was determined using RNA sequencing and qRT-PCR. The molecular axis of pro-fibrotic ncRNAs were exploited via luciferase reporter activity assay and RNA expression rescue experiments. Functional assays, including collagen gel contraction, wound healing ability, cell migration, and reactive oxygen species (ROS) production, were conducted to assess the changes in the myofibroblastic phenotypes of primary human buccal mucosal fibroblasts. Herein, we found that long non-coding RNA MetaLnc9 was upregulated in OSF specimens and positively associated with several fibrosis markers. Silencing of MetaLnc9 diminished the features of activated myofibroblasts and the production of ROS. We not only showed that MetaLnc9 functioned as a competitive endogenous RNA of microRNA (miR)-143, but also demonstrated that the pro-fibrosis effect of MetaLnc9 on myofibroblast activities was mediated by suppression of miR-143. Moreover, our data showed that fascin actin-bundling protein 1 (FSCN1) was a direct target of miR-143 and positively related to MetaLnc9. Upregulation of MetaLnc9 may enhance the activation of myofibroblasts by sponging miR-143 and titrating its inhibitory property on FSCN1. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) is an oral condition characterized by chronic progression, which may lead to the development of malignancy. Currently, available treatments for OSF only provide temporary relief of symptoms, and there is a limited availability of effective interventions that can effectively cure this condition. In this study, we aimed to investigate whether adiponectin (APN) could ameliorate OSF and the mechanisms involved in it. First, human oral mucosal fibroblasts (HOMFs) were cultured, an OSF model was established using arecoline, and APN and Imiquimod treatment were administered. Then we overexpressed NLRP3 and knocked down FOXO3A. FOXO3A, fibrosis-related factors (ɑ-SMA, COL1A, CTGF), TGF-β1/Smad3 signaling-related factors (TGF-β1, p-Smad3, Smad3), NLRP3 inflammasome-related factors (NLRP3, Caspase-1, IL-1β), and ROS levels were evaluated. Finally, we explored the effect of APN on OSF in mice by in vivo experiments. We found that arecoline significantly increased ɑ-SMA, COL1A, CTGF, and TGF-β1 expressions and promoted Smad3 phosphorylation, while APN significantly inhibited the elevation of these fibrosis-related factors. ROS production was significantly elevated in HOMFs after arecoline treatment, while APN treatment inhibited ROS production. However, the addition of Imiquimod and overexpression of NLRP3 exhibited a trend of elevated ROS, resisting the inhibitory effect of APN. Furthermore, adding Imiquimod and overexpression of NLRP3 elevated ɑ-SMA, COL1A and CTGF and activated TGF-β1/Smad3 signaling pathway. Additionally, knockdown of FOXO3A enhanced APN-inhibited ɑ-SMA and COL1A. In vivo experiments further confirmed that APN ameliorated OSF in mice by inhibiting ROS/NLRP3 inflammatory pathway. In conclusion, APN ameliorated arecoline-induced OSF by promoting FOXO3A expression and downregulating the ROS/NLRP3 pathway. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) is a chronic, progressive condition affecting the oral mucosa associated with areca nut consumption. It leads to restricted tongue movement, loss of papillae, blanching and stiffening of the mucosa, difficulty in opening the mouth, and challenges in eating due to inflammation and fibrosis. This report presents a rare case of oropharyngeal stenosis secondary to OSF in a 43-year-old male with a history of chewing betel nut. A surgical procedure similar to Uvulopalatopharyngoplasty was performed to excise the submucous oropharyngeal stenosis and to reconstruct the uvula, palatoglossal arch, and palatopharyngeal arch. At 8 years postoperatively, the patient exhibited a normal mouth opening and oropharyngeal aperture. [ABSTRACT FROM AUTHOR]

This article discusses the use of Raman spectroscopy in diagnosing oral cancers and predicting their recurrence. The study found that serum Raman spectroscopy was effective in identifying individuals at risk of oral cancer recurrence, with an efficiency of approximately 80%. Additionally, both salivary and serum Raman spectroscopy successfully distinguished individuals with oral premalignant diseases, such as leukoplakia and oral submucous fibrosis, with an efficiency of over 75%. The study also investigated the potential of Raman spectroscopy in urine samples for detecting oral cancers. Overall, the findings suggest that Raman spectroscopy of various biological fluids shows promise as a means for early detection, recurrence prediction, and classification of oral potentially malignant disorders. [Extracted from the article]

