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Arthritis and gene therapy

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https://www.readbyqxmd.com/read/29434816/effectiveness-of-lentivirus-mediated-rna-interference-targeting-mouse-tumor-necrosis-factor-%C3%AE-in-vitro-and-in-vivo
#1
Jibo Wang, Yingjie Zhao, Miaomiao Xin, Lin Pan, Liqin Wang, Kun Yang
The aim of the present study was to identify the effectiveness of lentivirus-mediated RNA interference (RNAi) targeting mouse tumor necrosis factor-α (TNF-α). RNAi lentivirus was used in vitro to transfect RAW264.7 cells, and the expression of TNF-α, interleukin (IL)-1β and IL-6 mRNAs and TNF-α protein in RAW264.7 cells was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay, respectively. In vivo, mice with collagen-induced arthritis (CIA) were injected intravenously with RNAi lentivirus, and CIA arthritis scores and the serum levels of TNF-α were detected...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29426578/tgf-%C3%AE-signalling-defect-is-linked-to-low-cd39-expression-on-regulatory-t-cells-and-methotrexate-resistance-in-rheumatoid-arthritis
#2
Raphael S Peres, Paula B Donate, Jhimmy Talbot, Nerry T Cecilio, Patricia R Lobo, Caio C Machado, Kalil W A Lima, Rene D Oliveira, Vanessa Carregaro, Helder I Nakaya, Thiago M Cunha, José Carlos Alves-Filho, Foo Y Liew, Paulo Louzada-Junior, Fernando Q Cunha
Rheumatoid arthritis (RA) is an autoimmune arthropathy characterized by chronic articular inflammation. Methotrexate (MTX) remains the first-line therapy for RA and its anti-inflammatory effect is associated with the maintenance of high levels of extracellular adenosine (ADO). Nonetheless, up to 40% of RA patients are resistant to MTX treatment and this is linked to a reduction of CD39 expression, an ectoenzyme involved in the generation of extracellular ADO by ATP metabolism, on circulating regulatory T cells (Tregs)...
February 6, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29408488/regulation-and-function-of-apoptosis-signal-regulating-kinase-1-ask1-in-rheumatoid-arthritis
#3
Gyrid Nygaard, Julie A Di Paolo, Deepa Hammaker, David L Boyle, Grant Budas, Gregory T Notte, Igor Mikaelian, Vivian Barry, Gary S Firestein
Despite improved therapy, rheumatoid arthritis (RA) remains an unmet medical need. Previous efforts to validate therapeutic targets in the mitogen-activated protein kinase (MAPK) family have had minimal success. Therefore, we evaluated the potential for targeting an upstream MAPK, namely apoptosis signal-regulating kinase 1 (ASK1), as an alternative approach. ASK1 protein and gene expression were observed in RA and osteoarthritis (OA) synovium as determined by immunohistochemistry (IHC) and qPCR, respectively, particularly in the synovial intimal lining...
February 2, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29401724/emerging-roles-of-tumor-necrosis-factor-stimulated-gene-6-in-the-pathophysiology-and-treatment-of-atherosclerosis
#4
REVIEW
Rena Watanabe, Yuki Sato, Nana Ozawa, Yui Takahashi, Shinji Koba, Takuya Watanabe
Tumor necrosis factor-stimulated gene-6 (TSG-6) is a 35-kDa glycoprotein that has been shown to exert anti-inflammatory effects in experimental models of arthritis, acute myocardial infarction, and acute cerebral infarction. Several lines of evidence have shed light on the pathophysiological roles of TSG-6 in atherosclerosis. TSG-6 suppresses inflammatory responses of endothelial cells, neutrophils, and macrophages as well as macrophage foam cell formation and vascular smooth muscle cell (VSMC) migration and proliferation...
