Background:Transforming acidic coiled-coil containing protein 1 (TACC1) is a key regulator of cellular differentiation, growth, and gene regulation. Despite the known interaction between full-length TACC1 and retinoic acid receptor alpha (RARα), the relationship between the short-form TACC1 variant 25 (TACC1v25) and RARα in head and neck squamous cell carcinomas (HNSCCs) remains unclear. This study aimed to evaluate the value of TACC1v25 on differentiation and invasion in HNSCC and its correlation with RARα. Methods:We analyzed the interaction between TACC1v25 and RARα by co-immunoprecipitation (Co-IP). The effects of TACC1v25 associated with RARα on the differentiation and invasion in HNSCC were assessed by western blot and transwell assays. RNA sequencing (RNA-seq) profiling and orthotopic xenograft modeling further validated the results. Results:TACC1v25 physically interacted with RARα. A portion of TACC1v25 and RARα was found at the same loci both in the nucleus and cytoplasm. After all-trans-retinoic acid (ATRA) treatment, TACC1v25 increased in the cytoplasm, whereas RARα increased in the nucleus (P<0.05). Overexpression of TACC1v25 significantly upregulated differentiation-related proteins in Cal27 and Fadu cells; however, ATRA treatment counteracted the pro-differentiation effect in Cal27-v25 cells (P<0.05). TACC1v25 overexpression inhibited cell invasion and migration, but similarly, ATRA-mediated RARα reversed these effects and counteracted the downregulated vimentin and p-AKT expression (P<0.05). Conclusions:TACC1v25 may be involved in cell differentiation, invasion, and migration in HNSCC cells, and the dissociation of activated RARα from TACC1v25 might partially counteract the effects of TACC1v25 in HNSCCs. It is possible that ATRA induces conformational changes and/or promotes nuclear translocation of RARα, which in turn reduces its interaction with TACC1v25 and modulates the downstream transcriptional effects. This may provide new ideas for treating HNSCCs.

Burning mouth syndrome (BMS) is a chronic condition with no effective treatment currently available. Low-level laser therapy (LLLT) shows promise for neuropathic pain management, but evidence comparing its efficacy across different wavelengths in BMS patients remains limited. This study aimed to assess the clinical efficacy of LLLT with three distinct wavelengths in BMS patients, and to determine the optimal therapeutic wavelength. This study was a single-blind randomized controlled trial, with blinding applied only to the participants. 201 participants were scheduled for enrollment, divided into three groups with 67 individuals each. Finally, 63 participants with BMS were enrolled from April 2019 to December 2022, with 53 completing the study. Randomization was performed using SPSS software to generate random numbers. Participants were sequentially assigned based on their enrollment order to the 660 nm group (n = 10, 50 mW, 1.5 J/cm2, 30 s/point), 810 nm group (n = 26, 500 mW, 3 J/cm2, 6 s/point), or 975 nm group (n = 17, 30 mW, 10 J/cm2, 33 s/point). Each participant underwent LLLT once a week for 4 sessions. Outcomes, including pain intensity, numbness, and altered taste, were assessed using the visual analogue scale (VAS). Efficacy was assessed by comparing VAS scores at baseline and after the last treatment, using the Kruskal-Wallis test for comparisons among the three groups and the Mann-Whitney U-test for pairwise analysis. Effect sizes were reported using Cohen's d. Statistically significant pain relief was observed in all groups (median reduction of 40%). The improvement of numbness in the 810 nm and 975 nm groups (median reduction of 40%) was also significant (p < 0.05). However, no significant differences in efficacy were noted among the three groups (p > 0.05). These results suggested that LLLT with three different wavelengths effectively reduced pain and that the 810 nm and 975 nm wavelengths also significantly alleviated numbness in BMS patients. However, further investigation is warranted to elucidate any potential differences in efficacy among the three groups. Clinical trial registration: ChiCTR1900021674 (March 5, 2019).

Supplemental Figure 3. A. Association between tumor stage of OSCC patients and NOTCH1 mutation-status. B. Table demonstrates differences in smoking and alcohol consumption rates between the OSCC and leukoplakia patients. C. Table demonstrates differences in smoking and alcohol consumption rates between the OSCC and leukoplakia lesions with mutated NOTCH1. D. The pattern of NOTCH1 base-pair mutations resulting from exposure to tobacco in OSCC and leukoplakia patients (in blue, base-pair mutations that found in both, smokers and non-smokers).