To evaluate the incidence of tobacco-related oral mucosal lesions in the adult population visiting ENT-OPD at Shri Maharaja Gulab Singh Hospital, GMC Jammu, India. From December 2021 to November 2022 we attempted to compile the prevalence of tobacco-induced oral mucosal lesions in the adult population visiting ENT-OPD at Shri Maharaja Gulab Singh Hospital Jammu, India. The study included a total of 400 patients of various age groups. The patients were divided as current users with a habit of tobacco consumption for atleast 6 months and ex-users who had used any form of tobacco in their lifetime for a minimum of 6 months but had abstained the use since last 1 year. Age group, gender, employment, type of tobacco use, site of placement of tobacco in the oral cavity, frequency and duration of use, and the types of mucosal lesions were all documented on a standardized interviewer-based questionnaire.The oral mucosal lesions were diagnosed in accordance with international recommendations. Males (55%) had somewhat more oral mucosal lesions than females (45%). Oral submucous fibrosis was found in 110 individuals, followed by leukoplakia in 102, erythroplakia in 14, tobacco pouch keratosis in 81, tobacco induced melanosis in 82 patients and malignancy in 11 patients. 107 conventional smokers (26.75%), 254 patients using smokeless tobacco (63.5%) and 39 patients using combined form of tobacco (9.75%) showed oral mucosal lesions. The most prevalent site of lesions was the labial comissure, which showed 117 lesions (29.25%), followed by 114 lesions on the buccal mucosa (28.5%), and 99 lesions (24.75%) on buccal sulcus. Gingiva showed 41 lesions (10.25%), tongue had 15 entities (3.75%) and palate had 14 (3.5%). The most frequent oral mucosal lesion was shown to be oral submucous fibrosis, followed by leukoplakia. Smokeless tobacco was the most commonly used tobacco product. This study emphasizes the need of routine evaluation of the oral mucosa and the need for patients to be urged to stop this hazardous behavior. [ABSTRACT FROM AUTHOR]

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. 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. 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. • Oral submucous fibrosis (OSF) be recognized as Areca nut-induced Oral Fibrosis (AIOF). • AIOF is distinctive and must be distinguished from other forms of oral fibrosis. • Areca nut as the primary causative agent of OSF justifies the redesignation of OSF. • Diagnosis of AIOF is crucial for making informed treatment decisions and management. [ABSTRACT FROM AUTHOR]

Introduction: A prospective study was conducted to find out an effective alternative in the form of non-vascularized abdominal dermal fat graft (ADFG) and to compare its efficacy with the vascularised nasolabial flap (NLF) for the treatment of oral submucous fibrosis (OSMF). Method: Comparative study comprising of 30 patients with Grade 3 and 4A OSMF, randomly divided into 2 groups: Group A (ADFG) and Group B (NLF). They were evaluated for mouth opening (MO), graft uptake, time taken for mucosalization, pain, intercommissure distance (ICD), scar, duration of surgery (DOS), patient satisfaction and thickness of masseter muscle on ultrasonography. Findings.: At 6 months, MO improved by 22.4 and 36.2 mm in Group A and Group B, respectively. There was statistically significant difference (p < 0.05) seen for the values between the groups for all the parameters except for ICD and VAS score, which was statistically insignificant (p > 0.05). Intraoral hair growth, facial scar, orocutaneous fistula and commissure tear was seen in Group B. Complete necrosis of graft followed by recurrence was seen in three cases in Group A. Conclusion: NLF holds better as compared to ADFG in the management of OSMF. However, the cornerstone of success remains habit cessation and aggressive physiotherapy. The limitations of the study are small sample size and short duration of follow-up. [ABSTRACT FROM AUTHOR]

