Publications by authors named "Youssef Haikel"

70 Publications

Dual role of tannic acid and pyrogallol incorporated in plaster of Paris: Morphology modification and release for antimicrobial properties.

Mater Sci Eng C Mater Biol Appl 2021 Aug 27;127:112209. Epub 2021 May 27.

Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000 Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1121, 11 rue Humann, 67085 Strasbourg Cedex, France. Electronic address:

The design of bioactive plasters is of major interest for the amelioration of dental and bone cements. In this article, a one pot and environmentally friendly strategy based on the addition of a cheap polyphenol-tannic acid (TA) or the main phenolic constituent of TA, namely pyrogallol (PY)- able to interact with calcium sulfate is proposed. Tannic acid and pyrogallol not only modify the morphology of the obtained plaster+TA/PY composites but a part of it is released and provides strong-up to twenty fold- antibacterial effect against Staphylococcus aureus. It is shown that the higher antibacterial efficiency of PY is related to a greater release compared to TA even if in solution the antibacterial effect of PY is lower than that of TA when reported on the basis of the molar concentration in PY units.
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http://dx.doi.org/10.1016/j.msec.2021.112209DOI Listing
August 2021

Insensitivity of dental pulp stem cells migration to substrate stiffness.

Biomaterials 2021 Jun 15;275:120969. Epub 2021 Jun 15.

Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France. Electronic address:

Dental pulp stem cells (DPSCs) are a promising cell source for regeneration of dental pulp. Migration is a key event but influence of the microenvironment rigidity (5 kPa at the center of dental pulp to 20 GPa for the dentin) is largely unknown. Mechanical signals are transmitted from the extracellular matrix to the cytoskeleton, to the nuclei, and to the chromatin, potentially regulating gene expression. To identify the microenvironmental influence on migration, we analyzed motility on PDMS substrates with stiffness increasing from 1.5 kPa up to 2.5 MPa. We found that migration speed slightly increases as substrate stiffness decreases in correlation with decreasing focal adhesion size. Motility is relatively insensitive to substrate stiffness, even on a bi-rigidity PDMS substrate where DPSCs migrate without preferential direction. Migration is independent of both myosin II activity and YAP translocation after myosin II inhibition. Additionally, inhibition of Arp2/3 complex leads to significant speed decrease for all rigidities, suggesting contribution of the lamellipodia in the migration. Interestingly, the chromatin architecture remains stable after a 7-days exposure on the PDMS substrates for all rigidity. To design scaffold mimicking dental pulp environment, similar DPSCs migration for all rigidity, leaves field open to choose this mechanical parameter.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120969DOI Listing
June 2021

Antibacterial and Bonding Properties of Universal Adhesive Dental Polymers Doped with Pyrogallol.

Polymers (Basel) 2021 May 11;13(10). Epub 2021 May 11.

Department of Endodontics, Faculty of Dental Medicine, Strasbourg University, 67000 Strasbourg, France.

This study investigated the antibacterial activity, bond strength to dentin (SBS), and ultra-morphology of the polymer-dentin interface of experimental adhesive systems doped with pyrogallol (PY), which is a ubiquitous phenolic moiety that is present in flavonoids and polyphenols. A universal adhesive containing 4-META and 10-MDP was used in this study. PY behaves as an antioxidant and anti-cancerogenic agent and it was incorporated into the adhesive at different concentrations (0.5 and 1 wt.%). The antibacterial activity and SBS were analyzed and the results were statistically analyzed. The ultra-morphology of the polymer-dentin interface was assessed using scanning electron microscopy (SEM). At 24 h, a lower antibacterial activity was observed for the control adhesive compared to those with 0.5% and 1% PY. No difference was seen in SBS between the three groups at 24 h. After 6 months, the SBS of the 0.5% PY adhesive was significantly lower than the other tested adhesives. The specimens created with 1% PY adhesive presented a higher bond strength at six months compared with that found at 24 h. No morphological differences were found at the polymer-dentin interfaces of the tested adhesives. Pyrogallol may be incorporated into modern universal adhesive systems to preserve the polymer-dentin bonding interface and confer a certain degree of antibacterial activity.
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http://dx.doi.org/10.3390/polym13101538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151108PMC
May 2021

Bond Strength of Universal Adhesives to Dentin: A Systematic Review and Meta-Analysis.

Polymers (Basel) 2021 Mar 7;13(5). Epub 2021 Mar 7.

Dental Materials Laboratory, Academic Area of Dentistry, Autonomous University of Hidalgo State, Circuito Ex Hacienda La Concepción S/N, San Agustín Tlaxiaca, Hidalgo 42160, Mexico.

Currently, the availability of a wide variety of universal adhesives makes it difficult for clinicians to choose the correct system for specific bonding situations to dentin substrate. This study aimed to determine whether there are any alternative techniques or additional strategies available to enhance the bond strength of universal adhesives to dentin through a systematic review and meta-analysis. Two reviewers executed a literature search up to September 2020 in four electronic databases: PubMed, ISI Web of Science, Scopus, and EMBASE. Only in vitro studies that reported the dentin bond strength of universal adhesives using additional strategies were included. An analysis was carried out using Review Manager Software version 5.3.5 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). The methodological quality of each in vitro study was assessed according to the parameters of a previous systematic. A total of 5671 potentially relevant studies were identified. After title and abstract examination, 74 studies remained in systematic review. From these, a total of 61 studies were included in the meta-analysis. The bond strength of universal adhesives to dentin was improved by the use of one of the following techniques: Previous application of matrix metalloproteinases (MMP) inhibitors ( < 0.001), prolonged application time ( = 0.007), scrubbing technique ( < 0.001), selective dentin etching ( < 0.001), non-atmospheric plasma ( = 0.01), ethanol-wet bonding ( < 0.01), prolonged blowing time ( = 0.02), multiple layer application ( = 0.005), prolonged curing time ( = 0.006), and hydrophobic layer coating ( < 0.001). On the other hand, the use of a shortened application time ( = 0.006), and dentin desensitizers ( = 0.01) impaired the bond strength of universal adhesives to dentin. Most of the analyses performed showed a high heterogenicity. The in vitro evidence suggests that the application of universal adhesives using some alternative techniques or additional strategies may be beneficial for improving their bonding performance to dentin. This research received no external funding. Considering that this systematic review was carried out only with in vitro studies, registration was not performed.
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http://dx.doi.org/10.3390/polym13050814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961712PMC
March 2021

Does Etching of the Enamel with the Rubbing Technique Promote the Bond Strength of a Universal Adhesive System?

