Submucous Fibrosis Research Articles

Oral submucous fibrosis (OSF) is a precancerous condition primarily caused by arecoline in betel nuts. The transforming growth factor (TGF)-β/mothers against decapentaplegic homolog 3 (Smad3) signaling pathway plays a pivotal role in its pathogenesis. This study explores the interaction between tropomyosin-1 (TPM1) and STIP1 homology and U-Box-containing protein 1 (STUB1) in regulating this pathway and its impact on OSF progression. We found that arecoline dose and time-dependently upregulates the expression of TPM1 mRNA and protein in human oral fibroblasts (HOrF). Treating HOrF with 20μg/mL arecoline for 48h could effectively drive fibroblast proliferation, fibrosis, migration and invasion. TPM1 knockdown reversed these effects. Mechanistically, arecoline upregulates TPM1 by activating the TGF-β/Smad3 signaling pathway. Notably, TPM1 overexpression rescued TGF-β/Smad3 activity even in the presence of the TGF-β inhibitor SB431542, revealing a positive feedback loop. Additionally, Western blotting and co-immunoprecipitation (Co-IP) analyses showed that arecoline downregulates STUB1, thereby inhibiting the ubiquitination of TGF-β/Smad3 in HOrF. Meanwhile, TPM1 competitively binds to STUB1, blocking its interaction with TGF-β/Smad3 and thereby stabilizing the pathway, which exacerbates fibrosis. Statistical analysis (one-way ANOVA with Tukey's HSD post-hoc test or independent-samples t-test) confirmed the significance of all major findings (p < 0.05). In conclusion, activation of the TGF-β/Smad3 pathway upregulates TPM1, which in turn blocks STUB1-mediated ubiquitination of the same cascade, establishing a positive-feedback loop that exacerbates arecoline-induced OSF. These findings improve our understanding of OSF's molecular pathogenesis and offer a potential target for its prevention and treatment.

Comparison of Efficacy of Tablet Rebamipide vs. Intralesional Triamcinolone and Hyaluronidase Injection for Treatment of Oral Submucous Fibrosis: A Randomized Clinical Study

Microbial signatures of areca nut chewing: Bridging the gap between oral dysbiosis and submucous fibrosis.

Oral submucous fibrosis (OSF), a potentially malignant disorder, is strongly linked to areca nut consumption, with arecoline inducing epithelial-mesenchymal transition (EMT) in fibroblasts. Therfeore, it is of interest to investigate EMT marker expression in OSF fibroblasts exposed to arecoline and assessed the inhibitory effects of curcumin and epigallocatechin-3-gallate (EGCG). Primary fibroblasts from OSF and normal mucosa were treated and EMT markers were analyzed by RT-qPCR, Western blotting and wound healing assays. Arecoline decreased E-cadherin and increased N-cadherin, vimentin, α-SMA, Snail, Twist and migration rate, whereas co-treatment with curcumin or EGCG significantly reversed these effects, with curcumin showing greater efficacy. Thus, we show that curcumin and EGCG inhibit arecoline-induced EMT and may serve as potential therapeutic agents in OSF management.

Oral and oropharyngeal malignancies, OSCC accounts for 95% of cases. Diagnosis and prognosis of OSCC relies upon the tumour staging, an important predictor of survival. Therefore, it is of interest to evaluate the changes in the salivary levels of IL-8 and LDH among Tobacco users without lesions, Individuals with Leukoplakia, Oral submucous fibrosis and OSCC. 40 cases were analysed in this study. We show that salivary IL8 and LDH which can serve as one reliable biomarker in early detection of OSCC and a prognostic indicator for OPMDs.

Curcumin suppresses EMT to alleviate oral submucous fibrosis progression through XIST/miR-25-3p-mediated inactivation of the TGF-β1/Smads signalling pathway.

INTRODUCTION. The review aimed to evaluate the therapeutic efficacy of holy basil (ocimum sanctum) in managing oral submucous fibrosis (OSMF), focusing on its impact on clinical symptoms such as burning sensation, mouth opening, tongue protrusion, cheek flexibility, blanching, and fibrosis. MATERIALS AND METHODS. A comprehensive search was conducted across PubMed-Medline, Scopus, Embase, Cochrane Library and Google Scholar from the earliest available date upto 5 th April, 2025. Studies included were randomized controlled trials (RCTs) and observational studies involving patients diagnosed with OSMF, assessing the efficacy of holy basil in any formulation (such as extract or oil) on clinical symptoms. Both Two reviewers independently performed data extraction and quality assessment using the Cochrane RoB 2.0 and ROBINS-I tools. Where appropriate, a metaanalysis (MA) was performed, where summarized raw mean (MRAW) standardized mean differences (SMDs) were calculated. RESULTS. A total of 7 studies met the inclusion criteria, comprising 5 observational and 2 experimental studies conducted in India between 2017 and 2023. The MA demonstrated significant improvements in maximal mouth opening with MRAW = 36.14 mm; 95% confidence interval [CI]: 22.3–49.98) and reduction in burning sensation (SMD = 2.6; 95% CI: 1.94–3.25) in patients receiving holy basil-based treatments. Substantial heterogeneity was noted for mouth opening outcomes (I 2 = 96%), whereas the results for burning sensation were relatively consistent across studies (I 2 &lt; 50%). Secondary outcomes, such as cheek flexibility, were reported in only one study, restricting broader generalization. CONCLUSIONS. The findings suggest that Holy Basil, administered in various formulations, shows promising potential in improving key clinical symptoms such as maximal mouth opening, burning sensation, and tongue protrusion.

