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1.
Am J Hum Genet ; 111(6): 1047-1060, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38776927

RESUMO

Lichen planus (LP) is a T-cell-mediated inflammatory disease affecting squamous epithelia in many parts of the body, most often the skin and oral mucosa. Cutaneous LP is usually transient and oral LP (OLP) is most often chronic, so we performed a large-scale genetic and epidemiological study of LP to address whether the oral and non-oral subgroups have shared or distinct underlying pathologies and their overlap with autoimmune disease. Using lifelong records covering diagnoses, procedures, and clinic identity from 473,580 individuals in the FinnGen study, genome-wide association analyses were conducted on carefully constructed subcategories of OLP (n = 3,323) and non-oral LP (n = 4,356) and on the combined group. We identified 15 genome-wide significant associations in FinnGen and an additional 12 when meta-analyzed with UKBB (27 independent associations at 25 distinct genomic locations), most of which are shared between oral and non-oral LP. Many associations coincide with known autoimmune disease loci, consistent with the epidemiologic enrichment of LP with hypothyroidism and other autoimmune diseases. Notably, a third of the FinnGen associations demonstrate significant differences between OLP and non-OLP. We also observed a 13.6-fold risk for tongue cancer and an elevated risk for other oral cancers in OLP, in agreement with earlier reports that connect LP with higher cancer incidence. In addition to a large-scale dissection of LP genetics and comorbidities, our study demonstrates the use of comprehensive, multidimensional health registry data to address outstanding clinical questions and reveal underlying biological mechanisms in common but understudied diseases.


Assuntos
Doenças Autoimunes , Estudo de Associação Genômica Ampla , Líquen Plano Bucal , Neoplasias Bucais , Humanos , Doenças Autoimunes/genética , Líquen Plano Bucal/genética , Líquen Plano Bucal/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Feminino , Masculino , Heterogeneidade Genética , Pessoa de Meia-Idade , Líquen Plano/genética , Líquen Plano/patologia , Predisposição Genética para Doença , Idoso , Adulto , Fatores de Risco , Polimorfismo de Nucleotídeo Único
2.
Cell Physiol Biochem ; 58(4): 311-321, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39012386

RESUMO

BACKGROUND/AIMS: The objectives of our study were to determine salivary α-amylase activity (stress biomarker) and its association with psychological status and quality of life (QoL), disease duration and intensity of symptoms (pain/burning) in patients with OLP. METHODS: A total of 50 subjects participated in this case-control study: 30 patients with oral lichen planus (OLP); 20 control subjects. Unstimulated whole saliva (UWS) was collected between 9 and 10 am to avoid diurnal fluctuations. Psychological status was assessed using the Croatian validated version of the original Depression, Anxiety and Stress Scale (DASS-21). The impact of oral health on QoL was assessed using the Croatian version of the Oral Health Impact Profile Questionnaire (OHIP-CRO14). RESULTS: There was no statistically significant difference in salivary α-amylase activity between patients with OLP (N=30) and control subjects (N=20) (133813.3 vs. 166815.5 U/L, p=0.314; t-test). Depression, anxiety and stress showed no statistically significant difference between patients with OLP and control subjects (p=0.076, p=0.111, p=0.209; t-test). The patients with OLP had statistically significantly poorer QoL (total) compared to control subjects (p=0.004, t-test). There was a moderate positive correlation between symptom intensity (pain/burning) and poor QoL (total) (r=0.584, p<0.001), the OHIP-CRO14 dimension "physical pain" (r=0.661, p<0.001), "psychological impossibility" (r=0.555, p<0.01), "handicap" (r=0.546, p<0.01). CONCLUSION: Although salivary α-amylase showed no statistically significant difference between patients with OLP and control subjects, the patients with OLP had poorer psychological status (three times higher scores for depression and two times higher scores for anxiety) and poorer QoL compared to the control subjects. Recognising and treating mental disorders in patients with OLP is important in order to break the "vicious circle" and achieve a better QoL in these patients.


