Potential salivary and serum biomarkers for burning mouth syndrome and their relationship with anxiety/depression.

Background/purpose: The pathophysiology of burning mouth syndrome (BMS), although considered a multifactorial etiology including psychological factors, is still not well understood. Hence, this study aimed to investigate the potential usage of salivary and serum biomarkers, including brain-derived neurotrophic factor (BDNF), interferon-gamma (IFN-γ), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α), in diagnosing BMS and their correlations with anxiety/depression. Materials and methods: 45 BMS patients and 14 healthy volunteers were enrolled. The patients were divided into BMS with anxiety/depression group and BMS without anxiety/depression group according to the scores of the Zung Self-rating Anxiety Scale (SAS) and Zung Self-rating Depression Scale (SDS). Additionally, concentrations of BDNF, IFN-γ, IL-1ß, IL-6, IL-8, and TNF-α in saliva and those in serum among the patients and healthy volunteers were assessed by multiplex assay using Luminex 200TM system and Enzyme-linked immunosorbent assay (ELISA), respectively. Results: Among all the serum biomarkers, only BDNF showed a statistically significant decrease in the patients than the healthy volunteers (P < 0.05). Regarding saliva biomarkers, BDNF, IL-1ß, and IL-8 all exhibited a statistically significant increase in all the BMS patients versus the healthy volunteers (P < 0.05) but only BDNF was significantly different between patients with anxiety/depression and healthy individuals when considering anxiety/depression. Among BMS patients with anxiety/depression, saliva TNF-α had positive associations with other biomarkers including BDNF, IFN-γ, IL-1ß, IL-6, and IL-8 (P < 0.05). Conclusion: The increased concentration of saliva BDNF holds strong potential for diagnosing BMS and the elevated level of saliva TNF-α is crucial in identifying BMS patients with anxiety/depression.

Evaluating photodynamic therapy for oral precancerous lesions: Highlighting outcome measure of malignant transformation.

The main outcome measure assessed in previous studies on photodynamic therapy (PDT) for oral precancerous lesions (OPL) is clinical response based on the alteration in lesion size after treatment. However, the primary and secondary outcome measures of the interventions for OPL should be malignant transformation and recurrence. Thus, the objective of this short communication is to summarize the evidence on PDT in preventing the recurrence and malignant transformation of OPL. There were 16 eligible studies which addressed the issue of OPL patients who received PDT with recurrence outcome, and the pooled recurrence rate (95% confidence interval) was analyzed to be 20.1% (16.2-24.6%). Notably, only 1 study reported that 7.5% of malignant transformation rate for OPL received PDT. These should be interpreted with caution due to low-level evidence, such as differences in study design, clinical and pathological features of patients enrolled, limited sample size, short follow-up time. Given few evaluated the effect of PDT on malignant transformation, we highlight that this primary outcome measure of OPL needs to be investigated in further well-designed longitudinal studies with adequate follow-up periods.

Oral mucosal disease recognition based on dynamic self-attention and feature discriminant loss.

OBJECTIVES: To develop a dynamic self-attention and feature discrimination loss function (DSDF) model for identifying oral mucosal diseases presented to solve the problems of data imbalance, complex image background, and high similarity and difference of visual characteristics among different types of lesion areas. METHODS: In DSDF, dynamic self-attention network can fully mine the context information between adjacent areas, improve the visual representation of the network, and promote the network model to learn and locate the image area of interest. Then, the feature discrimination loss function is used to constrain the diversity of channel characteristics, so as to enhance the feature discrimination ability of local similar areas. RESULTS: The experimental results show that the recognition accuracy of the proposed method for oral mucosal disease is the highest at 91.16%, and is about 6% ahead of other advanced methods. In addition, DSDF has recall of 90.87% and F1 of 90.60%. CONCLUSIONS: Convolutional neural networks can effectively capture the visual features of the oral mucosal disease lesions, and the distinguished visual features of different oral lesions can be extracted better using dynamic self-attention and feature discrimination loss function, which is conducive to the auxiliary diagnosis of oral mucosal diseases.

