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Anna V Cherepanova, Zhanna K Nazarkina, Pavel P Laktionov
Oligodeoxynucleotide (ODN) analogues of cell-surface-bound circulating DNA inhibit the dsRNA-induced production of pro-inflammatory interleukin 6, interferon beta and antibacterial peptide beta-defensin 2 not only in human gingival fibroblasts, but also in human primary endothelial and transformed cells (Hela and A431). ODN analogues do not effect dendritic cells activation by poly(I:C). The data obtained indicate that the early stages of the signal transduction cascade are violated by ODN analogues and the effects depend on the cell type...
2016: Advances in Experimental Medicine and Biology
Naeim Ehtesham, Fariborz Khorvash, Majid Kheirollahi
MicroRNAs (miRNAs) are crucial to the immunopathogenesis of multiple sclerosis (MS). The mechanism of action of interferon beta (IFN-β) in relapsing-remitting (RR) MS patients is largely unknown. miR-145 and miR-20a-5p previously reported as diagnosis biomarker in treatment naïve RRMS patients and their expression after IFN-β therapy might be indicative of molecular mechanism of IFN-β. Cross-talking between JAK/STAT pathway and complementary pathways like MAPK is important in IFN-β signaling. Here, in order to clarify the ambiguous molecular mechanism of IFN-β and evaluate the potential use of them as a biomarker for monitoring of therapy, we investigated the expression of miR-145 and miR-20a-5p in blood sample of 15 treatment naïve RRMS patients, 15 IFN-β-treated RRMS patients, and 15 healthy volunteers (HVs)...
October 17, 2016: Journal of Molecular Neuroscience: MN
Rodrigo Fabrizzio Inácio, Renata Gacielle Zanon, Mateus Vidigal de Castro, Henrique Marques de Souza, Marcio Chaim Bajgelman, Liana Verinaud, Alexandre Leite Rodrigues de Oliveira
Astrocytes are multifunctional glial cells that actively participate in synaptic plasticity in health and disease. Little is known about molecular interactions between neurons and glial cells that result in synaptic stability or elimination. In this sense, the main histocompatibility complex of class I (MHC I) has been shown to play a role in the synaptic plasticity process during development and after lesion of the CNS. MHC I levels in neurons appear to be influenced by astrocyte secreted molecules, which may generate endoplasmic reticulum stress...
October 14, 2016: Neuroscience Letters
B Perlman, D Heller, B Cracchiolo
OBJECTIVE: Postmenopausal bleeding must always be evaluated to rule out endometrial carcinoma, although there are many benign etiologies. There have been rare reports of premenopausal bleeding with interferon beta-1b, used to treat multiple sclerosis, but no prior reports in postmenopausal women. METHODS: Literature searches were performed using PubMed and Medline for articles with content related to premenopausal and postmenopausal bleeding while taking interferon beta-1b...
October 17, 2016: Climacteric: the Journal of the International Menopause Society
Luis Hernandez, Shien Guo, Hector Toro-Diaz, Stuart Carroll, Syed Feisal Syed Farooq
AIMS: Peginterferon beta-1a 125 mcg administered subcutaneously every two weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22 mcg, 30 mcg, and 44 mcg], interferon beta-1b, and glatiramer acetate 20 mg) in the treatment of RRMS, from the National Health Service and personal social services perspective in Scotland...
October 12, 2016: Journal of Medical Economics
Xinchun Ye, Delian Kong, Jun Wang, Tauheed Ishrat, Hongjuan Shi, Xiaohui Ding, Guiyun Cui, Fang Hua
Myeloid differentiation primary-response protein-88 (MyD88) is one of adaptor proteins mediating Toll-like receptors (TLRs) signaling. Activation of MyD88 results in the activation of nuclear factor kappa B (NFκB) and the increase of inflammatory responses. Evidences have demonstrated that TLRs signaling contributes to cerebral ischemia/reperfusion (I/R) injury. However, the role of MyD88 in this mechanism of action is disputed and needs to be clarified. In the present study, in a mouse model of cerebral I/R, we examined the activities of NFκB and interferon factor-3 (IRF3), and the inflammatory responses in ischemic brain tissue using ELISA, Western blots, and real-time PCR...
