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mimics rheumatoid arthritis

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https://www.readbyqxmd.com/read/28409894/genomic-responses-of-mouse-synovial-fibroblasts-during-tnf-driven-arthritogenesis-greatly-mimic-those-of-human-rheumatoid-arthritis
#1
Evangelos Ntougkos, Panagiotis Chouvardas, Fani Roumelioti, Caroline Ospelt, Mojka Frank-Bertoncelj, Andrew Filer, Christopher D Buckley, Steffen Gay, Christoforos Nikolaou, George Kollias
OBJECTIVE: Aberrant activation of synovial fibroblasts (SFs) is a key determinant in the pathogenesis of rheumatoid arthritis (RA). We aimed to produce a map of gene expression and epigenetic changes occurring in this cell type during disease progression in the human TNF-transgenic model of arthritis, and identify commonalities with human SFs. METHODS: We used deep sequencing to probe the transcriptome, the methylome and the chromatin landscape of cultured mouse arthritogenic SFs at three stages of disease, as well as SFs stimulated with human TNF...
April 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28408930/a-case-of-initially-undiagnosed-chikungunya-arthritis-developing-into-chronic-phase-in-a-nonendemic-area
#2
Pui Shan Julia Chan, Moon Ho Leung
This case report described a 40-year-old lady presented with fever, headache, arthralgia, myalgia, and impaired liver function after returning from the Philippines. Chikungunya virus (CHIKV) and dengue serology were negative. Eight weeks after initial presentation, she experienced inflammatory polyarthritis mimic rheumatoid arthritis. This time CHIKV-IgM was detected, together with a >4-fold rise of CHIKV-polyvalent-antibody titre. The first CHIKV-IgM negative sample was reexamined and was CHIKV-PCR positive...
2017: Case Reports in Medicine
https://www.readbyqxmd.com/read/28401267/paeonol-protects-against-tnf-%C3%AE-induced-proliferation-and-cytokine-release-of-rheumatoid-arthritis-fibroblast-like-synoviocytes-by-upregulating-foxo3-through-inhibition-of-mir-155-expression
#3
Ning Liu, Xue Feng, Wenbo Wang, Xingkai Zhao, Xia Li
BACKGROUND: Fibroblast-like synoviocytes (FLS) play an essential role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis. Paeonol (Pae) is a phenolic compound found in many traditional Chinese medicine remedies. However, the effects of Pae on TNF-α-stimulated FLS and the underlying molecular mechanism are unknown. In this study, we aimed to investigate the anti-proliferative and anti-inflammatory effect of Pae against activated FLS. MATERIALS AND METHODS: Rheumatoid arthritis FLS (RA-FLS) were pre-treated with different doses (25, 50, and 100 µM) of Pae or miR-155 inhibitor for 30 min or transfected with miR-155 mimic, and then treated with 50 ng/mL of tumor necrosis factor alpha (TNF-α) for 1 h...
April 11, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28382703/rationally-designed-ligand-independent-peptide-inhibitors-of-trem-1-ameliorate-collagen-induced-arthritis
#4
Zu T Shen, Alexander B Sigalov
Triggering receptor expressed on myeloid cells 1 (TREM-1) is critically involved in the pathogenesis of rheumatoid arthritis (RA). In contrast to cytokine blockers, therapeutic blockade of TREM-1 can blunt excessive inflammation while preserving the capacity for microbial control. However, the nature of the TREM-1 ligand(s) and mechanisms of TREM-1 signalling are still not yet well understood, impeding the development of clinically relevant inhibitors of TREM-1. The aim of this study was to evaluate the anti-arthritic activity of a novel, ligand-independent TREM-1 inhibitory nonapeptide GF9 that was rationally designed using the signalling chain homo oligomerization (SCHOOL) model of cell signalling...
April 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28376277/dendritic-cells-from-rheumatoid-arthritis-patient-peripheral-blood-induce-th17-cell-differentiation-via-mir-363-integrin-%C3%AE-v-tgf-%C3%AE-axis
#5
Feng Pan, Haiyan Xiang, Juzhen Yan, Liquan Hong, Lahong Zhang, Yuhua Liu, Xiao Feng, Chengsong Cai
BACKGROUND AND AIM: Dendritic cells (DCs) are critical regulators of immune responses. This study was to observe the effect of DCs from peripheral blood on the differentiation of Th17 in rheumatoid arthritis (RA) patients. METHODS AND RESULTS: Peripheral blood samples were collected from 30 RA patients and 20 healthy controls, respectively. Flow cytometry results showed that in contrast with Treg cells, the proportion of Th17 cells in T cells and the Th17/Treg ratio were both increased in RA patients...
