Dentistry Commons^™

Vwa Proteins Of Leptospira Interrogans Induce Hemorrhage In Leptospirosis By Competitive Inhibition Of Vwf/Gpib-Mediated Platelet Aggregation., Jia-Qi Fang, Muhammad Imran, Wei-Lin Hu, David M. Ojcius, Yang Li, Yu-Mei Ge, Kai-Xuan Li, Xu'ai Lin, Jie Yan

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BACKGROUD: Leptospira interrogans is the major causative agent of leptospirosis, a worldwide zoonotic disease. Hemorrhage is a typical pathological feature of leptospirosis. Binding of von Willebrand factor (vWF) to platelet glycoprotein-Ibα (GPIbα) is a crucial step in initiation of platelet aggregation. The products of L. interrogans vwa-I and vwa-II genes contain vWF-A domains, but their ability to induce hemorrhage has not been determined.

METHODS: Human (Hu)-platelet- and Hu-GPIbα-binding abilities of the recombinant proteins expressed by L. interrogans strain Lai vwa-I and vwa-II genes (rLep-vWA-I and rLep-vWA-II) were detected by flowcytometry, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Hu-platelet …

Src-Family Kinase-Cbl Axis Negatively Regulates Nlrp3 Inflammasome Activation., I-Che Chung, Sheng-Ning Yuan, Chun-Nan Ouyang, Hsin-Chung Lin, Kuo-Yang Huang, Yu-Jen Chen, An-Ko Chung, Ching-Liang Chu, David M. Ojcius, Yu-Sun Chang, Lih-Chyang Chen

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Activation of the NLRP3 inflammasome is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Pyk2 is essential for NLRP3 inflammasome activation. Here we show that the Src-family kinases (SFKs)-Cbl axis plays a pivotal role in suppressing NLRP3 inflammasome activation in response to stimulation by nigericin or ATP, as assessed using gene knockout and gene knockdown cells, dominant active/negative mutants, and pharmacological inhibition. We reveal that the phosphorylation of Cbl is regulated by SFKs, and that phosphorylation of Cbl at Tyr371 suppresses NLRP3 inflammasome activation. Mechanistically, Cbl decreases the level of phosphorylated Pyk2 …

Nlrx1 Modulates Differentially Nlrp3 Inflammasome Activation And Nf-Κb Signaling During Fusobacterium Nucleatum Infection, Shu Chen Hung, Pei Rong Huang, Cassio Luiz Coutinho Almeida-Da-Silva, Kalina R. Atanasova, Ozlem Yilmaz, David M. Ojcius

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NOD-like receptors (NLRs) play a large role in regulation of host innate immunity, yet their role in periodontitis remains to be defined. NLRX1, a member of the NLR family that localizes to mitochondria, enhances mitochondrial ROS (mROS) generation. mROS can activate the NLRP3 inflammasome, yet the role of NLRX1 in NLRP3 inflammasome activation has not been examined. In this study, we revealed the mechanism by which NLRX1 positively regulates ATP-induced NLRP3 inflammasome activation through mROS in gingival epithelial cells (GECs). We found that depletion of NLRX1 by shRNA attenuated ATP-induced mROS generation and redistribution of the NLRP3 inflammasome adaptor protein, …

A Novel Fas-Binding Outer Membrane Protein And Lipopolysaccharide Of Leptospira Interrogans Induce Macrophage Apoptosis Through The Fas/Fasl-Caspase-8/-3 Pathway., Peng Du, Shi-Jun Li, David M. Ojcius, Kai-Xuan Li, Wei-Lin Hu, Xu'ai Lin, Ai-Hua Sun, Jie Yan

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Leptospira interrogans is the major causative agent of leptospirosis, an emerging, globally spreading zoonotic infectious disease. The pathogen induces macrophage apoptosis, but the molecular basis and mechanism remain unknown. In the present study, we found that L. interrogans caused apoptosis of phagocytosis-inhibited macrophages, and the product of the L. interrogans LB047 gene (Lep-OMP047) was the unique protein captured by mouse and human Fas proteins. The recombinant expressed Lep-OMP047 (rLep-OMP047) strongly bound mouse and human Fas proteins with equilibrium association constant (K

Anticancer Chemotherapy And Radiotherapy Trigger Both Non-Cell-Autonomous And Cell-Autonomous Death., Isabelle Martins, Syed Qasim Raza, Laurent Voisin, Haithem Dakhli, Awatef Allouch, Frédéric Law, Dora Sabino, Dorine De Jong, Maxime Thoreau, Elodie Mintet, Delphine Dugué, Mauro Piacentini, Marie-Lise Gougeon, Fanny Jaulin, Pascale Bertrand, Catherine Brenner, David M. Ojcius, Guido Kroemer, Nazanine Modjtahedi, Eric Deutsch, Jean-Luc Perfettini

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Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and …

Lipoxin A4 Attenuates The Inflammatory Response In Stem Cells Of The Apical Papilla Via Alx/Fpr2, A. Gaudin, Miroslav Tolar, Ove A. Peters

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Similar to the onset phase of inflammation, its resolution is a process that unfolds in a manner that is coordinated and regulated by a panel of mediators. Lipoxin A4 (LXA₄) has been implicated as an anti-inflammatory, pro-resolving mediator. We hypothesized that LXA₄ attenuates or prevents an inflammatory response via the immunosuppressive activity of Stem Cells of the Apical Papilla (SCAP). Here, we report for the first time in vitro that in a SCAP population, lipoxin receptor ALX/FPR2 was constitutively expressed and upregulated after stimulation with lipopolysaccharide and/or TNF-α. Moreover, LXA₄ significantly enhanced proliferation, migration, and wound …

Salivary Biomarkers For The Diagnosis And Monitoring Of Neurological Diseases, R. Farah, H. Haraty, Z. Salame, Y. Fares, David M. Ojcius, N. Said Sadier

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Current research efforts on neurological diseases are focused on identifying novel disease biomarkers to aid in diagnosis, provide accurate prognostic information and monitor disease progression. With advances in detection and quantification methods in genomics, proteomics and metabolomics, saliva has emerged as a good source of samples for detection of disease biomarkers. Obtaining a sample of saliva offers multiple advantages over the currently tested biological fluids as it is a non-invasive, painless and simple procedure that does not require expert training or harbour undesirable side effects for the patients. Here, we review the existing literature on salivary biomarkers and examine their …

Demetallization Of Enterococcus Faecalis Biofilm: A Preliminary Study, Carlos Estrela, Rodrigo Costa E Silva, Roberta Cerasi Urban, Pablo Jose Gonçalves, Julio A. Silva, Jesus Djalma Pecora, Ove A. Peters

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Objectives: To determine the concentration of calcium, iron, manganese and zinc ions after the application of chelator to Enterococcus faecalis biofilms.

Material and Methods: Fifty bovine maxillary central incisors were prepared and inoculated with E. faecalis for 60 days. The following were used as irrigation solutions: 17% EDTA (pH 3, 7 and 10), 2.5% sodium hypochlorite (NaOCl) combined with 17% EDTA (pH 3, 7 and 10), distilled water (pH 3, 7 and 10), and 2.5% NaOCl. Each solution was kept in the root canal for five minutes. Fifteen uncontaminated root canals were irrigated with 17% EDTA (pH 3, 7 and …