Submucous Fibrosis Research Articles

Assessment of the role of coronoid in restrictive jaw disorders and physiologic mandibular movements

Introduction: Restricted mouth opening has major health implications, such as malnutrition, difficulty in speech, and poor oral hygiene resulting in a functional shortage of the masticatory system. Reduced mouth opening can occur due to trismus, as in the oral submucous fibrosis (OSMF) condition. Excision of fibrous bands in OSMF leads to reestablishment of the mouth opening. Other than trismus, temporomandibular joint (TMJ) ankylosis is another common condition that causes fibrosis or bony ankylosis between articular surfaces. Coronoidectomy is a useful procedure that various authors nowadays apply. It is the most popular surgical procedure used as a conventional method of treatment, which includes the detachment of temporalis muscle. Materials and Methods: A group of 15 patients with OSMF and TMJ ankylosis with written informed consent were selected for the study and were operated on under general anesthesia. Preoperative and postoperative assessment was done for bite force management, measuring and comparing mandibular movements, and the electromyography (EMG) study. Results: Statistical analysis shows the increase in maximum mouth opening and lateral excursions in OSMF and TMJ ankylosis patients on the seventh, 15th, 90th days, and six months postoperatively treated either without coronoidectomy and with coronoidectomy; however, there was no significant difference was found in mean EMG and bite force readings in both groups. Conclusion: The present study concludes that the coronoidectomy not only increases the mouth opening, but masticatory efficacy is also improved with an increase in mandibular movements postoperatively in patients with OSMF and TMJ ankylosis.

Osthole mitigates the myofibroblast properties in oral submucous fibrosis by suppressing the TGF-β/smad2 signaling pathway and NCK-AS1 expression

Background/purposeNatural products are gaining increasing recognition as an alternative source for alleviating fibrosis as they can regulate various mediators or pathways against fibrosis by targeting non-coding RNAs. In the current study, we aimed to investigate the therapeutic effects of osthole in oral submucous fibrosis (OSF), a precancerous condition of the oral cavity. Materials and methodsThe cytotoxicity of osthole to normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues was assessed using MTT assay. Collagen gel contraction and transwell migration assays were conducted to examine the myofibroblast activities. Besides, the expression of TGF-β/Smad2 signaling as well as α-SMA and type I collagen were measured. Additionally, RNA sequencing was used to identify a potential target involved in the anti-fibrotic effect of osthole. ResultsOsthole exhibited a higher cytotoxic effect on fBMFs compared to normal BMFs and dose-dependently reduced several myofibroblast activities, including collagen gel contractility and transwell migration ability. In addition, the expression of the TGF-β/Smad2 pathway was inhibited along with a lower expression of α-SMA and type I collagen in osthole-receiving cells. Moreover, the administration of osthole downregulated the expression of NCK1-AS1 in fBMFs, which was proven to mediate the anti-fibrosis property of osthole. ConclusionOur results indicate that osthole may be a promising compound to inhibit the progression of OSF.

Carvacrol inhibits the progression of oral submucous fibrosis via downregulation of PVT1/miR-20a-5p-mediated pyroptosis.

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.

The Evaluation of Tumor Budding in Oral Squamous Cell Carcinoma Arising in the Background of Oral Submucous Fibrosis.