April 4, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28338763/mesenchymal-stromal-cells-and-autoimmunity
#6
Vito Pistoia, Lizzia Raffaghello
Mesenchymal stromal cells (MSCs) are committed progenitors of mesodermal origin that are found virtually in every organ and exhibit multilineage differentiation into osteocytes, adipocytes and chondrocytes. MSCs also mediate a wide spectrum of immunoregulatory activities that usually dampen innate and adaptive immune responses. These features have attracted interest in the perspective of developing novel cell therapies for autoimmune disease. However, depending on the microenvironmental conditions, MSCs may show a plastic behavior and switch to an immunostimulatory phenotype...
February 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28261963/phosphoproteome-analysis-of-synoviocytes-from-patients-with-rheumatoid-arthritis
#7
Masayoshi Katano, Manae S Kurokawa, Kosuke Matsuo, Kayo Masuko, Naoya Suematsu, Kazuki Okamoto, Toshikazu Kamada, Hiroshi Nakamura, Tomohiro Kato
AIM: To explore disease-associated molecules in rheumatoid arthritis (RA), we comprehensively analyzed phosphoproteins purified from RA synoviocytes. METHOD: Synoviocytes were obtained from three patients with RA and three patients with osteoarthritis (OA). Profiles of phosphoproteins purified from the synoviocytes were compared by two-dimensional differential gel electrophoresis (2D-DIGE) between the RA and OA groups. Protein spots with significantly different phosphorylation levels were identified by mass spectrometry...
March 5, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28213049/impaired-nk-cell-functionality-and-increased-tnf-%C3%AE-production-as-biomarkers-of-chronic-chikungunya-arthritis-and-rheumatoid-arthritis
#8
Subrat Thanapati, Mohini Ganu, Prashant Giri, Shruti Kulkarni, Meenal Sharma, Prasad Babar, Ashok Ganu, Anuradha S Tripathy
The chronic chikungunya arthritis symptoms closely mimic the rheumatoid arthritis (RA) symptoms, thus making it difficult to distinguish between these two clinical entities. The current comparative study characterizes NK (CD3(-)CD56(+)) and NK-like T (CD3(+)CD56(+)) cell responses in patients with chronic chikungunya arthritis and RA. Phenotype and functions of NK and NK-like T cells repertoire were assessed in 56 chronic chikungunya arthritis, 26 RA patients and 82 controls using flow cytometry. TNF-α and IFN-γ-secreting NK-like T cells were high in both chronic arthritis patients than in controls...
April 2017: Human Immunology
https://www.readbyqxmd.com/read/28148840/therapy-with-ctla4-ig-and-an-antiviral-monoclonal-antibody-controls-chikungunya-virus-arthritis
#9
Jonathan J Miner, Lindsey E Cook, Jun P Hong, Amber M Smith, Justin M Richner, Raeann M Shimak, Alissa R Young, Kristen Monte, Subhajit Poddar, James E Crowe, Deborah J Lenschow, Michael S Diamond
In 2013, chikungunya virus (CHIKV) transmission was documented in the Western Hemisphere, and the virus has since spread throughout the Americas with more than 1.8 million people infected in more than 40 countries. CHIKV targets the joints, resulting in symmetric polyarthritis that clinically mimics rheumatoid arthritis and can endure for months to years. At present, no approved treatment is effective in preventing or controlling CHIKV infection or disease. We treated mice with eight different disease-modifying antirheumatic drugs and identified CLTA4-Ig (abatacept) and tofacitinib as candidate therapies based on their ability to decrease acute joint swelling...