J Contemp Dent Pract 2020 Oct 1;21(10):1117-1121. Epub 2020 Oct 1.

Department of Biomaterials and Bioengineering, INSERM UMR_S 1121, Biomaterials and Bioengineering, Strasbourg, France; Department of Endodontics, Faculty of Dental Medicine, Strasbourg University, Strasbourg, France.

Aim: The aim of this research was to study the effect of etching by phosphoric acid with rubbing technique on the shear bond strength (SBS) of adhesive universal to enamel.

Materials And Methods: Sixty extracted teeth were obtained. Three application methods (self-etch, etch-and-rinse, and etch-and-rinse with rubbing technique) were performed to bond the enamel surfaces by a universal adhesive. After 24 hours of immersion in water at 37°C, the specimens were prepared for the SBS test. Scanning electron microscopy was performed to observe the adhesive-enamel interfaces. Optical numeric microscope was used to observe the failure style. Statistical analyses were done with one-way analysis of variance test.

Results: Statistically significant higher bond strength values were observed for etch-and-rinse mode with rubbing technique (25.98 ± 5.70) MPa then for the etch-and-rinse without rubbing (22.07 ± 5.27) MPa and self-etch modes (9.96 ± 2.98) MPa.

Conclusion: Enamel etched by 37% phosphoric acid with rubbing technique for 20 seconds showed an increase in the SBS of the universal adhesive to enamel surfaces. The tags of the adhesive can be presented more efficiently by rubbing the acid before the bonding process, consequently, an optimal interface for the bonding.

Clinical Significance: According to the results of this study, the selective enamel etching mode with rubbing technique is advisable when using the universal adhesive, as it significantly increased the bond strength of this adhesive to enamel surfaces. The clinician should etch the enamel using phosphoric acid with rubbing technique for 20 seconds to promote the bond strength of the universal adhesive system.
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October 2020

Tannic acid speeds up the setting of mineral trioxide aggregate cements and improves its surface and bulk properties.

J Colloid Interface Sci 2021 May 8;589:318-326. Epub 2021 Jan 8.

Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000 Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1121, 11 rue Humann, 67085 Strasbourg Cedex, France. Electronic address:

Hypothesis: The setting time and mechanical properties of cements are a major technical concern for a long time in civil engineering. More recently those practical problems became a major concern for biomedical applications -in bone surgery and in dentistry- in particular concerning the setting time which should be minimized. The possibility to add organic additives to interact with the different constituting ions in cements constitutes a way to modify the setting kinetics. We made the assumption that a hydrolysable polyphenol like tannic acid could modify the setting time and the physical properties of Mineral Trioxide Aggregate (MTA).

Experiments: Tannic acid is added in variable proportions to the water used to set MTA. The formation of the hybrid organic-mineral cements is investigated using a combination of structural, chemical and mechanical methods. X-ray tomography was also used to investigate the changes in porosity and pore size distribution upon incorporation of tannic acid in MTA based cements. The hydrophilicity of the cements was evaluated by measuring the permeation kinetics of small water droplets.

Findings: We found that tannic acid allowed to reduce markedly the setting time of MTA based cements. The obtained cements have an increased hydrophilicity and display excellent resistance to compression. The number of pores but not the average pore size is also affected. The possible roles of tannic acid in modifying the cement properties are discussed.
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http://dx.doi.org/10.1016/j.jcis.2020.12.115DOI Listing
May 2021

Microscopic and chemical evaluation of the filling quality of five obturation techniques in oval-shaped root canals.

Clin Oral Investig 2021 Jun 26;25(6):3757-3765. Epub 2020 Nov 26.

Department of Endodontics and Conservative Dentistry, Faculty of Dental Medicine, University of Strasbourg, 67000, Strasbourg, France.

Objectives: The aim of this study was to assess the filling quality of five obturation techniques in oval-shaped root canals.

Materials And Methods: A total of 212 mandibular first molars with one distal oval canal were selected. Distal canals, shaped with WaveOne Gold Primary, were randomly divided in five groups (n = 40) for obturation: continuous wave condensation, GuttaCore, Thermafil, single cone with AH plus, and single cone with BioRoot RCS. The proportions of gutta-percha-filled areas (GPFA), sealer-filled areas (SFA), void areas (VA), and the sealer/gutta tags into dentinal tubules at 4 mm and 2 mm from the apex were analyzed by an optical numeric microscope, SEM, and energy-dispersive X-ray (EDX). Data were then compared by Kruskal-Wallis one-way ANOVA on ranks (α = 0.05).

Results: At 4 mm, a statistically significant higher GPFA and lower SFA were observed in the GuttaCore and Thermafil groups compared with the 3 other groups. A statistically significant lower VA was observed in the continuous wave condensation, GuttaCore, and Thermafil groups than in the two single-cone groups. At 2 mm, there were a statistically significant higher GPFA and lower SFA and VA in GuttaCore and Thermafil groups than in the 3 other groups. At the two levels investigated, the presence of gutta-percha tags was clearly demonstrated for GuttaCore and Thermafil groups; no tags were observed in the 3 other groups.

Conclusions: Obturation quality was overall improved in GuttaCore and Thermafil groups.

Clinical Relevance: Carrier-based techniques may significantly improve the filling quality compared to continuous wave condensation and single-cone technique. The single-cone technique might have inherent limitations especially in oval root canals regardless of the sealer used.
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http://dx.doi.org/10.1007/s00784-020-03703-9DOI Listing
June 2021

In Vitro Evaluation of Different Irrigation Protocols on Intracanal Smear Layer Removal in Teeth with or without Pre-Endodontic Proximal Wall Restoration.

J Clin Med 2020 Oct 16;9(10). Epub 2020 Oct 16.

Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Sainte Elisabeth, 67000 Strasbourg, France.

To investigate the influence of pre-endodontic coronal wall restoration on smear layer removal during different root canal irrigation strategies, single-root premolars were prepared with a mesio-occlusal cavity. Half were left untreated (G1), while the mesial walls of the remaining half were reconstructed using a resin composite (G2). The specimens were divided into control (ctrl) groups, which used the conventional needle irrigation method, and four experimental subgroups according to irrigation strategy: Sonic activation using the Endoactivator, sonic activation using the EQ-S, mechanical activation using the XP-Endo finisher, and ultrasonic activation using the EndoUltra. Smear layer removal was assessed through SEM and the results were statistically analyzed. At the coronal and middle thirds, no significant difference ( > 0.05) was detected for G1 and G2, except for the control subgroups (G1ctrl vs G2 ctrl) at the middle third. At the apical third, the smear layer removal was significantly greater for G2 than G1. In G1, both at the middle and apical level, EQ-S and EndoUltra showed greater smear layer removal ( < 0.05) compared to the others G1 subgroups. In G2, at the apical level, the EQ-S and EndoUltra were the most effective in smear layer removal. Pre-endodontic coronal wall restoration may improve the smear layer removal during root canal irrigation.
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http://dx.doi.org/10.3390/jcm9103325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602818PMC
October 2020

Physicochemical and Antibacterial Properties of Novel, Premixed Calcium Silicate-Based Sealer Compared to Powder-Liquid Bioceramic Sealer.

J Clin Med 2020 Sep 25;9(10). Epub 2020 Sep 25.

Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Sainte Elisabeth, 67000 Strasbourg, France.

The aim of this study was to compare the physicochemical properties, filling ability, and antibacterial activity of a premixed calcium silicate-based sealer to those of a powder-liquid bioceramic sealer. Ceraseal (CS) and BioRoot (BR) materials were analyzed using scanning electron microscopy and energy-dispersive X-ray spectroscopy at 7 and 14 d of immersion in distilled water. The filling ability of the two sealers as well as the water contact angle, solubility, flow, roughness, crystalline microstructure, pH, and compressive strength were also evaluated. The antibacterial activity was assessed through an agar diffusion as well as through direct tests. All the results were statistically analyzed using one-way or two-way analysis of variance tests. Statistically significant lower void percentages were observed for CS at 2 and 8 mm from the working length (WL) compared to those for the BR group, whilst no significant difference was observed at 5 mm from the WL. BR sealer showed higher alkaline pH, rougher surface, lower water contact angle values, lower flowability, and higher solubility compared to CS. BR showed globular and needle-like crystalline microstructure, whilst CS had globular and flower-like crystalline microstructure up to 72 h. No statistical difference was found for the compressive strength between the two sealers. BR and CS showed no antibacterial effect against after 3 h, whilst both sealers showed antibacterial capacity after 24 and 72 h. BR demonstrated higher antibacterial activity after 24 h. In conclusion, the use of bioceramic sealers may play an important role in controlling bacterial growth. Moreover, CS may have superior filling ability and lower solubility than the BioRoot sealer due to its specific chemical composition and mixing method.
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http://dx.doi.org/10.3390/jcm9103096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600315PMC
September 2020

Polyphenols in Dental Applications.

Bioengineering (Basel) 2020 Jul 7;7(3). Epub 2020 Jul 7.

Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Sainte Elisabeth, 67000 Strasbourg, France.

(1) Background: polyphenols are a broad class of molecules extracted from plants and have a large repertoire of biological activities. Biomimetic inspiration from the effects of tea or red wine on the surface of cups or glass lead to the emergence of versatile surface chemistry with polyphenols. Owing to their hydrogen bonding abilities, coordination chemistry with metallic cations and redox properties, polyphenols are able to interact, covalently or not, with a large repertoire of chemical moieties, and can hence be used to modify the surface chemistry of almost all classes of materials. (2) Methods: the use of polyphenols to modify the surface properties of dental materials, mostly enamel and dentin, to afford them with better adhesion to resins and improved biological properties, such as antimicrobial activity, started more than 20 years ago, but no general overview has been written to our knowledge. (3) Results: the present review is aimed to show that molecules from all the major classes of polyphenolics allow for low coast improvements of dental materials and engineering of dental tissues.
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http://dx.doi.org/10.3390/bioengineering7030072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552636PMC
July 2020

Melanoma stem cell maintenance and chemo-resistance are mediated by CD133 signal to PI3K-dependent pathways.

Oncogene 2020 08 2;39(32):5468-5478. Epub 2020 Jul 2.

Institut National de la Santé et de la Recherche Médicale, Strasbourg, France.

Melanoma stem cells (MSCs) are characterized by their unique cell surface proteins and aberrant signaling pathways. These stemness properties are either in a causal or consequential relationship to melanoma progression, treatment resistance and recurrence. The functional analysis of CD133 and CD133 cells in vitro and in vivo revealed that melanoma progression and treatment resistance are the consequences of CD133 signal to PI3K pathway. CD133 signal to PI3K pathway drives two downstream pathways, the PI3K/Akt/MDM2 and the PI3K/Akt/MKP-1 pathways. Activation of PI3K/Akt/MDM2 pathway results in the destabilization of p53 protein, while the activation of PI3K/Akt/MKP-1 pathway results in the inhibition of mitogen-activated protein kinases (MAPKs) JNK and p38. Activation of both pathways leads to the inhibition of fotemustine-induced apoptosis. Thus, the disruption of CD133 signal to PI3K pathway is essential to overcome Melanoma resistance to fotemustine. The pre-clinical verification of in vitro data using xenograft mouse model of MSCs confirmed the clinical relevance of CD133 signal as a therapeutic target for melanoma treatment. In conclusion, our study provides an insight into the mechanisms regulating MSCs growth and chemo-resistance and suggested a clinically relevant approach for melanoma treatment.
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http://dx.doi.org/10.1038/s41388-020-1373-6DOI Listing
August 2020

Root Anatomy of Mandibular Second Premolars in French Subpopulation: A Retrospective Observational Case Series.

