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Matrix metalloproteinase-9 (MMP-9) produced by tumor cells is known to be implicated in the invasion of squamous cell carcinoma (SCC). In the process of searching for agents to inhibit MMP-9 in cancer, immunosuppressive factors, dexamethasone (DEX) and interleukin-4 (IL-4) were found to inhibit protein production as well as gene expression of MMP-9 in tumor necrosis factor α (TNFα)-stimulated SCC cells. DEX and IL-4 could also suppress the expression of urokinase type plasminogen activator (uPA) to prevent the conversion from the proenzyme form of MMP-9 to its active form. Regarding their mechanisms to inhibit the expression of MMP-9 and uPA, DEX and IL-4 had no effect on the cell surface levels of TNFα receptors, but inhibited the activation of NF-κB and NF-κB-dependent gene expression. DEX, but not IL-4, could strongly augment the TNFα-induced expression of IκBα in SCC cells. These results suggest that DEX and IL-4 suppress not only immunological reactions, but also tumor invasion by targeting NF-κB. [Copyright &y& Elsevier]

Simple Summary: Clinically, early-stage oral cancers are difficult to distinguish from oral potentially malignant disorders (OPMDs) because they show a variety of mucosal pathologies. Therefore, invasive tissue biopsies should be performed to determine the treatment strategy. Previously, we focused on gargle fluid as a noninvasive testing method and reported aberrant methylation in gargle fluid in patients with oral cancer. In this study, we successfully identified aberrantly methylated genes in early-stage oral cancer and reported that a combination of methylation of six genes could distinguish early-stage oral cancer from OPMDs, with high diagnostic performance. In addition, the methylation panel more accurately reflected the presence of early-stage oral cancer than cytology testing. Our results suggest that the methylation panel using gargle fluid has the potential to be used as a noninvasive screening tool to diagnose early-stage cancer. Clinically, early-stage oral cancers are difficult to distinguish from oral potentially malignant disorders (OPMDs), and invasive tissue biopsy should be performed to determine a treatment strategy. Previously, we focused on gargle fluid as a noninvasive testing method and reported aberrant methylation in gargle fluid in patients with oral cancer. This study aimed to distinguish early-stage oral cancer from clinically diagnosed OPMDs using gargle fluid samples. We collected gargle fluid samples from 40 patients who were clinically diagnosed with OPMDs in the training set; among them, 9 patients were pathologically diagnosed with oral cancer. Methylation levels of 25 tumor suppressor genes were analyzed using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) method. We found that a combination of six genes (TP73, CASP8, RARB, KLLN, GSTP1, and CHFR) could distinguish oral cancer from clinically diagnosed OPMDs with high diagnostic performance (area under the curve [AUC], 0.885; sensitivity, 77.8%; and specificity, 87.1%). Additionally, the panel comprised of the six methylated genes was validated in the test set. Furthermore, when compared with cytology testing, the panel could accurately detect oral cancer. The present methylated gene panel may serve as a novel biomarker for oral cancer. [ABSTRACT FROM AUTHOR]

Sjögren syndrome (SS) is diagnosed based on invasive tissue biopsies and blood sampling. Therefore, a novel non-invasive and simple inspection diagnostic marker of SS is required. Here, we identified exosome-derived microRNAs (miRNAs) as biomarkers for SS using non-invasive mouthrinse samples collected from patients with SS and healthy volunteers. We compared miRNAs derived from exosomes in mouthrinse samples from the two groups using microarrays and real-time polymerase chain reaction (PCR) and identified 12 miRNAs as biomarker candidates. The expression ratios of four miRNAs were significantly increased in the SS group compared to the control group. Logistic regression analysis revealed a more significant influence of miR-1290 and let-7b-5p in the SS group than that in the control group. We combined these miRNAs to create a diagnostic prediction formula using logistic regression analysis. The combination of miR-1290 and let-7b-5p distinguished SS from the control samples with an AUC, sensitivity, specificity, positive predictive value, and negative predictive value of 0.856, 91.7%, 83.3%, 84.6%, and 90.9%, respectively. These results indicated that an increased ratio of these miRNAs could serve as a novel and non-invasive diagnostic marker for SS. This is the first report of diagnosis and screening of SS by adopting a non-invasive method using mouthrinse. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of colorectal cancer (CRC) has been increasing in recent years, and the gut microbiota is nowadays considered to be involved in the progression of CRC. Recent studies have investigated the involvement of the oral microbiota in CRC development using saliva and stool samples. However, the details regarding how oral bacteria alter the gut microbiota and affect CRC carcinogenesis remain unclear. In the present study, we identified four bacterial species that may affect the carcinogenesis and progression of CRC. These microorganisms may be potential biomarkers in saliva for diagnosing CRC. Oral microbiota is reportedly associated with gut microbiota and influences colorectal cancer (CRC) progression; however, the details remain unclear. This study aimed to evaluate the role of oral microbiota in CRC progression. Fifty-two patients with CRC and 51 healthy controls were included. Saliva and stool samples were collected, and microbiota were evaluated using 16S rRNA analysis and next-generation sequencing. Comparative analysis was performed on both groups. Linear discriminant analysis effect size (LEfSe) revealed the presence of indigenous oral bacteria, such as Peptostreptococcus, Streptococcus, and Solobacterium spp., at a significantly higher relative abundance in saliva and stool samples of CRC patients compared with controls. Next, CRC patients were divided into early stage (Stage I, II; n = 26; 50%) and advanced stage (Stage III, IV; n = 26; 50%) disease. LEfSe revealed that S. moorei was present at a significantly higher relative abundance in the advanced-stage group compared with the early-stage group, again consistent for both saliva and stool samples. Among bacterial species with significantly higher relative abundance in CRC patients, P. stomatis, S. anginosus, S. koreensis, and S. moorei originated from the oral cavity, suggesting indigenous oral bacteria may have promoted initiation of CRC carcinogenesis. Furthermore, S. moorei may influence CRC progression. [ABSTRACT FROM AUTHOR]

