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Phytomedicine : International Journal... Aug 2022Oral leukoplakia (OLK), an uncharacterized pathological condition that occurs as a white patch in the oral mucosa, is the most common precancerous condition. Scutellaria...
Deciphering the pharmacological mechanisms of Scutellaria baicalensis Georgi on oral leukoplakia by combining network pharmacology, molecular docking and experimental evaluations.
BACKGROUND
Oral leukoplakia (OLK), an uncharacterized pathological condition that occurs as a white patch in the oral mucosa, is the most common precancerous condition. Scutellaria baicalensis Georgi (SBG) is a medicinal plant with a wide range of pharmacological effects. Increased evidence shows that SBG has potential therapeutic effects on OLK. However, the therapeutic mechanisms of SBG against OLK have not yet been completely elucidated.
PURPOSE
This study aimed to clarify the active components and multi-target mechanisms of SBG against OLK via network pharmacology, molecular docking and experimental evaluations.
STUDY DESIGN AND METHODS
The active components and related targets of SBG were screened by the TCMSP database and Swiss Target Prediction database. Potential therapeutic targets of OLK were collected using the GeneCards and OMIM databases. Then, we established protein-protein interaction (PPI), compound-target-disease (C-T-D), and compound-target-pathway (C-T-P) networks by Cytoscape to identify the main components, core targets, and pharmacological pathways of SBG against OLK via applying data mining techniques and topological parameters. Metascape database was utilized for GO and KEGG pathway analysis. Molecular docking techniques were used to estimate the binding force between the components and the hub genes. Subsequently, a series of in vitro experiments, specifically CCK-8 assay, clone formation assay, wound healing assay, flow cytometry, RT-qPCR and western blotting were conducted for further verification.
RESULTS
There were 25 active components and 31 related target genes in SBG against OLK. PPI analysis showed that Akt1, VEGFA, EGFR, HIF1A and PTGS2 shared the highest centrality among all target genes. KEGG pathway analysis found that PI3K-Akt signaling pathway may occupy core status in the anti-OLK system. Molecular docking results showed that the main active components of SBG had a strong binding affinity to the hub genes. In vitro experiments showed that the leading component baicalein may inhibit proliferation, block cells in the S phase, induce DOK cell apoptosis, and downregulate the mRNA expression of 5 hub genes by inhibiting PI3K/Akt signaling pathway activation.
CONCLUSION
The most predominant component of SBG against OLK was baicalein and the key pathway was PI3K/Akt. The main components and hub genes had robust binding abilities. In vitro experiments showed that baicalein could inhibit the proliferation of DOK cells, induce apoptosis, block the cell cycle, and inhibit the mRNA expression level of the hub genes by inhibiting the PI3K/Akt pathway.
Topics: Drugs, Chinese Herbal; Leukoplakia, Oral; Molecular Docking Simulation; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; RNA, Messenger; Scutellaria baicalensis
PubMed: 35667260
DOI: 10.1016/j.phymed.2022.154195 -
Head and Neck Pathology Jun 2021The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management....
The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Five non-PVL histologic mimics were included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as "corrugated ortho(para)hyperkeratotic lesion, not reactive" and "SCC" (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the "Bulky hyperkeratotic epithelial proliferation, not reactive" category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) "corrugated ortho(para)hyperkeratotic lesion, not reactive;" (2) "bulky hyperkeratotic epithelial proliferation, not reactive;" and (3) "suspicious for," or "squamous cell carcinoma." Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.
Topics: Humans; Leukoplakia, Oral; Pathology, Oral
PubMed: 33415517
DOI: 10.1007/s12105-020-01262-9 -
Cleveland Clinic Journal of Medicine Feb 2023
Topics: Humans; Leukoplakia, Oral; Mouth Neoplasms
PubMed: 36724918
DOI: 10.3949/ccjm.90a.22044 -
European Review For Medical and... Sep 2019The aim of this review is to describe the "hot points" of current clinical governance for oral HPV comprising the use of new diagnostic molecular procedures, namely,... (Review)
Review
OBJECTIVE
The aim of this review is to describe the "hot points" of current clinical governance for oral HPV comprising the use of new diagnostic molecular procedures, namely, Pyrosequencing and Next Generation Sequencing.
MATERIALS AND METHODS
The data on oral HPV was collected through two levels of research. First for all, we used the canonical medical search engines, PubMed, and Medline, followed by the study of current commercial tools for HPV diagnosis, particularly within commercial companies involved in the molecular procedures for HPV detecting and genotyping.
RESULTS
Different medical procedures are now described and used throughout the world in HPV diagnosis and treatment. However, the laboratory methods are often validated and used for genital infections, and, in these cases, data are missing in the literature as regards the clinical approach for oral lesions.
CONCLUSIONS
Dental care units are often the front line for a clinical evaluation of a possible HPV lesion in the oral cavity, which means that correct clinical governance could avoid a viral neoplastic progression of this disease with great advantages for the patient. In this case, the problem is due to the difficulty in lesion recognition but also and more especially the absence of correct laboratory diagnosis and subsequent treatment in the clinical course.