Objective To explore the clinical application value of reflectance confocal microscopy(RCM) in the diagnosis of actinic cheilitis(AC). Methods After approval by the hospital ethics committee and informed consent given by the patients, from October 2020 to July 2022, 17 patients who were diagnosed with actinic cheilitis in the Ninth People's Hospital affiliated with Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The white keratotic lesions of the lips were scanned with reflectance confocal microscopy, and the image characteristics were summarized and analyzed, including epithelial hyperplasia/atrophy, hyperkeratosis, inflammatory cell infiltration, blood vessel dilatation, solar elastosis, atypical keratinocytes, widening of intercellular spaces, degeneration of basal cell layer, and pigmentation. We used the sample compliance rate to measure the correlation between RCM parameters and histopathological diagnostic criteria for AC and kappa concordance analysis to calculate the concordance between RCM and pathological diagnosis. Results Under RCM, the sample correct rates for epithelial hyperplasia/atrophy, hyperkeratosis, inflammatory cell infiltration, vasodilation, and solar elastosis were 76.5%, 100%, 100%, 64.7%, and 70.6%, the sample accuracy compared with pathological diagnosis was 82.4%, 47.1%, 94.1%, 88.2% and 76.5%, respectively. We also observed that 100%, 88.2%, 76.5%, and 88.2% of AC patients showed RCM features of atypical keratinocytes, widening of intercellular spaces, degeneration of the basal cell layer, and pigmentation, respectively. The kappa value of hyperkeratosis and inflammatory cell infiltration was 1. The kappa value of blood vessel dilatation was 0.645. Conclusion Reflectance confocal microscopy is noninvasive and versatile and has clinical application value in the diagnosis of actinic cheilitis.

Supplemental Figures and Tables legends

Supplementary Figure 1, Table 1 from Detection of Promoter Hypermethylation in Salivary Rinses as a Biomarker for Head and Neck Squamous Cell Carcinoma Surveillance

Supplemental Table 5. List of 108 primer pairs designed by Fluidigm Assay Design Group and used in this study for NOTCH1 amplification. Table summarizes the GC-content, length distribution and location of the Access Array amplicons.

Supplemental Figure 1. List of all NOTCH1 mutations found in Chinese OSCC patients. A. Mutations identified in 22 tumor-normal pairs. B. Mutations found in 28 OSCC samples without matching normal control.

Supplemental Tables 6-11. Supp. Table 6. List of all mutations identified in each of the normal samples. Supp. Table 7. List of the mutations in the unmatched OSCC and leukoplakia samples that were filtered-out as they were present in the normal samples or in the dbSNP. Supp. Table 8. Summary of the number of mutations present in each of the sets of samples and the number that were filtered-out during analysis. Supp. Table 9. Combined list of all mutations identified in Chinese OSCC patients in this study and by Song et. al (16). Supp. Table 10. List of all NOTCH1 mutations identified in Caucasians HNSCC samples. Supp. Table 11. List of all HNSCC samples from Caucasian patients used in this study: including exact site and HPV status.

Supplemental Tables 1-4. Supp. Table 1. A. List of all OSCC samples used in this study and clinical/pathological data. B. List of 22 matched tumor-normal pairs. Supp. Table 2. List of all normal samples used in this study and clinical/pathological data. Supp. Table 3. List of all oral leukoplakia samples used in this study and clinical/pathological data. Supp. Table 4. Summary of clinical characteristics for OSCC, leukoplakia and normal samples used in this study.

Supplemental Figure 2. List of all NOTCH1 mutations identified in Chinese patients with oral leukoplakia.

Journal of the European Academy of Dermatology and VenereologyVolume 36, Issue 7 p. e545-e548 Letter to the Editor In vivo reflectance confocal microscopy diagnostic features of actinic cheilitis: a retrospective case series M. Y. Zhang, M. Y. Zhang Department of Oral Mucosal Diseases, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China College of Stomatology, Shanghai Jiao Tong University, Shanghai, China National Center for Stomatology, Shanghai, China National Clinical Research Center for Oral Diseases, Shanghai, China Shanghai Key Laboratory of Stomatology, Shanghai, ChinaSearch for more papers by this authorW. W. Jiang, Corresponding Author W. W. Jiang wwjiang33@hotmail.com orcid.org/0000-0002-9738-3989 Department of Oral Mucosal Diseases, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China College of Stomatology, Shanghai Jiao Tong University, Shanghai, China National Center for Stomatology, Shanghai, China National Clinical Research Center for Oral Diseases, Shanghai, China Shanghai Key Laboratory of Stomatology, Shanghai, China Correspondence: W.-W. Jiang. E-mail: wwjiang33@hotmail.comSearch for more papers by this author M. Y. Zhang, M. Y. Zhang Department of Oral Mucosal Diseases, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China College of Stomatology, Shanghai Jiao Tong University, Shanghai, China National Center for Stomatology, Shanghai, China National Clinical Research Center for Oral Diseases, Shanghai, China Shanghai Key Laboratory of Stomatology, Shanghai, ChinaSearch for more papers by this authorW. W. Jiang, Corresponding Author W. W. Jiang wwjiang33@hotmail.com orcid.org/0000-0002-9738-3989 Department of Oral Mucosal Diseases, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China College of Stomatology, Shanghai Jiao Tong University, Shanghai, China National Center for Stomatology, Shanghai, China National Clinical Research Center for Oral Diseases, Shanghai, China Shanghai Key Laboratory of Stomatology, Shanghai, China Correspondence: W.-W. Jiang. E-mail: wwjiang33@hotmail.comSearch for more papers by this author First published: 19 February 2022 https://doi.org/10.1111/jdv.18018Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume36, Issue7July 2022Pages e545-e548 RelatedInformation