Palatal perforation caused by Alternaria alternata infection in an immunocompetent adolescent.

Opportunistic oral mucosal fungal infection caused by Alternaria alternata is extremely rare. Herein, we present a rare palatal perforation as a result of oral infection caused by A. alternata in an immunocompetent adolescent. An 18-year-old boy, who had previously been healthy, was admitted to our institution with persistent pain in the palate for the past 12 months. Upon impression of palatal bone resorption based on computed tomography imaging and chronic granulomatous inflammation based on biopsy (hematoxylin-eosin staining), the patient was examined for commonly relevant causes such as potential tumor and Mycobacterium tuberculosis infection. All test results were inconclusive. After a thorough diagnostic investigation, an unusual fungal infection, A. alternata infection, was confirmed by next-generation sequencing and biopsy (periodic acid-Schiff staining and immunofluorescence staining). The patient underwent surgical debridement and was subjected to voriconazole treatment postoperatively for over a period of 5 months. Thus, these findings highlight the importance of considering A. alternata as a potential pathogenic factor in an etiological palatal perforation.

Association of salivary miRNAs with onset and progression of oral potentially malignant disorders: Searching for noninvasive biomarkers.

Background/purpose: There is an urgent need for noninvasive biomarkers to diagnose oral potentially malignant disorders (OPMD). A wide range of over 20 miRNAs in saliva of OPMD patients have been investigated in different studies. Yet, which of the ones provide a better power of discrimination for the diagnosis of OPMD onset and progression are uncertain. Materials and methods: A total of 17 eligible studies including 426 cases of OPMD and 486 control subjects (352 normal mucosa and 134 oral squamous cell carcinoma) were summarized. Results: The bubble chart analysis showed that the most power salivary miRNA associated with OPMD onset was miR-21, followed by miR-31 and miR-142; the better power miRNAs associated with recurrence and malignant progression of OPMD were miR-31, miR-21, and miR-184. Conclusion: Salivary miRNAs, especially miR-21 and miR-31, were associated with onset and progression of OPMD, and could then serve as noninvasive biomarkers for screening OPMD and detecting malignant changes.

Dysregulation and implications of lncRNAs and miRNAs in oral tongue squamous cell carcinoma: In reply with emphasis on the role of ceRNAs.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) competitively sequestering microRNAs (miRNAs) participate in biological processes of oral tongue squamous cell carcinoma (TSCC). In this Letter, the ceRNA regulatory networks consisting of lncRNA/miRNA/mRNA axes in TSCC were summarized. Dysregulated profiles containing 33 lncRNAs and 31 miRNAs were identified by cancer-associated phenotypes verification. Almost all the lncRNAs could exert the oncogenic roles to sponge miRNAs and regulate targeting mRNA expression, thereby modulating cell proliferation, cell cycle, apoptosis, invasion, migration, metastasis, epithelial-mesenchymal transition, as well as chemoresistance. Significantly, the implications of functional ceRNAs deactivated in tumor cells contribute to the exploitation of novel diagnostic and therapeutic strategies for TSCC.

Autofluorescence imaging as a noninvasive tool of risk stratification for malignant transformation of oral leukoplakia: A follow-up cohort study.