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28129626/mir-650-inhibits-proliferation-migration-and-invasion-of-rheumatoid-arthritis-synovial-fibroblasts-by-targeting-akt2
#10
Xiaoyan Xu, Haiyan Chen, Qin Zhang, Jin Xu, Qing Shi, Meimei Wang
BACKGROUND AND OBJECTIVES: This study was aimed to investigate the effects of miR-650 on the proliferation, migration, invasion and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Synovial tissue samples were collected from 16 rheumatoid arthritis (RA) patients and 13 patients with joint trauma undergoing joint replacement surgery. The RASFs were isolated and cultured. MiR-650 and AKT2 expressions in both synovial tissues and cells were detected using the quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC)...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28120605/hemophagocytic-lymphohistiocytosis-mimics-many-common-conditions-case-series-and-review-of-literature
#11
A T Akenroye, N Madan, F Mohammadi, J Leider
Introduction. Hemophagocytic lymphohistiocytosis (HLH), a rare but potentially fatal disease, is characterized by excessive immune activation and cytokine release which stimulates bone marrow macrophages to engulf hematopoietic cells. HLH could be secondary to infections: viral, fungal, and bacterial; malignancies and autoimmune diseases. The diagnosis of HLH is usually delayed due to the presence of non-specific symptoms at presentation. This delay contributes to increased mortality. Cases and review. We present the case of 4 patients who presented with subjective fevers and extreme fatigue...
January 2017: European Annals of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28118944/microrna-155-contributes-to-enhanced-resistance-to-apoptosis-in-monocytes-from-patients-with-rheumatoid-arthritis
#12
Megha Rajasekhar, Anton M Olsson, Kathryn J A Steel, Mirella Georgouli, Ushan Ranasinghe, Christine Brender Read, Klaus S Frederiksen, Leonie S Taams
Monocytes and macrophages are key mediators of inflammation in rheumatoid arthritis (RA). Their persistence at the inflammatory site is likely to contribute to immunopathology. We sought to characterise one mechanism by which persistence may be achieved: resistance to apoptosis and the role of mir-155 in this process. CD14+ monocytes from peripheral blood (PBM) and synovial fluid (SFM) of RA patients were found to be resistant to spontaneous apoptosis relative to PBM from healthy control (HC) individuals. RA SFM were also resistant to anti-Fas-mediated apoptosis and displayed a gene expression profile distinct from HC and RA PBM populations...
January 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28098403/mir-338-5p-promotes-inflammatory-response-of-fibroblast-like-synoviocytes-in-rheumatoid-arthritis-via-targeting-spry1
#13
Yan Yang, Yanfeng Wang, Qingwei Liang, Lutian Yao, Shizhong Gu, Xizhuang Bai
Our purpose is to study the roles of microRNA-338-5p (miR-338-5p) on the proliferation, invasion and inflammatory response of fibroblast-like synoviocytes (SFs) in rheumatoid arthritis patients by regulating SPRY1. The target relationship between miR-338-5p and SPRY1 was validated through luciferase reporter system. The expression of miR-338-5p and SPRY1 in synovial tissues and synovial cells were detected using RT-PCR and western blot. The mimics and inhibitors of miR-338-5p were transfected into SFs. MTT, Transwell and ELISA assays were used to analyze cell proliferation, invasiveness and the secreted extracellular pro-inflammatory cytokines (such as IL-1a, IL-6, COX2) levels of SFs...
January 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28067317/glucose-6-phosphate-isomerase-g6pi-mediates-hypoxia-induced-angiogenesis-in-rheumatoid-arthritis
#14
Ying Lu, Shan-Shan Yu, Ming Zong, Sha-Sha Fan, Tian-Bao Lu, Ru-Han Gong, Li-Shan Sun, Lie-Ying Fan
The higher level of Glucose-6-phosphate isomerase (G6PI) has been found in both synovial tissue and synovial fluid of rheumatoid arthritis (RA) patients, while the function of G6PI in RA remains unclear. Herein we found the enrichment of G6PI in microvascular endothelial cells of synovial tissue in RA patients, where a 3% O2 hypoxia environment has been identified. In order to determine the correlation between the high G6PI level and the low oxygen concentration in RA, a hypoxia condition (~3% O2) in vitro was applied to mimic the RA environment in vivo...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27923216/efficacy-of-a-cellular-bone-allograft-for-foot-and-ankle-arthrodesis-and-revision-nonunion-procedures
#15
Travis J Dekker, Peter White, Samuel B Adams
BACKGROUND: Bone graft substitutes are often required in patients at risk for nonunion, and therefore, an allograft that most closely mimics an autograft is highly sought after. This study explored the utility and efficacy of a cellular bone allograft used for foot and ankle arthrodesis and revision nonunion procedures in a patient population at risk for nonunion. METHODS: An institutional review board-approved retrospective review of consecutive patients who underwent arthrodesis and revision nonunion procedures with a cellular bone allograft was performed at a single academic institution...
