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Aim: To compare the salivary proteomic profile of periodontitis‐affected (PA) parents and their offspring to periodontally healthy (PH) dyads in the pursuit of possible biomarkers for early diagnosis of this disease. Materials and Methods: Unstimulated saliva samples collected from 17 pairs of PA or PH individuals and their children were submitted to mass spectrometric analyses followed by proteomic analyses. Primary PA fibroblasts were triggered towards having an inflammatory response, and an immunoenzymatic assay of its supernatant was performed to validate the obtained data. Results: ANXA1, KRT4, GSTP1, HPX, A2M and KRT13 were lower in PA parents and their children, and IGHG1, CSTB, KRT9, SMR3B, IGHG4 and SERPINA1 were higher. ANXA1 presented the highest fold change, 7.1 times less produced in children of PA parents, and was selected as a potential biomarker for periodontitis. The in vitro assay also showed lower ANXA1 production by cells of PA patients. Conclusion: Before any clinical sign of periodontal loss, descendants of PA patients have an altered proteomic profile compared to PH individuals, presenting a lower abundance of ANXA1. This protein is suggested as a potential biomarker for periodontitis. [ABSTRACT FROM AUTHOR]

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules. [ABSTRACT FROM AUTHOR]

Aims: A disintegrin and metalloprotease 17 (ADAM17) modulates signaling events by releasing surface protein ectodomains such as TNFa and the EGFR-ligands. We have previously characterized cytoplasmic thioredoxin-1 (Trx-1) as a partner of ADAM17 cytoplasmic domain. Still, the mechanism of ADAM17 regulation by Trx-1 is unknown, and it has become of paramount importance to assess the degree of influence that Trx-1 has on metalloproteinase ADAM17. Results: Combining discovery and targeted proteomic approaches, we uncovered that Trx-1 negatively regulates ADAM17 by direct and indirect effect. We performed cell-based assays with synthetic peptides and site-directed mutagenesis, and we demonstrated that the interaction interface of Trx-1 and ADAM17 is important for the negative regulation of ADAM17 activity. However, both Trx-1K72A and catalytic site mutant Trx-1C32/35S rescued ADAM17 activity, although the interaction with Trx-1C32/35S was unaffected, suggesting an indirect effect of Trx-1. We confirmed that the Trx-1C32/35S mutant showed diminished reductive capacity, explaining this indirect effect on increasing ADAM17 activity through oxidant levels. Interestingly, Trx-1K72A mutant showed similar oxidant levels to Trx-1C32/35S, even though its catalytic site was preserved. We further demonstrated that the general reactive oxygen species inhibitor, Nacetylcysteine (NAC), maintained the regulation of ADAM17 dependent of Trx-1 reductase activity levels; whereas the electron transport chain modulator, rotenone, abolished Trx-1 effect on ADAM17 activity. Innovation: We show for the first time that the mechanism of ADAM17 regulation, Trx-1 dependent, can be by direct interaction and indirect effect, bringing new insights into the cross-talk between isomerases and mammalian metalloproteinases. Conclusion: This unexpected Trx-1K72A behavior was due to more dimer formation and, consequently, the reduction of its Trx-1 reductase activity, evaluated through dimer verification, by gel filtration and mass spectrometry analysis. Antioxid. Redox Signal. 29, 717–734. [ABSTRACT FROM AUTHOR]

Saliva is a biofluid that maintains the health of oral tissues and the homeostasis of oral microbiota. Studies have demonstrated that Oral squamous cell carcinoma (OSCC) patients have different salivary microbiota than healthy individuals. However, the relationship between these microbial differences and clinicopathological outcomes is still far from conclusive. Herein, we investigate the capability of using metagenomic and metaproteomic saliva profiles to distinguish between Control (C), OSCC without active lesion (L0), and OSCC with active lesion (L1) patients. The results show that there are significantly distinct taxonomies and functional changes in L1 patients compared to C and L0 patients, suggesting compositional modulation of the oral microbiome, as the relative abundances of Centipeda, Veillonella , and Gemella suggested by metagenomics are correlated with tumor size, clinical stage, and active lesion. Metagenomics results also demonstrated that poor overall patient survival is associated with a higher relative abundance of Stenophotromonas , Staphylococcus , Centipeda , Selenomonas , Alloscordovia , and Acitenobacter. Finally, compositional and functional differences in the saliva content by metaproteomics analysis can distinguish healthy individuals from OSCC patients. In summary, our study suggests that oral microbiota and their protein abundance have potential diagnosis and prognosis value for oral cancer patients. Further studies are necessary to understand the role of uniquely detected metaproteins in the microbiota of healthy and OSCC patients as well as the crosstalk between saliva host proteins and the oral microbiome present in OSCC. • Saliva metagenomics and metaproteomics analysis are promising meta-omics approach. • Saliva microbiome and their microbiota proteins distinguished C, L0, and L1 groups. • Proteins were modulated in OSCC and may be related to microbiota compositional and functional changes. • Oral microbiota and its proteins show potential use in prognosis of OSCC patients. [ABSTRACT FROM AUTHOR]