Contemp Clin Dent 2019 Jul-Sep;10(3):494-497

INSERM UMR_S 1121, "Biomaterials and Bioengineering," Strasbourg, France.

Aims: The purpose of this study is to illustrate endodontic anatomical variants in French subpopulations of human mandibular second premolars to show if the literature matches our findings.

Setting And Design: This was an observational retrospective study.

Subjects And Methods: This study was performed from September 2016 to September 2017. It was conducted on 56 successive cases of root canal therapies on the mandibular second premolars. All procedures were done in conformity with current state-of-the-art practices in endodontics. These included rigorous clinical and radiographic preaccess analysis, appropriate tooth restoration to insure watertight rubber dam installation, surgical microscopic manipulations for precision, systematic use of ultrasonic endodontic tips to manage cavity access preparation, and step-down technique to shape the root canal systems.

Statistical Analysis Used: Fifty-six mandibular second premolars were treated: 76.8% had one canal, and 23.2% had two or more canals.

Conclusions: The incidence of two or more canals on mandibular second premolars could be underestimated as our results show. To prevent any missing canals, clinicians must have a perfect knowledge of anatomic variants of the root canal system. Moreover, the systematic use of a surgical microscope, ultrasonic endodontic tips, and a modern step-down technique should facilitate and standardize access cavity preparation, canal localization, and instrumentation.
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http://dx.doi.org/10.4103/ccd.ccd_841_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150574PMC
April 2020

Technical Quality of Root Canal Filling in Preclinical Training at Strasbourg University Using Two Teaching Protocols.

Eur J Dent 2019 Oct 31;13(4):521-526. Epub 2019 Dec 31.

Department of Endodontic and Conservative Dentistry, Faculty of Dental Medicine, Strasbourg University, Strasbourg, France.

Objectives:  The aim of this study was to compare two teaching protocols according to the technical quality of root canal therapy (RCT) and the procedural errors occurred in preclinical training.

Materials And Methods:  Two different groups of students were concerned. The first one (G1) performed a crown-down technique to shape the root canal systems and cold lateral condensation technique to fill them. The second one (G2) performed a step-down technique without initial manual scouting to shape the root canal systems, and cold hydraulic condensation technique, to fill them. G2 used clinical operative microscope to check the access cavity preparation.

Statistical Analysis:  The quality of RCTs and procedural errors were recorded and analyzed using chi-squared test and -test.

Results:  Four hundred sixty-eight root canals from 152 maxillary molars were treated by the G1 students: 46.6% canals were judged as acceptable. Four hundred sixty-nine root canals from 152 mandibular molars were treated by G1: 58.8% canals were judged as acceptable. Five hundred fifteen root canals from 156 maxillary molars were treated by G2 students: 84.1% canals were judged as acceptable. Four hundred ninety-three root canals from 156 mandibular molars were treated by G2: 90.9% canals were judged as acceptable. Among the errors, the incidence of "ledges" and "fractured instruments" was statistically significant in G1 compared with G2, both on maxillary and on mandibular molars.

Conclusions:  The molar RCTs performed by G2, who got benefit from the new teaching protocol, resulted in a better quality of root filling and in fewer procedural errors compared with the molar RCTs performed by G1.
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http://dx.doi.org/10.1055/s-0039-1698848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938450PMC
October 2019

Effectiveness of Etching by Three Acids on the Morphological and Chemical Features of Dentin Tissue.

J Contemp Dent Pract 2019 Aug 1;20(8):915-919. Epub 2019 Aug 1.

INSERM UMR_S 1121, Biomaterials and Bioengineering, Strasbourg, France.

Aim: The purpose of this study was to evaluate the microscopic and chemical effects of phosphoric acid gel, phosphoric acid liquid, and polyacrylic acid application for 15 seconds (s) on coronal dentin.

Materials And Methods: Twelve extracted teeth were selected. Three etching acids were used to prepare the dentin surfaces. Scanning electron microscopy (SEM) and X-ray energy dispersive spectroscopy (EDX) were used to analyze the chemical and morphological changes of the dentinal surfaces, including the depth of demineralization. Collected data were statistically analyzed by the one-way analysis of variance test.

Results: Dentin etched with phosphoric acid gel or liquid showed greater peritubular dentin dissolution, including complete removal of the smear layer. In addition, there were many silica particles on the dentin etched by phosphoric acid gel 37%. The dentin that was etched with 25% polyacrylic acid for 15 seconds showed no smear layer removal. Chemical analysis (EDX) showed that dental surfaces etched with phosphoric acid liquid 37% for 15 seconds showed the strongest mineral dissolution at the calcium surface, with a calcium content of 5.25%. On the other hand, EDX analysis of the dental surface etched with 25% polyacrylic acid showed more surface enrichment in calcium (17.19%).

Conclusion: Although phosphoric acid (gel or liquid) 37% cleans the dental surface, phosphoric acid gel precipitates silica particles on the etched dentin surface. These particles cannot be removed by rinsing off this acid. The application of polyacrylic acid for 15 seconds does not noticeably demineralized dentin, nor remove the smear layer.

Clinical Significance: The clinician should use phosphoric acid (gel or liquid) to clean dental surfaces to prepare them for the bonding process. The low demineralizing effects of the polyacrylic acid permits its use near the pulp.
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August 2019

Effect of etching the coronal dentin with the rubbing technique on the microtensile bond strength of a universal adhesive system.

Dent Med Probl 2019 Oct-Dec;56(4):343-348

Inserm UMR_S 1121, Biomaterials and Bioengineering, University of Strasbourg, France.

Background: The adhesion of composite resins to the dentin substrate is influenced by the treatment of the smear layer. While etch-and-rinse systems require dentin to be conditioned with phosphoric acid, self-etching systems preserve the smear layer by incorporating it into the adhesive layer.

Objectives: The objective of this study was to evaluate the influence of etching with the rubbing technique on the microtensile bond strength (μTBS) of a universal adhesive to dentin.

