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We present the first crystal structures of a human protein bound to analogs of cocaine and heroin. Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that catalyzes the hydrolysis of heroin and cocaine, and the detoxification of organophosphate chemical weapons, such as sarin, soman and tabun. Crystal structures of the hCE1 glycoprotein in complex with the cocaine analog homatropine and the heroin analog naloxone provide explicit details about narcotic metabolism in humans. The hCE1 active site contains both specific and promiscuous compartments, which enable the enzyme to act on structurally distinct chemicals. A selective surface ligand-binding site regulates the trimer-hexamer equilibrium of hCE1 and allows each hCE1 monomer to bind two narcotic molecules simultaneously. The bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure. [ABSTRACT FROM AUTHOR]

Provides a correction in the article 'Structural Basis of Heroin and Cocaine Metabolism by a Promiscuous Human Drug-Processing Enzyme,' by Sompop Bencharit, Christopher L. Morton, Yu Xue, Philip M. Potter and Matthew R. Redinbo published in the 2003 issue of 'Nature Structural Biology.'

Purpose: A newly introduced sintering protocol promises to offer higher translucency while not significantly compromising the flexural strength of the material. However, the effect of the novel sintering protocol has not been thoroughly validated. The purpose of this study was to measure and compare the effect of two sintering protocols on the translucency and flexural strength of two multilayered zirconia materials., Materials and Methods: Two types of multilayered zirconia materials (ZirCAD Prime and Prime esthetic) were selected. Presintered disk specimens were obtained from Translucent, Gradient, and Dentin layers (n = 20). The disks were allocated to 2 groups: standard sintering protocol (peak temperature 1500°C) and high translucency sintering protocol (peak temperature 1600°C). After the sintering process, 10 specimens from each group were randomly selected. The optical values (L * , a * , b * ) were measured and used to assess translucency using the relative translucency parameter (RTP 00 ) and translucency differences (ΔRTP 00 ). Then, all 20 specimens were tested for biaxial flexural strength. The outcomes were analyzed. The analysis of variance is used to analyze any significant effects on translucency and flexural strength. Then, any significant difference in the translucency and flexural strength between all pairs of materials was analyzed using Bonferroni-corrected Student's t-test (α = 0.05)., Results: The high translucency sintering protocol significantly decreased biaxial strength in the Prime translucent and dentine layer, Prime esthetic translucent, and gradient layer. RTP 00 was significantly reduced in the Prime gradient and Prime esthetic gradient layer when sintered with a high translucency protocol. The lowest ΔRTP 00 was observed in the Prime dentine layer, while the highest ΔRTP 00 was observed in the Prime esthetic dentin layer., Conclusions: High translucency protocol significantly lowers the biaxial flexural strength of both multilayered materials, but the alteration in translucency is within clinically acceptable thresholds (TAT 00 = 2.62)., (© 2024 The Author(s). Journal of Prosthodontics published by Wiley Periodicals LLC on behalf of American College of Prosthodontists.)

