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https://www.readbyqxmd.com/read/28811529/disturbance-of-plasma-lipid-metabolic-profile-in-guillain-barre-syndrome
#1
Hsiang-Yu Tang, Daniel Tsun-Yee Chiu, Jui-Fen Lin, Cheng-Yu Huang, Kuo-Hsuan Chang, Rong-Kuo Lyu, Long-Sun Ro, Hung-Chou Kuo, Mei-Ling Cheng, Chiung-Mei Chen
Guillain-Barre Syndrome (GBS) is an inflammatory disease of the peripheral nervous system. Given that plasma metabolic profiles in GBS patients have never been explored, plasma samples of 38 GBS patients, 22 multiple sclerosis (MS) patients, and 40 healthy controls were analyzed by using untargeted and targeted metabolomics analysis. The untargeted analysis showed that levels of a set of plasma lipid metabolites were significantly decreased in GBS patients compared to the controls. Furthermore, the targeted analysis demonstrated that levels of 41 metabolites in GBS patients were significantly changed compared to either the controls or MS patients...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811143/nadph-oxidases-as-drug-targets-and-biomarkers-in-neurodegenerative-diseases-what-is-the-evidence
#2
REVIEW
Silvia Sorce, Roland Stocker, Tamara Seredenina, Rikard Holmdahl, Adriano Aguzzi, Adriano Chio, Antoine Depaulis, Freddy Heitz, Peter Olofsson, Tomas Olsson, Venceslas Duveau, Despina Sanoudou, Sara Skosgater, Antonia Vlahou, Dominique Wasquel, Karl-Heinz Krause, Vincent Jaquet
Neurodegenerative disease are frequently characterized by microglia activation and/or leukocyte infiltration in the parenchyma of the central nervous system and at the molecular level by increased oxidative modifications of proteins, lipids and nucleic acids. NADPH oxidases (NOX) emerged as a novel promising class of pharmacological targets for the treatment of neurodegeneration due to their role in oxidant generation and presumably in regulating microglia activation. The unique function of NOX is the generation of superoxide anion (O2(•-)) and hydrogen peroxide (H2O2)...
August 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28807667/inhibition-of-beta-catenin-signaling-in-the-skin-rescues-cutaneous-adipogenesis-in-systemic-sclerosis-a-randomized-double-blind-placebo-controlled-trial-of-c-82
#3
Robert Lafyatis, Julio C Mantero, Jessica Gordon, Nina Kishore, Mary Carns, Howard Dittrich, Robert Spiera, Robert W Simms, John Varga
Several studies have suggested that Wnts might contribute to skin fibrosis in systemic sclerosis (SSc) by affecting the differentiation of pluripotent dermal cells. We tested C-82, a therapeutic that inhibits canonical Wnt signaling by blocking the interaction of cAMP Response Element-Binding Protein with β-Catenin and inhibiting Wnt-activated genes. We utilized previously unreported trial design, formulating C-82 for topical application and conducting a placebo controlled, double-blinded clinical trial in which patients with diffuse cutaneous SSc were treated with C-82 or placebo on opposite forearms...
August 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28801400/protein-misfolding-amyotrophic-lateral-sclerosis-and-guanabenz-protocol-for-a-phase-ii-rct-with-futility-design-promise-trial
#4
Eleonora Dalla Bella, Irene Tramacere, Giovanni Antonini, Giuseppe Borghero, Margherita Capasso, Claudia Caponnetto, Adriano Chiò, Massimo Corbo, Roberto Eleopra, Massimiliano Filosto, Fabio Giannini, Enrico Granieri, Vincenzo La Bella, Christian Lunetta, Jessica Mandrioli, Letizia Mazzini, Sonia Messina, Maria Rosaria Monsurrò, Gabriele Mora, Nilo Riva, Romana Rizzi, Gabriele Siciliano, Vincenzo Silani, Isabella Simone, Gianni Sorarù, Paolo Volanti, Giuseppe Lauria
INTRODUCTION: Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28797111/angiogenic-t-cell-expansion-correlates-with-severity-of-peripheral-vascular-damage-in-systemic-sclerosis
#5
Mirko Manetti, Sara Pratesi, Eloisa Romano, Silvia Bellando-Randone, Irene Rosa, Serena Guiducci, Bianca Saveria Fioretto, Lidia Ibba-Manneschi, Enrico Maggi, Marco Matucci-Cerinic
The mechanisms underlying endothelial cell injury and defective vascular repair in systemic sclerosis (SSc) remain unclear. Since the recently discovered angiogenic T cells (Tang) may have an important role in the repair of damaged endothelium, this study aimed to analyze the Tang population in relation to disease-related peripheral vascular features in SSc patients. Tang (CD3+CD31+CXCR4+) were quantified by flow cytometry in peripheral blood samples from 39 SSc patients and 18 healthy controls (HC). Circulating levels of the CXCR4 ligand stromal cell-derived factor (SDF)-1α and proangiogenic factors were assessed in paired serum samples by immunoassay...