Assuntos
Ansiedade , Líquen Plano Bucal , Qualidade de Vida , Saliva , alfa-Amilases Salivares , Humanos , Estudos de Casos e Controles , Feminino , Masculino , Pessoa de Meia-Idade , Líquen Plano Bucal/psicologia , Líquen Plano Bucal/metabolismo , alfa-Amilases Salivares/metabolismo , alfa-Amilases Salivares/análise , Adulto , Saliva/metabolismo , Saliva/química , Saliva/enzimologia , Inquéritos e Questionários , Depressão , Idoso , Biomarcadores/metabolismo
3.
BMC Microbiol ; 24(1): 197, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849732

RESUMO

BACKGROUND: Emerging evidence emphasized the role of oral microbiome in oral lichen planus (OLP). To date, no dominant pathogenic bacteria have been identified consistently. It is noteworthy that a decreased abundance of Streptococcus, a member of lactic acid bacteria (LAB) in OLP patients has been commonly reported, indicating its possible effect on OLP. This study aims to investigate the composition of LAB genera in OLP patients by high-throughput sequencing, and to explore the possible relationship between them. METHODS: We collected saliva samples from patients with OLP (n = 21) and healthy controls (n = 22) and performed 16 S rRNA gene high-throughput sequencing. In addition, the abundance of LAB genera was comprehensively analyzed and compared between OLP and HC group. To verify the expression of Lactococcus lactis, real time PCR was conducted in buccal mucosa swab from another 14 patients with OLP and 10 HC. Furthermore, the correlation was conducted between clinical severity of OLP and LAB. RESULTS: OLP and HC groups showed similar community richness and diversity. The members of LAB, Lactococcus and Lactococcus lactis significantly decreased in saliva of OLP cases and negatively associated with OLP severity. In addition, Lactococcus and Lactococcus lactis showed negative relationship with Fusobacterium and Aggregatibacter, which were considered as potential pathogens of OLP. Similarly, compared with healthy controls, the amount of Lactococcus lactis in mucosa lesion of OLP patients was significantly decreased. CONCLUSIONS: A lower amount of Lactococcus at genus level, Lactococcus lactis at species level was observed in OLP cases and associated with disease severity. Further studies to verify the relationship between LAB and OLP, as well as to explore the precise mechanism is needed.


Assuntos
Lactobacillales , Líquen Plano Bucal , Microbiota , RNA Ribossômico 16S , Saliva , Humanos , Saliva/microbiologia , Feminino , Masculino , Líquen Plano Bucal/microbiologia , Pessoa de Meia-Idade , Lactobacillales/genética , Lactobacillales/isolamento & purificação , Lactobacillales/classificação , RNA Ribossômico 16S/genética , Adulto , Sequenciamento de Nucleotídeos em Larga Escala , Idoso , Mucosa Bucal/microbiologia , Estudos de Casos e Controles , DNA Bacteriano/genética , Lactococcus lactis/genética , Lactococcus lactis/isolamento & purificação
4.
Exp Dermatol ; 33(4): e15080, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628035

RESUMO

Erosive oral lichen planus (OLP) is a challenging disease. This T cell driven disorder frequently shows a treatment unresponsive course and strongly limits patients' quality of life. The disease lacks FDA or EMA approved drugs for its treatment and the efficacy of the commonly administered treatments (i.e. topical and systemic steroids, steroid sparing agents) is often only partial. Although the etiopathogenesis of the disease still needs to be fully elucidated, recent advances helped to identify interferon-É£ (IFN-É£) as a pivotal cytokine in OLP pathogenesis, thus making the interference with its signalling a therapeutic target. Janus kinase (JAK) inhibitors therefore gained relevance for their inhibitory effect on IFN-É£ signalling. While some drugs such as abrocitinib, upadacitinib, tofacitinib directly interfere with IFN-É£ signalling through blockade of JAK1 and/or JAK2, deucravacitinib, a selective TYK-2 inhibitor indirectly interferes on IFN-É£ activation through interference with interleukin (IL)-12, a potent promotor for Th1/IFN-É£ responses. This mechanism of action makes deucravacitinib a candidate drug for the treatment of OLP. Here we provide initial evidence that deucravacitinib 6 mg daily has a beneficial effect in three patients with oral OLP.


Assuntos
Compostos Heterocíclicos , Inibidores de Janus Quinases , Líquen Plano Bucal , Humanos , Citocinas , Compostos Heterocíclicos/uso terapêutico , Interferon gama , Inibidores de Janus Quinases/uso terapêutico , Líquen Plano Bucal/tratamento farmacológico , Qualidade de Vida , TYK2 Quinase/antagonistas & inibidores
5.
Inflamm Res ; 73(5): 867-876, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38563967