February 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29370129/influence-of-nkg2d-genetic-variants-on-response-to-anti-tnf-agents-in-patients-with-rheumatoid-arthritis
#5
Milena Iwaszko, Jerzy Świerkot, Katarzyna Kolossa, Sławomir Jeka, Piotr Wiland, Katarzyna Bogunia-Kubik
A natural killer group 2 member D (NKG2D) acts as a powerful activating and co-stimulatory receptor on immune effector cells including NK and T cells. Disruptions within the NKG2D signalling pathway may trigger an exacerbated immune response and promote autoimmune reactions. The objective of the study was to evaluate a plausible role of polymorphisms within the NKG2D gene as a predictor of how effective anti-tumor necrosis factor (TNF) therapy is in rheumatoid arthritis (RA) patients. A total of 280 RA patients receiving anti-TNF therapy were genotyped for NKG2D rs2255336 (A > G), rs1049174 (C > G), and rs1154831 (C > A)...
January 25, 2018: Genes
https://www.readbyqxmd.com/read/29328507/genetics-of-immune-mediated-inflammatory-diseases
#6
REVIEW
Trixy David, Stephanie Ling, Anne Barton
Immune-mediated inflammatory diseases (IMIDs) are characterised by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged...
January 12, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29318966/chronic-inflammatory-diseases-and-atherosclerotic-cardiovascular-disease-innocent-bystanders-or-partners-in-crime
#7
Peter Riis Hansen
Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research...
January 9, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29303924/arthritis-gene-therapy-approved-in-korea
#8
Christopher H Evans, Steven C Ghivizzani, Paul D Robbins
No abstract text is available yet for this article.
January 15, 2018: Journal of the American Academy of Orthopaedic Surgeons
https://www.readbyqxmd.com/read/29285715/gene-mutations-and-clinical-phenotypes-in-15-chinese-children-with-cryopyrin-associated-periodic-syndrome-caps
#9
Caifeng Li, Xiaohua Tan, Junmei Zhang, Shipeng Li, Wenxiu Mo, Tongxin Han, Weiying Kuang, Yifang Zhou, Jianghong Deng
The aim of our study is to explore the features of clinical manifestations and genetic mutations in Chinese CAPS patients. Fifteen confirmed patients with CAPS were enrolled. The onset time ranges from 2 days after birth to 6 years and 1 month. Recurrent urticaria rash (93.3%) with fever (100%) were two dominant characteristics of these patients that were presented as either acute or chronic process. Systemic involvements were found in all patients except for one with only rash and fever. The top three symptoms were fever (100%), rash (93...
December 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29274317/saikosaponin-a-inhibits-compound-48-80-induced-pseudo-allergy-via-the-mrgprx2-pathway-in-vitro-and-in-vivo
#10
Nan Wang, Delu Che, Tao Zhang, Rui Liu, Jiao Cao, Jue Wang, Tingting Zhao, Pengyu Ma, Xinzhong Dong, Langchong He
Pseudo-allergic reactions-adverse, non-immunologic, anaphylaxis-like sudden onset reactions mediated through an IgE-independent pathway-are activated by various basic compounds and occur at least as frequently as IgE-mediated reactions to drugs. A large family of G protein coupled receptors (Mas-related genes; Mrgprs) is closely related to pseudo-allergies. However, few therapies can directly target pseudo-allergies and related Mrgprs. Saikosaponin A (SSA) is effective in the treatment of passive cutaneous anaphylaxis (PCA), adjuvant arthritis, and delayed hypersensitiveness...
