RESUMEN
With the advent of 3D printing technologies in dentistry, the optimization of printing conditions has been of great interest, so this study analyzed the accuracy of 3D-printed temporary restorations of different sizes produced by digital light processing (DLP) and liquid crystal display (LCD) printers. Temporary restorations of 2-unit, 3-unit, 5-unit, 6-unit, and full-arch cases were designed and printed from a DLP printer using NextDent C&B or an LCD printer using Mazic D Temp (n = 10 each). The restorations were scanned, and each restoration standard tessellation language (STL) file was superimposed on the reference STL file, by the alignment functions, to evaluate the trueness through whole/point deviation. In the whole-deviation analysis, the root-mean-square (RMS) values were significantly higher in the 6-unit and full-arch cases for the DLP printer and in the 5-unit, 6-unit, and full-arch cases for the LCD printer. The significant difference between DLP and LCD printers was found in the 5-unit and full-arch cases, where the DLP printer exhibited lower RMS values. Color mapping demonstrated less shrinkage in the DLP printer. In the point deviation analysis, a significant difference in direction was exhibited in all the restorations from the DLP printer but only in some cases from the LCD printer. Within the limitations of this study, 3D printing was most accurate with less deviation and shrinkage when a DLP printer was used for short-unit restorations.
RESUMEN
RIG-I is a key cytosolic sensor that detects RNA viruses through its C-terminal region and activates the production of antiviral interferons (IFNs) and proinflammatory cytokines. While posttranslational modification has been demonstrated to regulate RIG-I signaling activity, its significance for the sensing of viral RNAs remains unclear. Here, we first show that the RIG-I C-terminal region undergoes deacetylation to regulate its viral RNA-sensing activity and that the HDAC6-mediated deacetylation of RIG-I is critical for viral RNA detection. HDAC6 transiently bound to RIG-I and removed the lysine 909 acetylation in the presence of viral RNAs, promoting RIG-I sensing of viral RNAs. Depletion of HDAC6 expression led to impaired antiviral responses against RNA viruses, but not against DNA viruses. Consequently, HDAC6 knockout mice were highly susceptible to RNA virus infections compared to wild-type mice. These findings underscore the critical role of HDAC6 in the modulation of the RIG-I-mediated antiviral sensing pathway.
Asunto(s)
ARN Helicasas DEAD-box/metabolismo , Histona Desacetilasas/metabolismo , Procesamiento Proteico-Postraduccional , ARN Viral/inmunología , ARN Viral/metabolismo , Animales , Línea Celular , Proteína 58 DEAD Box , Modelos Animales de Enfermedad , Predisposición Genética a la Enfermedad , Histona Desacetilasa 6 , Histona Desacetilasas/deficiencia , Humanos , Ratones Noqueados , Infecciones por Virus ARN/inmunología , Receptores InmunológicosRESUMEN
BACKGROUND: The zoonotic transmission of highly pathogenic avian influenza viruses and the global pandemic of H1N1 influenza in 2009 signified the need for a wider coverage of therapeutic options for the control of influenza. METHODS: An in-house compound library was screened using a cytopathic effect inhibition assay. Selected hits were then tested in vivo and used as a core skeleton for derivative synthesis. RESULTS: The hit compound (BMD-2601505) was effective [50% effective concentration (EC50) of 60-70 µM] in reducing the death rate of cells infected with human influenza A and B viruses as well as avian influenza A virus. Furthermore, BMD-2601505 reduced the weight loss and increased the survival after lethal infection. The compound was further modified to enhance its antiviral potency. Results show that one derivative with bromobenzene moiety was most effective (EC50 of 22-37 µM) against the influenza viruses tested. CONCLUSION: We identified a small benzamide compound exhibiting antiviral activity against influenza viruses. The results warrant further evaluation of antiviral activities against drug-resistant influenza isolates.