RESUMO

OBJECTIVE: γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells, thereby modulating immune responses. As the first line of host defense, γδ T cells are essential for mucosal homeostasis and immune surveillance. When abnormally activated or impaired, γδ T cells can contribute to pathogenic processes. Accumulating evidence has revealed substantial impacts of γδ T cells on the pathogenesis of cancers, infections, and immune-inflammatory diseases. γδ T cells exhibit dual roles in cancers, promoting or inhibiting tumor growth, depending on their phenotypes and the clinical stage of cancers. During infections, γδ T cells exert high cytotoxic activity in infectious diseases, which is essential for combating bacterial and viral infections by recognizing foreign antigens and activating other immune cells. γδ T cells are also implicated in the onset and progression of immune-inflammatory diseases. However, the specific involvement and underlying mechanisms of γδ T cells in oral diseases have not been systematically discussed. METHODS: We conducted a systematic literature review using the PubMed/MEDLINE databases to identify and analyze relevant literature on the roles of γδ T cells in oral diseases. RESULTS: The literature review revealed that γδ T cells play a pivotal role in maintaining oral mucosal homeostasis and are involved in the pathogenesis of oral cancers, periodontal diseases, graft-versus-host disease (GVHD), oral lichen planus (OLP), and oral candidiasis. γδ T cells mainly influence various pathophysiological processes, such as anti-tumor activity, eradication of infection, and immune response regulation. CONCLUSION: This review focuses on the involvement of γδ T cells in oral diseases, with a particular emphasis on the main functions and underlying mechanisms by which γδ T cells influence the pathogenesis and progression of these conditions. This review underscores the potential of γδ T cells as therapeutic targets in managing oral health issues.


Assuntos
Doenças da Boca , Humanos , Doenças da Boca/imunologia , Animais , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos Intraepiteliais/imunologia , Doença Enxerto-Hospedeiro/imunologia , Linfócitos T/imunologia
6.
J Oral Pathol Med ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054556

RESUMO

BACKGROUND: The specific mechanism underlying the role of oral lichen planus-activated fibroblasts in angiogenesis remains undefined. Herein, the expression of Galectin-3 in oral lichen planus and verifying whether Galectin-3 can promote angiogenesis through oral lichen planus-activated fibroblasts has been investigated. METHODS: The expression of Galectin-3 and CD34 in the oral lichen planus tissues (n = 30) and normal oral mucosa tissues (n = 15) was detected by immunohistochemistry. The expression of Galectin-3 in the oral lichen planus-activated fibroblasts was determined by reverse transcription-polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Galectin-3 overexpression lentiviral vector was constructed and transfected with oral lichen planus-activated fibroblasts. In addition, oral lichen planus-activated fibroblasts were treated with GB1107 (5 and 10 µM) to inhibit Galectin-3 expression and co-cultured with human umbilical vein vascular endothelial cells, and analyzed by Transwell and tube formation assays. The expression of VEGF and FGF2 in oral lichen planus-activated fibroblasts was detected, and the expression and phosphorylation levels of VEGFR2 and FAP in human umbilical vein vascular endothelial cells were determined. RESULTS: Oral lichen planus subcutaneous tissues highly expressed Galectin-3, positively correlated with angiogenesis. Oral lichen planus-activated fibroblasts expressed significantly higher Galectin-3 than NFs. Oral lichen planus-activated fibroblasts overexpressing Galectin-3 enhanced the migration and tube-forming capacity of co-cultured human umbilical vein vascular endothelial cells. In oral lichen planus-activated fibroblasts, 10 µM GB1107 reduced the proliferation and migration capacity, decreased the expression of α-SMA, FAP, VEGF, and FGF2, and inhibited the tube-forming capacity and the expression of VEGFR2 phosphorylation and FAK in co-cultured human umbilical vein vascular endothelial cells. CONCLUSIONS: The upregulation of Galectin-3 expression in oral lichen planus is associated with angiogenesis, and the oral lichen planus-activated fibroblasts promote human umbilical vein vascular endothelial cells migration and tube-forming differentiation through VEGFR2/FAP activation by Galectin-3.

7.
J Oral Pathol Med ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866540

RESUMO

BACKGROUND: Oral lichen planus (OLP) is a common T cell-mediated oral mucosal immune inflammatory disease. Intraepithelial lymphocytes (IELs) are a unique subset of T cells that play an important role in regulating immune response. This study aims to investigate the phenotype and the differentiation mechanism of IELs in OLP. METHODS: The expression of CD4, CD8α, CD8ß, T-helper-inducing POZ/Krueppel-like factor (ThPOK), and RUNX family transcription factor 3 (Runx3) in the epithelium and peripheral blood mononuclear cells (PBMCs) of OLP was determined by immunofluorescence and immunohistochemistry. Then, the correlations among them were analyzed. Naïve CD4+ T cells were sorted from blood of OLP patients and stimulated with retinoic acid (RA) and transforming growth factor-ß1 (TGF-ß1). Then the expression of CD4, CD8α, CD8ß, ThPOK, and Runx3 was investigated by immunocytochemistry. RESULTS: CD8α expression and CD8αα+ cells were upregulated in the epithelium of OLP, whereas they were downregulated in PBMCs of OLP. CD8ß was not expressed in the epithelium of OLP. CD4, CD8α, and Runx3 expression and CD4+CD8α+ cells were increased, whereas ThPOK expression was decreased in the epithelium of OLP. CD8α expression was positively correlated with Runx3 expression, whereas ThPOK expression was negatively correlated with Runx3 expression. After RA and TGF-ß1 stimulation, CD8α and Runx3 expression was upregulated, and ThPOK expression was downregulated in naïve CD4+ T cells. CONCLUSION: CD4+CD8αα+ IELs may be the dominant phenotype of IELs in OLP, and the differentiation of CD4+CD8αα+ IELs in OLP is negatively regulated by ThPOK and positively regulated by Runx3.

