OBJECTIVES: There is currently a lack of economic and suitable animal models that can accurately recapitulate the oral submucous fibrosis (OSF) disease state for indepth study. This is one of the primary reasons for the limited therapeutic methods available for OSF. Based on the underlying logic of pan-cancer analysis, this study systematically compares OSF and the other four types of organ fibrosis from the aspects of molecules, signaling pathways, biological processes, etc. A comprehensive analysis of the similarities and differences between OSF and other organ fibrosis is helpful for researchers to discover some general rules of fibrosis disease and may provide new ideas for studying OSF. METHODS: Microarray data of the GSE64216, GSE76882, GSE171294, GSE92592, and GSE90051 datasets were downloaded from GEO. Differentially expressed mRNAs (DEmRNAs) of each type of fibrosis were identified by Limma package. Weighted gene co-expression network analysis (WGCNA) was used to identify each type of fibrosis-related module. The similarities and differences of each fibrosis-related-module genes were analyzed by function and pathway enrichment analysis. RESULTS: A total of 6 057, 10 910, 27 990, 10 480, and 4 801 DEmRNAs were identified in OSF, kidney intestinal fibrosis (KIF), liver fibrosis (LF), idiopathic pulmonary fibrosis (IPF), and skin fibrosis (SF), respectively. By using WGCNA, each type of fibrosis-related module was identified. The co-expression networks for each type of fibrosis were constructed respectively. Except that KIF and LF have 5 common hub genes, other fibrotic diseases have no common hub genes with each other. The common pathways of OSF, KIF, LF, IPF, and SF mainly focus on immune-related pathways. CONCLUSIONS OSF and the other 4 types of fibrotic diseases are tissue- and organ-specific at the molecular level, but they share many common signaling pathways and biological processes, mainly in inflammation and immunity.
Animals ; Oral Submucous Fibrosis/genetics* ; Gene Expression Profiling ; Inflammation ; Signal Transduction ; Fibrosis

OBJECTIVES: This study was performed to review the efficacy of curcumin in the treatment of oral submucous fibrosis systematically. METHODS: We searched seven databases, including Web of Science, PubMed, EBSCO, The Cochrane Library, CNKI, WanFang Data, and VIP, to obtain randomized controlled trials related to the treatment of oral submucous fibrosis by curcumin. Each database was searched from inception to 30 June 2019. RevMan 5.3 software was used for the meta-analysis. RESULTS: Six randomized controlled trials involving 350 patients were included in this study. Meta-analysis showed that curcumin can increase the maximal mouth opening and improve burning sensation compared with placebo treatment. Curcumin was not as effective as the controls in achieving maximal mouth opening after 1 month of treatment. However, no statistically significant difference was observed between the treatments from 2 months to 6 months. Curcumin significantly improved burning sensation compared with the controls after 3 months of treatment. No statistically significant diffe-rence in burning sensation was observed between the curcumin and control groups after 1, 2, and 6 months of treatment. CONCLUSIONS The current evidence shows that curcumin is an effective treatment for improving maximal mouth opening and burning sensation in patients with oral submucous fibrosis. Given the limited number and low quality of the included studies, however, more high-quality studies are needed to verify these findings.
Curcumin ; Databases, Factual ; Humans ; Oral Submucous Fibrosis/drug therapy* ; Randomized Controlled Trials as Topic ; Treatment Outcome

The relationship between areca nut as a primary carcinogen and oral cancer has been widely concerned. Areca can change the levels of reactive oxygen species (ROS) and autophagy in cells, and the levels of ROS and autophagy are closely related to the occurrence and development of tumors. This paper reviewed the relationships among areca nut, intracellular ROS, and autophagy.
Areca ; Autophagy ; Humans ; Mouth Neoplasms ; Nuts ; Oral Submucous Fibrosis ; Reactive Oxygen Species

The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.
Animals ; Carcinoma, Squamous Cell ; pathology ; Cell Transformation, Neoplastic ; pathology ; Mice ; Mouth Mucosa ; Mouth Neoplasms ; pathology ; Oral Submucous Fibrosis ; pathology ; Stem Cells

