Redox control of IL-6-mediated dental pulp stem cell differentiation on alginate/hydroxyapatite biocomposites for bone ingrowth

Composites and porous scaffolds produced with biodegradable natural polymers are very promising constructs which show high biocompatibility and suitable mechanical properties, with the possibility to be functionalized with growth factors involved in bone formation. For this purpose, alginate/hydroxyapatite (Alg/HAp) composite scaffolds using a novel production design were successfully developed and tested for their biocompatibility and osteoconductive properties in vitro. Redox homeostasis is crucial for dental pulp stem cell (DPSC) differentiation and mineralized matrix deposition, and interleukin-6 (IL-6) was found to be involved not only in immunomodulation but also in cell proliferation and differentiation. In the present study, we evaluated molecular pathways underlying the intracellular balance between redox homeostasis and extracellular matrix mineralization of DPSCs in the presence of composite scaffolds made of alginate and nano-hydroxyapatite (Alg/HAp). Prostaglandin-2 (PGE2) and IL-6 secretion was monitored by ELISA assays, and protein expression levels were quantified by Western blotting. This work aims to demonstrate a relationship between DPSC capacity to secrete a mineralized matrix in the presence of Alg/HAp scaffolds and their immunomodulatory properties. The variation of the molecular axis Nrf2 (nuclear factor erythroid 2-related factor 2)/PGE2/IL-6 suggests a tight intracellular balance between oxidative stress responses and DPSC differentiation in the presence of Alg/HAp scaffolds

When the Machine Stops: The Impact of Information Technology Failure on Firm Value

Previous research on information technology (IT) failures has predominantly focused on determining the impact of security breaches on firm value. However, little is known about IT failures that emerge accidentally and are unrelated to security incidents. This study approaches this notable research gap by applying the resource weakness framework and utilizing event study methodology. Based on a sample of 571 failure events from publicly-traded European firms, we find that non-security-related IT failures result on average in a 0.32% decline in firm value over a two-day event window. Interestingly, this decline is diminishing in more recent years. Moreover, the loss in firm value is particularly pronounced if the failure is caused by a software error (1.08%). In sum, our findings suggest that the often-neglected resource weakness perspective – that complements resource strengths within resource-based view – has strong explanatory power regarding the contingency factors of IT failure events

Digitalisierung, Erschließung und Präsentation des Archivs der Regensburgischen Botanischen Gesellschaft

Ziel des Projekts der Universitätsbibliothek Regensburg ist die vollständige Digitalisierung der urheberrechtsfreien Dokumente des Archivs der Regensburgischen Botanischen Gesellschaft mit Erschließung und Bereitstellung der Digitalisate im Open Access. Damit wird der für Geobotaniker, Wissenschaftshistoriker, Sprach- und Kulturwissenschaftler einzigartige Bestand der ältesten noch bestehenden botanischen Gesellschaft der Welt aus dem Zeitraum 1790 bis ca. 1900 digital dauerhaft zugänglich gemacht und für eine ungehinderte wissenschaftliche Nutzung und Analyse, auch für das Forschungsgebiet der Digital Humanities, bereitgestellt. Die qualitativ hochwertigen Digitalisate schonen die unikalen Bestände, werden mit den entsprechenden Metadaten auf der Plattform des Bayerischen Multimedia-Servers bereitgestellt und bilden die Grundlage für Transkriptionen und weitere Analysen. Normdatenverknüpfungen für Personen, Körperschafts- und Ortsnamen eröffnen vielfältige Möglichkeiten zur Suche, Analyse und Vernetzung der Inhalte mit anderen Informationsquellen. Die Daten lassen sich so in andere virtuelle Forschungsumgebungen und Informationsplattformen einbinden und tragen damit zu einem Mehrwert für die wissenschaftliche Community bei

Toll-like Receptors, LPS, and Dental Monomers

Unreacted monomers released from dental resin-based composites at non-cytotoxic concentrations cause a depletion of glutathione and an increase of reactive oxygen species (ROS), leading to, e.g., DNA damage and apoptosis. ROS-sensitive MAP-kinases are activated by HEMA and TEGDMA. MAP-kinases are also involved in the bacteria-triggered cell responses of the innate immune system, e.g., after bacterial lipopolysaccharide (LPS) binding to the Toll-like receptor (TLR) 4. Therefore, both bacteria and monomers imply environmental stress to pulp tissue, and they may influence the target cell reactions in a combined way. In macrophages, cell-surface antigens and cytokines were up-regulated after exposure to LPS, but TEGDMA caused a significant downregulation. Regulation was dependent on exposure time, indicating that LPS and TEGDMA act differently on MAP-kinases. Furthermore, the cell type played a decisive role. Inhibition of the immune response may result in a decrease in inflammatory symptoms and/or a reduced defense capacity against bacteria

Bisphenol A-glycidyl methacrylate induces a broad spectrum of DNA damage in human lymphocytes