8.
Oral Dis ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38720635

RESUMO

OBJECTIVE: To evaluate whether hydroxychloroquine (HCQ) or chloroquine (CQ) are effective for the treatment of oral lichen planus (OLP). MATERIALS AND METHODS: A literature search was conducted in four databases. Clinical studies investigating the effect of HCQ/CQ in patients with OLP were included. RESULTS: Eleven studies were included. Four were RCTs and seven quasi-experimental studies. The studies included 390 patients diagnosed with OLP, of which 326 and 7 received HCQ and CQ, respectively. 46 patients received topical dexamethasone, 5 placebo and 6 griseofulvin as controls. Five studies assessed pain, and all of them obtained pain reduction with the use of HCQ. Six studies reported objective clinical improvement of OLP with the use of HCQ. Five studies that used a subjective scale obtained that 24%-100% of the patients achieved a complete/almost complete improvement of OLP lesions and its symptomatology. The most frequent side effects were vision problems, gastric discomfort, rash, nauseas, headaches, skin pigmentation, and elevated kidney function. 17 patients had to withdraw from the studies. CONCLUSIONS: Current evidence is scarce to confirm HCQ as a therapeutic option for OLP. More RCTs are needed to compare its efficacy with topical corticosteroids and to evaluate whether HCQ reduces relapses of OLP.

9.
Oral Dis ; 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735757

RESUMO

BACKGROUND: This study aimed to evaluate the incidence of implant failure in patients with oral lichen planus (OLP) and investigate the potential association between OLP and peri-implant diseases. MATERIALS AND METHODS: Embase, Web of Science, PubMed, and Scopus databases were searched for studies with no time restrictions. Meta-analysis was performed calculating pooled proportion of peri-implantitis (PI), peri-implant mucositis (PIM), and bleeding on probing (BOP) prevalence using fixed-effects model. Odds ratio and corresponding 95% CI were calculated to assess the potential risk of PI, PIM, and BOP in dental implant patients with OLP compared to healthy controls. RESULTS: Implant failure rate was 4.38% at the patient level and 4.37% at the implant level. Six patients (3.92%) from five studies were diagnosed with oral cancer after receiving implant. The prevalence of PI, PIM, and BOP at the implant level were 14.00%, 20.00%, and 40.00%, respectively. There was no significant difference in the occurrence of PI and PIM between OLP patients and healthy controls. CONCLUSIONS: Stabilized OLP is not considered a significant risk factor for peri-implant diseases. It is advised against placing implants or prostheses during the acute phase of the disease. Histopathological investigation to differentiate OLP from oral lichenoid dysplasia is crucial.

10.
Oral Dis ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720551

RESUMO

OBJECTIVE: Our previous studies have found that the composition ratio of Prevotella melaninogenica (Pm) on buccal mucosa surface of oral lichen planus (OLP) patients increased significantly compared with control. Furthermore, Pm could invade the epithelium of OLP patients. This study aimed to further explore the impact of Pm on oral keratinocytes. MATERIALS AND METHODS: The Pm-human oral keratinocyte (HOK) co-culture model was established to detect monolayer permeability, zona occludens-1 (ZO-1) expression, and intracellular survival of Pm. We performed RNA-seq followed by identification of differentially expressed genes (DEGs) and Gene Ontology (GO) analysis, with a particular focus on myosin light chain kinase (MLCK). An MLCK inhibitor ML-7 was utilized in Pm-HOK co-culture model to assess its effects on monolayer permeability and ZO-1 expression. RESULTS: HOK monolayer permeability was increased, and ZO-1 expression was decreased after co-culture (p < 0.05). Pm could survive in HOK cells. RNA-seq revealed MLCK was an upregulated common DEG. The expression of MLCK in the Pm-HOK co-culture model was upregulated. Inhibition of MLCK rescued the increased epithelial permeability, and ZO-1 expression was upregulated (p < 0.05). CONCLUSION: MLCK may be involved in disrupting epithelial barrier function by Pm.

