scholarly journals Molecular Mechanism of Oral Submucous Fibrosis induced by Arecoline: A Literature Review

2020 ◽  
Author(s):  
Lin Cui ◽  
Xinjia Cai ◽  
Junhui Huang ◽  
Huiling Li ◽  
Zhigang Yao
Keyword(s):  
Molecular Mechanism ◽  
Transforming Growth Factor ◽  
Oral Submucous Fibrosis ◽  
Transforming Growth Factor Β ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Research Progress ◽  
Areca Nut ◽  
Related Factors ◽  
Oral Potentially Malignant Disorders ◽  
Submucous Fibrosis

Oral Submucous Fibrosis (OSMF) is an oral mucosal disease with lamina propria collagen hyperplasia as the main pathological change, which belongs to Oral Potentially Malignant Disorders (OPMDs). Areca nut is identified as a class I carcinogen with complex components. Arecoline is the main component of areca nut which plays an important role in the pathogenesis of OSMF. Through the review of literature, it is shown that arecoline can lead to the change in level of cytokines in oral mucosa, which further leads to the imbalance of collagen metabolism. This article reviews the molecular mechanism research progress of arecoline in promoting the pathogenesis of OSMF in recent years, including Transforming Growth Factor-β (TGF-β) and Reactive Oxygen Species (ROS) associated with increased collagen production, Matrix Metalloproteinase (MMP) and Tissue Inhibitor of Metalloproteinase (TIMP) associated with reduced collagen degradation, hypoxia and microvascular related factors and in order to provide reference for the treatment of the disease at the molecular level.

scholarly journals Targeting lncRNA H19/miR-29b/COL1A1 Axis Impedes Myofibroblast Activities of Precancerous Oral Submucous Fibrosis

2021 ◽  
Vol 22 (4) ◽  
pp. 2216
Author(s):  
Cheng-Chia Yu ◽  
Yi-Wen Liao ◽  
Pei-Ling Hsieh ◽  
Yu-Chao Chang
Keyword(s):  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Oral Submucous Fibrosis ◽  
Ectopic Expression ◽  
Collagen Gel ◽  
Type I ◽  
Migration Ability ◽  
Potentially Malignant ◽  
Submucous Fibrosis

Oral submucous fibrosis (OSF) is known as a potentially malignant disorder, which may result from chemical irritation due to areca nuts (such as arecoline). Emerging evidence suggests that fibrogenesis and carcinogenesis are regulated by the interaction of long noncoding RNAs (lncRNAs) and microRNAs. Among these regulators, profibrotic lncRNA H19 has been found to be overexpressed in several fibrosis diseases. Here, we examined the expression of H19 in OSF specimens and its functional role in fibrotic buccal mucosal fibroblasts (fBMFs). Our results indicate that the aberrantly overexpressed H19 contributed to higher myofibroblast activities, such as collagen gel contractility and migration ability. We also demonstrated that H19 interacted with miR-29b, which suppressed the direct binding of miR-29b to the 3′-untranslated region of type I collagen (COL1A1). We showed that ectopic expression of miR-29b ameliorated various myofibroblast phenotypes and the expression of α-smooth muscle actin (α-SMA), COL1A1, and fibronectin (FN1) in fBMFs. In OSF tissues, we found that the expression of miR-29b was downregulated and there was a negative correlation between miR-29b and these fibrosis markers. Lastly, we demonstrate that arecoline stimulated the upregulation of H19 through the transforming growth factor (TGF)-β pathway. Altogether, this study suggests that increased TGF-β secretion following areca nut chewing may induce the upregulation of H19, which serves as a natural sponge for miR-29b and impedes its antifibrotic effects.

scholarly journals The Anti-Cancer Effects of a Zotarolimus and 5-Fluorouracil Combination Treatment on A549 Cell-Derived Tumors in BALB/c Nude Mice

2021 ◽  
Vol 22 (9) ◽  
pp. 4562
Author(s):  
Ching-Feng Wu ◽  
Ching-Yang Wu ◽  
Robin Y.-Y. Chiou ◽  
Wei-Cheng Yang ◽  
Chuen-Fu Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Nude Mice ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Transforming Growth Factor Β ◽  
Related Factors ◽  
Human Lung Adenocarcinoma