March 2017: Foot & Ankle International
https://www.readbyqxmd.com/read/27867381/a-critical-reappraisal-of-neutrophil-extracellular-traps-and-netosis-mimics-based-on-differential-requirements-for-protein-citrullination
#16
Maximilian F Konig, Felipe Andrade
NETosis, an antimicrobial form of neutrophil cell death, is considered a primary source of citrullinated autoantigens in rheumatoid arthritis (RA) and immunogenic DNA in systemic lupus erythematosus (SLE). Activation of the citrullinating enzyme peptidylarginine deiminase type 4 (PAD4) is believed to be essential for neutrophil extracellular trap (NET) formation and NETosis. PAD4 is therefore viewed as a promising therapeutic target to inhibit the formation of NETs in both diseases. In this review, we examine the evidence for PAD4 activation during NETosis and provide experimental data to suggest that protein citrullination is not a universal feature of NETs...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27864565/targeting-non-canonical-nuclear-factor-%C3%AE%C2%BAb-signalling-attenuates-neovascularization-in-a-novel-3d-model-of-rheumatoid-arthritis-synovial-angiogenesis
#17
Chrissta X Maracle, Paulina Kucharzewska, Boy Helder, Corine van der Horst, Pedro Correa de Sampaio, Ae-Ri Noort, Katinka van Zoest, Arjan W Griffioen, Henric Olsson, Sander W Tas
OBJECTIVE: Angiogenesis is crucial in RA disease progression. Lymphotoxin β receptor (LTβR)-induced activation of the non-canonical nuclear factor-κB (NF-κB) pathway via NF-κB-inducing kinase (NIK) has been implicated in this process. Consequently, inhibition of this pathway may hold therapeutic potential in RA. We describe a novel three-dimensional (3D) model of synovial angiogenesis incorporating endothelial cells (ECs), RA fibroblast-like synoviocytes (RAFLSs) and RA synovial fluid (RASF) to further investigate the contributions of NF-κB in this process...
November 17, 2016: Rheumatology
https://www.readbyqxmd.com/read/27824550/chikungunya-virus-infection-an-update-on-joint-manifestations-and-management
#18
REVIEW
Maria Krutikov, Jessica Manson
The advent of sophisticated diagnostics has enabled the discovery of previously unknown arthropod-borne viruses like Chikungunya. This infection has become increasingly prevalent in the last 10 years across the Indian Ocean and has been brought to media attention by a recent outbreak in the Caribbean. The outbreak has been aided by a drastic rise in air travel, allowing infected individuals to transport the virus to previously unaffected regions. In addition, a recently documented viral mutation has allowed its transmission by the Aedes albopictus mosquito, therefore facilitating outbreaks in Southern Europe and the USA...
October 31, 2016: Rambam Maimonides Medical Journal
https://www.readbyqxmd.com/read/27711748/solution-equilibria-and-the-x-ray-structure-of-cu-ii-complexation-with-3-amino-n-pyridin-2-ylmethyl-propanamide-a-pseudo-mimic-of-human-serum-albumin
#19
Graham E Jackson, Fatin M Elmagbari, Ahmed N Hammouda, Raffaele P Bonomo
Copper complexes have anti-inflammatory activity in the treatment of inflammation associated with rheumatoid arthritis (RA). The preferred route of administration is through the skin, so the rate of dermal absorption and bioavailability of copper is important. Based on previous studies, 3-amino-N-(pyridin-2-ylmethyl)-propanamide, [H(56)NH2], was designed as a potential chelator of copper. The stability constant measurements revealed that MLH-1 is the most stable species at the physiological pH of 7.4. The X-ray crystal structure of this species was solved and copper was found in a rectangular pyramidal geometry...
October 4, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27621203/modeling-therapeutic-antibody-small-molecule-drug-drug-interactions-using-a-three-dimensional-perfusable-human-liver-coculture-platform
#20
Thomas J Long, Patrick A Cosgrove, Robert T Dunn, Donna B Stolz, Hisham Hamadeh, Cynthia Afshari, Helen McBride, Linda G Griffith
Traditional in vitro human liver cell culture models lose key hepatic functions such as metabolic activity during short-term culture. Advanced three-dimensional (3D) liver coculture platforms offer the potential for extended hepatocyte functionality and allow for the study of more complex biologic interactions, which can improve and refine human drug safety evaluations. Here, we use a perfusion flow 3D microreactor platform for the coculture of cryopreserved primary human hepatocytes and Kupffer cells to study the regulation of cytochrome P450 3A4 isoform (CYP3A4) activity by chronic interleukin 6 (IL-6)-mediated inflammation over 2 weeks...
December 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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