11.
Oral Dis ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439057

RESUMO

OBJECTIVE: This study aimed to investigate the expression of tight junction, its distribution pattern in oral lichen planus samples and its potential association with the severity of oral lichen planus. MATERIALS AND METHODS: Cross-sectional study designs were conducted. Transcriptome sequencing was conducted using oral mucosal tissues from 22 patients with oral lichen planus and 11 healthy controls. Immunohistochemistry and quantitative reverse transcription PCR were performed to verify the expression of claudin-1, claudin-4, occludin and zonula occludens-1 in oral mucosal tissues from another 30 patients with oral lichen planus and 26 healthy controls. The relationship between tight junction protein expression and oral lichen planus severity was explored using correlation analysis. RESULTS: 5603 and 2475 differentially expressed genes were upregulated and downregulated respectively, in oral lichen planus tissues. KEGG analysis showed that tight junctions including CLDN1, CLDN4, OCLN and TJP1 were downregulated in oral lichen planus. Claudin-1, claudin-4, occludin and zonula occludens-1 expression was verified to be significantly lower in oral lichen planus. Furthermore, correlation analyses showed that decreased occludin expression was positively related to oral lichen planus severity. CONCLUSION: Decreased expression of TJ barrier proteins may be associated with the development of oral lichen planus.

12.
Oral Dis ; 30(2): 504-517, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36648368

RESUMO

OBJECTIVES: To investigate the role of oral lichen planus (OLP) on the long-term prognosis of oral epithelial dysplasia (OED). METHODS: Retrospective single-centre cohort study using the 2007-2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP, and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy and mortality. Cox proportional hazard and Poisson regression models were performed. RESULTS: A total of 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non-OLP/OED), were included. A pre-existing diagnosis of OLP was significantly associated with a twofold increased risk of subsequent primary OED events (HR = 2.02, p = 0.04), which also developed faster (1.46 vs. 2.96 years, p = 0.04) and with more involvement of non-cancer-prone sites (p = 0.001) than in the non-OLP/OED group. There was no difference between groups in the progression to malignancy or mortality. CONCLUSIONS: Oral lichen planus/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non-cancer-prone sites as compared to non-OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality.


Assuntos
Carcinoma de Células Escamosas , Líquen Plano Bucal , Neoplasias Bucais , Humanos , Líquen Plano Bucal/patologia , Neoplasias Bucais/patologia , Estudos Retrospectivos , Estudos de Coortes , Carcinoma de Células Escamosas/patologia , Hiperplasia , Prognóstico
13.
Oral Dis ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937944

RESUMO

OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disease characterized by a dense T-cell infiltration and the degeneration of basal keratinocytes. The potential functions of mucosal associated invariant T (MAIT) cells in OLP have been analyzed in our previous study. Keratinocytes under proinflammatory conditions have been demonstrated to activate T cells. This study was aimed to investigate how keratinocytes stimulate MAIT cells in OLP, and to explore the role of activated MAIT cells on keratinocytes. METHODS AND RESULTS: Increased MAIT cells and higher activation marker CD69 were detected in OLP lesions by flow cytometry. The enhanced expression of MHC class I-like molecule (MR1) required for MAIT cell activation in the epithelial layer of OLP lesions was determined by immunohistochemistry. Keratinocytes treated by 5-A-RU prodrug and lipopolysaccharide, respectively, exhibited higher expression of MR1 and secretion of IL-18. In direct coculture systems consisting of keratinocytes and peripheral blood mononuclear cells, both 5-A-RU prodrug-pretreated keratinocytes and lipopolysaccharide-pretreated keratinocytes activated MAIT cells to secrete granzyme B, contributing to elevated keratinocyte apoptosis. CONCLUSIONS: Keratinocytes were capable to activate MAIT cells via MR1 and cytokines in OLP, and granzyme B produced by activated MAIT cells intensified keratinocyte apoptosis, engaging in the pathogenesis of OLP.