Zotarolimus is a semi-synthetic derivative of rapamycin and a novel immunosuppressive agent used to prevent graft rejection. The pharmacological pathway of zotarolimus restricts the kinase activity of the mammalian target of rapamycin (mTOR), which potentially leads to reductions in cell division, cell growth, cell proliferation, and inflammation. These pathways have a critical influence on tumorigenesis. This study aims to examine the anti-tumor effect of zotarolimus or zotarolimus combined with 5-fluorouracil (5-FU) on A549 human lung adenocarcinoma cell line implanted in BALB/c nude mice by estimating tumor growth, apoptosis expression, inflammation, and metastasis. We established A549 xenografts in nude mice, following which we randomly divided the mice into four groups: control, 5-FU (100 mg/kg/week), zotarolimus (2 mg/kg/day), and zotarolimus combined with 5-FU. Compared the results with those for control mice, we found that mice treated with zotarolimus or zotarolimus combined with 5-FU retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; decreased inflammation cytokines levels (e.g., IL-1β, TNF-α, and IL-6); reduced inflammation-related factors such as cyclooxygenase-2 (COX-2) protein and nuclear factor-κB (NF-κB) mRNA; enhanced anti-inflammation-related factors including IL-10 and inhibitor of NF-κB kinase α (IκBα) mRNA; and inhibited metastasis-related factors such as transforming growth factor β (TGF-β), CD44, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). Notably, mice treated with zotarolimus combined with 5-FU had significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with the groups of mice treated with 5-FU or zotarolimus alone. The in vivo study confirmed that zotarolimus or zotarolimus combined with 5-FU could retard lung adenocarcinoma growth and inhibit tumorigenesis. Zotarolimus and 5-FU were found to have an obvious synergistic tumor-inhibiting effect on lung adenocarcinoma. Therefore, both zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents for treatment of human lung adenocarcinoma.

scholarly journals Vascular endothelial growth factor (VEGF) gene polymorphism in oral submucous fibrosis subjects - A preliminary study

2016 ◽  
Vol 7 (5) ◽  
pp. 10-16 ◽  
Author(s):  
Devishree V Rai ◽  
Kruthika S Guttal ◽  
Bhusan B Kulkarni ◽  
Shivaprakash Hiremath ◽  
Krishna N Burde
Keyword(s):  
Malignant Transformation ◽  
Oral Submucous Fibrosis ◽  
Mouth Opening ◽  
Control Group ◽  
Transformation Rate ◽  
Significant Finding ◽  
Vegf Gene ◽  
Oral Potentially Malignant Disorders ◽  
Male Predominance ◽  
Submucous Fibrosis

Background: Oral Submucous Fibrosis is one of the oral potentially malignant disorders presenting with progressive restriction in mouth opening. The condition having a high malignant transformation rate necessitates identification of biomarkers to be employed for early detection of malignant change. This will influence the prognosis in addition to adding better quality of life to patients.Aims and Objectives: To relate the association of VEGF -460C/T polymorphism in patients with OSMF and to compare the same among healthy subjects.Materials and Methods: Thirty patients with Oral submucous fibrosis and 20 controls free from habits and any form of lesions were included in the study. The polymorphism of VEGF gene was detected by polymerase chain reaction-based restriction analysis.Results: Sixty-four percent of the population in the study was in the age group of 21-40 yrs suggesting the prominence of disease in younger individuals with male predominance. With reference to polymorphism, 6.67% of the subjects from OSMF group showed CT polymorphism and 16.67% showed TT polymorphism. There were no statistically significant differences in the polymorphism between the study group and controls. However the frequency of T allele in the patient group 12 (20%) was greater than that in the control group 1 (2.5%), which was a significant finding. There was no association between the habits, frequency of habits, duration of quid placement, site of quid placement and style of chewing with the nature of polymorphism. Conclusion: VEGF 460C/T has the potential to be used as a prognostic marker in predicting the malignant transformation of OSMF.Asian Journal of Medical Sciences Vol.7(5) 2016 10-16

Sign in / Sign up

Export Citation Format

Share Document