During the past decade, zirconia-based ceramics have been successfully introduced into the clinic to fabricate fixed dental prostheses (FDPs), along with a dental computer-aided/computer-aided manufacturing (CAD/CAM) system. In this article (1) development of dental ceramics, (2) the current status of dental CAD/CAM systems, (3) CAD/CAM and zirconia restoration, (4) bond between zirconia and veneering ceramics, (5) bond of zirconia with resin-based luting agents, (6) surface finish of zirconia restoration and antagonist enamel wear, and (7) clinical evaluation of zirconia restoration are reviewed. Yttria partially stabilized tetragonal zirconia polycrystalline (Y-TZP) showed better mechanical properties and superior resistance to fracture than other conventional dental ceramics. Furthermore, ceria-stabilized tetragonal zirconia polycrystalline and alumina nanocomposites (Ce-TZP/A) had the highest fracture toughness and had resistance to low-temperature aging degradation. Both zirconia-based ceramics have been clinically available as an alternative to the metal framework for fixed dental prostheses (FDPs). Marginal adaptation of zirconia-based FDPs is acceptable for clinical application. The most frequent clinical complication with zirconia-based FDPs was chipping of the veneering porcelain that was affected by many factors. The mechanism for the bonding between zirconia and veneering ceramics remains unknown. There was no clear evidence of chemical bonding and the bond strength between zirconia and porcelain was lower than that between metal and porcelain. There were two alternatives proposed that might avoid chipping of veneering porcelains. One was hybrid-structured FDPs comprising CAD/CAM-fabricated porcelain parts adhering to a CAD/CAM fabricated zirconia framework. Another option was full-contour zirconia FDPs using high translucent zirconia. Combined application of silica coating and/or silane coupler, and 10-methacryloyloxydecyl dihydrogen phosphate is currently one of the most reliable bonding systems for zirconia. Adhesive treatments could be applied to luting the restorations and fabricating hybrid-structured FDPs. Full-contour zirconia FDPs caused concern about the wear of antagonist enamel, because the hardness of Y-TZP was over double that of porcelain. However, this review demonstrates that highly polished zirconia yielded lower antagonist wear compared with porcelains. Polishing of zirconia is possible, but glazing is not recommended for the surface finish of zirconia. Clinical data since 2010 are included in this review. The zirconia frameworks rarely got damaged in many cases and complications often occurred in the veneering ceramic materials. Further clinical studies with larger sample sizes and longer follow-up periods are required to investigate the possible influencing factors of technical failures.

Host cell death is an intrinsic immune defense mechanism in response to microbial infection. However, bacterial pathogens use many strategies to manipulate the host cell death and survival pathways to enhance their replication and survival. This manipulation is quite intricate, with pathogens often suppressing cell death to allow replication and then promoting it for dissemination. Frequently, these effects are exerted through modulation of the mitochondrial pro-death, NF-κB–dependent pro-survival, and inflammasome-dependent host cell death pathways during infection. Understanding the molecular details by which bacterial pathogens manipulate cell death pathways will provide insight into new therapeutic approaches to control infection.

Caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X₂-D-X₃ motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection.

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Selective autophagy of bacterial pathogens represents a host innate immune mechanism. Selective autophagy has been characterized on the basis of distinct cargo receptors but the mechanisms by which different cargo receptors are targeted for autophagic degradation remain unclear. In this study we identified a highly conserved Tectonin domain-containing protein, Tecpr1, as an Atg5 binding partner that colocalized with Atg5 at Shigella-containing phagophores. Tecpr1 activity is necessary for efficient autophagic targeting of bacteria, but has no effect on rapamycin- or starvation-induced canonical autophagy. Tecpr1 interacts with WIPI-2, a yeast Atg18 homolog and PI(3)P-interacting protein required for phagophore formation, and they colocalize to phagophores. Although Tecpr1-deficient mice appear normal, Tecpr1-deficient MEFs were defective for selective autophagy and supported increased intracellular multiplication of Shigella. Further, depolarized mitochondria and misfolded protein aggregates accumulated in the Tecpr1-knockout MEFs. Thus, we identify a Tecpr1-dependent pathway as important in targeting bacterial pathogens for selective autophagy.

Persistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. Here we examine the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and find that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene is increased in Hp-positive human gastric biopsies as compared with Hp-negative controls. Moreover, silencing of miR-210 in gastric epithelial cells promotes proliferation. We identify STMN1 and DIMT1 as miR-210 target genes and demonstrate that inhibition of miR-210 expression augments cell proliferation by activating STMN1 and DIMT1 . Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.

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