14.
Clin Oral Investig ; 28(1): 103, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236502

RESUMO

OBJECTIVES: The present preliminary study aimed to investigate the salivary metabolic profile in patients with asymptomatic oral lichen planus (OLP) using nuclear magnetic resonance (NMR) spectroscopy. MATERIAL AND METHODS: Stimulated whole mouth saliva (SWMS) samples were collected from 15 reticular OLP female patients and 15 from age- and sex-matched controls (HCs). A total of 23 metabolites were identified and quantified. Mann-Whitney's U test was used to compare the determined concentration salivary metabolite concentrations between OLP patients and the healthy controls. RESULTS: The concentration of acetate, methylamine, and pyruvate was elevated, whereas the concentration of tyrosine was decreased in the saliva of OLP patients compared with HCs. To identify a combination of metabolites, multivariate discrimination function analysis (DFA) was conducted. DFA analysis have shown that the most powerful discrimination between the groups was achieved when methylamine and tyrosine were considered as combined biomarkers. CONCLUSIONS: Salivary tyrosine was of particular interest and a promising finding for the screening of OLP and its progression. Further longitudinal studies are required to establish it as a reliable salivary biomarker in OLP. CLINICAL RELEVANCE: The salivary metabolic profiling can describe the pathologic characteristics of OLP on non-invasive saliva samples and NMR analysis. Salivary metabolites provide details to considered early detectors and to impact oral health of OLP patients.


Assuntos
Líquen Plano Bucal , Humanos , Feminino , Metilaminas , Ácido Pirúvico , Tirosina , Espectroscopia de Ressonância Magnética
15.
Clin Oral Investig ; 28(7): 364, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849649

RESUMO

OBJECTIVES: Diagnosing oral potentially malignant disorders (OPMD) is critical to prevent oral cancer. This study aims to automatically detect and classify the most common pre-malignant oral lesions, such as leukoplakia and oral lichen planus (OLP), and distinguish them from oral squamous cell carcinomas (OSCC) and healthy oral mucosa on clinical photographs using vision transformers. METHODS: 4,161 photographs of healthy mucosa, leukoplakia, OLP, and OSCC were included. Findings were annotated pixel-wise and reviewed by three clinicians. The photographs were divided into 3,337 for training and validation and 824 for testing. The training and validation images were further divided into five folds with stratification. A Mask R-CNN with a Swin Transformer was trained five times with cross-validation, and the held-out test split was used to evaluate the model performance. The precision, F1-score, sensitivity, specificity, and accuracy were calculated. The area under the receiver operating characteristics curve (AUC) and the confusion matrix of the most effective model were presented. RESULTS: The detection of OSCC with the employed model yielded an F1 of 0.852 and AUC of 0.974. The detection of OLP had an F1 of 0.825 and AUC of 0.948. For leukoplakia the F1 was 0.796 and the AUC was 0.938. CONCLUSIONS: OSCC were effectively detected with the employed model, whereas the detection of OLP and leukoplakia was moderately effective. CLINICAL RELEVANCE: Oral cancer is often detected in advanced stages. The demonstrated technology may support the detection and observation of OPMD to lower the disease burden and identify malignant oral cavity lesions earlier.


Assuntos
Leucoplasia Oral , Líquen Plano Bucal , Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Neoplasias Bucais/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Líquen Plano Bucal/diagnóstico , Leucoplasia Oral/diagnóstico , Sensibilidade e Especificidade , Fotografação , Diagnóstico Diferencial , Carcinoma de Células Escamosas/diagnóstico , Masculino , Feminino , Fotografia Dentária , Interpretação de Imagem Assistida por Computador/métodos
16.
Clin Oral Investig ; 28(6): 318, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38750317

RESUMO

OBJECTIVES: The aim of this study was to: (1) investigate the expression patterns of antimicrobial peptides (AMPs), specifically psoriasin (S100A7) and calgranulin A and B (S100A8/A9), in patients with oral lichen planus (OLP) compared to healthy individuals; (2) evaluate the oral health-related quality of life (OHrQoL) in OLP patients versus healthy controls; (3) investigate the impact of clinical severity of OLP on OHrQoL; and (4) assess the influence of AMP expression on clinical severity and OHrQoL in OLP patients. MATERIALS AND METHODS: Oral mucosal biopsies (n = 38) were collected from healthy individuals (n = 17) and patients with OLP (n = 21). Levels of AMPs (S100A7, S100A8, S100A9) and pro-inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) were assessed by RT-qPCR. AMP protein localization was identified by indirect immunofluorescence analysis. OHrQoL was assessed using the OHIP-G14 questionnaire, and clinical severity was evaluated with the Oral Disease Severity Score (ODSS). Correlations between OLP manifestation, OHrQoL, and AMP expression were evaluated. RESULTS: (1) S100A7 (p < 0.001), IL-8 (p < 0.001), and TNFα (p < 0.001) mRNA levels were significantly upregulated in OLP tissue compared to healthy tissue, while S100A8 (p < 0.001) and S100A9 (p < 0.001) mRNA levels were downregulated. Immunofluorescence staining revealed an enhanced expression of S100A7 and decreased protein expression of S100A9 in OLP tissue. (2) OLP patients (9.58 ± 8.32) reported significantly higher OHIP-G14 scores compared to healthy individuals (0.67 ± 0.87; p < 0.001), particularly in the categories "physical pain" (p < 0.001) and "psychological discomfort" (p = 0.025). (3,4) Clinical severity (25.21 ± 9.77) of OLP correlated positively with OHrQoL (ρ = 0.497) and psoriasin expression (ρ = 0.402). CONCLUSIONS: This study demonstrated differential expression patterns of AMPs in OLP and highlighted the correlation between the clinical manifestation of OLP and OHrQoL. Further research approaches should address the role of psoriasin in the risk of malignant transformation of OLP. CLINICAL RELEVANCE: Psoriasin is a putative biomarker to monitor disease severity including malignant transformation of OLP lesions. OHIP-G14 scores can be useful to monitor OHrQoL in OLP patients.


