Oral squamous cell carcinoma (OSCC) represents 90% of oral malignant neoplasms. The search for specific biomarkers for OSCC is a very active field of research contributing to establishing early diagnostic methods and unraveling underlying pathogenic mechanisms. In this work we investigated the salivary metabolites and the metabolic pathways of OSCC aiming find possible biomarkers. Salivary metabolites samples from 27 OSCC patients and 41 control individuals were compared through a gas chromatography coupled to a mass spectrometer (GC-MS) technique. Our results allowed identification of pathways of the malate-aspartate shuttle, the beta-alanine metabolism, and the Warburg effect. The possible salivary biomarkers were identified using the area under receiver-operating curve (AUC) criterion. Twenty-four metabolites were identified with AUC > 0.8. Using the threshold of AUC = 0.9 we find malic acid, maltose, protocatechuic acid, lactose, 2-ketoadipic, and catechol metabolites expressed. We notice that this is the first report of salivary metabolome in South American oral cancer patients, to the best of our knowledge. Our findings regarding these metabolic changes are important in discovering salivary biomarkers of OSCC patients. However, additional work needs to be performed considering larger populations to validate our results.

No abstract

In the oral cavity, Candida species form mixed biofilms with Streptococcus mutans, a pathogenic bacterium that can secrete quorum sensing molecules with antifungal activity. In this study, we extracted and fractioned culture filtrate of S. mutans, seeking antifungal agents capable of inhibiting the biofilms, filamentation, and candidiasis by Candida albicans. Active S. mutans UA159 supernatant filtrate components were extracted via liquid-liquid partition and fractionated on a C-18 silica column to resolve S. mutans fraction 1 (SM-F1) and fraction 2 (SM-F2). We found anti-biofilm activity for both SM-F1 and SM-F2 in a dose dependent manner and fungal growth was reduced by 2.59 and 5.98 log for SM-F1 and SM-F2, respectively. The SM-F1 and SM-F2 fractions were also capable of reducing C. albicans filamentation, however statistically significant differences were only observed for the SM-F2 (p = 0.004). SM-F2 efficacy to inhibit C. albicans was confirmed by its capacity to downregulate filamentation genes CPH1, EFG1, HWP1, and UME6. Using Galleria mellonella as an invertebrate infection model, therapeutic treatment with SM-F2 prolonged larvae survival. Examination of the antifungal capacity was extended to a murine model of oral candidiasis that exhibited a reduction in C. albicans colonization (CFU/mL) in the oral cavity when treated with SM-F1 (2.46 log) and SM-F2 (2.34 log) compared to the control (3.25 log). Although both SM-F1 and SM-F2 fractions decreased candidiasis in mice, only SM-F2 exhibited significant quantitative differences compared to the non-treated group for macroscopic lesions, hyphae invasion, tissue lesions, and inflammatory infiltrate. Taken together, these results indicate that the SM-F2 fraction contains antifungal components, providing a promising resource in the discovery of new inhibitors for oral candidiasis.

Previous studies showed that the crude extract obtained from Streptococcus mutans inhibited the growth of Candida albicans reference strains. In this study, we evaluated whether the antifungal effects of S. mutans extract can be extended to clinical Candida isolates, including C. albicans and non-abicans strains with different susceptibilities to fluconazole. We verified that S. mutans extract increased the survival of Galleria mellonella larvae infected with C. albicans and C. glabrata and inhibited the fungal cells in hemolymph. These antifungal effects occurred for both fluconazole-susceptible and fluconazole-resistant strains. However, larvae infected by C. krusei were not affected by S. mutans extract. Lay Summary Streptococcus mutans crude extract shows antifungal effects on clinical Candida strains susceptible and resistant to fluconazole in Galleria mellonella model.

The focus of bone tissue engineering is on the new strategies for developing bioactive and resorbable scaffolds, which have become an alternative to the treatment of bone diseases and trauma. β-tricalcium phosphate (β-TCP) is considered resorbable and has excellent osteoconductivity. In an attempt to achieve good densification of the β-TCP scaffold and improve its biological properties, it arises the possibility of combining this material with S53P4 bioactive glass. Several techniques are used to produce bioceramic scaffolds, among them, direct ink writing (DIW) a type of additive manufacturing based on material extrusion, which allows the production of customized parts, with high complexity and good reproducibility. This work prepared β-TCP and β-TCP/S53P4 (β-TCP/10-S53P4 = 10% wt of S53P4 and β-TCP/20-S53P4 = 20% wt of S53P4) scaffolds by DIW. The ceramic inks showed pseudoplastic behavior and the 3D-printed scaffolds showed similar aspects to the digital model. Also, the β-TCP/S53P4 scaffolds (β-TCP/10-S53P4 = 1.6 ± 0.6 MPa and β-TCP/20-S53P4 = 2.1 ± 0.9 MPa) showed an increase in compressive strength when compared to β-TCP scaffolds (0.9 ± 0.1 MPa). All scaffolds showed apatite-mineralization ability in SBF after soaking for 7 and 14 days, being that the β-TCP/20-S53P4 scaffold showed a higher ability of apatite formation compared to the other scaffolds. Concerning the biological in vitro assays, all the scaffolds showed good cell viability. Thus, the β-TCP/S53P4 scaffolds showed adequate properties which become them, good candidates, to be used in bone tissue engineering.