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https://www.readbyqxmd.com/read/28107669/medical-comorbidity-in-bipolar-disorder-the-link-with-metabolic-inflammatory-systems
#1
REVIEW
Ana SayuriYamagata, Elisa Brietzke, Joshua D Rosenblat, Ron Kakar, Roger S McIntyre
BACKGROUND: Bipolar disorder (BD) is associated with chronic low-grade inflammation, several medical comorbidities and a decreased life expectancy. Metabolic-inflammatory changes have been postulated as one of the main links between BD and medical comorbidity, although there are few studies exploring possible mechanisms underlying this relationship. Therefore, the aims of the current narrative review were 1) synthesize the evidence for metabolic-inflammatory changes that may facilitate the link between medical comorbidity and BD and 2) discuss therapeutic and preventive implications of these pathways...
January 4, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28107624/tocilizumab-alendronate-conjugate-for-treatment-of-rheumatoid-arthritis
#2
Hwiwon Lee, Suk Ho Bhang, Jeong Ho Lee, Hyemin Kim, Sei Kwang Hahn
An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS)...
January 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28107610/tonsil-derived-mesenchymal-stem-cells-t-mscs-prevent-th17-mediated-autoimmune-response-via-regulation-of-the-programmed-death-1-programmed-death-ligand-1-pd-1-pd-l1-pathway
#3
Ji-Yon Kim, Minhwa Park, Yu-Hee Kim, Kyung-Ha Ryu, Kyung Ho Lee, Kyung-Ah Cho, So-Youn Woo
Our knowledge of the immunomodulatory role of mesenchymal stem cells (MSCs) in both the innate and adaptive immune systems has dramatically expanded, providing great promise for treating various autoimmune diseases. However, the contribution of MSCs to Th17 dominant immune disease, such as psoriasis and its underlying mechanism remains elusive. In this study, we demonstrated that human palatine tonsil-derived MSCs (T-MSCs) constitutively express both the membrane-bound and soluble forms of programmed death-ligand 1 (PD-L1), which enables T-MSCs to be distinguished from MSCs originating from other organs (i...
January 20, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28107378/polymorphisms-in-stat4-ptpn2-psors1c1-and-traf3ip2-genes-are-associated-with-the-response-to-tnf-inhibitors-in-patients-with-rheumatoid-arthritis
#4
Paola Conigliaro, Cinzia Ciccacci, Cristina Politi, Paola Triggianese, Sara Rufini, Barbara Kroegler, Carlo Perricone, Andrea Latini, Giuseppe Novelli, Paola Borgiani, Roberto Perricone
OBJECTIVE: Rheumatoid Arthritis (RA) is a progressive autoimmune disease characterized by chronic joint inflammation and structural damage. Remission or at least low disease activity (LDA) represent potentially desirable goals of RA treatment. Single nucleotide polymorphisms (SNPs) in several genes might be useful for prediction of response to therapy. We aimed at exploring 4 SNPs in candidate genes (STAT4, PTPN2, PSORS1C1 and TRAF3IP2) in order to investigate their potential role in the response to therapy with tumor necrosis factor inhibitors (TNF-i) in RA patients...
2017: PloS One
https://www.readbyqxmd.com/read/28106896/the-2016-bowman-lecture-conjunctival-curses-scarring-conjunctivitis-30-years-on
#5
J K Dart
This review is in two sections. The first section summarises 35 conditions, both common and infrequent, causing cicatrising conjunctivitis. Guidelines for making a diagnosis are given together with the use of diagnostic tests, including direct and indirect immunofluorescence, and their interpretation. The second section evaluates our knowledge of ocular mucous membrane pemphigoid, which is the commonest cause of cicatrizing conjunctivitis in most developed countries. The clinical characteristics, demographics, and clinical signs of the disease are described...
January 20, 2017: Eye
https://www.readbyqxmd.com/read/28106799/rna-editing-adar1-and-the-innate-immune-response
#6
REVIEW
Qingde Wang, Xiaoni Li, Ruofan Qi, Timothy Billiar
RNA editing, particularly A-to-I RNA editing, has been shown to play an essential role in mammalian embryonic development and tissue homeostasis, and is implicated in the pathogenesis of many diseases including skin pigmentation disorder, autoimmune and inflammatory tissue injury, neuron degeneration, and various malignancies. A-to-I RNA editing is carried out by a small group of enzymes, the adenosine deaminase acting on RNAs (ADARs). Only three members of this protein family, ADAR1-3, exist in mammalian cells...
January 18, 2017: Genes
https://www.readbyqxmd.com/read/28106787/anti-nmda-receptor-encephalitis-and-vaccination
#7
Hsiuying Wang
Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106152/cancer-immunotherapy-immune-checkpoint-blockade-and-associated-endocrinopathies
#8
REVIEW
David J Byun, Jedd D Wolchok, Lynne M Rosenberg, Monica Girotra
Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease...