Background:Tacrolimus is a new type immunosuppressant. The aim of this study was to evaluate the effectiveness of topical tacrolimus 0.1% ointment at 2 different frequencies in treating patients with exfoliative cheilitis. Methods:A total of 40 patients with exfoliative cheilitis were randomly divided into the QD group receiving topical tacrolimus 0.1% ointment once a day or the QOD group receiving topical tacrolimus 0.1% ointment once-two-day. Patients were also applied wet dressing of saline twice a day. The effectiveness of treatment was defined as the percentage of improvement in signs or symptoms. Results:37 patients completed the 2-week treatment. And, a full set was analyzed. The effectiveness of topical tacrolimus 0.1% ointment for relief in objective sign and subjective symptom was 50% and 67.5%% in the QD group, respectively. For the QOD group, the effectiveness of sign and symptom relief was 50% and 73.5%. There was no significant difference of effectiveness between application topical tacrolimus once a day and once 2 days. Conclusion:Our data suggested that application of topical tacrolimus 0.1% ointment once a day and once 2 days had similar clinical effectiveness for sign and symptom relief in patients with exfoliative cheilitis.

Objective To study the role of DNA methylation in oral leukoplakia carcinogenesis. Methods DNA methylation was detected in forty cases of oral squamous cell carcinoma (OSCC), twenty-eight cases of oral leukoplakia (OLK) and forty cases of healthy oral mucosa. Download the expression profile data of OSCC, OLK and healthy oral mucosa from Gene Expression Omnibus (GEO) database. DNA methylation data and expression profile data were compared for repeatability, DNA methylation data for difference analysis and corresponding expression profile data for IPA pathway analysis. Results The data analysis showed that DNA methylation had greater flexibility and instability. Ingenuity Pathway Analysis (IPA) analysis showed that genes related to OLK differential methylation sites were mainly concentrated in the process of cell movement and differentiation. Genes related to differential methylation sites of OSCC are mainly enriched in cell proliferation, migration, oxidation regulation, and anti-apoptosis processes. The genes associated with OLK and OSCC differential methylation sites are co-enriched in phosphoinositol metabolism and phospholipase C signaling pathway. Conclusion DNA methylation is involved in the formation of oral squamous cell carcinoma, and the activation of phosphoinositol metabolism may promote oral leukinoma.

Transforming acidic coiled-coil containing protein1 (TACC1) is closely related to transcription, translation and centrosome dynamics. Dysregulation of TACC1 is associated with multiple malignancies. Alternative splicing (AS) of TACC1 produces multiple variants, which are of great significance in cancer biology. However, the expression and biological functions of TACC1 variants in head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we found for the first time that TACC1 variants exhibited a characteristic expression pattern and that TACC1 variant25 (TACC1v25) was downregulated in HNSCC tissues and cell lines. Overexpression of TACC1v25 in Cal27 and Fadu cells significantly inhibited proliferation and promoted autophagy. Moreover, expression levels of nuclear pERK and p-mTOR were significantly decreased, while the expression of Beclin-1 and the LC3II/LC3I ratio were increased in TACC1v25-overexpressed Cal27 and Fadu cells. After the addition of AKT activator SC79 to TACC1v25-overexpressed Cal27 and Fadu cells, the autophagy levels were remarkably rescued. In conclusion, TACC1v25 inhibits HNSCC progression through the ERK and AKT/mTOR pathways by inhibiting proliferation and increasing autophagy. TACC1v25 might have potential use as a tumour suppressor in HNSCC.

