Salivary analysis can be used to assess the severity of caries. Of the known salivary proteins, a paucity of information exists concerning the role of proteinase 3(PR3), a serine protease of the chymotrypsin family, in dental caries. Whole, unstimulated saliva was collected from children with varying degrees of active caries and tested using a Human Protease Array Kit and an enzyme-linked immunosorbent assay.A significantly decreased concentration of salivary PR3 was noted with increasing severity of dental caries(P,0.01); a positive correlation(r50.87; P,0.01; Pearson's correlation analysis) was also observed between salivary p H and PR3 concentration. In an antibacterial test,a PR3 concentration of 250 ng?m L21 or higher significantly inhibited Streptococcus mutans UA159 growth after 12 h of incubation(P,0.05). These studies indicate that PR3 is a salivary factor associated with the severity of dental caries, as suggested by the negative relationship between salivary PR3 concentration and the severity of caries as well as the susceptibility of S. mutans to PR3.
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?1,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.
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.
