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https://www.readbyqxmd.com/read/29234010/loss-of-the-molecular-clock-in-myeloid-cells-exacerbates-t-cell-mediated-cns-autoimmune-disease
#1
Caroline E Sutton, Conor M Finlay, Mathilde Raverdeau, James O Early, Joseph DeCourcey, Zbigniew Zaslona, Luke A J O'Neill, Kingston H G Mills, Annie M Curtis
The transcription factor BMAL1 is a core component of the molecular clock, regulating biological pathways that drive 24 h (circadian) rhythms in behaviour and physiology. The molecular clock has a profound influence on innate immune function, and circadian disruption is linked with increased incidence of multiple sclerosis (MS). However, the mechanisms underlying this association are unknown. Here we show that BMAL1 and time-of-day regulate the accumulation and activation of various immune cells in a CNS autoimmune disease model, experimental autoimmune encephalomyelitis (EAE)...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29233943/atg-dependent-phagocytosis-in-dendritic-cells-drives-myelin-specific-cd4-t-cell-pathogenicity-during-cns-inflammation
#2
Christian W Keller, Christina Sina, Monika B Kotur, Giulia Ramelli, Sarah Mundt, Isaak Quast, Laure-Anne Ligeon, Patrick Weber, Burkhard Becher, Christian Münz, Jan D Lünemann
Although reactivation and accumulation of autoreactive CD4+ T cells within the CNS are considered to play a key role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), the mechanisms of how these cells recognize their target organ and induce sustained inflammation are incompletely understood. Here, we report that mice with conditional deletion of the essential autophagy protein ATG5 in classical dendritic cells (DCs), which are present at low frequencies in the nondiseased CNS, are completely resistant to EAE development following adoptive transfer of myelin-specific T cells and show substantially reduced in situ CD4+ T cell accumulation during the effector phase of the disease...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29232394/external-auditory-exostoses-in-the-xuchang-and-xujiayao-human-remains-patterns-and-implications-among-eastern-eurasian-middle-and-late-pleistocene-crania
#3
Erik Trinkaus, Xiu-Jie Wu
In the context of Middle and Late Pleistocene eastern Eurasian human crania, the external auditory exostoses (EAE) of the late archaic Xuchang 1 and 2 and the Xujiayao 15 early Late Pleistocene human temporal bones are described. Xujiayao 15 has small EAE (Grade 1), Xuchang 1 presents bilateral medium EAE (Grade 2), and Xuchang 2 exhibits bilaterally large EAE (Grade 3), especially on the right side. These cranial remains join the other eastern Eurasian later Pleistocene humans in providing frequencies of 61% (N = 18) and 58% (N = 12) respectively for archaic and early modern human samples...
2017: PloS One
https://www.readbyqxmd.com/read/29229105/pulmonary-function-and-diffusion-capacity-are-associated-with-pulmonary-arterial-systolic-pressure-in-the-general-population-the-rotterdam-study
#4
Daan W Loth, Lies Lahousse, Maarten J G Leening, Bouwe P Krijthe, Janine F Felix, Henning Gall, Albert Hofman, H Ardeschir Ghofrani, Oscar H Franco, Bruno H Stricker, Guy G Brusselle
BACKGROUND: Pulmonary hypertension is a progressive heterogeneous syndrome, characterized by elevated pulmonary arterial pressure which can lead to right ventricular failure. Although the presence of elevated pulmonary arterial systolic pressure (PASP) in patients with a lung disease is a well-known occurrence, little is known about the association between pulmonary function and PASP in the general population. We hypothesized that pulmonary function and PASP are associated, irrespective of airflow limitation...
