Submucous Fibrosis Research Articles

Electromyography Analysis of the Masseter Muscle's Activity in the Management of Oral Submucous Fibrosis

Electromyography Analysis of the Masseter Muscle's Activity in the Management of Oral Submucous Fibrosis

Enzyme-linked immunosorbent assay and immunohistochemical analysis of mast cell related biochemicals in oral submucous fibrosis

Oral submucous fibrosis (OSMF), a potentially malignant disorder, is developed by progressive fibrous tissue deposition in connective tissue along with atrophy of oral mucosa. Histological sections also show the mast cell infiltration in submucosa which may indicate their possible role in this entity. Abundant availability of biochemicals in mast cells like histamine and serine proteases like chymase may be released and play specific pathways in the disease pathophysiology. Possibly, if the histamine release has some part to play, diamine oxidase may also be found to have a relationship as it metabolizes histamine. The present study is proposed to identify the presence of chymase, histamine, and diamine oxidase in both, serum as well as tissue by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) respectively. This study may provide probable insight into the mast cell-related chemicals and their association with OSMF.

Salivary and serum levels of lactate dehydrogenase in oral submucous fibrosis: A meta-analysis.

The occurrence of oral submucous fibrosis (OSF) is often accompanied by an increase in lactate dehydrogenase (LDH) levels. In this meta-analysis, we compared the salivary and serum levels of LDH levels between OSF patients and controls. A comprehensive search was conducted in PubMed, Embase, Web of Science, and Cochrane Library from the establishment of the database to June 2023, and the quality of the studies was checked by the Newcastle-Ottawa Quality Assessment scale. The mean difference (MD) and 95% confidence interval (CI) were calculated using RevMan 5.4 software. A total of 28 studies were retrieved from the database, and we included 5 studies in this meta-analysis. The salivary LDH level of OSF patients was higher than healthy controls (MD: 423.10 pg/L 95%CI: 276.42-569.77 pg/mL, P < .00001), the serum LDH level of OSF patients was also higher than that of healthy controls (MD: 226.20 pg/mL, 95%CI: 147.71-304.69 pg/mL, P < .00001). This meta-analysis showed that salivary and serum LDH levels were higher in OSF patients than in healthy controls, suggesting that LDH may be a potential biomarker for OSF.

A review on Sarvasara Mukharoga in Ayurveda w.s.r. Oral Submucous Fibrosis

Introduction: An inflammatory response juxta epithelial, fibroelastic changes in the lamina propria, epithelial atrophy, trismus, and recurrent glossitis attacks are the hallmarks of the subtle chronic disease known as oral submucous fibrosis (OSMF). It is one of the most common premalignant disorders in India is. OSMF is gaining popularity these days. A study on OSMF and its management according to Ayurveda values is more in the scientific field because Ayurveda’s main focus is on maintaining and promoting health care. In this conceptual paper, OSMF will be highlighted, evaluated, elaborated on, and discussed. Aim and Objectives: The aim of the study is to gain a better understanding of OSMF and its relationship to Sarvasara Mukharoga in Ayurveda. Materials and Methods: The contents of this article are based on modern medicine textbooks as well as Ayurvedic Samhitas. Clinical research published in both indexed and non-indexed journals was also consulted to obtain relevant content. Results: According to the Lakshanas described by Brihatrayi, OSMF can be equated symptomatically with the Sarvasara Mukharoga. In the event of OSMF, the management of Sarvasara Mukharoga should be applied. Conclusion: On the basis of signs and symptoms, OSMF can be correlated with Sarvasara Mukharoga. Early treatment of OSMF using Ayurvedic medications and the cessation of habits helps in the easy cure of the disease.