October 4, 2016: Biochemical and Biophysical Research Communications
Sheena L Dupuy, Fariha Khalid, Brian C Healy, Sonya Bakshi, Mohit Neema, Shahamat Tauhid, Rohit Bakshi
BACKGROUND: Spinal cord atrophy occurs early in multiple sclerosis (MS) and impacts disability. The therapeutic effect of interferon beta-1a (IFNβ-1a) on spinal cord atrophy in patients with relapsing-remitting (RR) MS has not been explored. METHODS: We retrospectively identified 16 consecutive patients receiving weekly intramuscular IFNβ-1a for 2 years [baseline age (mean ± SD) 47.7 ± 7.5 years, Expanded Disability Status Scale score median (range) 1...
October 5, 2016: BMC Medical Imaging
Alessandra Bua, Melania Ruggeri, Stefania Zanetti, Paola Molicotti
Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of the patients with multiple sclerosis...
October 4, 2016: Medical Microbiology and Immunology
Michael B Cheung, Viviana Sampayo-Escobar, Ryan Green, Martin L Moore, Subhra Mohapatra, Shyam S Mohapatra
Respiratory syncytial virus (RSV) has been reported to infect human mesenchymal stem cells (MSCs) but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts...
2016: PloS One
Marzieh Khoshbin Nazdik, Mohammad Taheri, Mir Davood Omrani, Elham Sajjadi, Shahram Arsang-Jang, Zeinab Kazaei Koohpar, Hidetoshi Inoko, Arezou Sayad
OBJECTIVES: Multiple sclerosis (MS) is an autoimmune disease involving the central nervous system (CNS) with unknown immunopathogenic mechanisms. Matrix metalloproteinase-9 (MMP-9) facilitates T-cell migration into the CNS while the tissue inhibitor matrix metalloproteinase-1 (TIMP-1) inhibits MMP-9 actions. The aim of this study was to evaluate the expression of TIMP-1 RNA and MMP-9/TIMP-1 RNA ratio in blood cells of Iranian patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFNb...
September 22, 2016: Human Antibodies
Brandon J Dixon, Di Chen, Yang Zhang, Jerry Flores, Jay Malaguit, Derek Nowrangi, John H Zhang, Jiping Tang
Neonatal hypoxic-ischemic encephalopathy (HIE) is an injury that often leads to detrimental neurological deficits. Currently, there are no established therapies for HIE and it is critical to develop treatments that provide protection after HIE. The objective of this study was to investigate the ability of interferon beta (IFNβ) to provide neuroprotection and reduce apoptosis after HIE. Postnatal Day 10 rat pups were subjected to unilateral carotid artery ligation followed by 2.5 hr of exposure to hypoxia (8% O2)...
October 2016: ASN Neuro
Stanley Cohan
Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit-risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56(bright) natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS...
2016: Biologics: Targets & Therapy
J Mallada, N Perez-Carmona, L Berenguer-Ruiz, R Sanchez-Perez, R Martin-Gonzalez, D Sola-Martinez, S Mola, J M Lopez-Arlandis, R Vela-Yebra, L Gabaldon-Torres, E Freire-Alvarez, A Garcia-Escriva, A P Sempere
INTRODUCTION: Post-authorisation studies are important to confirm whether the outcomes of clinical trials are reproduced in usual clinical practice. AIMS: To evaluate the effectiveness and safety of fingolimod in clinical practice in the province of Alicante. PATIENTS AND METHODS: A retrospective multi-centre study was conducted with remitting multiple sclerosis patients treated with fingolimod. Demographic, clinical and pharmacological data were collected...
September 5, 2016: Revista de Neurologia
A Oterino, D F Uria, J Pena, D Solar, J Villafani, P Oliva-Nacarino, R Suarez-Moro, V G Quintanilla
AIM: To evaluate the effectiveness and safety of fingolimod in routine clinical practice in the region of Asturias and Cantabria (Spain). PATIENTS AND METHODS: We conducted a retrospective multicentre study of patients with relapsing-remitting multiple sclerosis treated with fingolimod, in accordance with the product data sheet. Effectiveness was evaluated in patients with at least one year's treatment. The following were calculated: annualised relapse rate (ARR), the percentage of patients free from relapses and free from gadolinium-enhancing lesions, and those who improved/maintained their score on the Expanded Disability Status Scale (EDSS)...