2017: PloS One
https://www.readbyqxmd.com/read/28776347/the-anti-inflammatory-effects-of-oral-formulated-tacrolimus-in-mice-with-experimental-autoimmune-encephalomyelitis
#6
Myung Jin Kim, Jung Joon Sung, Seung Hyun Kim, Jeong Min Kim, Gye Sun Jeon, Seog Kyun Mun, Suk Won Ahn
Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group...
September 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28769926/serum-neuroinflammatory-disease-induced-central-nervous-system-proteins-predict-clinical-onset-of-experimental-autoimmune-encephalomyelitis
#7
Itay Raphael, Johanna Webb, Francisco Gomez-Rivera, Carol A Chase Huizar, Rishein Gupta, Bernard P Arulanandam, Yufeng Wang, William E Haskins, Thomas G Forsthuber
There is an urgent need in multiple sclerosis (MS) patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the blood-brain barrier (BBB) is tightly regulated, whereas, in MS, central nervous system (CNS) inflammation results in damage to neuronal tissues, disruption of BBB integrity, and potential release of neuroinflammatory disease-induced CNS proteins (NDICPs) into CSF and serum...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28742871/comprehensive-immune-profiling-reveals-substantial-immune-system-alterations-in-a-subset-of-patients-with-amyotrophic-lateral-sclerosis
#8
Michael P Gustafson, Nathan P Staff, Svetlana Bornschlegl, Greg W Butler, Mary L Maas, Mohamed Kazamel, Adeel Zubair, Dennis A Gastineau, Anthony J Windebank, Allan B Dietz
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a median lifespan of 2-3 years after diagnosis. There are few meaningful treatments that alter progression in this disease. Preclinical and clinical studies have demonstrated that neuroinflammation may play a key role in the progression rate of ALS. Despite this, there are no validated biomarkers of neuroinflammation for use in clinical practice or clinical trials. Biomarkers of neuroinflammation could improve patient management, provide new therapeutic targets, and possibly help stratify clinical trial selection and monitoring...
2017: PloS One
https://www.readbyqxmd.com/read/28730919/an-update-on-biomarker-discovery-and-use-in-systemic-sclerosis
#9
Takashi Matsushita, Kazuhiko Takehara
Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin and internal organs. Three major abnormalities, autoimmunity, vasculopathy, and fibrosis, are considered to play important roles in the pathophysiology of SSc. SSc is a heterogeneous disease with clinical features, disease progress, therapeutic response, and prognosis. Therefore, identification of biomarkers, which can predict the course of the disease, is required for the progress of clinical practice...
July 25, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28721050/the-use-of-natalizumab-for-multiple-sclerosis
#10
REVIEW
Rachel Brandstadter, Ilana Katz Sand
Natalizumab is a monoclonal antibody that acts as an α4 integrin antagonist to prevent leukocyte trafficking into the central nervous system. It is US Food and Drug Administration (FDA) approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Natalizumab demonstrated high efficacy in Phase III trials by reducing the annualized relapse rate, preventing multiple sclerosis (MS) lesion accumulation on magnetic resonance imaging, and decreasing the probability of sustained progression of disability...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28720279/metabolomic-analysis-identifies-altered-metabolic-pathways-in-multiple-sclerosis
#11
Simone Poddighe, Federica Murgia, Lorena Lorefice, Sonia Liggi, Eleonora Cocco, Maria Giovanna Marrosu, Luigi Atzori
Multiple sclerosis (MS) is a chronic, demyelinating disease that affects the central nervous system and is characterized by a complex pathogenesis and difficult management. The identification of new biomarkers would be clinically useful for more accurate diagnoses and disease monitoring. Metabolomics, the identification of small endogenous molecules, offers an instantaneous molecular snapshot of the MS phenotype. Here the metabolomic profiles (utilizing plasma from patients with MS) were characterized with a Gas cromatography-mass spectrometry-based platform followed by a multivariate statistical analysis and comparison with a healthy control (HC) population...