EFFECT OF BETEL NUTS AND TOBACCO DERIVATIVES ON ANTIOXIDANTS AND MICRONUTRIENTS IN ORAL SUBMUCOUS FIBROSIS AND ORAL CANCER PATIENTS IN GUJARAT POPULATION

Objective: In our previous study, we have find the significance of biochemical markers between precancerous and cancerous subject with normal healthy individuals in Gujarat population, taking into consideration the severity of biochemical markers in cancerous condition. We felt that other than comparison, effect of betel nuts and tobacco derivatives on antioxidants and micronutrients has required further evaluation to develop a better understanding. The objective of the present study is to measure the interdependence of antioxidants and micronutrients in oral submucous fibrosis and oral cancer patients and find its significance. Method: In this study, a total of 150 patients in which 50 diagnosed PMD patients and 50 diagnosed oral cancer patients with 50 healthy non-tobacco consuming were selected as a control group. Five to seven milliliters of venous blood was collected under aseptic precautions with patients consent. All the parameters were analyzed by standard methods using fully auto-analyzed with a ready-to-use kit. Result: This research was conducted on 150 patients, out of which 50 diagnosed potential malignant disorder patients and 50 oral squamous cell carcinoma patients matched with 50 healthy control individuals. Average age of patients with PMD and OSCC was 55.6±9.74-and that of control group was 35.83±8.90 years. Student t-test showed that there was a significant difference between the two groups with regard to age. Of the 100 patients with PMD, 72 (72% of total) were men and 28 (28% of total) were women. Among the individuals in the control group (n=50), 35 persons (70% of total) were men and 15 (30% of total) were women. Chi-square test showed that there was no significant difference between the two groups in terms of sex (p=0.891). The copper levels of PMD and OSCC, respectively, were 153.57±7.68 and 164.43±15.75. The value was statistically compared with OSCC which had significantly higher levels than healthy control (102.53±22.1). The iron levels of PMD and OSCC, respectively, were 77.62±15.27 and 50.04±19.97. The value was statistically compared with OSCC which had significantly lower levels than (138.4±13.2) healthy control. The Vitamin C levels of PMD and OSCC, respectively, are 0.55±0.10 and 0.44±0.9. The value was statistically compared to the OSCC which had significantly lower than 1.09±0.17 control. The Vitamin E levels of PMD and OSCC, respectively, 1.18±0.16 and 0.8±0.12 values were statistically compared the OSCC which had significantly lower levels than (1.39±3.64) healthy control. Conclusion: In our finding, Vitamin C showed positive correlation with serum iron and serum copper with malignant disorders. Trace elements and antioxidants exhibited interdependence in both physiologic and pathologic states such as oral cancer.

To Estimate and Compare the Level of Serum Immunoglobulin A in Patients of Oral Submucous Fibrosis, Leukoplakia, and Control Group

ABSTRACT 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.

Evaluation of stromal myofibroblasts in oral submucous fibrosis and its malignant transformation: An immunohistochemical study.

Oral submucous fibrosis (OSF) is a precancerous lesion, with oral squamous cell carcinoma (OSCC) being the most prevalent malignancy affecting the oral mucosa. The malignant transformation of OSF into OSCC is estimated to occur in 7-13% of cases. Myofibroblasts (MFs) play pivotal roles in both physiological and pathological processes, such as wound healing and tumorigenesis, respectively. This study aimed to explore the involvement of MFs in the progression of OSF and its malignant transformation. In total, 94 formalin-fixed paraffin-embedded tissue blocks were collected, including normal oral mucosa (NOM; n = 10), early-moderate OSF (EMOSF; n = 29), advanced OSF (AOSF; n = 29), paracancerous OSF (POSF; n = 21), and OSCC (n = 5) samples. Alpha-smooth muscle actin was used for the immunohistochemical identification of MFs. NOM exhibited infrequent expression of MFs. A higher staining index of MFs was found in AOSF, followed by EMOSF and NOM. Additionally, a significant increase in the staining index of MFs was found from EMOSF to POSF and OSCC. The staining index of MFs in NOM, EMOSF, AOSF, POSF, and OSCC was 0.14 ± 0.2, 1.69 ± 1.4, 2.47 ± 1.2, 3.57 ± 2.6, and 8.86 ± 1.4, respectively. All results were statistically significant (P < 0.05). The expression of MFs exhibited a gradual increase as the disease progressed from mild to malignant transformation, indicating the contributory role of MFs in the fibrogenesis and potential tumorigenesis associated with OSF.