January 20, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28106077/mesenchymal-stem-cell-transplantation-in-tight-skin-mice-identifies-mir-151-5p-as-a-therapeutic-target-for-systemic-sclerosis
#9
Chider Chen, Dandan Wang, Alireza Moshaverinia, Dawei Liu, Xiaoxing Kou, Wenjing Yu, Ruili Yang, Lingyun Sun, Songtao Shi
Systemic sclerosis (SSc), an autoimmune disease, may cause significant osteopenia due to activation of the IL4Rα/mTOR pathway. Mesenchymal stem cell transplantation (MSCT) can ameliorate immune disorders in SSc via inducing immune tolerance. However, it is unknown whether MSCT rescues osteopenia phenotype in SSc. Here we show that MSCT can effectively ameliorate osteopenia in SSc mice by rescuing impaired lineage differentiation of the recipient bone marrow MSCs. Mechanistically, we show that donor MSCs transfer miR-151-5p to the recipient bone marrow MSCs in SSc mice to inhibit IL4Rα expression, thus downregulating mTOR pathway activation to enhance osteogenic differentiation and reduce adipogenic differentiation...
January 20, 2017: Cell Research
https://www.readbyqxmd.com/read/28106049/food-grade-tio2-impairs-intestinal-and-systemic-immune-homeostasis-initiates-preneoplastic-lesions-and-promotes-aberrant-crypt-development-in-the-rat-colon
#10
Sarah Bettini, Elisa Boutet-Robinet, Christel Cartier, Christine Coméra, Eric Gaultier, Jacques Dupuy, Nathalie Naud, Sylviane Taché, Patrick Grysan, Solenn Reguer, Nathalie Thieriet, Matthieu Réfrégiers, Dominique Thiaudière, Jean-Pierre Cravedi, Marie Carrière, Jean-Nicolas Audinot, Fabrice H Pierre, Laurence Guzylack-Piriou, Eric Houdeau
Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer's patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105588/nogo-a-antibodies-for-progressive-multiple-sclerosis
#11
Benjamin V Ineichen, Patricia S Plattner, Nicolas Good, Roland Martin, Michael Linnebank, Martin E Schwab
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair...
January 19, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28105358/primary-autoimmune-myelofibrosis-with-severe-thrombocytopenia-mimicking-immune-thrombocytopenia-a-case-report
#12
Jian Hua, Shu Matayoshi, Tomoyuki Uchida, Morihiro Inoue, Masao Hagihara
Patients presenting with bone marrow fibrosis not accompanied by well-established autoimmune diseases, such as systemic lupus erythematosus, or malignant diseases, are considered to have primary autoimmune myelofibrosis (AIMF). Primary AIMF has been reported to follow a benign course and responds well to treatment with immunosuppressive agents. Immune thrombocytopenia (ITP) is also an autoimmune disorder characterized by antiplatelet-antibody-mediated thrombocytopenia in the absence of other causes of thrombocytopenia...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28105357/immunoglobulin-g4-mediated-sclerosing-cholangitis-as-a-risk-factor-for-cholangiocarcinoma-a-case-report
#13
Karin E Koopman, Elisabeth Bloemena, Geert Kazemier, Michael Klemt-Kropp
Immunoglobulin (Ig)G4-mediated disease is a systemic autoimmune disease, which occasionally presents solely as sclerosing cholangitis (SC). IgG4-mediated SC is challenging to diagnose, as it may mimic cholangiocarcinoma radiologically, and carcinoma cells may produce IgG4. The diagnosis of IgG4-mediated disease is based on histological consensus criteria and response to corticosteroids. In addition to the radiological and histological overlap between IgG4-mediated SC and cholangiocarcinoma, IgG4-mediated SC may be considered as a risk factor for the development of cholangiocarcinoma...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28105286/discovery-of-a-potent-selective-and-orally-available-pi3k%C3%AE-inhibitor-for-the-treatment-of-inflammatory-diseases
#14
Montse Erra, Joan Taltavull, Angelique Gréco, Francisco Javier Bernal, Juan Francisco Caturla, Jordi Gràcia, María Domínguez, Mar Sabaté, Stéphane Paris, Salomé Soria, Begoña Hernández, Clara Armengol, Judit Cabedo, Mónica Bravo, Elena Calama, Montserrat Miralpeix, Martin D Lehner
The delta isoform of the phosphatidylinositol 3-kinase (PI3Kδ) has been shown to have an essential role in specific immune cell functions and thus represents a potential therapeutic target for autoimmune and inflammatory diseases. Herein, the optimization of a series of pyrrolotriazinones as potent and selective PI3Kδ inhibitors is described. The main challenge of the optimization process was to identify an orally available compound with a good pharmacokinetic profile in preclinical species that predicted a suitable dosing regimen in humans...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28104447/celiac-disease-autoimmunity-is-associated-with-leukocyte-telomere-shortening-in-older-adults-the-u-s-national-health-and-nutrition-examination-survey
#15
Elena Kamycheva, Tadahiro Goto, Carlos A Camargo
PURPOSE: Telomeres are nucleotide sequences, and their function is to maintain cell surveillance. Exaggeration of the attrition rate of leukocyte telomere length (LTL) may result in genomic instability and tumorigenesis. Celiac disease (CD), an autoimmune inflammation of small intestine, has increasing prevalence in the elderly and may lead to lymphomas and gastrointestinal malignancies. We used nationally-representative datasets from the U.S. National Health and Nutrition Examination Survey (NHANES) to investigate if CD autoimmunity in older adults (age≥50years) is associated with shorter LTL...