Material And Methods: Eighteen extracted teeth were selected. Two etch-and-rinse techniques (with and without rubbing) and a self-etching technique were used to bond the dentin surfaces with a universal adhesive system. After 24 h, the bonded samples were prepared for the μTBS testing. The specimens were loaded with a tensile force at a crosshead speed of 0.5 mm/min until failure. The scanning electron microscope (SEM) analyses were used to reveal the failure modes. The data were statistically analyzed with the one-way analysis of variance (ANOVA) and χ2 tests.

Results: The etch-and-rinse system with rubbing produced significantly lower bond strength (42.11 ±9.26 MPa,) than the etch-and-rinse system without rubbing (47.30 ±8.12 MPa) and significantly higher bond strength than the self-etching system (38.07 ±9.49 MPa).

Conclusions: Under the conditions of this study, dentin etched with phosphoric acid for 3 s in the etchandrinse mode with the rubbing technique for a universal adhesive system decreases the μTBS of the composite to dentin.
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http://dx.doi.org/10.17219/dmp/111697DOI Listing
January 2020

Unusual Maxillary First Molars with C-Shaped Morphology on the Same Patient: Variation in Root Canal Anatomy.

Case Rep Dent 2019 22;2019:1857289. Epub 2019 Oct 22.

Inserm UMR_S 1121, Biomaterials and Bioengineering, Strasbourg University, 11 Rue Humann, 67085 Strasbourg, France.

A maxillary first molar should be considered a four-canal tooth until proved otherwise; however, a clinician should also be aware of the possibility of the presence of C-shaped root canal configuration with or without possibility of splitting into two or three canals. The two clinical cases reported in this paper describe the endodontic treatment of two maxillary first molars, on the same patient, with uncommon anatomy: the first case is about a maxillary first molar with only one C-shaped root and one oval canal with a large buccolingual diameter, a C1 type according to Fan's classification; the second case, about the contralateral maxillary first molar, is probably the first case documented of a maxillary first molar with a C-shaped root canal and C-shaped root with complete fusion of the three roots, having a C3 configuration.
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http://dx.doi.org/10.1155/2019/1857289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854219PMC
October 2019

Tumor necrosis factor-α triggers opposing signals in head and neck squamous cell carcinoma and induces apoptosis via mitochondrial- and non-mitochondrial-dependent pathways.

Int J Oncol 2019 Dec 17;55(6):1324-1338. Epub 2019 Oct 17.

INSERM UMR 1121, University of Strasbourg, 67000 Strasbourg, France.

Head and neck squamous cell carcinoma (HNSCC) remains one of the most common malignancies worldwide. Although the treatment outcomes of HNSCC have improved in recent years, the prognosis of patients with advanced-stage disease remains poor. Current treatment strategies for HNSCC include surgery as a primary therapy, while radio-, chemo-, and biotherapeutics can be applied as second-line therapy. Although tumor necrosis factor-α (TNF-α) is a potent tumor suppressor cytokine, the stimulation of opposing signals impairs its clinical utility as an anticancer agent. The aim of this study was to elucidate the mechanisms regulating TNF-α‑induced opposing signals and their biological consequences in HNSCC cell lines. We determined the molecular mechanisms of TNF-α-induced opposing signals in HNSCC cells. Our in vitro analysis indicated that one of these signals triggers apoptosis, while the other induces both apoptosis and cell survival. The TNF-α-induced survival of HNSCC cells is mediated by the TNF receptor-associated factor 2 (TRAF2)/nuclear factor (NF)-κB-dependent pathway, while TNF-α-induced apoptosis is mediated by mitochondrial and non-mitochondrial-dependent mechanisms through FADD-caspase-8-caspase-3 and ASK-JNK-p53-Noxa pathways. The localization of Noxa protein to both the mitochondria and endoplasmic reticulum (ER) was found to cause mitochondrial dysregulation and ER stress, respectively. Using inhibitory experiments, we demonstrated that the FADD‑caspase-8‑caspase-3 pathway, together with mitochondrial dysregulation and ER stress-dependent pathways, are essential for the modulation of apoptosis, and the NF-κB pathway is essential for the modulation of anti-apoptotic effects/cell survival during the exposure of HNSCC cells to TNF-α. Our data provide insight into the mechanisms of TNF-α-induced opposing signals in HNSCC cells and may further help in the development of novel therapeutic approaches with which to minimize the systemic toxicity of TNF-α.
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http://dx.doi.org/10.3892/ijo.2019.4900DOI Listing
December 2019

Microscopic and Chemical Assessments of the Filling Ability in Oval-Shaped Root Canals Using Two Different Carrier-Based Filling Techniques.

Eur J Dent 2019 May 1;13(2):166-171. Epub 2019 Oct 1.

Department of Endodontics, Faculty of Dental Medicine, Strasbourg University, Strasbourg, France.

Objectives: The aim of this study was to assess the filling ability in oval-shaped canals using two different carrier-based filling techniques.

Materials And Methods: Twenty-four human mandibular premolars with one oval canal were selected. Canals were shaped using WaveOne Gold Primary and ProGlider. Samples were divided into two groups and filled as follows: Thermafil and GuttaCore. The proportions of gutta-percha-filled areas (GPFAs), sealer-filled areas (SFAs), and void areas (VA), at 2 and 5 mm, were analyzed using optical numeric microscope, scanning electron microscope, and energy-dispersive X-ray.

Statistical Analysis: Data were compared by Kruskal-Wallis one-way analysis of variance on ranks, with statistical significance set at α = 0.05.

Results: At 2 and 5 mm distances from the apex, this study discloses no statistically different filling ability for the two techniques. Concerning each sample treated using both filling systems, the presence of tags was visualized. At working length (WL)-5, and WL-2, the maximum tag penetration depth for the GuttaCore group into the dentinal tubules was, respectively, 96 μm and 48 μm, whereas the values in the thermafil group were 109 μm, and 55 μm, respectively.

Conclusions: Our results clearly show that Thermafil and GuttaCore can fill oval-shaped canals in appropriate way. Furthermore, we can state that the GuttaCore obturator allows to preserve the same filling ability than Thermafil obturator, in view of the fact that there was no difference, in terms of GPFA, SFA, and VA between the two different carrier-based obturation techniques.
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http://dx.doi.org/10.1055/s-0039-1695661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777156PMC
May 2019

MEF2B is a member of the BCL6 gene transcriptional complex and induces its expression in diffuse large B-cell lymphoma of the germinal center B-cell-like type.