Background and objective Oral submucous fibrosis (OSMF) is a common and potentially malignant disorder with a high risk of malignant transformation to oral squamous cell carcinoma (OSCC). Tumor budding is a scattered pattern of invasion and is related to the aggressive behavior of malignant tumors, increased depth of invasion, higher clinical staging, size, and grade of the tumor. The present study aimed to evaluate tumor budding in OSCCarising in the background of OSMF. Materials and methods A total of 120 patients with OSCC (30 each of OSCC arising in the background of OSMF, well-differentiated, moderately differentiated, and poorly differentiated OSCC) were included in the study. Hematoxylin and eosin (H&E)-stained sections were evaluated for the presence of tumor buds at the invasive front of the tumor. Kappa statistics and chi-square tests were employed to statistically compare the results by using IBM SPSS Statistics 23 software (IBM Corp., Armonk, NY). A p-value of less than or equal to 0.05 was considered statistically significant. Results The mean age of the occurrence of OSCC arising in the background of OSMF was 45.3 ±7.62 years. A progressive increase in the tumor buds was noted in OSCC arising in the background of OSMF, well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (WDSCC), and poorly differentiated squamous cell carcinoma (PDSCC). The chi-square test showed no significant difference between OSCC in the setting of OSMF and WDSCC (p=0.604) groups; however, a significant difference was noted with MDSCC (p=0.001) and PDSCC (p=0.000) groups. Conclusions OSCC arising in the background of OSMF shows lower tumor budding at the invasive front of the tumor. This histopathological parameter can be easily identified in the H&E sections and is fairly reproducible. Hence, reporting the presence of tumor budding will help in predicting the prognosis of these patients.

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

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

Plasma fibrinogen degradation products with salivary coagulopathy in OSMF among Indians.

Oral submucous fibrosis (OSMF) produces changes localized to oral cavity. Hence, it is reasonable to assume that saliva may have an important role in its etiology. This prospective case control study included 37 patients with OSMF which were compared with age and gender matched healthy controls. Salivary coagulopathy procedures as described by Chatuvedi et al. and quantification of plasma fibrinogen degradation products using a commercially available kit were carried out. The obtained data was analyzed using Chi-square tests and Tukey HSD test. The salivary coagulopathy was strongly indicated in saliva of OSMF patients and was dependent on the severity of disease. There were also increased levels of plasma fibrinogen degradation products compared to the controls and were found to have a statistically significant correlation with increasing clinical grades of oral submucous fibrosis (p≤ 0.05).

Effect of turmeric and triphala in the treatment of oral submucous fibrosis among Indians.

Oral Submucous Fibrosis (OSMF) is a potentially malignant precancerous lesion. Various treatment modalities are tried to cure it including herbal medicaments. Therefore, it is of interest to determine whether using 1 gramme of triphala and 1 gramme of turmeric combined in a glycerine solution would be clinically effective in treating oral submucous fibrosis (OSMF). The study comprised thirty-six participants in the 18-50 age range who had no systemic problems. The medications prescribed for the patients were to be applied three to four times a day. Before and after therapy, blood samples were taken in order to check for any systemic outcomes of the drugs. Both before and after therapy, there were recordings of the burning feeling and mouth opening. For 4 months, patients were checked on a monthly basis after that. A statistical analysis was performed for the variations in the mouth opening and the changes in the burning sensation on the visual analogue scale (VAS). There was a statistically significant improvement in the mouth opening and burning sensation. Turmeric and triphala provide a natural product combination that is both safe and effective for treating OSMF symptoms.

Comparative Evaluation of Pfeiffer’s Blood Crystallization Test for Early Detection of Epithelial Dysplasia in OSMF and Healthy Individuals: A Cross-Sectional Study

Background: Unlike other malignancies, oral cancer is preceded by Oral Potentially Malignant Disorders (OPMDs). Oral Submucous Fibrosis (OSMF) is one such OPMD with malignant potential of 7.6%. The purpose of present study was to determine the efficacy of Pfeiffer’s blood Crystallization test for early detection of epithelia dysplasia in OSMF individuals. Material and methods: The study participants included were involved 50 OSMF subjects and 50 healthy controls. The blood drop collected was subjected to crystallization test and the crystal patterns formed were analyzed after 20 hours. Incisional biopsy was performed in OSMF subjects to grade the degree of epithelial dysplasia. The data obtained was subjected to statistical analysis. Results: The participant’s age in the study groups ranged up to 56 years. Difference in the crystallization pattern between diseased group and non-diseased group was significant (p-value < 0.05%) with more transverse pattern in diseased group. The OSMF participants with no epithelial dysplasia showed normal crystallization pattern and maximum participants with dysplasia showed transverse pattern and the difference was statistically significant (p-value<0.05%). The sensitivity and specificity of crystallization test for OSMF was found to be 91.4% and 100.0% respectively. Conclusion: Pfeiffer's Crystallization test can be considered as a less invasive and reliable screening aid for OSMF which helps clinicians to identify high‑risk individuals for malignant transformation.

