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Activation of macrophages and overexpression of TNFα is associated with the pathogenesis of chronic inflammatory diseases. However, the mechanisms leading to TNFα overexpression are still unknown. 5-methylocytosine (5-mC) is an epigenetic modification that is associated with silenced genes. Recent studies showed that it is converted to 5-hydroxylmethylocytosine (5-hmC) and reactivates gene expression through the action of the family of Ten-Eleven-Translocation (TET1-3) enzymes. In this study, we show that 5-hmC levels are increased globally and specifically in the TNFα promoter during the differentiation of monocytes to macrophages. In addition, the levels of 5-hmC are increased upon LPS stimulation of macrophages. Furthermore, CRIPSR stable knockout of TET1 decreases the expression of TNFα and other pro-inflammatory cytokines. In conclusion, we showed that TET1 contributes to the activation of macrophages possibly through regulation of 5-hydroxymethylation in the promoter of pro-inflammatory cytokine genes. The TET1 enzyme could be a promising therapeutic target to inhibit the persistent inflammation caused by macrophages in chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the interrelationship between tooth preparation and dental structure of Chinese maxillary central incisors and provide scientific guidance for clinical all-ceramic restoration. Forty-five specimens of maxillary central incisors were fabricated by 3D printer based on data of Micro CT scanning. Subsequently, every three specimens from the same natural tooth were randomly divided into three groups (n = 15): porcelain veneer, all ceramic crown, and the blank control group. All the specimen teeth were prepared according to routine clinical criteria, reconstructed into 3D models and then measured in software. The results showed that the mean quantity of reduction (volume fraction) was (28.35 ± 4.37) % and (56.93 ± 3.47) % for porcelain veneer and all-ceramic crown, respectively. The bonding areas of different all-ceramic restorations were (128.85 ± 11.73) mm2 and (97.15 ± 9.98) mm2 for all-ceramic crown and porcelain veneer respectively. In porcelain veneer group, the area of enamel adhesive was (54.80 ± 12.70) mm2, and the area of dentin was (42.35 ± 9.62) mm2. As the results of the one-sample t test, the mean distances from medullary angle to incisal edge or adjacent surface have significant differences with the test value which was set as 0.5 (P < .05). The reduction of the tooth for porcelain veneer is less than that of ceramic crown and the cementation of porcelain veneer is mostly dependent on the conservation of the enamel during preparation. The region from mesial adjacent surface to mesiopulpal angle is prone to have the problem of medullary perforation. [ABSTRACT FROM AUTHOR]

Gamma interferon (IFN-γ) is known to negatively regulate murine gammaherpesvirus-68 (MHV-68 or γHV-68) replication. This process involves the suppression of the viral gene replication and transcription activator (RTA) promoter, as well as activation of signal transducers and activators of transcription (STAT1). Notably, this effect is gradually attenuated during MHV-68 infection of bone marrow-derived macrophages (BMMs), which raised the possibility that the virus may utilize a mechanism that counteracts the antiviral effect of IFN-γ. By identifying the cellular factors that negatively regulate JAK-STAT1 signaling, we revealed that the infection of BMMs by MHV-68 induces the expression of suppressor of cytokine signaling 1 (SOCS1) and that depletion of SOCS1 restores the inhibitory effect of IFN-γ on virus replication. Moreover, we demonstrated that the expression of SOCS1 was induced as a result of the Toll-like receptor 3 (TLR3) mediated activation of the NF-κB signaling cascade. In conclusion, we report that TLR3-TRAF-NF-κB signaling pathway play a role in the induction of SOCS1 that counteracts the antiviral effect of IFN-γ during MHV-68 infection. This process is cell type-specific: it is functional in macrophages, but not in epithelial cells or fibroblasts. Our study reveals a mechanism that balances the immune responses and the escape of a gamma-herpesvirus in some antigen-presenting cells. [ABSTRACT FROM AUTHOR]

Background: Redox cofactors of NADH/NADPH participate in many cellular metabolic pathways for facilitating the electron transfer from one molecule to another in redox reactions. Transhydrogenase plays an important role in linking catabolism and anabolism, regulating the ratio of NADH/NADPH in cells. The cytoplasmic transhydrogenases could be useful to engineer synthetic biochemical pathways for the production of high-value chemicals and biofuels. Methodology/Principal Findings: A transhydrogenase activity was discovered for a FMN-bound diaphorase (DI) from Geobacillus stearothermophilus under anaerobic conditions. The DI-catalyzed hydride exchange were monitored and characterized between a NAD(P)H and a thio-modified NAD+ analogue. This new function of DI was demonstrated to transfer a hydride from NADPH to NAD+ that was consumed by NAD-specific lactate dehydrogenase and malic dehydrogenase. Conclusions/Significance: We discover a novel transhydrogenase activity of a FMN-DI by stabilizing the reduced state of FMNH2 under anaerobic conditions. FMN-DI was demonstrated to catalyze the hydride transfer between NADPH and NAD+. In the future, it may be possible to incorporate this FMN-DI into synthetic enzymatic pathways for balancing NADH generation and NADPH consumption for anaerobic production of biofuels and biochemicals. [ABSTRACT FROM AUTHOR]