Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.Peer reviewe

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) with asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthma is unclear. Objective: To explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthma. Methods: An IL-6TS gene signature, obtained from air-liquid interface (ALI) cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R, was used to stratify lung epithelium transcriptomic data (U-BIOPRED cohorts) by hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis and immunohistochemical analysis of bronchial biopsies. Results: Activation of IL-6TS in ALI cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of IL-6TS. High asthma patients with increased epithelial expression of IL-6TS inducible genes in absence of systemic inflammation. The IL-6TS High subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings, TLR pathway genes were up-regulated while the expression of tight junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, MMP3, MIP-1β, IL-8 and IL-1β. Conclusions: Local lung epithelial IL-6TS activation in absence of type 2 airway inflammation defines a novel subset of asthmatics and may drive airway inflammation and epithelial dysfunction in these patients

The influence of nanostructured alumina coating on bonding and optical properties of translucent zirconia ceramics

Thin, non-retentive, monolithic restorations fabricated from novel translucent zirconia ceramics are widely used in contemporary dentistry. Because of the chemical inertness of zirconia, debonding of such restorations remains the main clinical complication. Limited evidence on the bonding performance of novel translucent zirconia existstherefore, the present study aimed to evaluate, in vitro, the shear-bond strength (SBS) of translucent zirconia modified with a nanostructured alumina coating (NAC). The SBS of resin cement to translucent zirconia, materials containing 3, 4 or 5 mol.% of yttria modified with NAC, was measured and related to airborne-particle abraded (APA) zirconia surfaces. Half of each of the specimen groups (n = 20) were subjected to 37,500 thermocycles in water. In addition, to evaluate the effect of NAC on thin translucent zirconia discs (n = 10), the translucency parameter (TP) was measured and compared with APA. The results were statistically analyzed using a t-test and one-way ANOVA. NAC provided higher resin-zirconia SBS compared to APA, not affecting the zirconia optical properties. APA, on the other hand, lowered TP for all types of zirconia. NAC did not impair the mechanical or optical properties of translucent zirconia materials and should be regarded as a zirconia pretreatment alternative to APA

Pre-oxidation of selective-laser-melted titanium dental alloy

The heat treatment of dental alloys prior to porcelain application/veneering has been proposed as a way to ensure sufficient oxide scale and to promote the porcelain\u27s adherence in porcelain-fused-to-metal (PFM) fixed dental prostheses. The present study investigates the relationship between the bond strength of the dental porcelain to selective-laser-melted (SLM) titanium and the temperature of the titanium\u27s pre-oxidation. The SLM Ti-6Al-4V substrates were airborne-particle abraded and either left to passivate in air at room temperature (control) or pre-oxidized in a furnace under vacuum conditions (10kPa) at temperatures of 300, 600, 750, or 800 °C. The surface characteristics were determined using contact profilometry to measure the profile roughness (R$_a$), atomic force microscopy for the surface roughness (S$_a$) and Auger electron spectroscopy for the thickness of the oxide scale. Dental porcelain was applied to the metal substrates and the titanium-ceramic bond was assessed according to the ISO standard 9693-1:2012. The metal-ceramic interfaces were analyzed with scanning electron microscopy and energy-dispersive spectroscopy. The R$_a$ and S$_a$ values showed a strong positive correlation with the pre-oxidation temperature. The oxide scales covering the titanium surfaces thickened markedly at temperatures of 750 °C and above. However, the bond strength was negatively correlated with the pre-oxidation temperature. Room-temperature passivation in air following the airborne-particle abrasion of the SLM titanium resulted in a titanium-ceramic bond that is well above the ISO 9693-1:2012 recommended minimum value for metal-ceramic systems. Thus, no pre-oxidation of SLM titanium frameworks is necessary prior to the application/firing of porcelain

Bonding Performance of Surface-Treated Zirconia Cantilevered Resin-Bonded Fixed Dental Prostheses: In Vitro Evaluation and Finite Element Analysis

Debonding of zirconia cantilevered resin-bonded fixed dental prostheses (RBFDPs) remains the main treatment complication, therefore, the present in vitro study aimed to evaluate the effect of different surface pretreatments on the bonding of zirconia RBFDPs. Eighty milled zirconia maxillary central incisors, with complementary zirconia cantilevered RBFDPs, were randomly subjected to four different surface pretreatments (n = 20): as-machined (AM); airborne-particle abraded (APA); coated with nanostructured alumina coating (NAC); incisor air-abraded and RBFDP coated (NAC_APA). After bonding, half of each group (n = 10) was stored in deionized water (150 days/37 °C), thermocycled (37,500 cycles, 5–55 °C), and cyclically loaded (50 N/1.2 × 106). Load-bearing capacity (LBC) was determined using a quasi-static test. Additionally, finite element analysis (FEA) and fractography were performed. t-test and one-way ANOVA were used for statistical-analysis. Before aging, the NAC group provided superior LBC to other groups (p p ˃ 0.05). The FEA results correlated with the in vitro experiment and fractography, showing highly stressed areas in the bonding interface, cement layer, and in RBFDP’s retainer wing and connector. The NAC RBFDPs exhibited comparable long-term bonding performance to APA and should be regarded as a zirconia pretreatment alternative to APA