July 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28713377/th1-and-th17-cells-and-associated-cytokines-discriminate-among-clinically-isolated-syndrome-and-multiple-sclerosis-phenotypes
#12
Gabriel Arellano, Eric Acuña, Lilian I Reyes, Payton A Ottum, Patrizia De Sarno, Luis Villarroel, Ethel Ciampi, Reinaldo Uribe-San Martín, Claudia Cárcamo, Rodrigo Naves
Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. It is a heterogeneous pathology that can follow different clinical courses, and the mechanisms that underlie the progression of the immune response across MS subtypes remain incompletely understood. Here, we aimed to determine differences in the immunological status among different MS clinical subtypes. Blood samples from untreated patients diagnosed with clinically isolated syndrome (CIS) (n = 21), different clinical forms of MS (n = 62) [relapsing-remitting (RRMS), secondary progressive, and primary progressive], and healthy controls (HCs) (n = 17) were tested for plasma levels of interferon (IFN)-γ, IL-10, TGF-β, IL-17A, and IL-17F by immunoanalysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28702930/personalized-medicine-in-rheumatology-the-paradigm-of-serum-autoantibodies
#13
REVIEW
Silvia Sirotti, Elena Generali, Angela Ceribelli, Natasa Isailovic, Maria De Santis, Carlo Selmi
The sequencing of the human genome is now well recognized as the starting point of personalized medicine. Nonetheless, everyone is unique and can develop different phenotypes of the same disease, despite identical genotypes, as well illustrated by discordant monozygotic twins. To recognize these differences, one of the easiest and most familiar examples of biomarkers capable of identifying and predicting the outcome of patients is represented by serum autoantibodies. In this review, we will describe the concept of personalized medicine and discuss the predictive, prognostic and preventive role of antinuclear antibodies (ANA), anti-citrullinated peptide antibodies (ACPA), rare autoantibodies and anti-drug antibodies (ADA), to evaluate how these can help to identify different disease immune phenotypes and to choose the best option for treating and monitoring rheumatic patients in everyday practice...
December 2017: Auto- Immunity Highlights
https://www.readbyqxmd.com/read/28687351/prevalence-of-anti-nt5c1a-antibodies-in-japanese-patients-with-autoimmune-rheumatic-diseases-in-comparison-with-other-patient-cohorts
#14
Yoshinao Muro, Hirotaka Nakanishi, Masahisa Katsuno, Michihiro Kono, Masashi Akiyama
BACKGROUND: Sporadic inclusion body myositis (sIBM) is usually classified as an idiopathic inflammatory myopathies. Although the diagnosis of sIBM is sometimes challenging, recent studies have shown that the autoantibodies against cytosolic 5'-nucleotidase 1A (NT5C1A) are the possible diagnostic biomarker for sIBM. Few reports have shown the frequencies of anti-NT5C1A antibodies in systemic autoimmune rheumatic diseases (SARDs) using large cohorts of SARDs. METHODS: Serum samples obtained from 314 patients including dermatomyositis (DM) (n=144), systemic lupus erythematosus (SLE) (n=50), systemic sclerosis (SSc) (n=50), Sjögren's syndrome (SS) (n=50), polymyositis (PM) (n=10) and mixed connective tissue disease (n=10), and healthy controls (n=42) in addition to 10 patients with typical sIBM were analysed for the presence of autoantibodies using full-length recombinant NT5C1A ELISA...
July 4, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28677863/netrin-1-and-multiple-sclerosis-a-new-biomarker-for-neuroinflammation
#15
P Mulero, C Córdova, M Hernández, R Martín, B Gutiérrez, J C Muñoz, N Redondo, I Gallardo, N Téllez, M L Nieto
BACKGROUND AND PURPOSE: Netrin-1, an axon guidance protein, reduces serum levels of pro-inflammatory mediators and stabilizes the blood-brain barrier limiting the entrance of immune cells into the central nervous system. The aim was to investigate its presence in the experimental autoimmune encephalomyelitis (EAE) model and in multiple sclerosis (MS) patients with and without clinical activity. METHODS: Netrin-1 levels were evaluated in EAE mouse tissues. Afterwards, serum netrin-1 was cross-sectionally quantified in 90 patients with different MS phenotypes and 30 control subjects...