Background: Oral mucosal lesions (OMLs) are an important clinical and public health concern due to their association with high-risk habits, potential malignant transformation, and impact on quality of life. South Asia, particularly Pakistan, carries a disproportionate burden, driven largely by smokeless tobacco, areca nut (Areca catechu), and betel quid consumption. Objective: This study aimed to determine the prevalence and distribution of OMLs among patients visiting Qamar Dental Hospital in Karachi and to assess associations with demographic and behavioral risk factors. Methods: A cross-sectional study was conducted from February 2024 to February 2025, enrolling 1,236 patients. Comprehensive intraoral examinations were performed using World Health Organization (WHO) criteria, with incisional biopsy and histopathological examination in clinically ambiguous cases. Data were analyzed for prevalence, age- and gender-specific distribution, and associations with risk factors. Results: OMLs were diagnosed in 384 patients (31.1%). The most frequent lesions were oral leukoplakia (18.5%), oral submucous fibrosis (14.6%), oral lichen planus (12.0%), traumatic ulcerations (11.5%), and oral candidiasis (10.4%). Males had a higher prevalence of leukoplakia and submucous fibrosis, while females more often presented with oral lichen planus and candidiasis. Patients aged ≥40 years exhibited significantly higher rates of potentially malignant disorders (PMDs). Tobacco chewing, areca nut/betel quid use, and cigarette smoking were strongly associated with OMLs (p &lt; 0.05). Conclusion: The results highlight a significant load of OMLs in Karachi, where with a high prevalence of potentially malignant disorders that are associated with high-risk preventable habits. Dental clinics form an important point of opportunistic screening, behavioral counseling, and early therapeutic intervention, thus averting the risk of developing malignant transformation into oral squamous cell carcinoma and enhancing overall oral health outcomes

Oral submucous fibrosis is a chronic oral disease with malignant potential. This study assessed survival outcomes and cervical lymph node metastasis in patients with oral squamous cell carcinoma arising from oral submucous fibrosis in central China. 84 patients with carcinoma arising from oral submucous fibrosis treated between 2005 and 2019 were retrospectively reviewed and compared with 84 stage-matched patients with oral squamous cell carcinoma unrelated to oral submucous fibrosis. Clinical features, recurrence, second primary tumors, lymph node metastasis, and survival were analyzed using chi-square tests, Kaplan-Meier survival curves, Cox regression, and the Cochran-Mantel-Haenszel test. Patients with carcinoma arising from oral submucous fibrosis were more often male and had tumors predominantly located in the buccal mucosa. Compared with controls, these patients had significantly lower rates of cervical lymph node metastasis (p < 0.001) but higher rates of local recurrence (p = 0.012) and second primary tumors (p < 0.001). Kaplan-Meier analysis demonstrated superior overall survival in the oral submucous fibrosis group (p < 0.001). Multivariate Cox regression identified cervical lymph node metastasis (p = 0.042), histological grade (p = 0.038), local recurrence (p < 0.001), and second primary tumors (p = 0.012) as independent prognostic factors. The Cochran-Mantel-Haenszel test confirmed a tendency toward earlier nodal metastasis in oral submucous fibrosis-related cases (p < 0.001). Carcinoma arising from oral submucous fibrosis demonstrates better survival outcomes and higher tumor differentiation but carries an increased risk of recurrence and second primary tumors. Enhanced clinical surveillance is recommended to improve early detection and patient prognosis.

