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Lorenzo Massimi, Michela Fratini, Inna Bukreeva, Francesco Brun, Alberto Mittone, Gaetano Campi, Raffaele Spanò, Milena Mastrogiacomo, Nicole Kerlero de Rosbo, Alberto Bravin, Antonio Uccelli, Alessia Cedola
High resolution Synchrotron-based X-ray Phase Contrast Tomography (XPCT) allows the simultaneous detection of three dimensional neuronal and vascular networks without using contrast agents or invasive casting preparation. We show and discuss the different features observed in reconstructed XPCT volumes of the ex vivo mouse spinal cord in the lumbo-sacral region, including motor neurons and blood vessels. We report the application of an intensity-based segmentation method to detect and quantitatively characterize the modification in the vascular networks in terms of reduction in experimental visibility...
October 12, 2016: Physica Medica: PM
Pietro Maggi, Pascal Sati, Luca Massacesi
Magnetic resonance imaging (MRI) is an invaluable tool for the diagnosis and monitoring of patients with multiple sclerosis (MS) as well as for the study of the disease pathophysiology. Because of its strong clinical, radiological and histopathological similarities with the human disease, experimental autoimmune encephalomyelitis (EAE) in the common marmoset has been studied more intensively over the past several years. Here, we review the current knowledge on MRI in the marmoset EAE, and we outline the physiopathological significance and translational values of these studies with respect to MS...
October 8, 2016: Journal of Neuroimmunology
Kerstin Renner, Sonja Hellerbrand, Fabian Hermann, Christine Riedhammer, Yvonne Talke, Gabriela Schiechl, Manuel Rodriguez Gomez, Simone Kutzi, Dagmar Halbritter, Nicole Goebel, Hilke Brühl, Robert Weissert, Matthias Mack
Little is known about the role of IL-3 in multiple sclerosis (MS) in humans and in experimental autoimmune encephalomyelitis (EAE). Using myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE, we show that CD4(+) T cells are the main source of IL-3 and that cerebral IL-3 expression correlates with the influx of T cells into the brain. Blockade of IL-3 with monoclonal antibodies, analysis of IL-3 deficient mice, and adoptive transfer of leukocytes demonstrate that IL-3 plays an important role for development of clinical symptoms of EAE, for migration of leukocytes into the brain, and for cerebral expression of adhesion molecules and chemokines...
October 6, 2016: JCI Insight
Mithila Ferdous, Anna M D Kooistra-Smid, Kai Zhou, John W A Rossen, Alexander W Friedrich
Escherichia coli (E.coli) O157 that do not produce Shiga toxin and do not possess flagellar antigen H7 are of diverse H serotypes. In this study, the antibiotic resistance properties, genotype of a set of virulence associated genes and the phylogenetic background of E. coli O157:non-H7 groups were compared. Whole genome sequencing was performed on fourteen O157:non-H7 isolates collected in the STEC-ID-net study. The genomes were compared with E. coli O157 genomes and a typical Enteropathogenic E. coli (tEPEC) genome downloaded from NCBI...
2016: Frontiers in Microbiology
Jennifer N Hahn, Deepak K Kaushik, Manoj K Mishra, Jianxiong Wang, Claudia Silva, V Wee Yong
Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that is upregulated on leukocytes in active lesions in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Administration of anti-EMMPRIN Abs reduces the severity of EAE. Minocycline is a tetracycline antibiotic with immune-modulatory properties that decreases the severity of EAE; it was recently found to attenuate the conversion from a first demyelinating event to clinically definite MS in a phase III trial...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Annie C Bowles, Amy L Strong, Rachel M Wise, Robert C Thomas, Brittany Y Gerstein, Maria F Dutreil, Ryan S Hunter, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes...
October 12, 2016: Stem Cells
Dong-Mug Kang, Jong-Eun Kim, Ju-Young Kim, Hyun-Hee Lee, Young-Sik Hwang, Young-Ki Kim, Yong-Jin Lee
BACKGROUND: Because of the long asbestos-related disease latencies (10-50 years), detection, diagnosis, and epidemiologic studies require asbestos exposure history. However, environmental asbestos exposure source (EAES) data are lacking. OBJECTIVES: To survey the available data for past EAES and supplement these data with interviews. METHODS: We constructed an EAES database using a literature review and interviews of experts, former traders, and workers...