Analysis of single nucleotide polymorphism of p16 gene in cytological samples of patients with oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC)

Backgroundpl6 (CDKN2a) play a role in tumorigenesis in some head and neck squamous cell carcinomas. Frequent homozygous deletions of the pl6 gene have been reported in many tumor cell lines including the brain, breast, osteosarcomas, melanomas, kidney, bladder, and ovary. Materials and methods5 patients without any tobacco using habit were included in group I as controls. 10 clinically and histopathologically confirmed cases of oral potentially malignant disorders (OPMDs) [oral submucous fibrosis (OSMF) −7 & leukoplakia (moderate dysplasia) −3] were included in group II. 10 clinically and histopathologically confirmed cases of OSCC were categorized as group III. Buccal scrapings were taken and analyzed for exon 1, 2, 3 of p16 and homozygous deletion in exon 2 of p16 was also detected by PCR and gel electrophoresis. ResultsPCR amplification products of exon 1, 2, 3 of p16 were found in all 25 samples which include 10 cases of OSCC, 10 cases of OPMDs and 5 controls. Homozygous deletion in exon 2 was found only in 30 % of OSCC and 20 % of OPMD. ConclusionOur study showed that cytological samples yield sufficient amount of DNA, which showed 100 % positivity with exon 1, 2, 3 of p16 gene, but the percentage of genetic alteration of p16 gene seems to be less when compared with other related studies.

Estimation of the Salivary Copper Levels in Oral Submucous Fibrosis Condition: An In Vivo Study.

The aim of the present study was to estimate the salivary copper levels in oral submucous fibrosis (OSMF) condition. A total of 60 individuals of which an equal number of 30 each in normal healthy control group as well as in clinically and histopathologically (the biopsy was done once after the clinical confirmation of OSMF in the patient) confirmed patients of OSMF were included in the study group. Total of 51 males and 9 females were considered for the present study and the age distribution of these groups ranged from a minimum of 21 years to a maximum of 74 years. Unstimulated whole saliva was collected from the patient followed by the conventional biopsy practice. The collected saliva was then subjected for the analysis of copper levels. Trace element copper was estimated by using Digital Semiautomatic Analyzer with the help of copper kit. The clinical mouth opening of OSMF was estimated. Analysis of variance (ANOVA) and Tukey HSD post hoc test was used analyze the data wherein the participants were grouped into age ranges of 20-30, 31-40, 41-50, and >60 years. The mean salivary copper level among OSMF and control groups with respect to age in 20-30 years was 55.98 ± 15.50 and 30.87 ± 7.70, in 31-40 years was 63.96 ± 21.13 and 32.95 ± 4.56, in 41-50 years was 50.11 ± 6.83 and 30.46 ± 3.28, and >60 years was 45.65 and 13.67 µg/dL, respectively. The mean salivary copper levels among OSMF and Control groups with respect to males were 55.60 ± 15.27 and 31.18 ± 6.97 and among females were 67.0 ± 24.25 and 30.06 ± 5.77 µg/dL, respectively. The mean salivary copper levels with histopathological grades in very early stage was 47.18 ± 5.73, in early stage was 49.22 ± 7.65, in moderately advanced was 73.53 ± 10.62 and in OSMF with mild dysplasia was 79.98 ± 16.27 µg/dL, respectively. The mean salivary copper levels in individuals with clinical mouth opening more than 35 mm was 45.65 ± 6.57, in 25-35 mm was 48.94 ± 21.60, in 15-25 mm was 70.54 ± 3.52 and in less than 15 mm was 81.50 ± 16.66, respectively. The present study concluded that salivary trace element levels could be used as potential diagnostic and prognostic markers in patients with OSMF. Trace elements are involved in many different physiological and metabolic processes in humans, either directly or indirectly. Copper is involved in vital biochemical activities like different redox and free radical formation and in maintaining cellular proton homeostasis. It is also associated with the processing of oxygen and a component of arecanut in all forms, which is implicated in the etiology of OSMF. How to cite this article: Gupta R, Jayanti I, Das A, et al. Estimation of the Salivary Copper Levels in Oral Submucous Fibrosis Condition: An In Vivo Study. J Contemp Dent Pract 2024;25(5):498-502.