Oral Submucous Fibrosis (OSMF) is a chronic, progressive, and potentially malignant condition of the oral cavity that severely affects patients’ functional capacity and quality of life (QoL). This prospective, comparative, interventional study evaluated the therapeutic efficacy of combined Curcumin and Platelet-Rich Plasma (PRP) therapy versus Curcumin alone and PRP alone in improving QoL among OSMF patients. The study was conducted in the Department of Oral and Maxillofacial Surgery, Jinnah Hospital, Karachi, from January 2024 to January 2025, involving 90 clinically diagnosed OSMF patients randomized into three groups (n=30 each). Group A received Curcumin alone, Group B received PRP alone, and Group C received combined Curcumin + PRP therapy. Quality of life was assessed using the WHOQOL-BREF questionnaire, while clinical outcomes such as mouth opening and burning sensation were also recorded. Results demonstrated that the combined therapy group exhibited the greatest mean increase in mouth opening (9.4 ± 2.1 mm) and the most substantial reduction in burning sensation (VAS: 7.8 ± 1.2 to 1.3 ± 0.9), along with the highest WHOQOL-BREF score improvement (23.8 ± 5.6, p &lt; 0.001). No major adverse effects were reported. The synergistic anti-inflammatory and regenerative effects of Curcumin and PRP were reflected in improved mucosal flexibility, pain reduction, and enhanced overall QoL. The findings suggest that the Curcumin + PRP combination offers a superior, safe, and biologically integrative therapeutic option for OSMF management..

Arecoline stimulates the IL-33/13 axis and upregulates pro-fibrotic CTGF: A possible role in oral submucous fibrosis.

Cystatin as a Potential Diagnostic Marker in Oral Submucous Fibrosis: A Subtractive Proteomics Approach

.SignificanceOptical coherence elastography (OCE) is a noninvasive imaging technique with high sensitivity and resolution that can be used for mucocutaneous imaging. Oral submucous fibrosis (OSF) is a chronic disease that has a tendency to become cancerous. Nevertheless, there are a few noninvasive methods for early detection of OSF.AimA piezoelectric transducer-based (PZT) OCE technique was devised to noninvasively assess the structural and mechanical properties of mucosa in healthy and fibrotic oral diseases.ApproachWe first validated the accuracy and reliability of the OCE system for tissue elasticity detection by means of a heterogeneous agar model. The structural and biomechanical characteristics of the regional tissues were then evaluated by examining the oral mucosa of both healthy and fibrotic SD rats.ResultsNormal and fibrotic tissue stiffness differed significantly (). The elastic wave velocity was in the normal group and in the fibrotic group. After converting the results to Young’s modulus, the stiffness of the healthy buccal tissues and the fibrotic buccal tissues were and , respectively ().ConclusionsOCE can differentiate between normal and fibrotic tissue based on elasticity and optical properties. Healthy buccal tissues were softer than diseased tissues.

Oral submucous fibrosis (OSF) is a chronic progressive disease characterized by fibrosis. Panax notoginseng saponins (PNS) are effective components of the traditional Chinese medicine Panax notoginseng and play an important role in the treatment of OSF. However, the underlying mechanism of action for this medicine remains unclear. The aim of this study was to explore the effects of ferroptosis in OSF. The mice were divided into six groups. Mouth openings were detected. The buccal tissues were harvested for histomorphological analysis, western blot, and RT-qPCR. The cells were harvested for CCK8 detection, western blot, RT-qPCR, TEM, immunofluorescence, fluorescent probe, and colorimetry. PNS improved mouth opening, alleviated tissue cell damage, and inhibited ferroptosis and fibrosis in OSF rat models. Our study found that ferroptosis is closely related to arecoline-induced OSF and that PNS inhibits ferroptosis by upregulating glutathione peroxidase 4 (GPX4) to alleviate OSF. The research established OSF invivo and invitro, respectively, and the changes in the expression of fibrosis and ferroptosis-related markers in these models were studied to provide a theoretical and experimental basis for the clinical prevention and treatment of OSF.

Oral Submucous Fibrosis (OSMF) is a chronic, progressive, potentially malignant disorder of the oral cavity, predominantly associated with areca nut chewing. Oxidative stress and nutritional deficiencies, particularly of folate and vitamin B12, have been implicated in its pathogenesis. Homocysteine (Hcy), a sulfur-containing amino acid, serves as a sensitive biomarker for folate and B12 metabolism and is known to contribute to oxidative stress when elevated. This study aimed to evaluate the serum homocysteine levels in OSMF patients and assess its potential as a biochemical marker for disease severity and progression. A comparative study was conducted on 60 participants, including 30 clinically and histopathologically confirmed OSMF patients and 30 healthy age- and gender-matched controls. Serum homocysteine levels were estimated using ELISA. Clinical grading of OSMF was based on interincisal distance. Statistical analysis was performed using t-tests, ANOVA, and Receiver Operating Characteristic (ROC) curve analysis to determine the diagnostic utility of homocysteine levels. Mean serum homocysteine levels were significantly higher in the OSMF group (24.17 µmol/L) compared to controls (10.80 µmol/L) (p < 0.001). ANOVA revealed a progressive increase in homocysteine levels across OSMF grades: Grade I - 19.05 µmol/L, Grade II - 23.65 µmol/L, Grade III - 28.92 µmol/L, and Grade IV - 36.98 µmol/L. ROC analysis showed an AUC of 1.00, with an optimal cut-off of 15.90 µmol/L yielding 100% sensitivity and specificity for distinguishing OSMF from controls. Elevated serum homocysteine levels are significantly associated with OSMF and correlate with disease severity. Homocysteine may serve as a promising, non-invasive biochemical marker for early detection and progression monitoring in OSMF patients.