November 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/29226621/cenerimod-a-novel-selective-s1p1-receptor-modulator-with-unique-signaling-properties
#5
Luca Piali, Magdalena Birker-Robaczewska, Cyrille Lescop, Sylvie Froidevaux, Nicole Schmitz, Keith Morrison, Christopher Kohl, Markus Rey, Rolf Studer, Enrico Vezzali, Patrick Hess, Martine Clozel, Beat Steiner, Martin H Bolli, Oliver Nayler
Sphingosine-1-phosphate receptor 1 (S1P1 ) modulators sequester circulating lymphocytes within lymph nodes, thereby preventing potentially pathogenic autoimmune cells from exiting into the blood stream and reaching inflamed tissues. S1P1 receptor modulation may thus offer potential to treat various autoimmune diseases. The first nonselective S1P1-5 receptor modulator FTY720/fingolimod/Gilenya® has successfully demonstrated clinical efficacy in relapsing forms of multiple sclerosis. However, cardiovascular, hepatic, and respiratory side-effects were reported and there is a need for novel S1P1 receptor modulators with better safety profiles...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29224961/effective-combination-of-methylprednisolone-and-interferon-%C3%AE-secreting-mesenchymal-stem-cells-in-a-model-of-multiple-sclerosis
#6
Mi Jin Kim, Jung Yeon Lim, Soon A Park, Sang In Park, Won Shik Kim, Chung Heon Ryu, Sin-Soo Jeun
Methylprednisolone (MP) has been recommended as a standard drug in MS therapies. We previously demonstrated that IFNβ-secreting human bone marrow-derived mesenchymal stem cells (MSCs-IFNβ) exert immunomodulatory effects in experimental autoimmune encephalomyelitic (EAE) mice. In this study, we evaluated whether a combined treatment of MP and MSCs-IFNβ had enhanced therapeutic effects on EAE mice. The combination treatment resulted in enhanced immunomodulatory effects, including reduced production of pro-inflammatory cytokines and increased production of anti-inflammatory cytokines...
November 29, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29224959/metabolomics-approaches-in-experimental-allergic-encephalomyelitis
#7
S Battini, C Bund, F M Moussallieh, A E Çiçek, J De Sèze, I J Namer
A myelin basic protein (MBP)-induced experimental allergic encephalomyelitis (EAE) involves paraplegia due to a reversible thoracolumbar spinal cord impairment. The aims of this study were thus to find significant metabolic biomarkers of inflammation and identify the site of inflammation in the central nervous system (CNS) during the acute signs in of the disease using metabolomics. All the EAE samples were associated with higher levels of lactate, ascorbate, glucose and amino acids, and decreased level of N-acetyl-aspartate (NAA) compared to the control group...
December 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29222794/active-induction-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#8
Gabriella Contarini, Pietro Giusti, Stephen D Skaper
The protocol in this chapter presents a method to actively induce experimental autoimmune encephalomyelitis (EAE), one of the most widely used animal models to study efficacy of potential drugs for treatment of multiple sclerosis. Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system and the most common cause of chronic neurological impairment in young people. In this model EAE is induced in female C57BL/6 mice by immunization with an emulsion of myelin oligodendrocyte glycoprotein (fragment 35-55) in complete Freund's adjuvant, followed by administration of pertussis toxin in phosphate-buffered saline...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222624/dapsone-for-recalcitrant-eosinophilic-annular-erythema-a-case-report-and-literature-review
#9
Luke Wallis, Robert C Gilson, Robert T Gilson
Eosinophilic annular erythema (EAE) is a rare entity of unknown etiology that is possibly related to a hypersensitivity reaction and presents as annular erythematous plaques with tissue eosinophilia. It is classified as a figurate erythema with a controversial relationship to Wells syndrome (WS) in the literature, where it is generally considered a separate entity or subset based on clinical and histopathologic differences. EAE typically presents with recurrent, erythematous, arcuate, and annular plaques on the trunk and proximal extremities...
December 8, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/29222419/probenecid-arrests-the-progression-of-pronounced-clinical-symptoms-in-a-mouse-model-of-multiple-sclerosis
#10
Nadine Hainz, Sandra Wolf, Artjom Beck, Stefan Wagenpfeil, Thomas Tschernig, Carola Meier
While it has been established that Probenecid (PBN) prevents the onset of experimental autoimmune encephalomyelitis (EAE) in mice, it is not clear whether it has any effect on already manifest EAE. The aim of this study was therefore to analyze the therapeutic effect of PBN in pronounced EAE. Mice with manifest clinical symptoms of EAE were either treated with PBN or solvent for 20 days, or they were left untreated. The clinical symptoms were monitored daily. Inflammation, demyelination and oligodendrocyte numbers were determined in the spinal cord...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29217470/safe-and-effective-interferon-beta-gene-therapy-for-the-treatment-of-multiple-sclerosis-by-regulating-biological-activity-through-the-design-of-interferon-beta-galectin-9-fusion-proteins
#11
Atsushi Hamana, Yuki Takahashi, Akane Tanioka, Makiya Nishikawa, Yoshinobu Takakura
Multiple sclerosis (MS) is the most common demyelinating disease. Despite the historical use of interferon-beta (IFN-β) for the treatment of patients with MS, concerns exist regarding the side effects of IFN-β. In this study, we designed a series of novel IFN-β fusion proteins containing galectin-9 (gal-9), which exerts immunosuppressive effects through the binding to its receptor on activated Th1 cells. We hypothesized that these fusion proteins would improve the therapeutic effects and reduce the side effects of IFN-β...