Salivary Profile in Oral Submucous Fibrosis: A Scoping Review.

Diagnosing oral submucous fibrosis (OSMF) is invariably challenging. The disease can be detected after reaching its final stage and requires complex treatment. Changes in its salivary profile can be used as a reference to see this disorder and as a basis for diagnostic prediction. This study is aimed to analyze the salivary profile as a diagnosis marker in patients with OSMF. The study using Preferred Reporting Items for Systematic Reviews and Meta-analyses was conducted using PubMed, Science Direct, and Scopus databases. A thorough literature search between 1991 and 2023 was performed. Twenty-eight full-text articles were reviewed in detail. Twenty-eight articles were included; a total of 929 patients of OSMF and 826 controls were found. The scoping review showed that levels of salivary protein (including lactate hydrogenase, immunoglobulin G, immunoglobulin A, S1007A protein, 8-hydroxydeoxyguanosine, 8-isoprostane, malondialdehyde, matrix metalloproteinase-12, salivary C-reactive protein, fibrinogen producing factor, salivary miRNA-21, and salivary lipids [cholesterol, high-density lipoprotein, triglyceride) were higher in OSMF. Meanwhile, trace elements (vitamin C, vitamin E, iron, zinc, and magnesium) were lower; only copper was higher in OSMF patients. Alteration in salivary components such as protein, lipid, and trace elements detection can be a basis for providing a noninvasive supportive examination and thus be used as a diagnosis marker of OSMF.

Deciphering the MicroRNA Targets of Candidate Genes in Oral Submucous Fibrosis: A Computational Approach

Deciphering the MicroRNA Targets of Candidate Genes in Oral Submucous Fibrosis: A Computational Approach

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

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

Effect of Jiedu Huayu decoction on oral mucosal Axin and β-catenin expression in oral submucosal fibrosis model rats.

To investigate the protective effect of the Chinese herbal formula of Jiedu Huayu decoction (, JHD) on oral mucosa of rats with oral submucosal fibrosis (OSF) and its potential mechanism of action. Sprague-Dawley male OSF model rats were constructed by injection of betaine and topical rubbing and were randomly grouped and administered by gavage for 4 weeks. Mouth opening and buccal mucosa scores interleukin levels and the expression of Axin and β-catenin proteins or genes were measured before and after drug administration. After treatment with JHD the buccal mucosal lesions of rats were significantly reduced Axin protein and mRNA expression were significantly increased β-catenin protein and mRNA expression were significantly decreased interleukin-1β and interleukin-6 levels were decreased and interleukin-10 levels were increased. The mechanism of action of JHD can effectively alleviate the pathological damage of buccal mucosa in OSF rats which may be related to the promotion of Axin expression and inhibition of β-catenin expression.

Comparative Assessment of Lipid Peroxidase in Oral Cancer and Oral Potentially Malignant Disorders.