January 16, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28104261/multiple-sclerosis-association-of-gelatinase-b-matrix-metalloproteinase-9-with-risk-and-clinical-course-the-disease
#16
Ana Valado, Maria João Leitão, António Martinho, Rui Pascoal, João Cerqueira, Inês Correia, Sónia Batista, Lívia Sousa, Inês Baldeiras
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and axonal degeneration of the central nervous system and a leading cause of disability in young adults. The matrix metalloproteinases in general and specially gelatinase B/metalloproteinase-9 (MMP-9) plays a role in the pathogenesis of multiple sclerosis. OBJECTIVE: To investigate the presence of the MMP-9 -1562C/T polymorphism in a Portuguese population of MS patients and assess its impact in susceptibility and course of the disease...
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28104252/novel-zebrafish-eae-model-a-quick-in-vivo-screen-for-multiple-sclerosis
#17
Pushkar Kulkarni, Swapna Yellanki, Raghavender Medishetti, Dharmarajan Sriram, Uday Saxena, Perumal Yogeeswari
INTRODUCTION: Pre-clinical drug discovery for multiple sclerosis (MS) is a labor intensive activity to perform in rodent models. This is owing to the long duration of disease induction and observation of treatment effects in an experimental autoimmune encephalomyelitis (EAE) model. We propose a novel adult zebrafish based model which offers a quick and simple protocol that can used to screen candidates as a step between in vitro experiments and rodent studies. The experiments conducted for this manuscript were to standardize a suitable model of EAE in adult zebrafish and validate it using known modulators...
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28103916/tim-1-defines-a-human-regulatory-b-cell-population-that-is-altered-in-frequency-and-function-in-systemic-sclerosis-patients
#18
Octavio Aravena, Ashley Ferrier, Madhvi Menon, Claudia Mauri, Juan Carlos Aguillón, Lilian Soto, Diego Catalán
BACKGROUND: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by excessive production of extracellular matrix by fibroblasts on skin and internal organs. Although Th2 cells have been involved in fibroblast stimulation, hyperactivated B cells may also play an important role. Regulatory B cells (Bregs) are cells capable of inhibiting inflammatory responses and controlling autoimmune diseases. Although many Breg populations have in common the ability to produce high amounts of IL-10, a unique surface marker defining most human Bregs is lacking...
January 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28103239/identifying-t-cell-receptors-from-high-throughput-sequencing-dealing-with-promiscuity-in-tcr%C3%AE-and-tcr%C3%AE-pairing
#19
Edward S Lee, Paul G Thomas, Jeff E Mold, Andrew J Yates
Characterisation of the T cell receptors (TCR) involved in immune responses is important for the design of vaccines and immunotherapies for cancer and autoimmune disease. The specificity of the interaction between the TCR heterodimer and its peptide-MHC ligand derives largely from the juxtaposed hypervariable CDR3 regions on the TCRα and TCRβ chains, and obtaining the paired sequences of these regions is a standard for functionally defining the TCR. A brute force approach to identifying the TCRs in a population of T cells is to use high-throughput single-cell sequencing, but currently this process remains costly and risks missing small clones...
January 19, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28102734/fibroblast-like-synoviocytes-dependent-effector-molecules-as-a-critical-mediator-for-rheumatoid-arthritis-current-status-and-future-directions
#20
Ramamoorthi Ganesan, Mahaboobkhan Rasool
Rheumatoid arthritis (RA) is a systemic-autoimmune-mediated disease characterized by synovial hyperplasia and progressive destruction of joint. Currently available biological agents and inhibitor therapy that specifically target tumor necrosis factor-α, interleukin 1β (IL-1β), IL-6, T cells, B cells, and subcellular molecules (p38 mitogen-activated protein kinase and janus kinase) cannot facilitate complete remission in all patients and are unable to cure the disease. Therefore, further potent therapeutic targets need to be identified for effective treatment and successful clinical outcomes in patients with RA...
January 19, 2017: International Reviews of Immunology
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