Topics: Carcinoma, Verrucous; Cryosurgery; Focal Epithelial Hyperplasia; Humans; Laser Therapy; Leukoplakia, Oral; Lichen Planus, Oral; Mouth Diseases; Mouth Neoplasms; Papilloma; Papillomaviridae; Papillomavirus Infections; Photochemotherapy; Squamous Cell Carcinoma of Head and Neck; Warts
PubMed: 31599444
DOI: 10.26355/eurrev_201909_19035 -
BMC Oral Health Sep 2023Oral leukoplakia(OLK) is a common oral potentially malignant disorder. The global prevalence of solely OLK was published in 2003, while the prevalence varied among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral leukoplakia(OLK) is a common oral potentially malignant disorder. The global prevalence of solely OLK was published in 2003, while the prevalence varied among different studies. In recent years, large-scale summary and definition-related analyses obtain insufficient attention. This study aimed to perform a systematic review of prevalence studies of oral leukoplakia and assess predisposing factors of its occurrence.
METHODS
The search terms ("Oral leukoplakia" OR OLK OR leukoplakia) AND (prevalence OR incidence OR epidemiology) were searched in databases (Pubmed, Embase, Scopus, and Web of Science) for OLK studies published from January 1996 until December 2022. The estimated prevalence calculation and risk of bias analysis used STATA 16.0.
RESULTS
We obtained 69 studies, including 1,263,028 participants, from 28 countries, and 6 continents. The prevalence was 1.39%, varying from 0.12 to 33.33%. The overall pooled estimated prevalence of OLK was 2.23% for population-based studies, 1.36% for clinic-based population studies, and 9.10% for specific populations. The pooled prevalence in different continents ranged from 0.33 to 11.74% with a statistical difference in the population-based calculation. The estimated prevalence of OLK was higher in males than in females. Those who smoked and consumed alcohol had a higher prevalence than those who did not.
CONCLUSION
Combining data from 69 published studies, the prevalence of OLK was determined as 1.39% and the pooling estimated global prevalence was 3.41%. The prevalence was relatively consistent and stable across different continents and different definitions. A higher pooled estimated prevalence was found among males, those aged over 60 years old, smokers, and alcohol consumers. The results from the included studies in this systematic review revealed that the prevalence was relatively consistent and stable across various definitions and continents, which may help in developing global treatment and prevention strategies for oral leukoplakia.
Topics: Female; Male; Humans; Middle Aged; Aged; Prevalence; Leukoplakia, Oral; Databases, Factual; Ethanol; Research Design
PubMed: 37670255
DOI: 10.1186/s12903-023-03342-y -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2015In the past decades several definitions of oral leukoplakia have been proposed, the last one, being authorized by the World Health Organization (WHO), dating from 2005.... (Review)
Review
In the past decades several definitions of oral leukoplakia have been proposed, the last one, being authorized by the World Health Organization (WHO), dating from 2005. In the present treatise an adjustment of that definition and the 1978 WHO definition is suggested, being : "A predominantly white patch or plaque that cannot be characterized clinically or pathologically as any other disorder; oral leukoplakia carries an increased risk of cancer development either in or close to the area of the leukoplakia or elsewhere in the oral cavity or the head-and-neck region". Furthermore, the use of strict diagnostic criteria is recommended for predominantly white lesions for which a causative factor has been identified, e.g. smokers' lesion, frictional lesion and dental restoration associated lesion. A final diagnosis of such leukoplakic lesions can only be made in retrospect after successful elimination of the causative factor within a somewhat arbitrarily chosen period of 4-8 weeks. It seems questionable to exclude "frictional keratosis" and "alveolar ridge keratosis" from the category of leukoplakia as has been suggested in the literature. Finally, brief attention has been paid to some histopathological issues that may cause confusion in establishing a final diagnosis of leukoplakia.
Topics: Decision Trees; Humans; Leukoplakia, Oral; Terminology as Topic
PubMed: 26449439
DOI: 10.4317/medoral.21007 -
Medicina Oral, Patologia Oral Y Cirugia... Jan 2022MiRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level and have been associated with malignant transformation of oral... (Review)
Review
BACKGROUND
MiRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level and have been associated with malignant transformation of oral epithelial precursor lesions such as oral leukoplakia. The aim was to perform a scoping review of the contemporary literature about the different roles of miRNAs during the malignant transformation of oral leukoplakia.
MATERIAL AND METHODS
We conducted a systematic search with the following MeSH terms: 'oral leukoplakia', 'carcinoma in situ', 'microRNAs', 'mouth neoplasms' and 'epithelial-mesenchymal transition' in PubMed/MEDLINE, EMBASE and SpringerLink.
RESULTS
Fifteen articles were included for analysis, among which in vivo and in vitro articles were included. A total of 21 different miRNAs were found to be involved in the malignant transformation process of oral leukoplakia. Regarding their possible effects, 6 miRNAs were classified as oncogenic, 5 as tumour suppressors and 10 were related to epithelial-mesenchymal transition, invasion and migration.