July 5, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28676069/limited-cutaneous-systemic-sclerosis-skin-demonstrates-distinct-molecular-subsets-separated-by-a-cardiovascular-development-gene-expression-signature
#16
Emma C Derrett-Smith, Viktor Martyanov, Cecilia B Chighizola, Pia Moinzadeh, Corrado Campochiaro, Korsa Khan, Tammara A Wood, Pier Luigi Meroni, David J Abraham, Voon H Ong, Robert Lafyatis, Michael L Whitfield, Christopher P Denton
BACKGROUND: Systemic sclerosis (SSc; scleroderma) is an uncommon autoimmune rheumatic disease characterised by autoimmunity, vasculopathy and fibrosis. Gene expression profiling distinguishes scleroderma from normal skin, and can detect different subsets of disease, with potential to identify prognostic biomarkers of organ involvement or response to therapy. We have performed gene expression profiling in skin samples from patients with limited cutaneous SSc (lcSSc). METHODS: Total RNA was extracted from clinically uninvolved skin biopsies of 15 patients with lcSSc and 8 healthy controls (HC)...
July 4, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28675562/innate-and-adaptive-immunity-in-human-epilepsies
#17
REVIEW
Jan Bauer, Albert J Becker, Wassim Elyaman, Jukka Peltola, Stephan Rüegg, Maarten J Titulaer, James A Varley, Ettore Beghi
Inflammatory mechanisms have been increasingly implicated in the origin of seizures and epilepsy. These mechanisms are involved in the genesis of encephalitides in which seizures are a common complaint. Experimental and clinical evidence suggests different inflammatory responses in the brains of patients with epilepsy depending on the etiology. In general, activation of both innate and adaptive immunity plays a role in refractory forms of epilepsy. Epilepsies in which seizures develop after infiltration of cells of the adaptive immune system in the central nervous system (CNS) include a broad range of epileptic disorders with different (known or unknown) etiologies...
July 2017: Epilepsia
https://www.readbyqxmd.com/read/28675556/prospective-clinical-trials-to-investigate-clinical-and-molecular-biomarkers
#18
REVIEW
Stéphane Auvin, Lauren Walker, William Gallentine, Sergiusz Jozwiak, Mario Tombini, Graeme J Sills
Among clinical studies, randomized studies as well as well-designed observational studies are providing the highest quality data. In addition, these studies represent a good opportunity to examine biomarkers of ictogenesis and epileptogenesis. To date, no validated molecular or cellular biomarker exists for any aspect of epilepsy. We provide an overview of the inflammatory biomarkers under investigation in prospective clinical studies in epilepsy: proinflammatory cytokines in prolonged febrile seizure; High Mobility Group Box 1 (HMGB1) as a prognosis biomarker in epilepsy and the interaction between inflammation and metabolism, in particular, iron metabolism, in epilepsy...
July 2017: Epilepsia
https://www.readbyqxmd.com/read/28674995/biomarkers-in-neurodegenerative-diseases
#19
Andreas Jeromin, Robert Bowser
The past decade has seen tremendous efforts in biomarker discovery and validation for neurodegenerative diseases. The source and type of biomarkers has continued to grow for central nervous system diseases, from biofluid-based biomarkers (blood or cerebrospinal fluid (CSF)), to nucleic acids, tissue, and imaging. While DNA remains a predominant biomarker used to identify familial forms of neurodegenerative diseases, various types of RNA have more recently been linked to familial and sporadic forms of neurodegenerative diseases during the past few years...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28657431/csf-and-clinical-data-are-useful-in-differentiating-cns-inflammatory-demyelinating-disease-from-cns-lymphoma
#20
Ryotaro Ikeguchi, Yuko Shimizu, Satoru Shimizu, Kazuo Kitagawa
BACKGROUND: It is often difficult to diagnose central nervous system (CNS) inflammatory demyelinating diseases (IDDs) because they are similar to CNS lymphoma and glioma. OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) analysis can differentiate CNS IDDs from CNS lymphoma and glioma. METHODS: We measured CSF cell counts; concentrations of proteins, glucose, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), and myelin basic protein; and IgG index in patients with multiple sclerosis (MS, n = 64), neuromyelitis optica spectrum disorder (NMOSD, n = 35), tumefactive demyelinating lesion (TDL, n = 17), CNS lymphoma ( n = 12), or glioma ( n = 10)...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
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