February 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29250041/stenotrophomonas-maltophilia-as-an-emerging-ubiquitous-pathogen-looking-beyond-contemporary-antibiotic-therapy
#11
REVIEW
Anthony A Adegoke, Thor A Stenström, Anthony I Okoh
Stenotrophomonas maltophilia is a commensal and an emerging pathogen earlier noted in broad-spectrum life threatening infections among the vulnerable, but more recently as a pathogen in immunocompetent individuals. The bacteria are consistently being implicated in necrotizing otitis, cutaneous infections including soft tissue infection and keratitis, endocarditis, meningitis, acute respiratory tract infection (RTI), bacteraemia (with/without hematological malignancies), tropical pyomyositis, cystic fibrosis, septic arthritis, among others...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29198077/fibroblast-like-synoviocyte-migration-is-enhanced-by-il-17-mediated-overexpression-of-l-type-amino-acid-transporter-1-lat1-via-the-mtor-4e-bp1-pathway
#12
Zhao Yu, Wang Lin, Zhang Rui, Pan Jihong
In rheumatoid arthritis (RA), activated synovial fibroblasts have the ability to invade joint cartilage, actively contributing to joint destruction in RA. The mechanisms underlying this cell migration and invasion remain unclear. Our previous results and data from the GEO profile indicate that the L-type amino acid transporter gene, LAT1, is overexpressed in the synovium of RA. To identify its potential role in RA, fibroblast-like synoviocytes (FLS) from patients with RA were used to determine the effects of suppressing the LAT1 genes using RNA interference and the LAT inhibitor, BCH...
December 2, 2017: Amino Acids
https://www.readbyqxmd.com/read/29194108/epigenetics-of-inflammatory-arthritis
#13
Deepa Hammaker, Gary S Firestein
PURPOSE OF REVIEW: Aberrant epigenetic changes in DNA methylation, histone marks, and noncoding RNA expression regulate the pathogenesis of many rheumatic diseases. The present article will review the recent advances in the epigenetic profile of inflammatory arthritis and discuss diagnostic biomarkers and potential therapeutic targets. RECENT FINDINGS: Methylation signatures of fibroblast-like synoviocytes not only distinguish rheumatoid arthritis (RA) and osteoarthritis (OA), but also early RAs from late RAs or juvenile idiopathic arthritis...
November 30, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/29177079/effect-of-fc%C3%AE-receptor-3a-fcgr3a-gene-polymorphisms-on-rituximab-therapy-in-hungarian-patients-with-rheumatoid-arthritis
#14
Ildikó Pál, Szilvia Szamosi, Katalin Hodosi, Zoltan Szekanecz, László Váróczy
Background: Rheumatoid arthritis (RA) treatment includes the use of the anti-CD20 monoclonal antibody rituximab (RTX). RTX acts through Fcγ-receptors (FCGR) on effector natural killer cells and macrophages and it can be administered effectively in RA and in lymphomas. Based on the results of in vitro experiments, its efficacy may depend of FCGR gene polymorphisms in both diseases. Aim: As genetic background of diseases and therapeutic efficacy (pharmacogenetics) may vary among different geographical regions, we wished to assess possible relationships between FCGR3A polymorphism and the therapeutic outcome of RTX therapy in a Hungarian RA cohort...
2017: RMD Open
https://www.readbyqxmd.com/read/29166574/altered-tnf-%C3%AE-response-by-aconibal-%C3%A2-and-methotrexate-in-a-lipopolysaccharide-induced-setting-of-inflammatory-conditions-potential-on-a-synergistic-combination
#15
Gunhyuk Park, Seoung Hoon Lee, Ji-Ye Han, Dal-Seok Oh
ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii (AC) is a common herbal medicine used as anti-inflammatory and analgesic agent in Eastern Asia. In Korea, a commercial processed AC (Aconibal(®)) is traditionally used to treat the symptoms of spondylosis deformans and rheumatic pain. AIM OF STUDY: Rheumatoid arthritis (RA) is systemic and auto-immune disease characterized by chronic inflammation. Methotrexate (MTX) is often the first-line therapy for RA. If MTX monotherapy is ineffective or RA is initially severe, adding a tumor necrosis factor (TNF)-α inhibitor to the treatment can be beneficial...
November 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29160173/gene-delivery-to-joints-by-intra-articular-injection
#16
Christopher H Evans, Steven Craig Ghivizzani, Paul D Robbins
Most forms of arthritis are incurable, difficult to treat and a major cause of disability in western countries. Better local treatment of arthritis is impaired by the pharmacokinetics of the joint that make it very difficult to deliver drugs to joints at sustained, therapeutic concentrations. This is especially true of biologic drugs, such as proteins and RNA, many of which show great promise in pre-clinical studies. Gene transfer provides a strategy for overcoming this limitation. The basic concept is to deliver cDNAs encoding therapeutic products by direct intra-articular injection, leading to sustained, endogenous synthesis of the gene products within the joint...