Bisphenol A-glycidyl methacrylate (BisGMA) is monomer of dental filling composites, which can be released from these materials and cause adverse biologic effects in human cells. In the present work, we investigated genotoxic effect of BisGMA on human lymphocytes and human acute lymphoblastic leukemia cell line (CCRF-CEM) cells. Our results indicate that BisGMA is genotoxic for human lymphocytes. The compound induced DNA damage evaluated by the alkaline, neutral, and pH 12.1 version of the comet assay. This damage included oxidative modifications of the DNA bases, as checked by DNA repair enzymes EndoIII and Fpg, alkali-labile sites and DNA double-strand breaks. BisGMA induced DNA-strand breaks in the isolated plasmid. Lymphocytes incubated with BisGMA at 1 mM were able to remove about 50% of DNA damage during 120-min repair incubation. The monomer at 1 mM evoked a delay of the cell cycle in the S phase in CCRF-CEM cells. The experiment with spin trap—DMPO demonstrated that BisGMA induced reactive oxygen species, which were able to damage DNA. BisGMA is able to induce a broad spectrum of DNA damage including severe DNA double-strand breaks, which can be responsible for a delay of the cell cycle in the S phase

Comparative analysis of two colorimetric assays in dental pulp cell density

Nedel F, Soki FN, Conde MCM, Zeitlin BD, Tarquinio SBC, Nör JE, Seixas FK, Demarco FF. Comparative analysis of two colorimetric assays in dental pulp cell density. International Endodontic Journal , 44 , 59–64, 2011.To compare and contrast two colorimetric assays used for the measurement of proliferation using two dental pulp cell types: dental pulp stem cells (DPSC) and human dental pulp fibroblasts (HDPF).Dental pulp stem cells or HDPF were seeded at 0.25 × 10 4 cells per well in 96-well plates. Cell proliferation was evaluated after 24–72 h. At the end of the experimental period, the sulforhodamine B (SRB) assay or a water-soluble tetrazolium salt (WST-1) assay was performed. Optical densities were determined in a microplate reader (Genius; TECAN). Data were analysed by Student’s t -test (comparison between cell types) and one-way anova followed by Tukey test (time-point intervals). Pearson’ correlation tests were performed to compare the two assays for each cell line.Both assays showed that DPSC had higher proliferation rates than HDPF. A positive significant correlation between the two colorimetric assays tested for both cell types DPSC (Pearson’s correlation coefficient = 0.847; P  < 0.05) and HDPF (Pearson’s correlation coefficient = 0.775; P  < 0.05).Both tests demonstrated similar trends of cell proliferation, and thus are both appropriate for the evaluation of DPSC and HDPF. The choice of assay is therefore one of the practical applications. SRB stained plates can be dried and stored so may have utility in laboratories where data may require review or when access to analytical equipment is limited. WST-1 assays have the benefit of both ease and speed and may have utility in laboratories requiring either high throughput or rapid analyses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79110/1/j.1365-2591.2010.01796.x.pd

Dental methacrylates may exert genotoxic effects via the oxidative induction of DNA double strand breaks and the inhibition of their repair

Methacrylate monomers used in dentistry have been shown to induce DNA double strand breaks (DSBs), one of the most serious DNA damage. In the present work we show that a model dental adhesive consisting of 45% 2-hydroxyethyl methacrylate (HEMA) and 55% bisphenol A-diglycidyl dimethacrylate (Bis-GMA) at concentrations up to 0.25 mM Bis-GMA induced oxidative DNA in cultured primary human gingival fibroblasts (HGFs) as evaluated by the comet assay and probed with human 8-hydroxyguanine DNA-glycosylase 1. HEMA/Bis-GMA induced DSBs in HGFs as assessed by the neutral comet assay and phosphorylation of the H2AX histone and sodium ascorbate or melatonin (5-methoxy-N-acetyltryptamine) both at 50 μM reduced the DSBs, they also inhibited apoptosis induced by HEMA/Bis-GMA. The adhesive slowed the kinetics of the repair of DNA damage induced by hydrogen peroxide in HGFs, while sodium ascorbate or melatonin improved the efficacy of H2O2-induced damage in the presence of the methacrylates. The adhesive induced a rise in the G2/M cell population, accompanied by a reduction in the S cell population and an increase in G0/G1 cell population. Sodium ascorbate or melatonin elevated the S population and reduced the G2/M population. In conclusion, HEMA/Bis-GMA induce DSBs through, at least in part, oxidative mechanisms, and these compounds may interfere with DSBs repair. Vitamin C or melatonin may reduce the detrimental effects induced by methacrylates applied in dentistry

Molecular Toxicology of Substances Released from Resin–Based Dental Restorative Materials

Resin-based dental restorative materials are extensively used today in dentistry. However, significant concerns still remain regarding their biocompatibility. For this reason, significant scientific effort has been focused on the determination of the molecular toxicology of substances released by these biomaterials, using several tools for risk assessment, including exposure assessment, hazard identification and dose-response analysis. These studies have shown that substances released by these materials can cause significant cytotoxic and genotoxic effects, leading to irreversible disturbance of basic cellular functions. The aim of this article is to review current knowledge related to dental composites’ molecular toxicology and to give implications for possible improvements concerning their biocompatibility