OBJECTIVE: The aim of this study was to induce oral submucous fibrosis (OSF) in Sprague-Dawley(SD) rat models by arecoline and mechanical stimulation. METHODS: Two factors factorial design was used to divide 48 rats into 8 groups (n=6). Different concentrations of arecoline (0, 0.5, 2, and 8 mg·mL⁻¹) and mechanical stimulation (with or without brush) were treated. After 16 weeks of treatment, the mouth opening was measured, the pathological changes of the buccal mucosa were observed, and the expressions of type Ⅲ collagen, transforming growth factor β1 (TGF-β1), and interferon-γ (IFN-γ) were detected. RESULTS: In rats with moderate and high concentrations of arecoline, typical OSF pathological features were observed in the buccal mucosa, the mouth openings were significantly reduced, and the expression levels of type Ⅲ colla-gen and TGF-β1 were significantly increased (P<0.05). Although mechanical stimulation can increase the three indexes of mucosa (P<0.05), no pathological change and difference in the mouth opening was observed (P>0.05). CONCLUSIONS Moderate and high concentrations of arecoline can induce OSF in SD rats, but mechanical stimulation cannot induce OSF.
Animals ; Arecoline ; pharmacology ; Fibroblasts ; Mouth Mucosa ; Oral Submucous Fibrosis ; Rats ; Rats, Sprague-Dawley

To evaluate therapeutic effect of combined injection of salvizanolic acid B with triamcinolone acetonide on the treatment of the soft palate with oral submucous fibrosis.
 Methods: Salvizanolic acid B combined with triamcinolone acetonide was consecutively applied once a week for 30 weeks for 33 patients with middle and later periods of oral submucous fibrosis. The response rate of color change in the soft palate and the increase of capillary vessels (determined by degree I-IV visual analog scale) were evaluated at the 12th, 24th, and 36th months after 30 weeks treatment.
 Results: Thirty-three patients were fulfilled the study without obvious adverse reactions and they were followed up for 24 months, while 31 patients were followed up for 36 months. The color change in the soft palatal mucus and the increase of capillary vessels at the 36th month follow-up after treatment were significantly better than those at the 12th month (P=0.004).
 Conclusion: Combined injection of salvizanolic acid B with triamcinolone acetonide in the treatment of the soft palate with oral submucous fibrosis is effective.
Glucocorticoids ; Humans ; Oral Submucous Fibrosis ; drug therapy ; Palate, Soft ; Treatment Outcome ; Triamcinolone Acetonide ; therapeutic use

OBJECTIVES: The objective of the study was to evaluate the results of nasolabial/extended nasolabial flaps as a modality for treatment of oral submucous fibrosis. MATERIALS AND METHODS: Eleven patients of Stage III or IVa maximum interincisal opening were selected to be operated. Nasolabial/extended nasolabial flaps were done for both the sides. All of the flaps were done in a single stage and were inferiorly based. A similar flap harvest/surgical technique was utilized for all the cases. RESULTS: The preoperative mouth opening ranged from 5 to 16 mm, with a mean of 10.09 mm. At 6 months the mouth opening ranged from 29 to 39 mm. Some of the complications encountered were poor scar, wisdom tooth traumatising the flap, decreased mouth opening due to non compliance and too much bulk. All of theses were managed satisfactorily. CONCLUSION: The nasolabial flap is a very reliable flap to restore the function of oral cavity. Important adjuvant measures are habit cessation, lifestyle changes, and aggressive physiotherapy.
Cicatrix ; Compliance ; Humans ; Life Style ; Molar, Third ; Mouth ; Mucous Membrane ; Oral Submucous Fibrosis*