November 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29159853/the-use-of-cell-conditioned-medium-for-musculoskeletal-tissue-regeneration
#17
REVIEW
Francesca Veronesi, Veronica Borsari, Maria Sartori, Monia Orciani, Monica Mattioli-Belmonte Cima, Milena Fini
Tissue regenerative medicine combines the use of cells, scaffolds and molecules to repair damaged tissues. Different cell types are employed for musculoskeletal diseases, both differentiated and mesenchymal stromal cells (MSCs). In recent years, the hypothesis that cell-based therapy is guided principally by cell-secreted factors has become increasingly popular. The aim of the present literature review was to evaluate preclinical and clinical studies that used conditioned medium (CM), rich in cell-factors, for musculoskeletal regeneration with a cell-free approach...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29158815/tethering-interleukin-22-to-apolipoprotein-a-i-ameliorates-mice-from-acetaminophen-induced-liver-injury
#18
Wei Chen, Xuyao Zhang, Jiajun Fan, Wenjing Zai, Jingyun Luan, Yubin Li, Shaofei Wang, Qicheng Chen, Yichen Wang, Yanxu Liang, Dianwen Ju
Increasing evidence indicates that interleukin-22 (IL-22) holds tremendous potential as a protective agent in preventing liver injury, but its pleiotropic effects and pathogenic role in carcinogenesis, rheumatoid arthritis and psoriasis restrict its systemic application. Here, we first developed a nanoparticle (liposIA) as a liver-targeted agent through IL-22 tethered to apolipoprotein A-I (ApoA-I) in a gene therapy vector. LiposIA was prepared using thin film dispersion method and the complexes exhibited desirable nanoparticle size, fine polydisperse index, highly efficient transfection, and excellent serum and storage stability...
2017: Theranostics
https://www.readbyqxmd.com/read/29143979/analysis-of-anti-tnf-induced-skin-lesions-reveals-strong-th1-activation-with-some-distinct-immunological-characteristics
#19
E Stoffel, H Maier, E Riedl, M-C Brüggen, B Reininger, M Schaschinger, C Bangert, E Guenova, G Stingl, P M Brunner
BACKGROUND: Psoriasiform and eczematous eruptions are the most common dermatological adverse reaction linked to anti-TNF-α therapy. Yet, a detailed characterization of their immune phenotype is lacking. OBJECTIVES: We sought to characterize anti-TNF-α induced inflammatory skin lesions on a histopathologic, cellular and molecular level, compared to psoriasis, eczema (atopic dermatitis), and healthy control skin. METHODS: Histopathologic evaluation, gene expression (quantitative RT-PCR) and computer-assisted immunohistologic studies (TissueFAXS) were performed on 19 skin biopsies from IBD (n=17) and rheumatoid arthritis (n=2) patients with new-onset inflammatory skin lesions during anti-TNF-α-therapy...
November 16, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29137139/deduction-of-novel-genes-potentially-involved-in-osteoblasts-of-rheumatoid-arthritis-using-next-generation-sequencing-and-bioinformatic-approaches
#20
Yi-Jen Chen, Wei-An Chang, Ya-Ling Hsu, Chia-Hsin Chen, Po-Lin Kuo
The role of osteoblasts in peri-articular bone loss and bone erosion in rheumatoid arthritis (RA) has gained much attention, and microRNAs are hypothesized to play critical roles in the regulation of osteoblast function in RA. The aim of this study is to explore novel microRNAs differentially expressed in RA osteoblasts and to identify genes potentially involved in the dysregulated bone homeostasis in RA. RNAs were extracted from cultured normal and RA osteoblasts for sequencing. Using the next generation sequencing and bioinformatics approaches, we identified 35 differentially expressed microRNAs and 13 differentially expressed genes with potential microRNA-mRNA interactions in RA osteoblasts...
November 11, 2017: International Journal of Molecular Sciences
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