Introduction Oral potentially malignant disorders (OPMD) are abnormally altered tissues that could potentially develop into oral cancer. From the literature, it is understandable that not all OPMDs develop into oral cancer. Hence, it is essential to identify the high-risk lesions that are more likely to develop into oral cancer. Lipid peroxidase (LPO) is a byproduct of phospholipidmetabolism, and its levels are an oxidative stress marker that can probably help us predict the onset of cancer in OPMDS. This study aimed to assess the levels of LPO in OPMD, oral cancer, and normal patients. Materials and methods The sample size estimated was 15 per group. There were four groups in total. The estimation was done with the Abbkine LPO enzyme-linked immunosorption assay (ELISA) kit (Atlanta, Georgia, USA). An enzyme-substrate reaction was carried out, and the degree of the color change was measured using a microplate reader. The values were tabulated, and statistics were carried out using Statistical Package for Social Sciences(SPSS) version 26.0 (IBM Corp., Armonk, NY, USA). Both descriptive and inferential statistics were carried out. Results LPO levels (nmol/L) in each of the four groups were as follows: Group 1 (oral cancer): 171.86±78.86, Group 2 (controls): 71.66±28.36, Group 3: (oral leukoplakia): 127.50±103.53, and Group 4 (oral submucous fibrosis and oral lichen planus): 100.39±41.06.The results, when compared, were statistically significant (P< 0.05). Discussion From the above results, it is understandable that oral cancer patients experience increased oxidative stress compared to the OPMD group. The current study concluded that the obtained results showed differences in LPO levels, suggesting LPO could be used as a marker and screening tool to assess the rate and severity of cellular damage in patients with oral potentially malignant disorders.

Prevalence of oral submucous fibrosis linking with Areca Nut usage among Indians.

The prevalence of oral submucous fibrosis amongst population of Southern Rajasthan is of interest to dentists. Hence, a cross sectional study had been conducted on 3548 patients from 18-60 years age group who visited the Department of the Oral Medicine and Radiology, Pacific Dental College and Research Centre, Bedla, Udaipur was completed. They were subjected to thorough case history related to quid habit in arecanut (Areca catechu L.) form and to diagnose OSMF clinically. 1645 processed form of arecanut users were identified. The prevalence of arecanut chewers in study population has been reported to be 46.36%. The prevalence of OSMF in study population has been reported to be 458 (12.9%). Exact component associated and the mechanism involved in the occurrence of OSMF is still not available in literature and research is going on regarding unveiling this mysterious lesion.

Assessment of the Efficacy of Orally Administered Lycopene in Improving the Mean Maximum Incisal Opening in Individuals Suffering from Oral Submucous Fibrosis

Objective: To compare the effectiveness of orally administered lycopene versus a placebo in increasing mean maximum incisal opening in patients with oral submucous fibrosis (OSF). Methodology: This randomized controlled trial, conducted at the Oral and Maxillofacial Surgery Department of Lahore Medical and Dental College from January to July 2020, enrolled 68 eligible patients. Two groups were formed: Group 1 (received oral lycopene) and Group 2 (received placebo). A block size of 4 was utilized for patient allocation, alternating between groups until the sample size was met. Both groups underwent a comprehensive 3-month treatment plan, including habit cessation and daily physiotherapy involving tongue spatula insertion between teeth (with spatula replacement). Only Group 1 received an additional 40mg oral lycopene daily. Follow-up appointments occurred monthly for 3 months, measuring maximal incisal opening with a Vernier Caliper. Results: Baseline incisal opening was 25.39 ± 2.92 mm in Group 1 and 25.23 ± 3.03 mm in Group 2. At the 3-month mark, Group 1 showed an incisal opening of 31.71 ± 2.84 mm, while Group 2 had 28.31 ± 2.98 mm. The mean change in incisal opening was 6.32 ± 0.96 mm for Group 1 and 3.08 ± 0.90 mm for Group 2. Group 1 exhibited a significantly higher mean change in incisal opening compared to Group 2 (p=&lt;0.001). Conclusion: Lycopene administration is more effective than a placebo in improving mouth opening in OSF patients. Therefore, lycopene should be considered as a treatment option to enhance maximal incisal opening and improve the quality of life for individuals with OSF. Keywords: Maximum incisal opening, Oral submucous fibrosis, lycopene orally, Nutt eating