To analyze the incidence and distribution of oral mucosal diseases in Hunan Province and provide reference for prevention and treatment.
 Methods: The clinical data for all patients, who were treated in Xiangya Hospital of Central South University from April 2013 to March 2017, were collected. After screening, weighing and classifying, sex and age distribution for the disease was analyzed.
 Results: The female with the age between 40 to 49 were in the majority among 21 972 patients. The ratio between men to women was 1:1.05. According to the classification of diseases, the most common diseases were as follows: recurrent aphthous ulcer (27.17%), burning mouth syndrome (15.72%), oral submucous fibrosis (14.75%), oral lichen planus (10.38%), oral leukoplakia (4.21%), traumatic ulceration (4.14%), chronic cheilitis (3.47%), oral fungal infection (3.26%), and atrophic glossitis (2.74%). Recurrent oral ulcer (28.65%), burning mouth syndrome (23.70%) and oral lichen planus (13.31%) were the most common 3 kinds of oral mucosal diseases during females in Hunan. Oral submucous fibrosis was the most common oral mucosal disease among males in Hunan (28.56%).
 Conclusion: Recurrent oral ulcer, burning mouth syndrome and oral lichen planus are very popular in women in Hunan Province, and oral submucous fibrosis is the most common disease in male in this region. It shows a high trend of incidence in the surrounding provinces.
Adult ; Age Distribution ; Burning Mouth Syndrome ; epidemiology ; China ; epidemiology ; Female ; Fibrosis ; Humans ; Incidence ; Leukoplakia, Oral ; epidemiology ; Lichen Planus, Oral ; epidemiology ; Male ; Middle Aged ; Mouth Diseases ; epidemiology ; therapy ; Mouth Mucosa ; pathology ; Oral Submucous Fibrosis ; Oral Ulcer ; epidemiology ; Sex Distribution ; Stomatitis, Aphthous ; epidemiology

BACKGROUND: To evaluate the versatility and reach of modified nasolabial flap used in reconstruction of defects created in and around the oral cavity. METHODS: A total number of 20 cases were selected. Out of which 13 were males and 7 females. The age of these patients ranged from 24–63 years. 29 modified nasolabial flaps were raised in twenty patients. Based on clinical and histopathological examination, out of 20 patients, 14 patients were diagnosed with oral submucous fibrosis, 3 with verrucous carcinoma, 1 with squamous papilloma, 1 with oro-antral fistula and 1 with traumatic loss of lower lip. RESULTS: Minimum preoperative interincisal distance (IID) was 0 mm and maximum was 15 mm with mean of 6.00±4.76 mm in patients with oral submucous fibrosis and 12 months postoperatively minimum IID was 16 mm and maximum was 41 mm with mean of 28.00±8.96 mm. In one case, dehiscence (3.4%) was noted on the anterior tip for which tip revision was done. Bulky appearance of the flap intraorally was observed in 2 cases (6.9%). Five (17.2%) among the 29 flaps had visible scar at the donor site postoperatively up to 3 months. CONCLUSION: Numerous reconstructive techniques have been employed in the reconstruction of small to intermediate sized defects of oral cavity. Modified nasolabial flap is a versatile flap which has robust vascularity and can be successfully used with minimal complications. It can be rotated intraorally to extend from the soft palate to the lip. Thus, it can be used efficiently to treat the small defects of the oral cavity as well as recreating lost lip structure.
Carcinoma, Verrucous ; Cicatrix ; Female ; Fistula ; Humans ; Lip ; Male ; Mouth ; Oral Submucous Fibrosis ; Palate, Soft ; Papilloma ; Precancerous Conditions ; Reconstructive Surgical Procedures ; Surgery, Oral* ; Surgical Flaps ; Tissue Donors

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.
Activation, Metabolic ; Areca ; Asian Continental Ancestry Group ; Cytochrome P-450 Enzyme System ; Deglutition ; DNA ; DNA Damage ; Epithelium ; Female ; Fibroblasts ; Fibrosis ; Humans ; Incidence ; Lobeline ; Male ; Mastication ; Mouth ; Mouth Neoplasms ; Nicotine ; Nitrosamines ; Nuts ; Oral Submucous Fibrosis ; Prevalence ; Reactive Oxygen Species ; Risk Factors ; RNA ; Tobacco ; Tobacco, Smokeless