Purpose: While additive manufacturing (3D printing) has recently enhanced removable prosthodontics, the properties of new 3D printed materials are not well understood. This study aims to elucidate the physical properties of these materials, focusing on bonding to a 3D printed denture base material and wear resistance., Methods: For denture tooth-denture base bonding analyses, the same denture tooth material (Premium Teeth, Formlabs) was used with three denture base-bonding group assignments (n=6 each group) bonded using three protocols: Group A1 was bonded with Lucitone Digital Print-3D Denture Base using the Lucitone Fuse System (Dentsply), Group A2 with Formlabs Denture Base using the Formlabs Denture Base Bonding System, and Group A3 with Formlabs Denture Base using the Ivoclar Ivotion Bonding System (Ivoclar). Specimens were made according to the ISO-TS-19736-2027 standard. A 3D printed tooth mimicking a central incisor was bonded to the denture base and subjected to a palatal load at the incisal region at 90° from the long axis of the tooth until failure. The fracture surface was examined at 10× magnification. ANOVA with α=0.05 was used to determine statistically significant differences. For wear analysis, the same denture base material and bonding system (Lucitone Digital Print-3D Denture Base/Lucitone Fuse System, Dentsply) was used with four denture tooth material group assignments (n=8 each group): Group B1 used Formlabs Premium Teeth, Group B2 used SprintRay High Impact Denture Teeth, Group B3 used Lucitone Digital IPN Premium Tooth, and Group B4 used Ivotion Polymethyl Methacrylate (PMMA) Milled Teeth (Ivoclar). A premolar denture tooth bonded with the denture base was subjected to a chewing simulation cyclic loading of 1,200,000 cycles. Sample failures, vertical wear, and volume loss were documented. ANOVA with α=0.05 was used to determine statistically significant differences., Results: The fracture load to failure values for A1, A2, and A3 were 175±106 N, 167±46.3 N, and 183±48.9 N, respectively (p=0.95). Most failure characteristics were mixed, except one of A2 was cohesive and half of A3 was cohesive. For cyclic loading, B4 was the only group where all specimens failed within 1,200,000 cycles, while B1, B2, and B3 had four, three, and five sample failures, respectively. Vertical wear was 0.93±0.34 mm, 1.22±0.37 mm, 1.05±0.27 mm, and 0.37±0.02 mm for B1, B2, B3, and B4, respectively (p<0.01). Abrasion volumes were 9.5±3.7 mm³, 12.2±4.7 mm³, 10.6±3.5 mm³, and 2.2±1.3 mm³ for B1, B2, B3, and B4, respectively. Vertical height loss per chewing cycle (μm/cycle) was 0.0022±0.0019, 0.0030±0.0029, 0.0012±0.00005, and 0.0080±0.0050 for B1, B2, B3, and B4, respectively (p<0.01). Abrasion volume per chewing cycle (μm³/cycle) was 17650.8±9682.9, 27263.4±24746.8, 11836.5±4200.8, and 70436.8±73602.5 for B1, B2, B3, and B4, respectively (p=0.02)., Conclusion: The bonding strength and wear resistance of 3D printed denture materials vary by manufacturer. Formlabs Denture Base with Ivoclar Ivotion showed the highest fracture load, indicating superior bonding strength. In wear analysis, Ivoclar Ivotion PMMA Milled Teeth exhibited the least vertical wear and abrasion volume but had the highest failure rate under cyclic loading. While printed denture materials excel in bonding strength, their wear resistance may not be as good as milled denture teeth, highlighting the need to balance these properties in clinical applications., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The sample preparations, experiment execution, and experimental funding were supported by Formlabs. However, the manufacturer has no role in the data interpretation, report summary, manuscript preparation, and submission of this work. Financial relationships: Sompop Bencharit declare(s) a grant and non-financial support from Formlabs. The author's research was partly supported by Formlabs through non-financial materials and equipment grants as well as funding for research experiments. Sompop Bencharit declare(s) personal fees from Ivoclar. Ivoclar supports the author's research through education and material support and grants. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bencharit et al.)

The epithelial sodium channel (ENaC) is responsible for Na(+) and fluid absorption across colon, kidney, and airway epithelia. Short palate lung and nasal epithelial clone 1 (SPLUNC1) is a secreted, innate defense protein and an autocrine inhibitor of ENaC that is highly expressed in airway epithelia. While SPLUNC1 has a bactericidal permeability-increasing protein (BPI)-type structure, its NH2-terminal region lacks structure. Here we found that an 18 amino acid peptide, S18, which corresponded to residues G22-A39 of the SPLUNC1 NH2 terminus inhibited ENaC activity to a similar degree as full-length SPLUNC1 (∼2.5 fold), while SPLUNC1 protein lacking this region was without effect. S18 did not inhibit the structurally related acid-sensing ion channels, indicating specificity for ENaC. However, S18 preferentially bound to the βENaC subunit in a glycosylation-dependent manner. ENaC hyperactivity is contributory to cystic fibrosis (CF) lung disease. Unlike control, CF human bronchial epithelial cultures (HBECs) where airway surface liquid (ASL) height was abnormally low (4.2 ± 0.6 μm), addition of S18 prevented ENaC-led ASL hyperabsorption and maintained CF ASL height at 7.9 ± 0.6 μm, even in the presence of neutrophil elastase, which is comparable to heights seen in normal HBECs. Our data also indicate that the ENaC inhibitory domain of SPLUNC1 may be cleaved away from the main molecule by neutrophil elastase, suggesting that it may still be active during inflammation or neutrophilia. Furthermore, the robust inhibition of ENaC by the S18 peptide suggests that this peptide may be suitable for treating CF lung disease.