Elucidating the pathogenesis of oral submucous fibrosis: A comprehensive review.

To determine and compare the therapeutic efficacy of Curcuma caesia Roxb over Curcuma Longa in managing Oral Submucous Fibrosis (OSMF). A clinical trial was conducted on 51 patients diagnosed with oral submucous fibrosis, who were equally divided into two groups. The first group received a treatment of powdered Curcuma caesia Roxb mixed with honey in an equal ratio. In contrast, the second group received powdered Curcuma longa mixed with honey in a similar ratio. Both groups were instructed to apply the mixture thrice daily for three months. Additionally, a control group received a placebo, and all patients were advised to continue physiotherapeutic mouth-opening exercises for three months. The parameters evaluated included burning sensation, cheek flexibility, mouth opening, and tongue protrusion. Statistically significant results were observed after 3 months (P < 0.001). Group A showed more symptomatic improvement than Group B. Group A experienced a significant reduction in burning sensation and increased mouth opening, while Group B showed significant improvement in cheek flexibility. The mean percentage increase in mouth opening was significantly greater in Group A compared to Group B, but VAS scores for burning sensation did not show marked differences. P-value was statistically significant in both cases to show promising results. The study shows that Group A patients had reduced burning sensation, improved tongue protrusion, and increased mouth opening, while Group B had slightly better cheek flexibility. Curcuma caesia roxib improved clinical parameters like burning, tongue flexibility, and mouth opening. The study concludes that combination therapy can manage complex conditions like Oral Submucous Fibrosis effectively. Larger-scale studies with bigger sample sizes are recommended.

To review the literature on the application potential of ultrasound in the treatment of various oral and dental diseases. Two reviewers carried out a computer-based literature search using PubMed and Web of Science to identify papers published up to February 2025. The keywords used in the investigation were "therapeutic ultrasound", " low-intensity pulsed ultrasound", and various words related to oral and dental disease (oral submucosal fibrosis, burning mouth syndrome, periodontitis, orthodontic tooth movement, and tooth trauma or caries). Therapeutic ultrasound, particularly low-intensity pulsed ultrasound (LIPUS), showed beneficial effects in interfering with pathological fibrosis, suppressing inflammatory responses, promoting periodontal tissue regeneration, and facilitating the repair of dentin-pulp complex injuries in oral and dental diseases. Therapeutic ultrasound, particularly low-intensity pulsed ultrasound (LIPUS), showed beneficial effects in interfering with oral and dental diseases and may become an important adjunctive treatment modality in oral and dental medicine in the future.

Preoperative intramuscular botulinum Toxin-A to enhance postoperative outcomes in oral submucous fibrosis surgery: A randomized controlled trial.

Background. Oral cancer is the eighth leading cause of cancer-related mortality worldwide, particularly prevalent in regions with high tobacco and betel nut consumption. The associated high mortality and morbidity rates could be reduced through early detection, prompting researchers to focus on identifying early markers of carcinogenesis. Methods. This systematic review evaluated the effectiveness of oxidative stress markers as diagnostic tools. An electronic search was conducted in PubMed and Google Scholar to identify case‒control studies published between January 2000 and June 2024 that explored the use of oxidative stress markers as diagnostic biomarkers. A manual search was also performed in relevant journals, including oral oncology and oral diseases. Initially, 38 studies were screened, and after applying the inclusion criteria, only nine studies were included. The Newcastle-Ottawa Scale (NOS) tool was used to assess the risk of bias. Results. Eight studies were conducted in India, while one was from Saudi Arabia. These studies analyzed oxidative stress markers in oral squamous cell carcinoma (OSCC), oral submucous fibrosis (OSMF), and leukoplakia. Control groups were matched based on age and sex, with only two studies also considering socioeconomic status. A significant difference (P&lt;0.05) in oxidative stress marker levels was observed between cases and controls, particularly in patients with OSCC and OSMF. Conclusion. Oxidative stress markers show promise as diagnostic and prognostic indicators. Standardized methodologies and therapeutic approaches targeting oxidative stress could enhance early detection and treatment, especially in resource-limited settings. However, the findings must be interpreted with caution due to methodological limitations, geographic bias, and the lack of inclusion of grey literature.