Assuntos
Líquen Plano Bucal , Qualidade de Vida , Proteína A7 Ligante de Cálcio S100 , Índice de Gravidade de Doença , Regulação para Cima , Humanos , Líquen Plano Bucal/metabolismo , Feminino , Proteína A7 Ligante de Cálcio S100/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto , Biópsia , Inquéritos e Questionários , Estudos de Casos e Controles , Proteínas S100/metabolismo , Calgranulina A/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Idoso
17.
BMC Oral Health ; 24(1): 547, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730315

RESUMO

BACKGROUND: Antiresorptive therapy (AR) disrupts osseous homeostasis and can induce direct irritation over the gastrointestinal mucosa; however, its possible erosive effects on the oral epithelium have not been totally described. Among the most frequent oral erosive lesions, oral lichen planus (OLP) frequently presents as painful mucosal ulcerations, arising from basal membrane inflammatory damage. Thus, the aim of this retrospective study was to describe the association between AR and the incidence of OLP. METHODS: This case-control study included data from 148 patients (17 patients undergoing AR therapy (AR group) / 131 without AR therapy (Control group)). Each patient record was systematically processed and the association between AR drugs and OLP clinical characteristics within both groups was assessed. RESULTS: The erosive form of OLP was significantly more frequent in the AR group than in the Control group (p = 0.029). Indeed, the AR treatment using alendronic acid (41.2%) was the most frequently reported. Additionally, the erosive form of OLP showed the strongest association with pain and burning sensation among the OLP types (p < 0.050). However, disease worsening and AR consumption were not significantly associated (p = 0.150). CONCLUSIONS: Patients under AR therapy show more clinical symptoms associated to the erosive type of OLP. Regardless of the AR therapy, the erosive type of OLP is associated with more severe symptoms.


Assuntos
Conservadores da Densidade Óssea , Líquen Plano Bucal , Humanos , Estudos Retrospectivos , Feminino , Masculino , Estudos de Casos e Controles , Idoso , Pessoa de Meia-Idade , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Prevalência , Índice de Gravidade de Doença , Adulto , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Alendronato/efeitos adversos
18.
BMC Oral Health ; 24(1): 556, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38735922

RESUMO

INTRODUCTION: Oral Lichen Planus (OLP) is a chronic and relatively common mucocutaneous disease that often affects the oral mucosa. Although, OLP is generally not life-threatening, its consequences can significantly impact the quality of life in physical, psychological, and social aspects. Therefore, the aim of this research is to investigate the relationship between clinical symptoms of OLP and oral health-related quality of life in patients using the OHIP-14 (Oral Health Impact Profile-14) questionnaire. MATERIALS AND METHODS: This descriptive-analytical study has a cross-sectional design, with case-control comparison. In this study, 56 individuals were examined as cases, and 68 individuals were included as controls. After recording demographic characteristics and clinical features by reviewing patients' records, the OHIP-14 questionnaire including clinical severity of lesions assessed using the Thongprasom scoring system, and pain assessed by the Visual Analog Scale (VAS) were completed. The ADD (Additive) and SC (Simple Count) methods were used for scoring, and data analysis was performed using the T-test, Mann-Whitney U test, Chi-Square, Spearman's Correlation Coefficient, and SPSS 24. RESULTS: Nearly all patients (50 individuals, 89.3%) reported having pain, although the average pain intensity was mostly mild. This disease has affected the quality of life in 82% of the patients (46 individuals). The patient group, in comparison to the control group, significantly expressed a lower quality of life in terms of functional limitations and physical disability. There was a statistically significant positive correlation between clinical symptoms of OLP, gender, location (palate), and clinical presentation type (erosive, reticular, and bullous) of OLP lesions with OHIP-14 scores, although the number or bilaterality of lesions and patient age did not have any significant correlation with pain or OHIP scores. CONCLUSION: It appears that certain aspects of oral health-related quality of life decrease in patients with OLP, and that of the OLP patient group is significantly lower in terms of functional limitations and physical disability compared to the control group. Additionally, there was a significant correlation between clinical symptoms of OLP and pain as well as OHIP scores.