BACKGROUND: There is few longitudinal study on oral potentially malignant disorder (OPMDs) focusing on oral leukoplakia (OLK) with clinical endpoints to investigate the role of autofluorescence imaging (AFI) for surveilling the malignant transformation. METHODS: Based on our previous prospective diagnostic study enrolled 517 OPMD patients, 184 OLK patients were retrieved to further investigate the role of AFI using VELscope in predicting malignant transformation. During a median follow-up period of 44 months, 19 (10.33%) developed into oral cancer. RESULTS: OLK patients were divided into loss of autofluorescence (LAF, n = 124) and retention of autofluorescence (RAF, n = 60) groups according to the results of AFI. Interestingly, difference between malignant transformation rate (MTR, 14.52%) of group LAF and overall MTR (10.33%) was not significant, but MTR (1.67%) of group RAF was significantly lower than overall MTR. Kaplan-Meier and Cox-regression analyses revealed that LAF could not directly distinguish the high-risk lesions, but RAF significantly discriminate the low-risk lesions. Importantly, time-dependent ROC curve analysis found that the sensitivity and negative predictive value (NPV) of AFI for the prediction of malignant transformation was 100% and 100% (2-year follow-up), 94.7% and 98.3% (5-year follow-up), respectively. Also, calibration curve and decision curve analyses showed high levels of predictive value and clinical relevance. CONCLUSION: This follow-up cohort study firstly evaluated AFI using VELscope for risk stratification of OLK malignant transformation. Whether conservative management is appropriate for OLK patients with RAF imaging due to minimal rate and risk of malignant transformation and great specificity and NPV is required to be further investigated.

LncRNA IFITM4P promotes immune escape by up-regulating PD-L1 via dual mechanism in oral carcinogenesis.

Oral squamous cell carcinoma (OSCC), which is typically preceded by oral leukoplakia (OL), is a common malignancy with poor prognosis. However, the signaling molecules governing this progression remain to be defined. Based on microarray analysis of genes expressed in OL and OSCC samples, we discovered that the long non-coding RNA IFITM4P was highly expressed in OSCC, and ectopic expression or knockdown of IFITM4P resulted in increased or decreased cell proliferation in vitro and in xenografted tumors, respectively. Mechanistically, in the cytoplasm IFITM4P acted as a scaffold to facilitate recruiting SASH1 to bind and phosphorylate TAK1 (Thr187), and in turn to increase the phosphorylation of nuclear factor κB (Ser536) and concomitant induction of PD-L1 expression, resulting in activation of an immunosuppressive program that allows OL cells to escape anti-cancer immunity in cytoplasm. In nucleus, IFITM4P reduced Pten transcription by enhancing the binding of KDM5A to the Pten promoter, thereby upregulating PD-L1 in OL cells. Moreover, mice bearing tumors with high IFITM4P expression had notable therapeutic sensitivity to PD-1 monoclonal antibody (mAb) treatment. Collectively, these data demonstrate that IFITM4P may serve as a new therapeutic target in blockage of oral carcinogenesis, and PD-1 mAb can be an effective reagent to treat OSCC.

Ablative fractional laser-assisted photodynamic therapy vs. ablative fractional laser for oral leukoplakia treatment: A randomized, controlled pilot study.

BACKGROUND: Ablative fractional laser-assisted photodynamic therapy (AFL-PDT) is explored as an effective method in some premalignant diseases, whereas the effect of AFL-PDT on oral leukoplakia (OL), the best-known precursor of oral squamous cell carcinoma, remains undetermined. METHODS: Forty-eight patients, histologically diagnosed with OL, were randomized (1:1) to receive either AFL-PDT or ablative fractional laser (AFL) treatment. All patients were followed up at 1, 3, 6 and 12 months postoperatively. The primary endpoints of efficacy and clinical recurrence and the secondary endpoint of side effects were assessed. RESULTS: Forty-four patients completed the study. The 100% effective cure rate in the AFL-PDT group was higher than that in AFL group (80.9%, P<0.05) with 19.1% difference (95%CI: 0.7-40.0%). Compared to AFL group, recurrence observed at 6 and 12 months post-treatment tended to occur in fewer patients in the AFL-PDT group (P<0.05). No severe adverse events or systemic side effects were observed in either group. CONCLUSIONS: AFL-PDT may effectively reduce recurrence of OL with high clinical efficacy and good tolerability, suggesting it may be a promising treatment for OL.