目的 通过大数据分析Aurora-A在头颈部鳞状细胞癌(HNSCC)中的表达及作用.方法 应用Oncomine、GEPIA2、ULCAN、The Human Protein Atlas、HNC Database、Starbase、miRCancer平台探究Aurora-A在HNSCC组织中的表达及该基因表达是否受微小RNAs(miRNAs)调节.同时,采用qPCR分析Aurora-A在CAL27、JHU022两种HNSCC细胞株及原代口腔角质形成细胞株(HOK)中的表达.结果 Aurora-A mRNA在HNSCC组织中高表达,且表达上调2倍以上(P<0.05).免疫组织化学检测显示,Aurora-A在HNSCC组织中的表达较正常组织略高,同时HPV阳性的HNSCC组织中Aurora-A表达显著高于HPV阴性的HNSCC组织及正常组织.Aurora-A高表达者生存率较差.同时,随着组织学分级增加,Aurora-A表达显著升高.此外,Aurora-A上有多个与HNSCC相关的miRNA分子靶标,hsa-let-7d、hsa-miR-149和hsa-miR-363既在Aurora-A 3'UTR端存在潜在作用靶点,又在HNSCC中表达下调.qPCR检测显示,与HOK细胞株比较,Aurora-A在CAL27和JHU022细胞株中的表达均明显升高(P<0.05).结论 Aurora-A在HNSCC中表达升高,其表达可能受miRNA调控,有望成为HNSCC诊断和预后预测的生物标记物.

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目的:明确D-半乳糖对正常人口腔黏膜细胞(normalhuman oral keratinocytes,NHOKs)促衰老作用,并探索潜在机制.方法:体外分离培养NHOKs,角形蛋白和波形蛋白免疫细胞化学染色法鉴定NHOKs.分别以10、20、40、80g/LD-半乳糖处理诱导细胞作为实验组,正常培养液组作为对照组.通过CCK-8法检测细胞增殖活力,采用衰老相关β半乳糖苷酶染色(senescence-associated-β-galactosidase,SA-β-gal)分析细胞衰老情况,Western blot检测衰老相关蛋白p53和p21表达水平.活性氧(reactive oxygen species,ROS)检测试剂盒检测细胞内氧化应激水平,Western blot检测氧化应激相关蛋白sirtl的表达.结果:D-半乳糖抑制NHOK细胞增殖,具有时间和浓度依赖性.D-半乳糖增加SA-p-gal染色阳性率,上调衰老相关基因p53和p21,显著升高细胞内ROS,降低氧化应激相关蛋白sirtl表达.结论:D-半乳糖可诱导NHOKs发生衰老,该过程可能与细胞氧化应激有关.

BACKGROUNDBiological age reflects the functional status of an individual. The purpose of the study was to develop a model for estimating oral biological age with oral and systemic parameters.METHODSA total of 248 subjects who had a routine health check were assessed with oral and general clinical examination. Chi-square test was performed to screen oral clinical candidate indicators. General parameters were analyzed by Pearson correlation coefficient and principal component analysis to develop a general biological age score. A final comprehensive model of oral biological age score was established by combining oral and general biological age score.RESULTSA total of eight oral indicators (mucosal blood blister, mucosal dryness, impacted tooth, missing teeth, residual crowns, dental calculus, gingival hyperemia, and gingival recession) and 10 general clinical indicators (triglyceride, creatinine, blood urea nitrogen, glucose, total cholesterol, mean erythrocyte hemoglobin concentration, mean erythrocyte hemoglobin, uric acid, body weight, and systolic blood pressure) were selected for oral and general biological age score, respectively (r > 0.25, P < 0.05). A model of comprehensive oral biological age score was then formed by principal component analysis: 0.046 triglyceride + 0.010 creatinine + 0.141 blood urea nitrogen + 0.048 glucose + 0.068 total cholesterol + 0.014 mean erythrocyte hemoglobin concentration + 0.082 mean erythrocyte hemoglobin + 0.001 uric acid + 0.020 body weight + 0.005 systolic blood pressure + 0.037 oral biological age score -10.908. The score was increased accordingly with CA.CONCLUSIONOral biological age can be easily estimated clinically by the model of comprehensive oral biological age score using oral and systemic clinical parameters by general practitioners.

Burning mouth syndrome (BMS) is a chronic disease that consists of pain or a burning sensation on the oral mucosa in the absence of clinical or laboratory signs. The aim of this study was to compare the efficacy of low-level laser (LLL) treatment with different wavelengths on patients with BMS to provide an optimized approach for clinical management. The PubMed and Wanfang databases were searched for studies in English or Chinese until September 30, 2018 using “burning mouth syndrome” and “laser” as keywords. Fifteen clinical trials were analyzed for data extraction. LLL treatment for BMS was effective. A LLL with a wavelength of 790 nm showed the greatest efficiency. However, the parameters in the trials, such as wavelength (650–980 nm), power (20–1,500 mW), energy density (0.53–200 J/cm 2 ), time (10 s–15 min), sessions (1–20 s), and irradiated frequency, varied widely. More randomized controlled trials (RCTs) are needed to draw a clear conclusion to provide evidence for optimized clinical management.