PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling / 国际口腔科学杂志·英文版

Oral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC. In this study, we analysed the expression levels of protein kinase D3 (PKD3) and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers. We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis and invasion of OSCC cells, while its overexpression promoted these processes. Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1, which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway, thereby promoting tumour growth and metastasis. Furthermore, silencing PKD3 significantly inhibited the expression of PD-L1, and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model. Thus, our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.

Saliva: potential diagnostic value and transmission of 2019-nCoV / 国际口腔科学杂志·英文版

2019-nCoV epidemic was firstly reported at late December of 2019 and has caused a global outbreak of COVID-19 now. Saliva, a biofluid largely generated from salivary glands in oral cavity, has been reported 2019-nCoV nucleic acid positive. Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2. Close contact or short-range transmission of infectious saliva droplets is a primary mode for 2019-nCoV to disseminate as claimed by WHO, while long-distance saliva aerosol transmission is highly environment dependent within indoor space with aerosol-generating procedures such as dental practice. So far, no direct evidence has been found that 2019-nCoV is vital in air flow for long time. Therefore, to prevent formation of infectious saliva droplets, to thoroughly disinfect indoor air and to block acquisition of saliva droplets could slow down 2019-nCoV dissemination. This review summarizes diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-nCoV by saliva droplets, expecting to contribute to 2019-nCoV epidemic control.

Salivary protease spectrum biomarkers of oral cancer / 国际口腔科学杂志·英文版

Proteases are important molecules that are involved in many physiological and pathological processes of the human body, such as growth, apoptosis and metastasis cancer cells. They are potential targets in cancer diagnosis and biotherapy. In this study, we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC), oral benign masses and chronic periodontitis, as well as that of health, using human protease array kits, enzyme-linked immunosorbent assay, western blot and immunofluorescence. The salivary protease spectrum was found to be associated with oral diseases. For example, the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health. The levels of matrix metalloproteinase (MMP)-1, MMP-2, MMP-10, MMP-12, A disintegrin and metalloprotease (ADAM)9, A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13), cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups. Taking MMP-1, cathepsin V, kallikrein 5 and ADAM9 as biomarkers of OSCC, cutoff values were199, 11.34, 9.29 and 202.55 pg·mL, respectively. From the area under the curve, sensitivity and specificity, the combination of cathepsin V/kallikrein5/ADAM9 was an optimal biomarker for diagnosing OSCC. Thus, analysis of the salivary protease spectrum may be an innovative and cost-efficient approach to evaluating the health status of the oral cavity. Specifically, increases in cathepsin V, kallikrein 5 and ADAM9 may be useful biomarkers in the screening and diagnosis of OSCC.

Salivary mycobiome dysbiosis and its potential impact on bacteriome shifts and host immunity in oral lichen planus / 国际口腔科学杂志·英文版

The biodiversity of the mycobiome, an important component of the oral microbial community, and the roles of fungal-bacterial and fungal-immune system interactions in the pathogenesis of oral lichen planus (OLP) remain largely uncharacterized. In this study, we sequenced the salivary mycobiome and bacteriome associated with OLP. First, we described the dysbiosis of the microbiome in OLP patients, which exhibits lower levels of fungi and higher levels of bacteria. Significantly higher abundances of the fungi Candida and Aspergillus in patients with reticular OLP and of Alternaria and Sclerotiniaceae_unidentified in patients with erosive OLP were observed compared to the healthy controls. Aspergillus was identified as an "OLP-associated" fungus because of its detection at a higher frequency than in the healthy controls. Second, the co-occurrence patterns of the salivary mycobiome-bacteriome demonstrated negative associations between specific fungal and bacterial taxa identified in the healthy controls, which diminished in the reticular OLP group and even became positive in the erosive OLP group. Moreover, the oral cavities of OLP patients were colonized by dysbiotic oral flora with lower ecological network complexity and decreased fungal-Firmicutes and increased fungal-Bacteroidetes sub-networks. Third, several keystone fungal genera (Bovista, Erysiphe, Psathyrella, etc.) demonstrated significant correlations with clinical scores and IL-17 levels. Thus, we established that fungal dysbiosis is associated with the aggravation of OLP. Fungal dysbiosis could alter the salivary bacteriome or may reflect a direct effect of host immunity, which participates in OLP pathogenesis.

Variations in protein concentration and albumin/globulin ratio of whole unstimulated saliva obtained from healthy people and patients with chronic periodontitis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>We detected and analyzed the clinical values of total protein (TP), albumin (ALB), globulin (GLB), and ALB/GLB ratio (A/G) of whole unstimulated saliva of healthy people to determine the time of day when saliva composition is relatively stable. We compared the protein concentration and A/G of whole unstimulated saliva of patients with chronic periodontitis with those of healthy volunteers to provide references for diagnostic methods and clinical applications of saliva.</p><p><b>METHODS</b>The whole saliva of 37 healthy subjects were collected at 8:00, 9:30, 11:30, 13:00, 16:30, and 21:00. Meanwhile, the whole saliva of 24 patients with periodontitis was collected in the morning. Bicinchoninic acid method was used to detect the TP content. Saliva ALB was detected by GF-D800 semi-automatic biochemical analyzer, and the GLB and A/G were calculated. Finally, the results were statistically analyzed using SPSS 19.0.</p><p><b>RESULTS</b>Salivary protein compositions were stable in the morning on an empty stomach. Healthy people: TP, (1 354.35±389.52) µg.mL-1; ALB, (139.55±27.19) µg.mL-1; GLB, (1 211.80±360.73) µg.mL-1; A/G, 0.126 3±0.041 7. Subjects with chronic periodontitis: TP, (2 611.56±231.62) µg.mL-1; ALB, (296.27±17.34) µg.mL-1; GLB, (2 315.69±221.67) µg.mL-1; A/G, 0.156 2±0.017 3. The contents of TP, ALB, and GLB in healthy individuals at different periods within a day showed significant differences (P<0.05), which were mainly reflected in the levels before and after meals. No significant difference was detected in A/G. The concentrations of TP, ALB, and GLB were significantly increased in patients with chronic periodontitis compared with those in healthy volunteers. However, no significant difference existed in A/G.</p><p><b>CONCLUSION</b>Salivary protein compositions are more stable in the morning than in other periods. Thus, mornings can be set as the time of specimen collection in future research. The concentrations of TP, ALB, and GLB in patients with chronic periodontitis are higher than those in healthy people.</p>