Lab Invest 2019 04 16;99(4):539-550. Epub 2018 Nov 16.

Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA.

Myocyte enhancer-binding factor 2B (MEF2B) has been implicated as a transcriptional regulator for BCL6. However, details about the interaction between MEF2B and BCL6 during expression, as well as the relationship of MEF2B to the expression of other germinal center (GC) markers, have not yet been fully explained. Using germinal center B-cell-like diffuse large B-cell lymphoma (GC-DLBCL) and activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell lines, we analyzed the expression of MEF2B and its associations with BCL6, CD10, and ERK. Furthermore, small interfering RNA (siRNA) was used to study the possible effects of MEF2B knockdown on these proteins and cell growth. Analysis of the BCL6 transcriptional complex was performed using electrophoretic mobility shift assay. The correlation between MEF2B expression and the genetic type of DLBCL was assessed using immunohistochemistry on 111 patient samples, and via in silico analysis of publicly available microarray (Gene Expression Omnibus (GEO)) datasets. Our results indicate that the expression of MEF2B protein is important for the growth of GC-DLBCL cells, as evidenced by MEF2B knockdown inhibition of cell growth and the subsequent suppression of BCL6, CD10, and ERK phosphorylation. Analysis of BCL6 transcription factors in nuclear extracts of MEF2-expressing DLBCL cells showed involvement of MEF2B with AP-2α and BCL6 proteins in the formation of the BCL6 gene transcriptional complex. Indeed, differential expression of MEF2B in the GC-DLBCL is statistically significant compared to the ABC-DLBCL in the GEO datasets, as well as in tissue microarray, as indicated via immunohistochemistry (Visco-Young algorithm). Our findings indicate that MEF2B is an essential component of the BCL6 gene transcriptional complex for the regulation of DLBCL growth via the promotion of BCL6 expression. Beyond its regulatory role in DLBCL growth, MEF2B expression correlated positively with BCL6 and CD10 expression, and was preferentially expressed in the GBC-DLBCL group.
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http://dx.doi.org/10.1038/s41374-018-0152-2DOI Listing
April 2019

Chromatin de-condensation by switching substrate elasticity.

Sci Rep 2018 08 23;8(1):12655. Epub 2018 Aug 23.

Inserm UMR-S1121, 11 rue Humann, 67085, Strasbourg, France.

Mechanical properties of the cellular environment are known to influence cell fate. Chromatin de-condensation appears as an early event in cell reprogramming. Whereas the ratio of euchromatin versus heterochromatin can be increased chemically, we report herein for the first time that the ratio can also be increased by purely changing the mechanical properties of the microenvironment by successive 24 h-contact of the cells on a soft substrate alternated with relocation and growth for 7 days on a hard substrate. An initial contact with soft substrate caused massive SW480 cancer cell death by necrosis, whereas approximately 7% of the cells did survived exhibiting a high level of condensed chromatin (21% heterochromatin). However, four consecutive hard/soft cycles elicited a strong chromatin de-condensation (6% heterochromatin) correlating with an increase of cellular survival (approximately 90%). Furthermore, cell survival appeared to be reversible, indicative of an adaptive process rather than an irreversible gene mutation(s). This adaptation process is associated with modifications in gene expression patterns. A completely new approach for chromatin de-condensation, based only on mechanical properties of the microenvironment, without any drug mediation is presented.
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http://dx.doi.org/10.1038/s41598-018-31023-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107547PMC
August 2018

D-Cateslytin: a new antifungal agent for the treatment of oral Candida albicans associated infections.

Sci Rep 2018 06 18;8(1):9235. Epub 2018 Jun 18.

INSERM UMR 1121, Biomatériaux et Bioingénierie, Université de Strasbourg, 11 rue Humann, 67085, Strasbourg, France.

The excessive use of antifungal agents, compounded by the shortage of new drugs being introduced into the market, is causing the accumulation of multi-resistance phenotypes in many fungal strains. Consequently, new alternative molecules to conventional antifungal agents are urgently needed to prevent the emergence of fungal resistance. In this context, Cateslytin (Ctl), a natural peptide derived from the processing of Chromogranin A, has already been described as an effective antimicrobial agent against several pathogens including Candida albicans. In the present study, we compared the antimicrobial activity of two conformations of Ctl, L-Ctl and D-Ctl against Candida albicans. Our results show that both D-Ctl and L-Ctl were potent and safe antifungal agents. However, in contrast to L-Ctl, D-Ctl was not degraded by proteases secreted by Candida albicans and was also stable in saliva. Using video microscopy, we also demonstrated that D-Ctl can rapidly enter C. albicans, but is unable to spread within a yeast colony unless from a mother cell to a daughter cell during cellular division. Besides, we revealed that the antifungal activity of D-Ctl could be synergized by voriconazole, an antifungal of reference in the treatment of Candida albicans related infections. In conclusion, D-Ctl can be considered as an effective, safe and stable antifungal and could be used alone or in a combination therapy with voriconazole to treat Candida albicans related diseases including oral candidosis.
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http://dx.doi.org/10.1038/s41598-018-27417-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006364PMC
June 2018

D-Cateslytin, a new antimicrobial peptide with therapeutic potential.

Sci Rep 2017 11 9;7(1):15199. Epub 2017 Nov 9.

Université de Strasbourg, Faculté de Chirurgie Dentaire, 3 rue Sainte Elisabeth, 67000, Strasbourg, France.

The rise of antimicrobial resistant microorganisms constitutes an increasingly serious threat to global public health. As a consequence, the efficacy of conventional antimicrobials is rapidly declining, threatening the ability of healthcare professionals to cure common infections. Over the last two decades host defense peptides have been identified as an attractive source of new antimicrobials. In the present study, we characterized the antibacterial and mechanistic properties of D-Cateslytin (D-Ctl), a new epipeptide derived from L-Cateslytin, where all L-amino acids were replaced by D-amino acids. We demonstrated that D-Ctl emerges as a potent, safe and robust peptide antimicrobial with undetectable susceptibility to resistance. Using Escherichia coli as a model, we reveal that D-Ctl targets the bacterial cell wall leading to the permeabilization of the membrane and the death of the bacteria. Overall, D-Ctl offers many assets that make it an attractive candidate for the biopharmaceutical development of new antimicrobials either as a single therapy or as a combination therapy as D-Ctl also has the remarkable property to potentiate several antimicrobials of reference such as cefotaxime, amoxicillin and methicillin.
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http://dx.doi.org/10.1038/s41598-017-15436-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680178PMC
November 2017

Hepatitis C virus-associated pruritus: Etiopathogenesis and therapeutic strategies.

