The role of the novel Th17 cytokine IL-26 in intestinal inflammation

Background and aims: Interleukin 26 (IL-26), a novel IL-10-like cytokine without a murine homologue, is expressed in T helper 1 (Th1) and Th17 cells. Currently, its function in human disease is completely unknown. The aim of this study was to analyse its role in intestinal inflammation.Methods: Expression studies were performed by reverse transcription-PCR (RT-PCR), quantitative PCR, western blot and immunohistochemistry. Signal transduction was analysed by western blot experiments and ELISA. Cell proliferation was measured by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. IL-26 serum levels were determined by an immunoluminometric assay (ILMA).Results: All examined intestinal epithelial cell (IEC) lines express both IL-26 receptor subunits IL-20R1 and IL-10R2. IL-26 activates extracellular signal-related kinase (ERK)-1/2 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein (MAP) kinases, Akt and signal transducers and activators of transcription (STAT) 1/3. IL-26 stimulation increases the mRNA expression of proinflammatory cytokines but decreases cell proliferation. In inflamed colonic lesions of patients with Crohn's disease, an elevated IL-26 mRNA expression was found that correlated highly with the IL-8 and IL-22 expression. Immunohistochemical analysis demonstrated IL-26 protein expression in colonic T cells including Th17 cells expressing the orphan nuclear receptor ROR\textgreekgt, with an increased number of colonic IL-26-expressing cells in active Crohn's disease.Conclusion: Intestinal cells express the functional IL-26 receptor complex. IL-26 modulates IEC proliferation and proinflammatory gene expression and its expression is upregulated in active Crohn's disease, indicating a role for this cytokine system in the innate host cell response during intestinal inflammation. For the first time, IL-26 expression is demonstrated in colonic ROR\textgreekgt-expressing Th17 cells in situ, supporting a role for this cell type in the pathogenesis of Crohn's disease

Peri-implant diseases: Consensus Report of the Sixth European Workshop on Periodontology

Issues related to peri-implant disease were discussed. It was observed that the most common lesions that occur, i.e. peri-implant mucositis and peri-implantitis are caused by bacteria. While the lesion of peri-implant mucositis resides in the soft tissues, peri-implantitis also affects the supporting bone. Peri-implant mucositis occurs in about 80% of subjects (50% of sites) restored with implants, and peri-implantitis in between 28% and 56% of subjects (12-40% of sites). A number of risk indicators were identified including (i) poor oral hygiene, (ii) a history of periodontitis, (iii) diabetes and (iv) smoking. It was concluded that the treatment of peri-implant disease must include anti-infective measures. With respect to peri-implant mucositis, it appeared that non-surgical mechanical therapy caused the reduction in inflammation (bleeding on probing) but also that the adjunctive use of antimicrobial mouthrinses had a positive effect. It was agreed that the outcome of non-surgical treatment of peri-implantitis was unpredictable. The primary objective of surgical treatment in peri-implantitis is to get access to the implant surface for debridement and decontamination in order to achieve resolution of the inflammatory lesion. There was limited evidence that such treatment with the adjunctive use of systemic antibiotics could resolve a number of peri-implantitis lesions. There was no evidence that so-called regenerative procedures had additional beneficial effects on treatment outcome

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

A microtubule interactome: complexes with roles in cell cycle and mitosis.

addresses: Department of Zoology, University of Oxford, Oxford, United Kingdom.notes: PMCID: PMC2323305types: Journal Article; Research Support, Non-U.S. Gov'tCopyright: © 2008 Hughes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The microtubule (MT) cytoskeleton is required for many aspects of cell function, including the transport of intracellular materials, the maintenance of cell polarity, and the regulation of mitosis. These functions are coordinated by MT-associated proteins (MAPs), which work in concert with each other, binding MTs and altering their properties. We have used a MT cosedimentation assay, combined with 1D and 2D PAGE and mass spectrometry, to identify over 250 MAPs from early Drosophila embryos. We have taken two complementary approaches to analyse the cellular function of novel MAPs isolated using this approach. First, we have carried out an RNA interference (RNAi) screen, identifying 21 previously uncharacterised genes involved in MT organisation. Second, we have undertaken a bioinformatics analysis based on binary protein interaction data to produce putative interaction networks of MAPs. By combining both approaches, we have identified and validated MAP complexes with potentially important roles in cell cycle regulation and mitosis. This study therefore demonstrates that biologically relevant data can be harvested using such a multidisciplinary approach, and identifies new MAPs, many of which appear to be important in cell division

Влияние тяжелых металлов на жизнеспособность пыльцы некоторых древесных

The influence of Сu, Zn, Pb, Cr on sensitivity male gametophyte of Acer negundo, Robinia pseudoacacia, Philadelphus coronarius, Aesculus hippocastanum, Betula pendula, Catalpa bignonioides, Tilia cordata, Elaeagnus angustifolia was investigated. The most sensitive to metals have appeared the following species: to Cu and Zn - Betula pendula, Catalpa bignonoides, to Pb - Philadelphus coronarius, Catalpa bignonoides to Cr - Philadelphus coronarius, Catalpa bignonoides. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/1074