October 11, 2016: International Journal of Occupational and Environmental Health
Ahmed Elsadek Fakhr, Maha Kamal Gohar, Amal Hassan Atta
Fecal contamination of drinking water is a major health problem which accounts for many cases of diarrhea mainly in infants and foreigners. This contamination is a complex interaction of many parameters. Antibiotic resistance among bacterial isolates complicates the problem. The study was done to identify fecal contamination of drinking water by Diarrheagenic Antibiotic-Resistant Escherichia coli in Zagazig city and to trace reasons for such contamination, three hundred potable water samples were investigated for E...
2016: International Journal of Microbiology
Ahmed T Kurdi, Ribal Bassil, Marta Olah, Chuan Wu, Sheng Xiao, Mariko Taga, Michael Frangieh, Thomas Buttrick, William Orent, Elizabeth M Bradshaw, Samia J Khoury, Wassim Elyaman
RORγt is a master transcription factor of Th17 cells and considered as a promising drug target for the treatment of autoimmune diseases. Here, we show the guanine nucleotide exchange factor, Tiam1, and its cognate Rho-family G protein, Rac1, regulate interleukin (IL)17A transcription and autoimmunity. Whereas Tiam1 genetic deficiency weakens IL-17A expression partially and inhibits the development of experimental autoimmune encephalomyelitis (EAE), deletion of Rac1 in T cells exhibits more robust effects on Th17 cells and EAE...
October 11, 2016: Nature Communications
Jueqiong Wang, Congying Zhao, Peng Kong, Guanyun Bian, Zhe Sun, Yafei Sun, Li Guo, Bin Li
Methylene blue (MB) is an effective neuroprotectant in many neurological disorders. AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1 (SIRT1) plays a crucial role in maintaining inflammatory responses and shows a synergistic effect on cell homeostasis. We investigated the effect of MB on experimental autoimmune encephalomyelitis (EAE), a classical animal model of multiple sclerosis (MS). MB treatment reduced the clinical scores of EAE significantly and attenuated pathological injuries in spinal cords...
October 15, 2016: Journal of Neuroimmunology
Ana María Vega-Letter, Mónica Kurte, Catalina Fernández-O'Ryan, Melanie Gauthier-Abeliuk, Patricia Fuenzalida, Ivón Moya-Uribe, Claudia Altamirano, Fernando Figueroa, Carlos Irarrázabal, Flavio Carrión
BACKGROUND: Recently, it has been observed that mesenchymal stem cells (MSCs) can modulate their immunoregulatory properties depending on the specific in-vitro activation of different Toll-like receptors (TLR), such as TLR3 and TLR4. In the present study, we evaluated the effect of polyinosinic:polycytidylic acid (poly(I:C)) and lipopolysaccharide (LPS) pretreatment on the immunological capacity of MSCs in vitro and in vivo. METHODS: C57BL/6 bone marrow-derived MSCs were pretreated with poly(I:C) and LPS for 1 hour and their immunomodulatory capacity was evaluated...
October 10, 2016: Stem Cell Research & Therapy
Paschalis Theotokis, Olga Touloumi, Roza Lagoudaki, Evangelia Nousiopoulou, Evangelia Kesidou, Spyridon Siafis, Theodoros Tselios, Athanasios Lourbopoulos, Dimitrios Karacostas, Nikolaos Grigoriadis, Constantina Simeonidou
BACKGROUND: Nogo-A and its putative receptor NgR are considered to be among the inhibitors of axonal regeneration in the CNS. However, few studies so far have addressed the issue of local NgR complex multilateral localization within inflammation in an MS mouse model of autoimmune demyelination. METHODS: Chronic experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice. Analyses were performed on acute (days 18-22) and chronic (day 50) time points and compared to controls...
October 11, 2016: Journal of Neuroinflammation
Sabrina Torre, Maria J Polyak, David Langlais, Nassima Fodil, James M Kennedy, Irena Radovanovic, Joanne Berghout, Gabriel A Leiva-Torres, Connie M Krawczyk, Subburaj Ilangumaran, Karen Mossman, Chen Liang, Klaus-Peter Knobeloch, Luke M Healy, Jack Antel, Nathalie Arbour, Alexandre Prat, Jacek Majewski, Mark Lathrop, Silvia M Vidal, Philippe Gros
Genes and pathways in which inactivation dampens tissue inflammation present new opportunities for understanding the pathogenesis of common human inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. We identified a mutation in the gene encoding the deubiquitination enzyme USP15 (Usp15(L749R)) that protected mice against both experimental cerebral malaria (ECM) induced by Plasmodium berghei and experimental autoimmune encephalomyelitis (EAE). Combining immunophenotyping and RNA sequencing in brain (ECM) and spinal cord (EAE) revealed that Usp15(L749R)-associated resistance to neuroinflammation was linked to dampened type I interferon responses in situ...