Background Oral potentially malignant disorders (OPMDs) not only harbour the risk of malignant transformation but can also affect patients’ quality of life owing to severe symptoms. Therefore, there is an urgent need for therapeutic strategies to improve patients’ quality of life. The objective of this meta-analysis was to comprehensively assess the efficacy of curcumin in the management of OPMDs. Methods PubMed, Embase, the Cochrane Library, and Web of Science were searched for clinical trials evaluating the efficacy of curcumin in the treatment of OPMDs from inception until March 2024. RevMan 5.4 software was used to perform statistical and subgroup analyses. Results Sixteen randomised controlled trials (1,089 patients) were selected. Curcumin exhibited comparable efficacy to conventional controls in alleviating pain (I2 = 98%, P = 0.49) and improving tongue protrusion (I2 = 94%, P = 0.51) in oral submucous fibrosis (OSF). Additionally, topical use of curcumin had an efficacy equivalent to that of conventional therapy in reducing pain (I2 = 83%, P = 0.31) and facilitating clinical remission (I2 = 67%, P = 0.38) of oral lichen planus (OLP). Conclusion The topical use of curcumin may palliate pain and promote clinical healing in OLP patients. Systemic curcumin can ameliorate the degree of pain and tongue protrusion in OSF. Therefore, our study suggests that curcumin could serve as an alternative treatment for managing OPMDs with lower medical toxicity than steroids, especially when steroids are not suitable. Further studies with larger sample sizes and adequate follow-up periods are required to validate our results.

Purpose The aim is to offer a comprehensive overview of oral submucous fibrosis (OSF) prevalence and explore its epidemiological characteristics across various demographic groups and geographical locations, thereby helping the formulation of public health management policies. Methods Studies reporting OSF prevalence were identified from electronic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, EMBASE via OVID, and Web of Science. Pooled prevalence and quality assessment using the New-Ottawa Scale were conducted. Two reviewers screened and selected records, assessed quality, and independently extracted data. This systematic review and meta-analysis followed the PRISMA guidelines and was registered on PROSPERO (CRD42024532975). Results Sixty-three studies, encompassing 11,434 cases in a total population of 769,860, reported OSF prevalence. The majority of studies (forty-one) were from India. The pooled prevalence of OSF across all populations was 3.0% (95% CI [2.8–3.2]%). In non-risk populations, risk populations, and consecutive dental patients, the pooled prevalence stood at 2.4% (95% CI [2.1–2.6]%), 4.5% (95% CI 3.5-5.6%), and 5.6% (95% CI [3.8–7.5]%), respectively. Subgroup analysis by age, sex, and geographical region revealed higher prevalence rates among those aged 50 and above (4.2%, 95% CI [3.0–5.4]%), males (3.3%, 95% CI [2.9–3.7]%), and in India (4.0%, 95% CI [3.7–4.3]%). As the exposure to risk factors exceeded 50% in the surveyed population, the prevalence of OSF notably increased. Most studies met satisfactory quality standards. Conclusions Our research findings reveal a comprehensive prevalence of OSF across all populations at 3.0% (95% CI [2.8–3.2]%). And, existing evidence indicates a relatively low prevalence of OSF associated with tobacco, alcohol, and Areca (betel) nut use. However, further large-scale studies are recommended to validate these findings. Understanding the prevalence and distribution patterns of OSF may assist in healthcare intervention planning and alleviate the oral cancer burden associated with OSF.

Objective Oral submucous fibrosis (OSMF) is a chronic progressive disorder of the oral cavity characterized by an increased malignant transformation rate. Understanding the pathogenetic components is crucial for the design and development of effective targeted therapies. Interleukins are a group of cytokines found to be altered in many fibrotic disorders of the oral cavity. Their signature in OSMF, especially at the tissue level, will help unveil novel pathogenesis and help in better understanding the disease. Method For the current study, a total of 21 OSMF and 10 healthy participants were enrolled, and tissue samples were collected by incisional biopsy. The LEGENDplex™ Human Cytokine Panel 2 kit was used for the analysis of the cytokines with the help of flow cytometry. Interleukins analyzed included IL-1α, IL-1β, IL-12p40, IL-12p70, IL-15, IL-17, IL-18, IL-23, IL-27, and IL-33. Results According to the study results, interleukin levels significantly increased during the early and late stages of the disease. IL-1α, IL-1β, IL-18, and IL-33 showed significant upregulation. Other interleukins such as IL-12p40, IL-12p70, IL-15, IL-17, IL-23, and IL-27 exhibited downregulation in late-stage OSMF. Conclusions This study aids in associating the dynamics of cytokines with the stage of the disease, thus providing a comprehensive understanding of the individual effect of the cytokines on the progression.