Assuntos
Líquen Plano Bucal , Saúde Bucal , Qualidade de Vida , Humanos , Líquen Plano Bucal/psicologia , Líquen Plano Bucal/complicações , Líquen Plano Bucal/patologia , Feminino , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Idoso , Inquéritos e Questionários , Medição da Dor
19.
BMC Oral Health ; 24(1): 726, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914986

RESUMO

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that is classified as a premalignant condition. Epithelial growth factor receptor (EGFR) is associated with tumorigenesis and tumor progression and is overexpressed in several oral malignant disorders. Despite the association of EGFR overexpression with oral potentially malignant lesions, few studies have analyzed its expression in OLP, showing controversial results. This study aimed to compare the expression of EGFR as a protein marker in Reticular and Erosive OLP. METHODS: This descriptive-analytical cross-sectional was conducted on 15 paraffin blocks of reticular lichen planus lesions, 16 paraffin blocks of erosive OLP lesions, and 8 paraffin blocks of inflammatory fibrous hyperplasia lesions as the control group (39 in total). After immunohistochemical staining for EGFR, samples were simultaneously observed by two maxillofacial pathologist, and the percentage of stained cells, intensity of staining, pattern of staining, and the location of stained cells were obtained. RESULTS: The Mann-Whitney-U test showed that there was no significant difference in the mean percentage of stained cells between erosive OLP and reticular OLP (P-value = 0.213) and between reticular OLP and control group (P-value = 0.137), but there was a significant difference between erosive OLP and control group (P-value = 0.035). Fisher's exact test showed that there was no significant difference between the frequency distribution of staining patterns in three types of lesions (P-value = 0.90). Kruskal-Wallis test showed that there was no significant difference between the intensity of staining in the three groups (P-value = 0.19) and also there was no significant difference between the location of stained cells in different layers of the epithelium in the three groups (P-value = 0.90). CONCLUSIONS: The results of this study showed that in comparison of reticular OLP, erosive OLP, and the control group there was a significant difference just between erosive OLP and control group in the percentage of stained cells.


Assuntos
Receptores ErbB , Líquen Plano Bucal , Líquen Plano Bucal/patologia , Líquen Plano Bucal/metabolismo , Humanos , Receptores ErbB/metabolismo , Receptores ErbB/análise , Estudos Transversais , Masculino , Pessoa de Meia-Idade , Feminino , Biomarcadores/análise , Adulto , Idoso , Imuno-Histoquímica , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/metabolismo
20.
BMC Oral Health ; 24(1): 756, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951854

RESUMO

OBJECTIVE: Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible for the oncogenic behavior in certain cases. Hypoxia-inducible factor-1a (HIF-1), and its possible correlation to Galactin-3 (Gal-3) and matrix metalloproteinase-9 (MMP-9) over expression represents an important indicator for malignant transformation. The investigation of these factors may present evidence-based information on malignant transformation of the disease. SUBJECTS AND METHODS: The study investigated the expression of HIF-1, Gla-3 and MMP-9 in tissue samples of OLP compared to control subjects of un-inflamed gingival overgrowth. 20 biospecimen were allocated in each group. RESULTS: Immunohistochemical findings of OLP showed immunoreactivity for Galectin 3, HIF1a and MMP-9 by most of the epithelial cells. There was a positive correlation between HIF1α and MMP-9, r = 0.9301 (P-value < 0.00001). A positive correlation was detected between Galectin 3 and MMP-9, r = 0.7292 (P-value = 0.000264) between Galectin 3 and HIF1α, r = 0.5893 (P-value = 0.006252). CONCLUSION: These findings confirm the hypothesis that the adaptive pathways to hypoxia as Gal 3 and MMP-9 expressions and their HIF-1 may play a crucial role in carcinogenesis of OLP.


Assuntos
Galectina 3 , Subunidade alfa do Fator 1 Induzível por Hipóxia , Líquen Plano Bucal , Metaloproteinase 9 da Matriz , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Líquen Plano Bucal/metabolismo , Líquen Plano Bucal/patologia , Galectina 3/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Galectinas/metabolismo , Adulto , Transformação Celular Neoplásica , Células Epiteliais/metabolismo , Estudos de Casos e Controles , Imuno-Histoquímica , Proteínas Sanguíneas
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