Effect of professional dental prophylaxis on the surface gloss and roughness of CAD/CAM restorative materials

This study aimed to evaluate the effect of dental prophylaxis on the surface gloss and roughness of different indirect restorative materials for computer-aided design/computer-aided manufacturing (CAD/CAM): two types of CAD/CAM composite resin blocks (Shofu Block HC and Estelite Block) and two types of CAD/CAM ceramic blocks (IPS Empress CAD and Celtra DUO). After polishing the CAD/CAM blocks and applying prophylaxis pastes, professional dental prophylaxis was performed using four different experimental protocols (n = 5 each): mechanical cleaning with Merssage Regular for 10 s four times (Group 1); four cycles of mechanical cleaning with Merssage Regular for 10 s and Merssage Fine for 10 s (Group 2); four cycles of mechanical cleaning with Merssage Regular for 10 s and Merssage Fine for 30 s (Group 3); and mechanical cleaning with Merssage Fine for 10 s four times (Group 4). A glossmeter was used to measure surface gloss before and after mechanical cleaning, and a contact stylus profilometer was used to measure surface roughness (Ra). Polishing with prophylactic paste led to a significant reduction in surface gloss and increase in surface roughness among resin composite blocks, whereas the polishing-related change in surface gloss or roughness was smaller in Celtra DUO, a zirconia-reinforced lithium silicate block. Changes in surface gloss and roughness due to polishing with a prophylactic paste containing large particles were not improved by subsequent polishing with a prophylactic paste containing fine particles

Structural comparison of the C-terminal domain of functionally divergent lyssavirus P proteins

Lyssavirus P protein is a multifunctional protein that interacts with numerous host-cell proteins. The C-terminal domain (CTD) of P is important for inhibition of JAK-STAT signaling enabling the virus to evade host immunity. Several regions on the surface of rabies virus P are reported to interact with host factors. Among them, an extended, discrete hydrophobic patch of P CTD is notable. Although structures of P CTD of two strains of rabies virus, and of mokola virus have been solved, the structure of P CTD for Duvenhage virus, which is functionally divergent from these species for immune evasion function, is not known. Here, we analyze the structures of P CTD of Duvenhage and of a distinct rabies virus strain to gain further insight on the nature and potential function of the hydrophobic surface. Molecular contacts in crystals suggest that the hydrophobic patch is important to intermolecular interactions with other proteins, which differ between the lyssavirus species. (C) 2020 Elsevier Inc. All rights reserved

Tumor Accumulation of PIP-Based KRAS Inhibitor KR12 Evaluated by the Use of a Simple, Versatile Chicken Egg Tumor Model

Background: The KRAS inhibitor KR12, based on pyrrole-imidazole polyamide (PIP), has been developed and shown to exhibit efficacy in mouse experiments. Because some PIP species exhibit tumor accumulation capability, we decided to evaluate whether the PIP portion of KR12 exhibits tumor accumulation. We employed the CAM assay that provides a simple method for tumor accumulation evaluation. Methods: KR12 PIP was synthesized and conjugated to TAMRA to produce a fluorescently labeled reagent (KR12-TAMRA). This reagent was injected into a fertilized chicken egg that has been transplanted with human cancer cells. Distribution of the red fluorescence was examined by cutting out tumor as well as various organs from the embryo. Results: The red fluorescence of KR12-TAMRA was found to overlap with the green fluorescence of the tumor formed with GFP-expressing cancer cells. We also observed nuclear localization of KR12-TAMRA. Treatment of KR12 that contained the alkylating agent CBI in the tumor-bearing chicken egg resulted in tumor growth inhibition. Conclusions: KR12 contains a PIP that has two key features: tumor accumulation and nuclear localization. KR12 conjugated with CBI exhibits inhibition of tumor growth in the CAM model

Resting Energy Expenditure in Older Inpatients: A Comparison of Prediction Equations and Measurements