Development and validation of a risk model for noninvasive detection of cancer in oral potentially malignant disorders using DNA image cytometry.

OBJECTIVE: To elucidate whether DNA aneuploidy was an independent discriminator for carcinoma within oral potentially malignant disorders (OPMDs), and further establish and validate a risk model based on DNA aneuploidy for the detection of oral cancer. METHODS: A total of 810 consecutive patients with OPMD were prospectively enrolled from March 2013 to December 2018, and divided into a training set (n = 608) and a test set (n = 202). Brushing and biopsy samples from each patient were processed by DNA-DNA image cytometry and histopathological examination, respectively. RESULTS: DNA aneuploidy of an outside DNA index ≥ 3.5 in OPMD was an independent marker strongly associated with malignant risk [adjusted odds ratio: 13.04; 95% confidence interval (CI): 5.46-31.14]. In the training and test sets, the area under the curve (AUC) was 0.87 (95% CI: 0.82-0.91) and 0.77 (95% CI: 0.57-0.97), respectively, for detecting carcinoma in OPMD patients. The independent risk factors of lateral/ventral tongue and non-homogenous type combined with a risk model built with a multivariate logistic regression revealed a more favorable diagnostic efficacy associated with the training set (AUC: 0.93; 95% CI: 0.91-0.96) and test set (AUC: 0.94; 95% CI: 0.90-0.98). The sensitivity and specificity of carcinoma detection within OPMD was improved to 100% and 88.1%, respectively. CONCLUSIONS: This large-scale diagnostic study established a risk model based on DNA aneuploidy that consisted of a noninvasive strategy with lateral/ventral tongue and non-homogenous features. The results showed favorable diagnostic efficacy for detecting carcinoma within OPMD, irrespective of the clinical and pathological diagnoses of OPMD. Multicenter validation and longitudinal studies are warranted to evaluate community practices and clinical applications.

Matrine Regulates Proliferation, Apoptosis, Cell Cycle, Migration, and Invasion of Non-Small Cell Lung Cancer Cells Through the circFUT8/miR-944/YES1 Axis.

BACKGROUND: Non-small cell lung carcinoma (NSCLC) is the major histological subtype of cancer cases. In the present study, we investigated the association between Matrine, an active component of Chinese medicine, and circFUT8 in NSCLC cells. METHODS: The proliferation ability of NSCLC cells was assessed by MTT and colony-forming assays. Flow cytometry assay was performed to show the apoptosis and cell cycle distribution in NSCLC cells. The protein expression levels of Bcl-2, Cleaved Caspase-3 (C-Caspase3), and YES proto-oncogene 1 (YES1) were measured by Western blot assay. Migration and invasion of NSCLC cells were determined by transwell assay. The expression levels of circFUT8, miR-944 and YES1 were quantified by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The interaction relationship between miR-944 and circFUT8 or YES1 was confirmed by dual-luciferase reporter assay. The anti-tumor role of Matrine in vivo was explored by a xenograft experiment. RESULTS: Matrine functioned as a carcinoma inhibitor by repressing proliferation, cell cycle process, migration, and invasion while inducing apoptosis in NSCLC cells. Importantly, overexpression of circFUT8 counteracted Matrine-induced effects on NSCLC cells. MiR-944, interacted with YES1, was a target of circFUT8. Under Matrine condition, overexpression of circFUT8 increased proliferation, migration, and invasion while inhibited apoptosis, which was abolished by the upregulation of miR-944. Whereas the silencing of YES1 counteracted miR-944 inhibitor-induced effects on NSCLC cells. Eventually, we also confirmed that Matrine impeded NSCLC tumor growth in vivo. CONCLUSION: Matrine regulated proliferation, apoptosis, cell cycle, migration, and invasion of NSCLC cells through the circFUT8/miR-944/YES1 axis, which provided novel information for Matrine in NSCLC.