CONCLUSIONS
Based on the current review, we concluded that miRNAs-21, 345, 181-b and 31* seem to be potential markers of malignant transformation of oral leukoplakia. However, further clinical prospective studies are needed in order to validate their utility as prognostic biomarkers.
Topics: Cell Transformation, Neoplastic; Humans; Leukoplakia, Oral; MicroRNAs; Mouth Neoplasms; Prospective Studies
PubMed: 34564679
DOI: 10.4317/medoral.24975 -
Organogenesis Dec 2023Oral leukoplakia (OLK) and oral lichen planus (OLP) are common precancerous lesions of the oral mucosa. The role of circular RNAs (circRNAs) in OLK and OLP is unclear....
BACKGROUND
Oral leukoplakia (OLK) and oral lichen planus (OLP) are common precancerous lesions of the oral mucosa. The role of circular RNAs (circRNAs) in OLK and OLP is unclear. The aim of this study was to evaluate the circRNA expression profiles of OLK and OLP, and further explore the potential role of circRNAs in the pathogenesis of these two diseases.
METHODS
High throughput sequencing technology was performed to detect the differentially expressed circRNA in OLK ( = 6), OLP ( = 6), oral squamous cell carcinoma ( = 6), and normal oral mucosa tissues ( = 6). Expression of selected circRNAs was validated by qRT-PCR, enzyme tolerance assay, and Sanger sequencing. Expanded sample size validation was done in 20 tissue pairs. The biological processes and signal pathways involved in differential circRNA were analyzed by GO and KEGG enrichment. TargetScan and MiRanda were used to predict miRNAs downstream of circRNA and draw competitive endogenous RNA network diagram.
RESULTS
Forty-nine circRNAs were significantly altered in OLK and OLP, including 30 upregulated and 19 downregulated circRNAs. The five selected circRNAs were validated by qRT-PCR, Sanger sequencing, and RNase R assay. GO and KEGG analyses indicated that the upregulated circHLA-C may be involved in the biological process of immune function of OLK and OLP. Bioinformatics analysis indicated that circHLA-C may be involved in the progression of OLK and OLP as a ceRNA. In validation with expanded sample size, PCR results showed that circHLA-C expression was significantly upregulated in OLK and OLP. ROC analysis indicated that circHLA-C has potential diagnostic value with good accuracy and specificity.
CONCLUSION
Our study revealed that circHLA-C is the most significantly upregulated circRNA co-existing in OLK and OLP, and we preliminarily discuss the role of circHLA-C in the etiopathogenesis and progression of OLK and OLP.
Topics: Humans; RNA, Circular; Mouth Neoplasms; Carcinoma, Squamous Cell; Lichen Planus, Oral; Leukoplakia, Oral; MicroRNAs
PubMed: 37531467
DOI: 10.1080/15476278.2023.2234504 -
Oral Diseases Mar 2023To identify possible associations between patients' demographics and habits and the clinical aspects and histopathological characteristics of oral leukoplakia (OL) at...
OBJECTIVES
To identify possible associations between patients' demographics and habits and the clinical aspects and histopathological characteristics of oral leukoplakia (OL) at patients' first visit.
METHOD
A total of 140 consecutive patients with OL at a single institute between 1997 and 2019. All biopsies were microscopically examined for classic dysplasia (CD) (WHO definition oral epithelial dysplasia) and differentiated dysplasia (DD) known from differentiated vulvar intraepithelial neoplasia. Clinical characteristics were correlated to histopathological diagnosis and odds ratios (OR) were calculated.
RESULTS
A total of 96 females and 44 males, mean age 58 years, were presented. OLs were found mainly on the tongue (41%) and floor of mouth (FOM) (18%). Homogeneous OLs (58%) were associated with smoking, FOM and size <2cm and non-homogeneous OLs (42%) with non-smokers. No dysplasia was present in 40% and any dysplasia (AD) in 60%. Tongue OLs were correlated with AD (OR:6.0) and CD (OR:5.7). FOM OLs were correlated with CD (OR:4.5). DD was correlated with non-homogeneous OLs (OR:2.6).
CONCLUSIONS
CD was most frequently observed in tongue and FOM OLs, while DD was associated with non-homogeneous OLs. In this series of patients, there was no consistent reliable association between the clinical and histopathological features and clinical characteristics can therefore not substitute microscopic examination of biopsies.
Topics: Male; Female; Humans; Middle Aged; Leukoplakia, Oral; Smoking; Tongue; Carcinoma, Squamous Cell; Hyperplasia; Cell Transformation, Neoplastic
PubMed: 34601770
DOI: 10.1111/odi.14038 -
Oral Surgery, Oral Medicine, Oral... Jun 2018
Topics: Cell Transformation, Neoplastic; Diagnosis, Oral; Disease Progression; Erythroplasia; Humans; Leukoplakia, Oral; Pathology, Oral; Precancerous Conditions; Risk Factors
PubMed: 29706483
DOI: 10.1016/j.oooo.2018.04.001