December 5, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29215297/virulence-genes-and-antimicrobial-resistance-in-escherichia-coli-from-cheese-made-from-unpasteurized-milk-in-brazil
#12
Anna C L P de Campos, Juan J Puño-Sarmiento, Leonardo P Medeiros, Luís E S Gazal, Renato Pariz Maluta, Armando Navarro, Renata K T Kobayashi, Eder P Fagan, Gerson Nakazato
Cow raw milk cheese is widely eaten in Brazil. These products may be contaminated with pathogenic bacteria. In this work, we investigated the presence of Escherichia coli in raw milk cheese from different States in Brazil. From 147 "Minas" cheese samples, 28 cheeses were positive for E. coli. Among 39 E. coli isolates of the cheeses, one was positive for eae and negative for bpfA and efa1/lifA using PCR, and so was classified as atypical Enteropathogenic E. coli (aEPEC). Two other isolates were positive for extraintestinal pathogenic E...
December 7, 2017: Foodborne Pathogens and Disease
https://www.readbyqxmd.com/read/29212956/icam1-neutrophils-promote-chronic-inflammation-via-asprv1-in-b-cell-dependent-autoimmune-encephalomyelitis
#13
Ryder F Whittaker Hawkins, Alexandre Patenaude, Aline Dumas, Rajiv Jain, Yodit Tesfagiorgis, Steven Kerfoot, Takeshi Matsui, Matthias Gunzer, Patrice E Poubelle, Catherine Larochelle, Martin Pelletier, Luc Vallières
Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29212210/mir-21-silencing-ameliorates-experimental-autoimmune-encephalomyelitis-by-promoting-the-differentiation-of-il-10-producing-b-cells
#14
Hui Wang, Wenrong Xu, Qixiang Shao, Qing Ding
IL-10-producing regulatory B (IL-10+ Breg) cells promote tolerance in autoimmune diseases and transplantation. However, it remains unclear whether microRNAs are involved in the development of IL-10+ Breg cells. Here, we found that microRNA-21 (miR-21) acts as an upstream regulator of IL-10 by targeting the 3' untranslated region of IL-10 mRNA. We also demonstrated that IL-10+ Breg cells exhibit lower miR-21 expression than non-Breg cells and that miR-21 acts as a potent negative regulator of the differentiation of IL-10+ Breg cells...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29205193/molecular-characterization-of-locus-of-enterocyte-effacement-pathogenicity-island-in-shigatoxic-escherichia-coli-isolated-from-human-cattle-in-west-bengal-india
#15
Suresh Chandra Das, Thandavanaryanalu Ramamurthy, Santanu Ghosh, Gururaja Perumal Pazhani, Tista Sen, Raghubir Singh
BACKGROUND & OBJECTIVES: Shigatoxic Escherichia coli (STEC) recovered from dairy animals of Kolkata, India, harboured the putative virulence genes; however, the animals did not exhibit clinical symptoms. Similarly, human isolates in this locality also showed variations in degree of symptoms. Hence, this study was designed to know the presence of recognized gene(s) in the locus of enterocyte effacement (LEE) pathogenicity island in these STEC isolates and functional status of the cardinal gene (eae) related to pathogenicity...