Targeting MetaLnc9/miR-143/FSCN1 axis inhibits oxidative stress and myofibroblast transdifferentiation in oral submucous fibrosis

Background/purposePersistent 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 methodsExpression 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. ResultsHerein, 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. ConclusionUpregulation of MetaLnc9 may enhance the activation of myofibroblasts by sponging miR-143 and titrating its inhibitory property on FSCN1.

Effects of lactobacillus pentosus postbiotics on fibrotic response in arecoline-induced oral fibrogenesis

Background/purposeOral 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 methodsThe 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. ResultsArecoline 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. ConclusionOur 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.

Awareness of Oral Submucous Fibrosis among the Quid-Chewing South-Asian Expatriates in the United Arab Emirates

ABSTRACT Oral submucous fibrosis (OSF) is a chronic disorder prevalent in South and Southeast Asia and is mainly related to the habit of chewing betel quid. Although there are numerous South-Asian studies about OSF, there is no study that evaluates the awareness of OSF among expatriate populations of South-Asian origin. Evaluated the awareness of OSF among South-Asian expatriate patients reporting to a dental hospital in Sharjah. Prevalidated questionnaires were given to 150 expatriate patients of South-Asian origin with quid-chewing habit reporting to the teaching clinics of a dental hospital in the United Arab Emirates. Among the 150 patients, 103 responded to the questionnaire. Among the 103 respondents, 11.65% were aware of OSF. Respondents living in shared residency and labor camps had significantly (P = 0.43) lower awareness of OSF compared to respondents living with their families. The results of our study show that the awareness of OSF is lower among the respondents living in labor camps and shared residencies. The younger respondents had more awareness of OSMF and were more likely to quit the quid-chewing habit.

Evaluation of salivary tumor necrosis factor α as a diagnostic biomarker in oral submucosal fibrosis and squamous cell carcinoma of the oral cavity and oropharynx: a cross sectional observational study.

Tumor necrosis factor α (TNF-α) is known to be associated with chronic inflammation, and its expression has been shown to increase in advanced cancers. Chronic inflammation is a characteristic feature of oral submucous fibrosis (OSMF), which is a potentially malignant disorder (PMD). Squamous cell carcinoma (SCC) is associated with considerable mortality and morbidity and an early detection or monitoring would greatly help in achieving an effective cure. TNF-α was thus evaluated for use as a biomarker in the present study according to the stage of OSMF and histological grade of SCC in the oral cavity and oropharynx. This study included 45 patients divided into 3 groups-OSMF group, SCC group and control group-each comprising 15 participants. Saliva samples were collected from each patient, and salivary TNF-α levels were estimated using an ELISA kit. Statistical analysis revealed no significant differences in TNF-α levels among the OSMF, SCC and control groups; however, there was an increase in the salivary TNF-α level in patients with stage 3 disease according to the clinical stage of OSMF, for which the p value was 0.027. An increase in the TNF-α concentration with increasing clinical stage suggested a role for TNF-α in the spread of OSMF involvement in anatomical structures of the oral cavity and oropharynx. No significant difference in salivary TNF-α levels was noted among the OSMF, SCC and control groups. The study showed a positive correlation of TNF-α with increasing stages of OSMF but was not a reliable biomarker in the categorization of the same.

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

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

Development of Epigallocatechin 3-gallate-Loaded Hydrogel Nanocomposites for Oral Submucous Fibrosis

