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CD4+Foxp3+Tregs maintain immune homeostasis, but distinct mechanisms underlying their functional heterogeneity during infections are driven by specific cytokine milieu. Here we show that MyD88 deletion in Foxp3+ cells altered their function and resulted in increased fungal burden and immunopathology during oral Candida albicans (CA) challenge. Excessive inflammation due to the absence of MyD88 in Tregs coincided with a reduction of the unique population of IL-17A expressing Foxp3+ cells (Treg17) and an increase in dysfunctional IFN-γ+/Foxp3+ cells (TregIFN-γ) in infected mice. Failure of MyD88-/- Tregs to regulate effector CD4+ T cell functions correlated with heightened levels of IFN-γ in CD4+ T cells, as well as increased infiltration of inflammatory monocytes and neutrophils in oral mucosa in vivo. Mechanistically, IL-1β/MyD88 signaling was required for the activation of IRAK-4, Akt, and mTOR, which led to the induction and proliferation of Treg17 cells. In the absence of IL-1 receptor signaling, Treg17 cells were reduced, but IL-6-driven expansion of TregIFN-γ cells was increased. This mechanism was physiologically relevant during Candida infection in aged mice, as they exhibited IL-1 receptor/MyD88 defect in Foxp3+ cells, loss of p-mTORhighTreg17 cells and reduced levels of IL-1β in oral mucosa, which coincided with persistent tongue inflammation. Concurrent with Treg dysfunction, aging was associated with increased CD4+ T cell hyperactivation and heightened levels of IL-6 in mice and humans in oral mucosa in vivo. Taken together, our data identify IL-1β/MyD88/Treg axis as a new component that modulates inflammatory responses in oral mucosa. Also, dysregulation of this axis in an aging immune system may skew host defense towards an immunopathological response in mucosal compartments. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the machinability of four CAD/CAM materials (n = 13) assessed by brittleness index, Vickers hardness, and fracture toughness and interaction among such mechanical properties. The materials selected in this in vitro study are Feldspathic ceramic [FC], Lithium-disilicate glass ceramic [LD], leucite-reinforced glass ceramic [LR], and nanofilled resin material [RN]. Slices were made from the blocks following original dimensions 14 x 12 x 3 mm (L x W x H), using a precision slow-speed saw device and then surfaces were regularized through a polishing device. Brittleness index and fracture toughness were calculated by the use of specific equations for each one of the properties. The Vickers hardness was calculated automated software in the microhardness device. One-way Anova and Pearson's correlation were applied to data evaluation. LD obtained the highest values for brittleness index and was not significantly different from FC. LR presented statistically significant difference compared with RN, which had the lowest mean. Vickers hardness showed LD with the highest average, and no statistical difference was found between FC and LR. RN presented the lowest average. Fracture toughness showed FC and LR not statistically different from each other, likewise LD and RN. The brittleness index, considered also as the machinability of a material, showed within this study as positively dependent on Vickers hardness, which leads to conclusion that hardness of ceramics is related to its milling capacity. In addition, fracture toughness of pre-sintered ceramics is compared to polymer-based materials. [ABSTRACT FROM AUTHOR]

CD4 + Foxp3 + T regs maintain immune homeostasis, but distinct mechanisms underlying their functional heterogeneity during infections are driven by specific cytokine milieu. Here we show that MyD88 deletion in Foxp3 + cells altered their function and resulted in increased fungal burden and immunopathology during oral Candida albicans (CA) challenge. Excessive inflammation due to the absence of MyD88 in T regs coincided with a reduction of the unique population of IL-17A expressing Foxp3 + cells (T reg 17) and an increase in dysfunctional IFN-γ + /Foxp3 + cells (T reg IFN-γ) in infected mice. Failure of MyD88 -/- T regs to regulate effector CD4 + T cell functions correlated with heightened levels of IFN-γ in CD4 + T cells, as well as increased infiltration of inflammatory monocytes and neutrophils in oral mucosa in vivo . Mechanistically, IL-1β/MyD88 signaling was required for the activation of IRAK-4, Akt, and mTOR, which led to the induction and proliferation of T reg 17 cells. In the absence of IL-1 receptor signaling, T reg 17 cells were reduced, but IL-6-driven expansion of T reg IFN-γ cells was increased. This mechanism was physiologically relevant during Candida infection in aged mice, as they exhibited IL-1 receptor/MyD88 defect in Foxp3 + cells, loss of p-mTOR high T reg 17 cells and reduced levels of IL-1β in oral mucosa, which coincided with persistent tongue inflammation. Concurrent with T reg dysfunction, aging was associated with increased CD4 + T cell hyperactivation and heightened levels of IL-6 in mice and humans in oral mucosa in vivo . Taken together, our data identify IL-1β/MyD88/T reg axis as a new component that modulates inflammatory responses in oral mucosa. Also, dysregulation of this axis in an aging immune system may skew host defense towards an immunopathological response in mucosal compartments., (Copyright © 2020 Bhaskaran, Faddoul, Paes da Silva, Jayaraman, Schneider, Mamileti, Weinberg and Pandiyan.)

Background: Bio cellulose is a byproduct of sweet tea fermentation known as kombusha. During the biosynthesis by bacteria cellulose chains are polymerized by enzyme from activated glucose. The single chains are then extruded through the bacterial cell wall. Interestingly, a potential of the Kombucha's byproduct bio cellulose (BC) as biomaterial had come into focus only in the past few decades. The unique physical and mechanical properties such as high purity, an ultrafine and highly crystalline network structure, a superior mechanical strength, flexibility, pronounced permeability to gases and liquids, and an excellent compatibility with living tissue that reinforced by biodegradability, biocompatibility, large swelling ratios., Material and Methods: The bio-cellulose film specimens were provided by the R.P Dressel dental materials laboratory, Department of Comprehensive Care, School of Dental Medicine, Case Western Reserve University, Cleveland, US. The films were harvested, washed with water and dried at room temperature overnight. 1wt% of PEG-2000 and 10wt% of NaOH were added into ultrapure water to prepare PEG/NaOH solution. Then bio-cellulose film was added to the mixture and swell for 3 h at room temperature. All bio-cellulose film specimens were all used in the TA Instruments Q500 Thermogravmetric Analyzer to investigate weight percent lost and degradation. The TGA was under ambient air conditions at a heating rate of 10ºC/min., Results and Conclusions: PEG control exhibited one transition with the peak at 380ºC. Cellulose and cellulose/ PEG films showed 3 major transitions. Interestingly, the cellulose/PEG film showed slightly elevated temperatures when compared to the corresponding transitions for cellulose control. The thermal gravimetric analysis (TGA) degradation curves were analyzed. Cellulose control film exhibited two zero order transitions, that indicate the independence of the rate of degradation from the amount on the initial substance. The activation energies for three transitions for cellulose and cellulose/PEG showed increasingly higher values for the transitions at higher temperatures. Key words: TGA, Bio-cellulose, PEG., Competing Interests: Conflict of interest statement:The authors hereby report no conflicts of interest with regards to this work.