July 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/29203425/tgf%C3%AE-1-transduction-enhances-immunomodulatory-capacity-of-neural-stem-cells-in-experimental-autoimmune-encephalomyelitis
#16
Chong Xie, Xing Li, Xiajun Zhou, Zezhi Li, Yuan Zhang, Li Zhao, Yong Hao, Guang-Xian Zhang, Yangtai Guan
Bone marrow-derived neural stem cells (BM-NSCs) have therapeutic effect on EAE, an animal model of multiple sclerosis. However, the beneficial effect is suboptimal due to the limited immunomodulatory capacity of these cells. In this study, we engineered BM-NSCs with inducible TGFβ1, a potent immunosuppressive cytokine, to enhance their anti-inflammatory capacity. We found that i.v. injected TGFβ1-BM-NSCs more effectively suppressed clinical severity, inflammation and demyelination of the central nervous system of EAE mice...
December 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29203302/immunomodulatory-effects-of-a-rationally-designed-peptide-mimetic-of-human-ifn%C3%AE-in-eae-model-of-multiple-sclerosis
#17
Mansour Poorebrahim, Matin Asghari, Mohammad Foad Abazari, Hassan Askari, Solmaz Sadeghi, Asghar Taheri-Kafrani, Mohammad Hossein Nasr-Esfahani, Pegah Ghoraeian, Maryam Nouri Aleagha, Seyed Shahriar Arab, Derek Kennedy, Alireza Montaseri, Mahsa Mehranfar, Nima Sanadgol
The efficiency of interferon beta (IFNβ)-based drugs is considerably limited due to their undesirable properties, especially high immunogenicity. In this study, for the first time we investigated the impact of a computationally designed peptide mimetic of IFNβ, called MSPEP27, in the animal model of MS. A peptide library was constructed using the Rosetta program based on the predominant IFNAR1-binding site of IFNβ. Molecular docking studies were carried out using ClusPro and HADDOCK tools. The GROMACS package was subsequently used for molecular dynamics (MD) simulations...
December 1, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29200738/in-vitro-bioassay-guided-isolation-of-radioprotective-fractions-from-extracts-of-pinus-koraiensis-bark
#18
Keli Yun, Jian-Hai Bai, ZhenYu Wang
Objective: The aim of this study was to evaluate radioprotective effect of extracts of Pinus koraiensis bark and its fractions on rat splenocytes by using bioassay-guided isolation in order to obtain the best active fraction. Materials and Methods: P. koraiensis bark was ground and extracted with water, 40% acetone, 95% ethanol. Bio-guided assay was selected as an evaluation method to further fractionate radioprotective component from P. koraiensis bark extract...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29198746/valproic-acid-attenuates-inflammation-of-optic-nerve-and-apoptosis-of-retinal-ganglion-cells-in-a-rat-model-of-optic-neuritis
#19
Qiang Liu, Haining Li, Juan Yang, Xiaoyan Niu, Chunmei Zhao, Li Zhao, Zhenhai Wang
AIMS: Optic neuritis (ON) is an inflammatory disease of the optic nerve, which often occurs in patients with multiple sclerosis (MS) and leads to retinal ganglion cell (RGC) death and even severe visual loss. Valproic acid (VPA) is a short-chain branched fatty acid with anti-epileptic, neuro-protective and anti-inflammatory effects. Here, we examined the effects of VPA in experimental autoimmune encephalomyelitis (EAE) rats and explored the underlying mechanisms. MAIN METHODS: EAE was induced by subcutaneous injection with myelin basic protein, emulsified with complete Freund's adjuvant and Mycobacterium tuberculosis H37Ra into the Lewis rats...
November 30, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29194293/multiple-pathological-mechanisms-contribute-to-hippocampal-damage-in-the-experimental-autoimmune-encephalomyelitis-model-of-multiple-sclerosis
#20
Elizabeth L Kyran, Christine Robinson, Pece Kocovski, Zhenjiang Li, Phuc T Dang, Matthew W Hale, Jacqueline M Orian
Emotional and cognitive deficits and associated hippocampal damage observed in multiple sclerosis (MS) are now recognized as primary disease manifestations. However, the pathological substrate of these dysfunctions is unclear. In the experimental autoimmune encephalomyelitis (EAE) MS model, impaired hippocampal-dependent functions are concomitant with severe microglial reactivity and neurodegeneration, but reports vary with respect to evidence of lymphocytic infiltration, raising questions as to the nature of the underlying neurodegenerative mechanisms...
January 3, 2018: Neuroreport
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