Oral submucous fibrosis (OSF) is a chronic progressive disease associated with increased collagen deposition and TGF-β1 release. The current therapy and management have been a limited success due to low efficacy and adverse drug reactions. This study aimed to evaluate epigallocatechin 3-gallate (EGCG) encapsulated nanoparticles loaded mucoadhesive hydrogel nanocomposite (HNC) for OSF. Developed HNC formulations were evaluated for their permeation behaviour using in vitro as well as ex vivo studies, followed by evaluation of efficacy and safety by in vivo studies using areca nut extract-induced OSF in rats. The disease condition in OSF-induced rats was assessed by mouth-opening and biochemical markers. The optimized polymeric nanoparticles exhibited the required particle size (162.93 ± 13.81 nm), positive zeta potential (22.50 ± 2.94 mV) with better mucoadhesive strength (0.40 ± 0.002 N), and faster permeation due to interactions of the positively charged surface with the negatively charged buccal mucosal membrane. HNC significantly improved disease conditions by reducing TGF-β1 and collagen concentration without showing toxicity and reverting the fibroid buccal mucosa to normal. Hence, the optimized formulation can be further tested to develop a clinically alternate therapeutic strategy for OSF.Graphical

Comparative evaluation of efficacy of a smartphone application for oral submucous fibrosis (OSMF) self-examination in follow-up of the patients compared to routine Outpatient Department-based follow-up: a clinical interventional study

Background: Sushruta (600 B.C.) described a condition called "Vidari" linked with progressive narrowing of mouth, depigmentation of the oral mucosa, and pain on taking food, oral submucous fibrosis (OSMF). In 1952, Schwartz called this illness, which affected five Indian women existing in Kenya, "atrophica idiopathica mucosae oris." Pindborg and Sirsat coined the term "oral submucous fibrosis" in 1966, which is still in use today. With an overall Indian prevalence rate of between 0.2–0.5%, OSMF is primarily found in India and Southeast Asia, according to global estimations. Patients with OSMF need regular follow-ups and to maintain this follow-up it is not always possible for the patient to visit a dental clinic. Hence developing a smartphone-based application for the follow-up of OSMF will be of great value to the patients. The study aims to evaluate the effectiveness of a smartphone application on OSMF self-examination in the follow-up of patients. Methods: There will be three phases of the research. The first phase will be the development of a smartphone-based application for the follow-up of patients with OSMF. The second phase will be distribution and training the patients regarding the usage of the application and the third phase will be evaluating the effectiveness of the smartphone application in maintaining the follow-up of the patients. Expected results: The follow-up of patients with OSMF is expected to be better and feasible using a smartphone application as compared to regular Outpatient Department-based follow-up. Conclusions: Designing a mobile application for the ease of users presents difficulties since it must take accessibility into account, which influences how well the application is received by users. The goal of OSMF examination awareness facilitation and intervention is to raise public knowledge. Educational activities significantly contribute to the advancement of information, convictions, and OSMF screening practice. CTRI registration: CTRI/2023/06/054514 (registration pending)

A Study to Assess the Role of Psychological Stress in the Severity of Oral Lichen Planus, OSMF, and Leukoplakia and its Correlation with Serum Cortisol Levels

ABSTRACT Introduction: The most prevalent oral mucosal conditions in humans are leukoplakia, oral lichen planus (OLP), and oral submucous fibrosis (OSMF). These conditions should be studied as psychosomatic conditions, but little research has been done on how these conditions relate to stress. Materials and Methods: A total of 280 patients of both genders with ages 35–60 years were divided into four groups: leukoplakia, OSMF, OLP, and control. Whole blood samples were collected from all the participants and analyzed for serum cortisol by using ELISA with a commercial kit. Detailed case history and DASS-21 questionnaire were recorded for psychological assessment. To assess the variables, the student t test and Chi-square test were used. P values of &lt;0.05 were regarded as significant. Results: In this study, it was found that higher levels of serum cortisol were found in OLP patients, with advanced erosive lesions showing the highest levels of serum cortisol, followed by OSMF and leukoplakia. Patients with Oral Lichen Planus showed higher levels of stress, anxiety and depression than patients of OSMF and leukoplakia. Conclusion: This study emphasized stress and anxiety as a predisposing factor in the occurrence and progression of OSMF apart from re-establishing the role of stress and anxiety in OLP with consideration to depression in triggering role for OLP. Furthermore, it demonstrated that serum cortisol levels play a significant role as an indicator of psychological stress.