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

Síndrome de Stevens-Johnson. Apresentação de Caso Clínico

Introdução: A Síndrome de Stevens-Johnson (SSJ) é uma doença mucocutânea rara e potencialmente fatal, mais frequente no sexo masculino, cuja incidência aumenta com a idade e em determinados grupos de risco. A SSJ e a Necrólise Tóxica Epidérmica (NET) são duas entidades da mesma doença, com severidade diferente. A etiologia não é clara, mas pensa-se que se deva maioritariamente a reacções adversas a fármacos. Caso clínico: Um jovem de 17 anos de idade, sem antecedentes pessoais relevantes, foi observado no Serviço de Urgência por surgimento de lesões maculopapulares, com 3 dias de evolução, dispersas pela face, cavidade oral, tronco e extremidades, com prostração e taquicardia. Foi internado com o diagnóstico de SSJ. Discussão e Conclusões: O SSJ e a NET têm grande morbilidade e considerável mortalidade. O rápido reconhecimento desta identidade, com a remoção do fármaco desencadeador é essencial. A perda da função de barreira da pele, com a consequente alteração da homeostasia, implica muitas vezes a manutenção da terapêutica de suporte em Unidades de Cuidados Intensivos ou de Queimados.info:eu-repo/semantics/publishedVersio

A double-blind crossover rct analyzing technical and clinical performance of monolithic zro2 implant fixed dental prostheses (Ifdp) in three different digital workflows

This double-blind randomized controlled trial with a crossover design analyzed the technical and clinical performance of three-unit monolithic ZrO2 implant-fixed dental prostheses (iFDPs), prepared using two complete digital workflows (Test-1, Test-2) and one mixed analog–digital workflow (Control). Each of the 20 study patients received three iFDPs, resulting in 60 restorations for analysis. The quality of the restorations was assessed by analyzing laboratory cross-mounting and calculating the chairside adjustment time required during fitting. All iFDPs could be produced successfully with all three workflows. The highest cross-mounting success rate was observed for the original pairing iFDP/model of the Control group. Overall, 60% of iFDPs prepared with Test-1 workflow did not require chairside adjustment compared with 50% for Test-2 and 30% for Controls. The mean total chairside adjustment time, as the sum of interproximal, pontic, and occlusal corrections was 2.59 ± 2.51 min (Control), 2.88 ± 2.86 min (Test-1), and 3.87 ± 3.02 min (Test-2). All tested workflows were feasible for treatment with iFDPs in posterior sites on a soft tissue level type implant system. For clinical routine, it has to be considered that chairside adjustments may be necessary, at least in every second patient, independent on the workflow used

Precision of maxillo-mandibular registration with intraoral scanners in vitro

Purpose: To compare the precision of maxillo-mandibular registration and resulting full arch occlusion produced by three intraoral scanners in vitro. Methods: Six dental models (groups A–F) were scanned five times with intraoral scanners (CEREC, TRIOS, PLANMECA), producing both full arch and two buccal maxillo-mandibular scans. Total surface area of contact points (defined as regions within 0.1 mm and all mesh penetrations) was measured, and the distances between four pairs of key points were compared, each two in the posterior and anterior. Results: Total surface area of contact points varied significantly among scanners across all groups. CEREC produced the smallest contact surface areas (5.7–25.3 mm2), while PLANMECA tended to produce the largest areas in each group (22.2–60.2 mm2). Precision of scanners, as measured by the 95% CI range, varied from 0.1–0.9 mm for posterior key points. For anterior key points the 95% CI range was smaller, particularly when multiple posterior teeth were still present (0.04–0.42 mm). With progressive loss of posterior units (groups D–F), differences in the anterior occlusion among scanners became significant in five out of six groups (D–F left canines and D, F right canines, p < 0.05). Conclusions: Maxillo-mandibular registrations from three intraoral scanners created significantly different surface areas of occlusal contact. Posterior occlusions revealed lower precision for all scanners than anterior. CEREC tended towards incorrect posterior open bites, whilst TRIOS was most consistent in reproducing occluding units

Recent trends and future direction of dental research in the digital era

The digital transformation in dental medicine, based on electronic health data information, is recognized as one of the major game-changers of the 21st century to tackle present and upcoming challenges in dental and oral healthcare. This opinion letter focuses on the estimated top five trends and innovations of this new digital era, with potential to decisively influence the direction of dental research: (1) rapid prototyping (RP), (2) augmented and virtual reality (AR/VR), (3) artificial intelligence (AI) and machine learning (ML), (4) personalized (dental) medicine, and (5) tele-healthcare. Digital dentistry requires managing expectations pragmatically and ensuring transparency for all stakeholders: patients, healthcare providers, university and research institutions, the medtech industry, insurance, public media, and state policy. It should not be claimed or implied that digital smart data technologies will replace humans providing dental expertise and the capacity for patient empathy. The dental team that controls digital applications remains the key and will continue to play the central role in treating patients. In this context, the latest trend word is created: augmented intelligence, e.g., the meaningful combination of digital applications paired with human qualities and abilities in order to achieve improved dental and oral healthcare, ensuring quality of life