October 10, 2016: Nature Immunology
Derrick P McCarthy, Jonathan Woon-Teck Yap, Christopher T Harp, W Kelsey Song, Jeane Chen, Ryan M Pearson, Stephen D Miller, Lonnie D Shea
Tolerogenic nanoparticles (NPs) are rapidly being developed as specific immunotherapies to treat autoimmune disease. However, many NP-based therapies conjugate antigen (Ag) directly to the NP posing safety concerns due to antibody binding or require the co-delivery of immunosuppressants to induce tolerance. Here, we developed Ag encapsulated NPs comprised of poly(lactide-co-glycolide) [PLG(Ag)] and investigated the mechanism of action for Ag-specific tolerance induction in an autoimmune model of T helper type 1/17 dysfunction - relapse-remitting experimental autoimmune encephalomyelitis (R-EAE)...
October 6, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Begoña M Escribano, Francisco J Medina-Fernández, Macarena Aguilar-Luque, Eduardo Agüera, Montserrat Feijoo, Fe I Garcia-Maceira, Rafael Lillo, Patricia Vieyra-Reyes, Ana I Giraldo, Evelio Luque, René Drucker-Colín, Isaac Túnez
Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord...
October 7, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Ana Gutiérrez-Franco, Herena Eixarch, Carme Costa, Vanessa Gil, Mireia Castillo, Laura Calvo-Barreiro, Xavier Montalban, José A Del Río, Carmen Espejo
Semaphorin 7A (sema7A) is classified as an immune semaphorin with dual functions in the immune system and in the central nervous system (CNS). These molecules are of interest due to their potential role in multiple sclerosis (MS), which is a chronic demyelinating and neurodegenerative disease of autoimmune origin. In this study, we elucidated the role of sema7A in neuroinflammation using both in vitro and in vivo experimental models. In an in vitro model of neuroinflammation, using cerebellar organotypic slice cultures, we observed that challenge with lipopolysaccharide (LPS) endotoxin did not affect demyelination or cell death in sema7A-deficient cultures compared to wild-type cultures...
October 6, 2016: Molecular Neurobiology
Samuel S Duffy, Chamini J Perera, Preet G S Makker, Justin G Lees, Pascal Carrive, Gila Moalem-Taylor
Pain is a widespread and debilitating symptom of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. Although central neuroinflammation and demyelination have been implicated in MS-related pain, the contribution of peripheral and central mechanisms during different phases of the disease remains unclear. In this study, we used the animal model experimental autoimmune encephalomyelitis (EAE) to examine both stimulus-evoked and spontaneous pain behaviors, and neuroinflammatory changes, over the course of chronic disease...
2016: Frontiers in Immunology
Kristbjörg Bjarnadóttir, Mahdia Benkhoucha, Doron Merkler, Martin S Weber, Natalie L Payne, Claude C A Bernard, Nicolas Molnarfi, Patrice H Lalive
Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B-TGF-β1(-/-)) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG)...
October 6, 2016: Scientific Reports
Magdalena Paterka, Jan Oliver Voss, Johannes Werr, Eva Reuter, Sophia Franck, Tina Leuenberger, Josephine Herz, Helena Radbruch, Tobias Bopp, Volker Siffrin, Frauke Zipp
Counter-balancing regulatory mechanisms, such as the induction of regulatory T cells (Treg), limit the effects of autoimmune attack in neuroinflammation. However, the role of dendritic cells (DCs) as the most powerful antigen-presenting cells, which are intriguing therapeutic targets in this context, is not fully understood. Here, we demonstrate that conditional ablation of DCs during the priming phase of myelin-specific T cells in experimental autoimmune encephalomyelitis (EAE) selectively aborts inducible Treg (iTreg) induction, whereas generation of T helper (Th)1/17 cells is unaltered...
October 2, 2016: Journal of Autoimmunity
Claudia Cantoni, Francesca Cignarella, Laura Ghezzi, Bob Mikesell, Bryan Bollman, Melissa M Berrien-Elliott, Aaron R Ireland, Todd A Fehniger, Gregory F Wu, Laura Piccio
Myeloid-derived cells play important modulatory and effector roles in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells, composed of monocytic (MO) and polymorphonuclear (PMN) fractions, which can suppress T cell activities in EAE. Their role in MS remains poorly characterized. We found decreased numbers of circulating MDSCs, driven by lower frequencies of the MO-MDSCs, and higher MDSC expression of microRNA miR-223 in MS versus healthy subjects...
October 4, 2016: Acta Neuropathologica
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