Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate‐binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3‐O‐β‐d‐rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB‐MDA‐231, selected as representative for triple‐negative breast cancer and (ii) MCF‐7 used as a well‐characterized model of HER2‐negative breast cancer. To assess the cytocompatibility of rutin against non‐cancer cells, primary human mammary fibroblasts were used as control and non‐target cells. In MDA‐MB‐231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24–48–72 h, and decreased the activity of the adenosine triphosphate‐binding cassette transporters, namely, P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 μM and 50 μM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non‐selective inhibition of P‐gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple‐negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John Wiley & Sons, Ltd.

Chlorhexidine (CHX), one of the most effective drugs administered for periodontal treatment, presents collateral effects including toxicity when used for prolonged periods; here, we have evaluated the bactericidal potency and the cytocompatibility of Juniperus excelsa M. Bieb essential oil (EO) in comparison with 0.05% CHX. The EO was extracted from berries by hydrodistillation and components identified by gas chromatography and mass spectrometry. Bacterial inhibition halo analysis, quantitative cell viability 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino) carbonyl]-2H-tetrazolium hydroxide assay (XTT), and colony forming unit (CFU) count were evaluated against the two biofilm formers Aggregatibacter actinomycetemcomitans and Streptococcus mutans. Finally, cytocompatibility was assessed with human primary gingival fibroblasts (HGF) and mucosal keratinocytes (HK). The resulting EO was mainly composed of monoterpene hydrocarbons and oxygenated monoterpenes. An inhibition halo test demonstrated that both bacteria were sensitive to the EO; XTT analysis and CFU counts confirmed that 10-fold-diluted EO determined a statistically significant (p < 0.05) reduction in bacteria count and viability towards both biofilm and planktonic forms in a comparable manner to those obtained with CHX. Moreover, EO displayed higher cytocompatibility than CHX (p < 0.05). In conclusion, EO exhibited bactericidal activity similar to CHX, but a superior cytocompatibility, making it a promising antiseptic alternative to CHX.

Peri-implantitis is a severe condition affecting the success of transmucosal dental implants: tissue healing is severely limited by the inflammatory processes that come about to control homeostasis in the surrounding tissues. The main cause of peri-implantitis is bacterial biofilm infection; gingival fibroblasts play a pivotal role in regulating the inflammatory cascades. A new technology aimed at preventing bacterial colonization of titanium (Ti) implants, and enhancing the spread of gingival fibroblasts, is presented. Using electro-spinning, mirror-polished Ti disks were uniformly coated with keratin fibers obtained from discarded wool via sulfitolysis. The keratin-coated surfaces were then doped with silver (Ag) to introduce antibacterial properties, using different concentrations of silver nitrate as a precursor (0.01, 0.05 and 0.1 M). The resulting specimens were characterized in terms of morphology and chemical composition by FESEM, FTIR and XPS, revealing silver concentrations between 1.7 and 1.9%. Silver release into the medium was evaluated in the presence of cells (α-MEM) or bacteria (LB) by ICP; release was 0.2–1.4 mg l⁻¹ for α-MEM, and 10–40 mg l⁻¹ for LB. The antibacterial properties of the Ag-doped specimens were tested against a multidrug-resistant Staphylococcus aureus biofilm through morphology (FESEM) and metabolic assay (XTT); reduction in viability was significant (p < 0.05; >80% reduction within 72 h). Lastly, the cytocompatibility of the specimens was confirmed using human primary gingival fibroblasts, whose viability, spread and matrix deposition were found to be comparable to those of untreated Ti polished controls (p > 0.05). Thus, Ag surface enrichment was effective in reducing viability and maturation of S. aureus biofilm, without compromising human cell viability. Moreover, cell spread was found to be very sensitive to keratin fiber stimulation. The strategy thus appears to be very promising to introduce surface features in line with the main requirements for transmucosal dental implants.

Mounting evidence indicates that the microbiota, the unique combination of micro-organisms residing in a specific environment, plays an essential role in the development of a wide range of human diseases, including skin cancer. Moreover, a persistent imbalance of microbial community, named dysbiosis, can also be associated with oxidative stress, a well-known emerging force involved in the pathogenesis of several human diseases, including cutaneous malignancies. Although their interplay has been somewhat suggested, the connection between microbiota, oxidative stress, and skin cancer is a largely unexplored field. In the present review, we discuss the current knowledge on these topics, suggesting potential therapeutic strategies.