The Influence of Crown Ferrule on Fracture Resistance of Endodontically Treated Maxillary Central Incisors

Background: Prefabricated zirconia posts can contribute to increasing the fracture resistance of the endodontically treated teeth. Purpose. This in vitro study compared the fracture resistance of endodontically treated central maxillary incisors prepared with 2 mm ferrule length to the ones without ferrule

Sintering Strategies for Dental Zirconia Ceramics: Slow Versus Rapid?

PURPOSE OF REVIEW: Advances in zirconia ceramics have expanded their application in dentistry, necessitating faster delivery of zirconia-based restorations. With the introduction of high translucency grades of zirconia ceramics, the rapid sintering strategies that aim to reduce processing times can have a central impact on clinically relevant properties. The present review has surveyed the available literature evaluating the properties of rapidly sintered dental zirconia ceramics. RECENT FINDINGS: Recent studies emphasize the evolution of sintering protocols for zirconia ceramics, especially highlighting differences between conventional sintering (CS) and rapid methods like speed (SS) and high-speed sintering (HSS). These modern rapid sintering techniques transform the microstructure of zirconia ceramics, impacting its translucency, flexural strength, and aging resistance. These properties exhibit variability based on zirconia type and chosen sintering process, with HSS showing particular promise. SUMMARY: Rapid sintering protocols offer efficient alternatives to traditional zirconia ceramic processing, with benefits in cost and time. Despite the recent findings, discrepancies persist within zirconia generations, calling for further standardization and investigation

Factors Influencing the Survival Rate of Teeth and Implants in Patients after Tumor Therapy to the Head and Neck Region—Part 2: Implant Survival

During prosthetic rehabilitation after tumor therapy (TT) in the head and neck region, the dentist must assess whether the prognosis of the remaining teeth is sufficiently good or whether implants should be used to anchor dentures. Thus, the aim of the present study was to compare the survival rate of teeth and implants after TT and to evaluate factors potentially influencing implant survival. One hundred fifteen patients (male: 70.3%; mean age: 63.2 ± 12.4 years) having received dental treatment before and after TT at the Martin Luther University Halle-Wittenberg were enrolled in the study. Clinical examination including assessment of dental status and stimulated salivary flow rate was performed. Information about disease progression and therapy was retrieved from medical records. After TT, from a total of 1262 teeth, 27.2% had to be extracted. Of 308 implants inserted after TT, 7.0% were lost. Teeth exhibited lower 5-year survival probability (76.8%) than implants (89.9%; p = 0.001). The risk of loss (RL) of implants increased with age, nicotine use, intraoral defects, and RCT. Radiotherapy did not independently increase the RL. Thus, implants seem to be a reliable treatment option in case of progressive tooth decay after TT, particularly after RT

Lactational exposure to dioxin-like polychlorinated biphenyl 169 and nondioxin-like polychlorinated biphenyl 155

Exposure to polychlorinated biphenyls (PCBs), which are persistent lipophilic environmental pollutants, has a variety of adverse effects on wildlife and human health, including bone mineralization, growth and mechanical strength. The present study evaluated the effects of lactational exposure to nondioxin-like PCB-155 and dioxin-like PCB-169, individually and in combination, on pubertal rat femur development and its biomechanics. After offspring delivery, Wistar rat mothers were divided into four groups, i.e., PCB-169, PCB-155, PCB-155+169 and control, and were administered PCBs intraperitoneally. Data on bone geometry, biomechanics and mineral composition were obtained by analysis of femurs from 42-day-old offspring by microCT scanning, three-point bending test and inductively coupled plasma mass spectrometry. Decreased somatic mass and femur size, i.e., mass, periosteal circumference and cross sectional area, were observed in the PCB-169 and PCB-155 groups. Additionally, lactational exposure to planar PCB-169 resulted in harder and more brittle bones containing higher amounts of minerals. Combined exposure to structurally and functionally different PCBs demonstrated only mild alterations in bone width and mineralization. To conclude, our results demonstrated that alterations, observed on postnatal day 42, were primarily induced by PCB-169, while toxicity from both of the individual congeners may have been reduced in the combined group