World J Gastroenterol 2017 Feb;23(5):743-750

Youssef Alhmada, Mohamed Hassan, Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, United States.

In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile acids in patients' sera and tissues as a consequence of liver damage is considered the main cause of pruritus. In addition to their role in dietary lipid absorption, bile acids can trigger the activation of specific receptors, such as the G protein-coupled bile acid receptor (GPBA/ TGR5). These types of receptors are known to play a crucial role in the modulation of the systemic actions of bile acids. TGR5 expression in primary sensory neurons triggers the activation of the transient receptor potential vanilloid 1 (TRPV1) leading to the induction of pruritus by an unknown mechanism. Although the pathologic phenomenon of pruritus is common, there is no uniformly effective therapy available. Understanding the mechanisms regulating the occurrence of pruritus together with the conduction of large-scale clinical and evidence-based studies, may help to create a standard treatment protocol. This review focuses on the etiopathogenesis and treatment strategies of pruritus associated with chronic HCV infection.
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http://dx.doi.org/10.3748/wjg.v23.i5.743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296191PMC
February 2017

Interferon gamma-induced apoptosis of head and neck squamous cell carcinoma is connected to indoleamine-2,3-dioxygenase via mitochondrial and ER stress-associated pathways.

Cell Div 2016 2;11:11. Epub 2016 Aug 2.

Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216 USA ; Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, Kirrberger Str. 100, 66421 Homburg/Saar, Germany ; Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France ; Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216 USA.

Background: Tumor response to immunotherapy is the consequence of a concerted crosstalk between cytokines and effector cells. Interferon gamma (IFNγ) is one of the common cytokines coordinating tumor immune response and the associated biological consequences. Although the role of IFNγ in the modulation of tumor immunity has been widely documented, the mechanisms regulating IFNγ-induced cell death, during the course of immune therapy, is not described in detail.

Results: IFNγ triggered apoptosis of CLS-354 and RPMI 2650 cells, enhanced the protein expression and activation of indoleamine 2,3-dioxygenase (IDO), and suppressed the basal expression of heme oxygenase-1(HO-1). Interestingly, IFNγ induced the loss of mitochondrial membrane potential (Δψm) and increased accumulation of reactive oxygen species (ROS). The cytokine also induced the activation of Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT)1, apoptosis signal-regulating kinase 1 (ASK1), p38, c-jun-N-terminal kinase (JNK) and NF-κB pathways and the transcription factors STAT1, interferon regulatory factor 1 (IRF1), AP-1, ATF-2, NF-κB and p53, and expression of Noxa protein. Furthermore, IFNγ was found to trigger endoplasmic reticulum (ER) stress as evidenced by the cleavage of caspase-4 and activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol-requiring-1α (IRE1α) pathways. Using specific inhibitors, we identified a potential role for IDO as apoptotic mediator in the regulation of IFNγ-induced apoptosis of head and neck squamous cell carcinoma (HNSCC) cells via Noxa-mediated mitochondrial dysregulation and ER stress.

Conclusion: In addition to the elucidation of the role of IDO in the modulation of apoptosis, our study provides new insights into the molecular mechanisms of IFNγ-induced apoptosis of HNSCC cells during the course of immune therapy.
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http://dx.doi.org/10.1186/s13008-016-0023-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969639PMC
August 2016

Cancer stem cell as therapeutic target for melanoma treatment.

Histol Histopathol 2016 Dec 15;31(12):1291-301. Epub 2016 Jun 15.

Department of Pathology, University of Mississippi Medical Center, Jackson, USA.

Human malignant melanoma is a highly aggressive skin tumor that is characterized by its extraordinary heterogeneity, propensity for dissemination to distant organs and resistance to cytotoxic agents. Although chemo- and immune-based therapies have been evaluated in clinical trials, most of these therapeutics do not show significant benefit for patients with advanced disease. Treatment failure in melanoma patients is attributed mainly to the development of tumor heterogeneity resulting from the formation of genetically divergent subpopulations. These subpopulations are composed of cancer stem-like cells (CSCs) as a small fraction and non-cancer stem cells that form the majority of the tumor mass. In recent years, CSCs gained more attention and suggested as valuable experimental model system for tumor study. In melanoma, intratumoral heterogeneity, progression and drug resistance result from the unique characteristics of melanoma stem cells (MSCs). These MSCs are characterized by their distinct protein signature and tumor growth-driving pathways, whose activation is mediated by driver mutation-dependent signal. The molecular features of MSCs are either in a causal or consequential relationship to melanoma progression, drug resistance and relapse. Here, we review the current scientific evidence that supports CSC hypothesis and the validity of MSCs-dependent pathways and their key molecules as potential therapeutic target for melanoma treatment.
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http://dx.doi.org/10.14670/HH-11-791DOI Listing
December 2016

Antibacterial Peptide-Based Gel for Prevention of Medical Implanted-Device Infection.

PLoS One 2015 14;10(12):e0145143. Epub 2015 Dec 14.

Institut National de la Santé Et de la Recherche Médicale, Unité Mixte de Recherche-S 1121, Biomatériaux et Bioingénierie, Strasbourg, France.