Dermatoglyphic Pattens in OSMF and Leukoplakia - A Comparative Study

ABSTRACT The term dermatoglyphics was first used in 1926 by anatomist Cummins. Dermatoglyphic is a term that refers to “a skin carving.” The unique carve present on the skin surface of humans and other living beings is referred to as dermatoglyphics. This research was conducted to understand the variations in patterns and assess the usefulness of dermatoglyphics among individuals diagnosed with potentially malignant diseases and mouth cancer. Three hundred subjects were selected. The study consisted of three groups. Patients were divided into the following groups Group I: oral submucous fibrosis (OSMF) (100), Group II: ORAL LEUKOPLAKIA (100), and Group III: Healthy Individuals (100). Our research study indicates a difference in dermatoglyphic patterns between patients and healthy individuals. Specifically, there is a lower percentage of loop patterns and an increase in arch patterns in OSMF and leukoplakia patients. These findings suggest that dermatoglyphics may have relevance in understanding or identifying certain health conditions.

Comparing the efficacy of Leishman–Giemsa Cocktail Stain, Giemsa Stain, and Papanicolaou Stain in Potentially Malignant Disorders: A Comparative Study.

Objective: To estimate the efficacy of the Leishman Giemsa cocktail stain, Giemsa stain, and Papanicolaou for the screening of potentially malignant lesions by exfoliative cytology. Study Design: Comparative study. Setting: Department of Oral Medicine and Oral Pathology, Isra Dental College, Faculty of Dentistry and Allied Sciences Hyderabad, Pakistan. Period: 1st February 2022 to 31st January 2023. Material &amp; Methods: A total of 90 participants were enrolled in the study, 30 subjects of normal healthy individuals were categorized in Group-I and 60 patients with diagnosed potentially malignant lesions (Oral submucous Fibrosis, Oral Lichen Planus, and Leukoplakia) were categorized in Group II. Participants were advised to rinse their mouth with water and the sample was taken by moving a brush clockwise and anti-clockwise over mucosa and the surface of the lesion. Three smears were prepared from each sample, one was fixed with biofix spray and stained with Papanicolaou stain, and other two smears were air-dried and stained with Leishman Giemsa and Giemsa stain. Stained slides were observed under a microscope and the slides were interpreted. Results: In Group-I Leishman Giemsa cocktail stain was highly significant compared to Papanicolaou and Giemsa stain, the mean value of the Leishman Giemsa cytoplasmic stain was 1.16, Papanicolaou was 1.0 and Giemsa was 0.52. Whereas in group II, the mean score of cytoplasmic staining of the Leishman Giemsa cocktail was 1.16, Papanicolaou was 1.10 and Giemsa was 0.67. There was no significant difference found in the mean score of cytoplasmic staining of Group-I and Group II respectively. Conclusion: According to current research study results, the Leishman Giemsa cocktail stain is a better staining technique for the screening of potentially malignant lesions along with the Papanicolaou stain.

Prevalence and risk factors of oral potentially malignant disorders in Indonesia: a cross-sectional study undertaken in 5 provinces

Detection of subjects with oral potentially malignant disorders in a population is key to early detection of oral cancer (OC) with consequent reduction of cancer-related morbidity and mortality. Our aim was to investigate the prevalence and associated risk factors for OPMD in representative provinces of Indonesia. This cross-sectional study was undertaken in five Indonesian provinces: West Java (WJ), Jakarta (JKT), West Papua (WP), West Kalimantan (WK) and Banda Aceh (BA). Respondents answered a previously validated questionnaire including information on ethnicity, occupation, socioeconomic status (SES), oral health practices, and behaviours associated with oral cancer. An oral examination was undertaken using WHO standardized methodology. Data were analysed using ANOVA, Chi-Square, and logistic regression to assess association between risk factors and mucosal disease. A total of 973 respondents between the ages of 17 and 82 years was enrolled (WJ 35.5%,JKT 13.3% WP 18.3%, WK 9%, BA 23.9%). Tobacco smoking (14.8%), Betel quid (BQ) chewing (12.6%) and alcohol drinking (4%) varied geographically. A well-established OPMD was detected in 137 (14.1%) respondents and 2 (0.2%) presented with chronic ulceration later diagnosed as OC. Leukoplakia was the most common OPMD found (9.7%), while the prevalence of oral submucous fibrosis (OSMF), not previously described in the nation, was 2.3%. Poor knowledge of OC risk factors, poor oral hygiene behaviours, low-income SES and ethnicity were significantly associated with the presence of an OPMD. There is a previously under-reported high prevalence of OPMD in Indonesia. Overall, we found a strong correlation between the presence of an OPMD and individual habituation to known risk factors.