Oral Submucous Fibrosis - Case Series

Oralsubmucous fibrosis is regarded as a collagen metabolic disorder with an overall increased collagen production and decreased collagen degradation resulting in increased collagen deposition in the oral tissues, and fibrosis due to alkaloid exposure. We report three case reports of oral submucous fibrosis. Clinical findings and histopathologic findings were consistent with the diagnosis of stage 2 oral submucous fibrosis. The patient was educated on the effects of areca nut and chances of malignant transformation. Keywords Malignant Transformation, Oral Submucous Fibrosis, Pathogenesis, Management

New physiotherapy device for interincisal mouth opening in oral submucous fibrosis patients: A pilot study

Objectives: It is estimated that 0.2–0.5% of Indians suffer from oral submucous fibrosis. The states of Gujarat, Bihar, Madhya Pradesh, and Maharashtra are the most severely impacted by this illness. Antioxidants, effective physiotherapy exercises, and topical corticosteroid injections are among the treatment options available for oral submucous fibrosis (OSMF). Despite being widely used, there are few studies assessing the effectiveness and patient compliance of the conventionally used technique for physiotherapy in patients with OSMF, such as ice cream sticks, tapered screws, and Heister jaw opener. Material and Methods: A device for physical rehabilitation that may be used at home was made using 3D printing technology. Ten patients participated in a pilot study that was carried out. These patients participated in the device’s pilot testing to assess the mechanical features and its ability to improve interincisal mouth opening, comfort (pain and control), and enjoyment. Comfort [Pain, comfort, control] with device use, ease of use [Portability] and satisfaction with device use. Results: A statistically significant (P &lt; 0.0006) improvement in the mean mouth opening of OSMF patients was shown by quantitative data. After 1 month of use, there was a 1.8 mm difference in mouth opening. This implies that the device worked well for these people. Based on feedback, the majority of patients reported that the device was comfortable, easy to use, and showed satisfaction with the device use. Conclusion: It was found that people with OSMF can open their mouth more with the use of a new physiotherapy device. In addition to pharmacological therapy, this pilot study needs more investigation with a bigger sample size and a randomized control trial. Considering that this method of managing OSMF seems to be effective.

Arecoline promotes fibroblast activation and M2-macrophage polarization by up-regulating the expression of IL-4

ObjectiveTo determine the biological effects of arecoline on oral submucous fibrosis (OSF). DesignThe differential genes between OSF tissue and normal oral tissue were collected form GSE64216 dataset, analyzed by Gene Expression Omnibus (GEO) database. Real-time PCR and immunohistochemistry were used to analyze the expression of IL-4 gene and protein in oral tissue. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression of exocrine IL-4 protein in human oral fibroblasts (HOF) pre-treated by arecoline. Cell Counting Kit-8 (CCK-8) and transwell assays were used to analyze the proliferation and migration of HOF cells, respectively. After IL-4 was knocked down by short hairpin (sh) plasmid, the proliferation and migration of HOF cells were detected. Flow cytometry was used to analyze the proportion of M2-macrophages. Real-time PCR and immunohistochemistry were used to verify the expression of biomarker proteins of macrophages in OSF tissues. ResultsThe expression of IL-4 gene and protein were both up-regulated in OSF tissue. Arecoline could enhance the expression of IL-4 gene and exocrine protein in HOF cells, and promote the proliferation and migration of HOF cells. While knockdown of IL-4 could inhibit arecoline-induced proliferation and migration in HOF cells. The results of flow cytometry showed that recombinant human IL-4 (rhIL-4) protein could increase the proportion of M2-macrophages. Similarly, the results of real-time PCR and immunohistochemistry showed the expression of ARG1 (Biomarker proteins of M2-macrophage) was up-regulated in OSF tissues. ConclusionArecoline promotes activation of fibroblasts and polarization of M2-macrophages by up-regulating the expression of IL-4.