September 5, 2016: Revista de Neurologia
Stanley Cohan, Chiayi Chen, Elizabeth Baraban, Tamela Stuchiner, Lois Grote
BACKGROUND: Since the application of MRI scanning to the diagnosis and treatment of multiple sclerosis, it has been recognized that only a small fraction of lesions seen on MRI scans produce recognizable symptoms or neurological findings. Because new lesions may occur without clinical detection, the recommendation has been made that MRI scanning be performed on a routine scheduled basis, usually yearly, even in patients who are clinically stable. METHODS: A retrospective chart review study was conducted on MS patients who had MRI scans of the central nervous system between 2009 and 2012 at Providence Multiple Sclerosis Center...
2016: BMC Neurology
Musa Ozturk, Fulya Basoglu, Murvet Yilmaz, Ayse Aysim Ozagari, Sevim Baybas
BACKGROUND: Interferon beta (IFN β) subtypes are largely used as immunomodulatory agents in Multiple Sclerosis (MS) treatment. While being generally well tolerated, they can cause various side effects. Adverse effects related to kidney are rarely reported. CASE REPORT: We report a 32 years old male patient who developed nephrotic syndrome while receiving IFN β for MS. Biopsy showed focal segmental glomerulosclerosis. He went into remisson after cessation of drug and with the aid of angiotensin II antagonists...
September 2016: Multiple Sclerosis and related Disorders
Emer Fogarty, Susanne Schmitz, Niall Tubridy, Cathal Walsh, Michael Barry
INTRODUCTION: Randomised studies have demonstrated efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear how the magnitude of treatment efficacy varies across all currently available therapies. OBJECTIVE: To perform a systematic review and network meta-analysis to evaluate the comparative efficacy of available therapies in reducing relapses and disability progression in RRMS. METHODS: A systematic review identified 28 randomised, placebo-controlled and direct comparative trials...
September 2016: Multiple Sclerosis and related Disorders
Jasna Jancic, Blazo Nikolic, Nikola Ivancevic, Vesna Djuric, Ivan Zaletel, Dejan Stevanovic, Sasa Peric, John N van den Anker, Janko Samardzic
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease. The disease in children almost always presents in the relapsing-remittent form. The therapy involves treatment of relapses, and immunomodulatory and symptomatic treatment...
September 17, 2016: Neurology and Therapy
Arinjay Banerjee, Noreen Rapin, Megan Miller, Philip Griebel, Yan Zhou, Vincent Munster, Vikram Misra
It is speculated that bats are important reservoir hosts for numerous viruses, with 27 viral families reportedly detected in bats. Majority of these viruses have not been isolated and there is little information regarding their biology in bats. Establishing a well-characterized bat cell line supporting the replication of bat-borne viruses would facilitate the analysis of virus-host interactions in an in vitro model. Currently, few bat cell lines have been developed and only Tb1-Lu, derived from Tadarida brasiliensis is commercially available...
November 2016: Journal of Virological Methods
John S Cho, Terry C Fang, Taylor L Reynolds, Daniel J Sofia, Stefan Hamann, Linda C Burkly
Systemic sclerosis (SSc) is a chronic autoimmune disorder that can result in extensive tissue damage in the skin and, in advanced cases, internal organs. Vasculopathy, aberrant immune activation, and tissue fibrosis are three hallmarks of the disease that have been identified, with vasculopathy and aberrant immunity being amongst the earliest events. However, a mechanistic link between these processes has not been established. Here, we have identified a novel role of platelet derived growth factor-BB (PDGF-BB)/PDGFRβ activation in combination with dermal injury induced by bleomycin as a driver of early, aberrant expression of interferon stimulatory genes (ISGs) and inflammatory monocyte infiltration...
2016: PloS One
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