Determining energy requirements are an important component of nutritional support for patients with malnutrition; however, the validity of prediction equations for resting energy expenditure (REE) is disputed in older hospitalized patients. We aimed to assess the validity of these equations in older hospitalized patients in Japan. This was a single-center, cross-sectional study of 100 patients aged ≥70 years, hospitalized between January 2020 and December 2021. REE was measured using an indirect calorimeter and was compared to the predicted values calculated from five REE prediction equations. The mean (95% confidence interval) measured REE was 968.1 (931.0, 1005.3) kcal/day, and the mean predicted REE was higher for the FAO/WHO/UNU (1014.3 [987.1, 1041.6] kcal/day, p = 0.164) and Schofield (1066.0 [1045.8, 1086.2] kcal/day, p < 0.001) equations and lower for the Harris-Benedict (898.6 [873.1, 924.1] kcal/day, p = 0.011), Ganpule (830.1 [790.3, 869.9] kcal/day, p < 0.001), and body weight (kg) × 20 (857.7 [821.9, 893.5] kcal/day, p < 0.001) equations. In the age group analysis, none of the predicted values were within a 10% error for more than 80% of patients aged 70–89 years and ≥90 years. The five REE prediction equations did not provide accurate estimates. Validated REE prediction equations need to be developed for older hospitalized patients

Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system

Abstract Intrahepatic cholangiocarcinoma (IHCC) is a highly aggressive malignancy with a poor prognosis. It is thought to originate from cholangiocytes, which are the component cells of intrahepatic bile ducts. However, as patients with viral hepatitis often develop IHCC, it has been suggested that transformed hepatocytes may play a role in IHCC development. To investigate whether IHCC cells can be converted to functional hepatocytes, we established organoids derived from human IHCC and cultured them under conditions suitable for hepatocyte differentiation. IHCC organoids after hepatocyte differentiation acquired functions of mature hepatocytes such as albumin secretion, bile acid production and increased CYP3A4 activity. Studies using a mouse model of IHCC indicate that Wnt3a derived from macrophages recruited upon inflammation in the liver may promote the malignant transformation of hepatocytes to IHCC cells. The results of the present study support the recently proposed hypothesis that IHCC cells are derived from hepatocytes

The Measles Virus V Protein Binding Site to STAT2 Overlaps That of IRF9

Measles virus (MeV) is a highly immunotropic and contagious pathogen that can even diminish preexisting antibodies and remains a major cause of childhood morbidity and mortality worldwide despite the availability of effective vaccines. MeV is one of the most extensively studied viruses with respect to the mechanisms of JAK-STAT antagonism. Of the three proteins translated from the MeV P gene, P and V are essential for inactivation of this pathway. However, the lack of data from direct analyses of the underlying interactions means that the detailed molecular mechanism of antagonism remains unresolved. Here, we prepared recombinant MeV V protein, which is responsible for human JAK-STAT antagonism, and a panel of variants, enabling the biophysical characterization of V protein, including direct V/STAT1 and V/STAT2 interaction assays. Unambiguous direct interactions between the host and viral factors, in the absence of other factors such as Jak1 or Tyk2, were observed, and the dissociation constants were quantified for the first time. Our data indicate that interactions between the C-terminal region of V and STAT2 is 1 order of magnitude stronger than that of the N-terminal region of V and STAT1. We also clarified that these interactions are completely independent of each other. Moreover, results of size exclusion chromatography demonstrated that addition of MeV-V displaces STAT2-core, a rigid region of STAT2 lacking the N- and C-terminal domains, from preformed complexes of STAT2-core/IRF-associated domain (IRF9). These results provide a novel model whereby MeV-V can not only inhibit the STAT2/IRF9 interaction but also disrupt preassembled interferon-stimulated gene factor 3. IMPORTANCE To evade host immunity, many pathogenic viruses inactivate host Janus kinase signal transducer and activator of transcription (STAT) signaling pathways using diverse strategies. Measles virus utilizes P and V proteins to counteract this signaling pathway. Data derived largely from cell-based assays have indicated several amino acid residues of P and V proteins as important. However, biophysical properties of V protein or its direct interaction with STAT molecules using purified proteins have not been studied. We have developed novel molecular tools enabling us to identify a novel molecular mechanism for immune evasion whereby V protein disrupts critical immune complexes, providing a clear strategy by which measles virus can suppress interferon-mediated antiviral gene expression