Recent advancements in mass spectrometric proteomics provide a promising result in utilizing saliva to explore biomarkers for diagnostic purposes. However, the issues of specificity or redundancy of disease-associated salivary biomarkers have not been described. This systematic review was therefore aimed to define and summarize disease-related salivary biomarkers identified by mass spectrometry proteomics. Peer-reviewed articles published through July 2009 within three databases were reviewed. Out of 243 articles, 21 studies were selected in this systematic review with conditions including Sjögren's syndrome, squamous cell carcinoma, dental caries, diabetes, breast cancer, periodontitis, gastric cancer, systemic sclerosis, oral lichen planus, bleeding oral cavity, and graft-versus-host disease. The sample size ranged from 3-41 in both diseased and control subjects, with no consensus on sample collection protocol. One hundred eighty biomarkers were identified in total; 87 upregulated, 63 downregulated, and 30 varying based on disease. Except for Sjögren's syndrome, the majority of studies with the same disease produce inconsistent biomarkers. Larger sample size and standardization of sample collection/treatment protocol may improve future studies.

Subperiosteal implants used to be prescribed to partially and fully edentulous patients to restore occlusion and esthetics prior to the emergence of the more successful endosseous implants that are used today. Because subperiosteal implants had a high incidence of failure, difficulty of placement, and post-operative complications, the use of subperiosteal implants declined significantly. However, some subperiostal implants placed 20-30 years ago still survive. Little information is available in the literature on how to treat patients whose subperiosteal implants still remain. This clinical case report thereby describes a treatment for a patient with a maxillary subperiosteal implant placed 23 years ago. The patient was offered a treatment option that included surgical implant removal, bone grafting and placement of endosseous implants to support a new maxillary overdenture. This treatment plan was not feasible due to the financial constraints of the patient and the complexity of the treatment. The patient chose a more conservative treatment plan, preserving the existing implant. The existing maxillary subperiosteal implant was restored with MICRO ERA attachments and a maxillary implant-retained overdenture was fabricated. The patient was satisfied with the esthetics and functional aspects of the treatment. No further peri-implant bone loss or other complications were found after a six-month recall. This clinical report suggests an alternative treatment plan for patients with existing subperiosteal implants that wish to avoid complex surgical procedures.

Introduction: Although human dental pulp stem cells isolated from healthy teeth have been extensively characterized, it is unknown whether stem cells also exist in clinically compromised teeth with irreversible pulpitis. Here we explored whether cells retrieved from clinically compromised dental pulp have stem cell-like properties., Methods: Pulp cells were isolated from healthy teeth (control group) and from teeth with clinically diagnosed irreversible pulpitis (diseased group). Cell proliferation, stem cell marker STRO-1 expression, and cell odonto-osteogenic differentiation competence were compared., Results: Cells from the diseased group demonstrated decreased colony formation capacity and a slightly decreased cell proliferation rate, but they had similar STRO-1 expression and exhibited a similar percentage of positive ex vivo osteogenic induction and dentin sialophosphoprotein expression from STRO-1-enriched pulp cells., Conclusions: Our study provides preliminary evidence that clinically compromised dental pulp might contain putative cells with certain stem cell properties. Further characterization of these cells will provide insight regarding whether they could serve as a source of endogenous multipotent cells in tissue regeneration-based dental pulp therapy., (Copyright (c) 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Recent advancement in mass spectrometry leads us to a new era of proteomic analysis. Human saliva can be easily collected; however, the complexity of the salivary proteome in the past prevented the use of saliva for proteomic analysis. Here we review the development of proteomic analyses for human saliva and focus on the use of a new mass spectrometric technology known as surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF). SELDI-TOF, a modification of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF), combines the precision of mass spectrometry and the high-through-put nature of protein arrays known as Protein Chips. This technology shows a promising future for salivary proteomic analysis in monitoring treatments and diseases, as well as novel biomarker discovery.