Oral hypofunction is a new concept that addresses the oral function of older adults. Few studies have investigated the relationship between oral hypofunction and general health conditions such as frailty, sarcopenia, and mild cognitive impairment. This paper explores these relationships in a large-scale, cross-sectional cohort study. The relationships of oral hypofunction with frailty, sarcopenia, and mild cognitive impairment were examined using data from 832 individuals who participated in the 2018 health survey of the residents of Tarumizu City, Kagoshima Prefecture, Japan. Individuals with frailty, sarcopenia, and mild cognitive impairment had significantly higher rates of oral hypofunction. Frailty was independently associated with deterioration of the swallowing function (odds ratio 2.56; 95% confidence interval, 1.26–5.20), and mild cognitive impairment was independently associated with reduced occlusal force (odds ratio 1.48; 95% confidence interval, 1.05–2.08) and decreased tongue pressure (odds ratio 1.77; 95% confidence interval, 1.28–2.43). There was no independent association found between sarcopenia and oral function. In conclusion, early intervention for related factors such as deterioration of the swallowing function in frailty, reduced occlusal force, and decreased tongue pressure in mild cognitive impairment could lead to the prevention of general hypofunction in older adults. [ABSTRACT FROM AUTHOR]

Simple Summary: Although early detection of oral squamous cell carcinoma (OSCC) is considered vital, classical biomarkers have shown poor sensitivity and specificity for early detection and monitoring of OSCC. Therefore, identification of reliable and sensitive biomarkers allowing for early detection and monitoring of OSCC is of the utmost importance. In this study, we successfully identified significantly upregulated or downregulated microRNAs in OSCC patients, and reported that a combination of six microRNAs could distinguish between OSCC and the control group with a higher degree of accuracy. Furthermore, compared with serum squamous cell carcinoma (SCC) antigen, the miRNA panel reflected the presence of OSCC accurately. The present results suggest that the combined microRNA panel based on serum microRNA levels shows potential as a novel diagnostic biomarker of OSCC. A lack of reliable biomarkers for oral squamous cell carcinoma (OSCC) poses a major clinical issue. The sensitivity and specificity of classical serum tumor markers, such as the squamous cell carcinoma antigen (SCC-Ag), are quite poor, especially for early detection. This study aimed to identify specific serum miRNAs potentially serving as OSCC biomarkers. The expression levels of candidate miRNAs in serum samples from 40 OSCC patients and 40 healthy controls were quantitatively analyzed via microarray and reverse transcription PCR (RT-PCR) analyses. To enhance the accuracy of detection, we used Fisher's linear discriminant analysis to establish a diagnostic model that incorporated a combination of selected miRNAs. Consequently, miR-19a and miR-20a were significantly upregulated in the patient group (p = 0.014 and 0.036, respectively), whereas miR-5100 was downregulated (p = 0.001). We found that a combination of six miRNAs (miR-24, miR-20a, miR-122, miR-150, miR-4419a, and miR-5100) could distinguish between OSCC and the control group with a higher degree of accuracy (Area Under the Curve, AUC: 0.844, sensitivity: 55%, and specificity: 92.5%). Furthermore, compared to serum SCC antigen, the 6-miRNA panel could accurately detect the presence of OSCC. The present specific miRNAs panel may serve as a novel candidate biomarker of oral cancer. [ABSTRACT FROM AUTHOR]