Aberrantly downregulated FENDRR by arecoline elevates ROS and myofibroblast activation via mitigating the miR-214/MFN2 axis

Long non-coding RNA FENDRR possesses both anti-fibrotic and anti-cancer properties, but its significance in the development of premalignant oral submucous fibrosis (OSF) remains unclear. Here, we showed that FENDRR was downregulated in OSF specimens and fibrotic buccal mucosal fibroblasts (fBMFs), and overexpression of FENDRR mitigated various myofibroblasts hallmarks, and vice versa. In the course of investigating the mechanism underlying the implication of FENDRR in myofibroblast transdifferentiation, we found that FENDRR can directly bind to miR-214 and exhibit its suppressive effect on myofibroblast activation via titrating miR-214. Moreover, we showed that mitofusin 2 (MFN2), a protein that is crucial to the fusion of mitochondria, was a direct target of miR-214. Our data suggested that FENDRR was positively correlated with MFN2 and MFN2 was required for the inhibitory property of FENDRR pertaining to myofibroblast phenotypes. Additionally, our results showed that the FENDRR/miR-214 axis participated in the arecoline-induced reactive oxygen species (ROS) accumulation and myofibroblast transdifferentiation. Building on these results, we concluded that the aberrant downregulation of FENDRR in OSF may be associated with chronic exposure to arecoline, leading to upregulation of ROS and myofibroblast activation via the miR-214-mediated suppression of MFN2.

Association of Oral Submucous Fibrosis Risk with GSTM1 and GSTT1 Gene Polymorphisms.

To determine the association of GSTM1 and GSTT1 polymorphisms with oral submucous fibrosis (OSF). A case-control study. Place and Duration of the Study: Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore and Oral and Maxillofacial Surgery Department, de Montmorency, College of Dentistry/ Punjab Dental Hospital, Lahore, Pakistan, from 1st April 2019 to 31st April 2020. OSF patients were diagnosed with different clinical staging of mouth opening by Vernier caliper with the help of a professional dentist in the Department of Oral and Maxillofacial, de Montmorency, College of Dentistry, Lahore. One hundred and eight blood samples of OSF patients and 108 samples of normal controls were collected. Genomic DNA was obtained from whole-blood extraction. Multiplex PCR amplification using GSTM1, GSTT1, and β -Globin gene primers was performed. GSTM1 and GSTT1 null genotypes frequencies were found in 43.5% (47/108) and 13.9% (15/108) of controls, whereas 54.6% (59/108) and 25.9% (28/108) of OSF patients, respectively. OSF patients had a greater frequency rate of GSTM1 and GSTT1 null genotypes than controls [OR 1.56, 95% CI 0.91-2.67 (p=0.13)]and [OR 2.17, 95% CI 1.08-4.34 (p=0.04)], respectively. The GSTT1 genotype was found statistically significant with OSF (p=0.05), and risk was also determined. The cumulative effect of null genotypes of GSTM1/GSTT1 did not show any association with the controls and in OSF patients. Proportions of active and null alleles of the patient group were; 86.1%/13.9%; and in control, it was 92.6%/7.4% (OR = 2.01; CI: 0.82-4.97; p=0.18), respectively. The study determined a statistically significant association of GSTT1 gene polymorphism with OSF. Oral submucous fibrosis, GSTM1, GSTT1, Gene polymorphisms, Genetic risk.