Implanted medical devices are prone to infection. Designing new strategies to reduce infection and implant rejection are an important challenge for modern medicine. To this end, in the last few years many hydrogels have been designed as matrices for antimicrobial molecules destined to fight frequent infection found in moist environments like the oral cavity. In this study, two types of original hydrogels containing the antimicrobial peptide Cateslytin have been designed. The first hydrogel is based on alginate modified with catechol moieties (AC gel). The choice of these catechol functional groups which derive from mussel's catechol originates from their strong adhesion properties on various surfaces. The second type of gel we tested is a mixture of alginate catechol and thiol-terminated Pluronic (AC/PlubisSH), a polymer derived from Pluronic, a well-known biocompatible polymer. This PlubisSH polymer has been chosen for its capacity to enhance the cohesion of the composition. These two gels offer new clinical uses, as they can be injected and jellify in a few minutes. Moreover, we show these gels strongly adhere to implant surfaces and gingiva. Once gelled, they demonstrate a high level of rheological properties and stability. In particular, the dissipative energy of the (AC/PlubisSH) gel detachment reaches a high value on gingiva (10 J.m-2) and on titanium alloys (4 J.m-2), conferring a strong mechanical barrier. Moreover, the Cateslytin peptide in hydrogels exhibited potent antimicrobial activities against P. gingivalis, where a strong inhibition of bacterial metabolic activity and viability was observed, indicating reduced virulence. Gel biocompatibility tests indicate no signs of toxicity. In conclusion, these new hydrogels could be ideal candidates in the prevention and/or management of periimplant diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145143PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682826PMC
July 2016

Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment.

World J Exp Med 2015 Nov 20;5(4):206-17. Epub 2015 Nov 20.

Mohamed Hassan, Denis Selimovic, Matthias Hannig, Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, University Hospital, Saarland University, D-66421 Homburg/Saar, Germany.

Melanoma is the most aggressive form of skin cancer. Disrupted intracellular signaling pathways are responsible for melanoma's extraordinary resistance to current chemotherapeutic modalities. The pathophysiologic basis for resistance to both chemo- and radiation therapy is rooted in altered genetic and epigenetic mechanisms that, in turn, result in the impairing of cell death machinery and/or excessive activation of cell growth and survival-dependent pathways. Although most current melanoma therapies target mitochondrial dysregulation, there is increasing evidence that endoplasmic reticulum (ER) stress-associated pathways play a role in the potentiation, initiation and maintenance of cell death machinery and autophagy. This review focuses on the reliability of ER-associated pathways as therapeutic targets for melanoma treatment.
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http://dx.doi.org/10.5493/wjem.v5.i4.206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655250PMC
November 2015

Imiquimod-induced apoptosis of melanoma cells is mediated by ER stress-dependent Noxa induction and enhanced by NF-κB inhibition.

J Cell Mol Med 2016 Feb 18;20(2):266-86. Epub 2015 Nov 18.

Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.

Melanoma is characterized by dysregulated intracellular signalling pathways including an impairment of the cell death machinery, ultimately resulting in melanoma resistance, survival and progression. This explains the tumour's extraordinary resistance to the standard treatment. Imiquimod is a topical immune response modifier (imidazoquinoline) with both antiviral and antitumour activities. The mechanism by which imiquimod triggers the apoptosis of melanoma cells has now been carefully elucidated. Imiquimod-induced apoptosis is associated with the activation of apoptosis signalling regulating kinase1/c-Jun-N-terminal kinase/p38 pathways and the induction of endoplasmic stress characterized by the activation of the protein kinase RNA-like endoplasmic reticulum kinase signalling pathway, increase in intracellular Ca(2+) release, degradation of calpain and subsequent cleavage of caspase-4. Moreover, imiquimod triggers the activation of NF-κB and the expression of the inhibitor of apoptosis proteins (IAPs) such as, X-linked IAP (XIAP) together with the accumulation of reactive oxygen species (ROS). Also, imiquimod triggers mitochondrial dysregulation characterized by the loss of mitochondrial membrane potential (Δψm), the increase in cytochrome c release, and cleavage of caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP). Inhibitors of specific pathways, permit the elucidation of possible mechanisms of imiquimod-induced apoptosis. They demonstrate that inhibition of NF-kB by the inhibitor of nuclear factor kappa-B kinase (IKK) inhibitor Bay 11-782 or knockdown of XIAP induces melanoma apoptosis in cells exposed to imiquimod. These findings support the use of either IKK inhibitors or IAP antagonists as adjuvant therapies to improve the effectiveness topical imiquimod in the treatment of melanoma.
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http://dx.doi.org/10.1111/jcmm.12718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727561PMC
February 2016

Harnessing the multifunctionality in nature: a bioactive agent release system with self-antimicrobial and immunomodulatory properties.

Adv Healthc Mater 2015 Sep;4(13):2026-36

Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, 11 rue Humann, 67085, Strasbourg, France.

Major problems with biomedical devices in particular implants located in nonsterile environments concern: (i) excessive immune response to the implant, (ii) development of bacterial biofilms, and (iii) yeast and fungi infections. An original multifunctional coating that addresses all these issues concomitantly is developed. A new exponentially growing polyelectrolyte multilayer film based on polyarginine (PAR) and hyaluronic acid (HA) is designed. The films have a strong inhibitory effect on the production of inflammatory cytokines released by human primary macrophage subpopulations. This could reduce potential chronic inflammatory reaction following implantation. Next, it is shown that PAR, due to its positive charges, has an antimicrobial activity in film format against Staphylococcus aureus for 24 h. In order to have a long-term antimicrobial activity, a precursor nanoscale silver coating is deposited on the surface before adding the PAR/HA films. Moreover, the PAR/HA films can be easily further functionalized by embedding antimicrobial peptides, like catestatin (CAT), a natural host defense peptide. This PAR/HA+CAT film proves to be effective as an antimicrobial coating against yeast and fungi and its cytocompatibility is also assessed. Finally, this all-in-one system constitutes an original strategy to limit inflammation and prevents bacteria, yeast, and fungi infections.
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http://dx.doi.org/10.1002/adhm.201500546DOI Listing
September 2015

Corrigendum to "Bortezomib/proteasome inhibitor triggers both apoptosis and autophagy-dependent pathways in melanoma cells". [Cell Signal. 25(1)Jan 2013 308-18].

Cell Signal 2015 Feb 6. Epub 2015 Feb 6.

Institut National de la Santé et de la Recherche Médicale, U 977, France; Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.cellsig.2015.02.002DOI Listing
February 2015