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Arthritis and gene therapy

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/29090217/systems-study-on-the-antirheumatic-mechanism-of-tibetan-medicated-bath-therapy-using-wuwei-ganlu-yaoyu-keli
#10
Tianhong Wang, Jian Yang, Xing Chen, Kehui Zhao, Jing Wang, Yi Zhang, Jing Zhao, Yang Ga
In clinical practice at Tibetan area of China, Traditional Tibetan Medicine formula Wuwei-Ganlu-Yaoyu-Keli (WGYK) is commonly added in warm water of bath therapy to treat rheumatoid arthritis (RA). However, its mechanism of action is not well interpreted yet. In this paper, we first verify WGYK's anti-RA effect by an animal experiment. Then, based on gene expression data from microarray experiments, we apply approaches of network pharmacology to further reveal the mechanism of action for WGYK to treat RA by analyzing protein-protein interactions and pathways...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29069507/blockade-of-gm-csf-pathway-induced-sustained-suppression-of-myeloid-and-t-cell-activities-in-rheumatoid-arthritis
#11
Xiang Guo, Brandon W Higgs, Anne-Christine Bay-Jensen, Yuling Wu, Morten A Karsdal, Michael Kuziora, Alex Godwood, David Close, Patricia C Ryan, Lorin K Roskos, Wendy I White
Objectives: Targeting the granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway holds great potential in the treatment of inflammatory diseases. Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody, has demonstrated clinical efficacy in RA. Our current study aimed to elucidate mechanisms of action and identify peripheral biomarkers associated with therapeutic responses of GM-CSF antagonism in RA. Methods: A 24-week placebo (PBO)-controlled trial was conducted in 305 RA patients who received mavrilimumab (30, 100 or 150 mg) or PBO once every 2 weeks...
October 23, 2017: Rheumatology
https://www.readbyqxmd.com/read/29045979/-changes-of-serum-krebs-von-den-lungen-6-levels-in-interstitial-lung-disease-associated-with-dermatomyositis-and-secondary-sj%C3%A3-gren-s-syndrome-a-case-report
#12
J F Yu, Y B Jin, J He, Y An, Z G Li
Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. The underlying pathogenesis of ILDs is complex and associated with multiple rheumatologic conditions, such as systemic sclerosis, rheumatoid arthritis, pollymyositis and dermatomyositis, Sjögren's syndrome, and systemic lupus erythematosus. As the disease progresses, excessive pulmonary fibrosis impairs alveolar gas exchange and damages pulmonary function...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/29041934/h-syndrome-5-new-cases-from-the-united-states-with-novel-features-and-responses-to-therapy
#13
Jessica L Bloom, Clara Lin, Lisa Imundo, Stephen Guthery, Shelly Stepenaskie, Csaba Galambos, Amy Lowichik, John F Bohnsack
BACKGROUND: H Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). Less than 100 patients with H syndrome have been described in the literature, with the majority being of Arab descent, and only a few from North America. CASE PRESENTATION: Here we report five pediatric patients from three medical centers in the United States who were identified to have H syndrome by whole exome sequencing...
October 17, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/29030294/type-i-interferon-pathway-activation-in-copa-syndrome
#14
Stefano Volpi, Jessica Tsui, Marcello Mariani, Claudia Pastorino, Roberta Caorsi, Oliviero Sacco, Angelo Ravelli, Anthony K Shum, Marco Gattorno, Paolo Picco
Mutations of the COPA gene cause an immune dysregulatory disease characterised by polyarticular arthritis and progressive interstitial lung disease with pulmonary haemorrhages. We report the case of a young girl that presented at age 3 with polyarticular arthritis, chronic cough and high titer rheumatoid factor. Radiologic imaging showed interstitial lung disease with tree-in-a-bud nodules and air-filled cysts. Targeted genetic analysis of COPA gene showed the reported c.698G>A mutation. The patient was lost to follow up for 3years during which therapy was discontinued with the development of joint damage and deformities...
October 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28987932/ethyl-pyruvate-ameliorates-inflammatory-arthritis-in-mice
#15
Seung Min Jung, Jaeseon Lee, Seung Ye Baek, Juhyun Lee, Se Gwang Jang, Seung-Min Hong, Jin-Sil Park, Mi-La Cho, Sung-Hwan Park, Seung-Ki Kwok
OBJECTIVES: Ethyl pyruvate (EP) is the ethyl ester of pyruvate and has antioxidative and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of EP in inflammatory arthritis and to identify the underlying mechanisms. METHODS: Mice with collagen-induced arthritis (CIA) were treated with the vehicle control or EP at 20mg/kg, and clinical and histological analyses were performed on the animals. The differentiation of murine CD4+ T cells into T helper 17 (Th17) cells in the presence of EP was investigated in vitro...
November 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28987811/the-interferon-gene-signature-is-increased-in-early-treatment-na%C3%A3-ve-rheumatoid-arthritis-and-predicts-a-poorer-response-to-initial-therapy
#16
Faye Ah Cooles, Amy E Anderson, Dennis W Lendrem, Julie Norris, Arthur G Pratt, Catharien Hilkens, John D Isaacs
The interferon gene signature in early, disease modifying drug naïve rheumatoid arthritis predicts clinical outcomes at 6 months after therapy initiation. We suggest type 1 interferons may be a future therapeutic target in early RA.
October 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28973003/salt-inducible-kinases-sik-inhibition-reduces-rankl-induced-osteoclastogenesis
#17
Maria Stella Lombardi, Corine Gilliéron, Majoska Berkelaar, Cem Gabay
Osteoclasts are large multinucleated cells responsible for bone resorption. Excessive inflammatory activation of osteoclasts leads to bony erosions, which are the hallmark of several diseases such as rheumatoid arthritis (RA). Salt-inducible kinases (SIK) constitute a subfamily of kinases comprising three members (SIK1, -2, and -3). Inhibition of SIK kinase activity induces an anti-inflammatory phenotype in macrophages. Since osteoclasts originate from precursors of macrophage origin, we hypothesized a role of SIK in osteoclastogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28959261/a-novel-approach-to-reinstating-tolerance-in-experimental-autoimmune-myasthenia-gravis-using-a-targeted-fusion-protein-mcta1-t146
#18
Alessandra Consonni, Sapna Sharma, Karin Schön, Cristina Lebrero-Fernández, Elena Rinaldi, Nils Yngve Lycke, Fulvio Baggi
Reinstating tissue-specific tolerance has attracted much attention as a means to treat autoimmune diseases. However, despite promising results in rodent models of autoimmune diseases, no established tolerogenic therapy is clinically available yet. In the experimental autoimmune myasthenia gravis (EAMG) model several protocols have been reported that induce tolerance against the prime disease-associated antigen, the acetylcholine receptor (AChR) at the neuromuscular junction. Using the whole AChR, the extracellular part or peptides derived from the receptor, investigators have reported variable success with their treatments, though, usually relatively large amounts of antigen has been required...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28918656/diagnosing-kingella-kingae-infections-in-infants-and-young-children
#19
Pablo Yagupsky
Kingella kingae is currently recognized as the prime etiology of skeletal system infections in children aged 6-48 months. The organism is notoriously fastidious, its growth is inhibited by synovial fluid and bone exudates, and its presence in clinical specimens is commonly missed by traditional culture methods. Areas covered: The present review discusses the use of improved laboratory methods to detect the organism in normally sterile body fluids, exudates, and upper respiratory tract specimens. Expert commentary: While inoculation of joint and bone exudates into blood culture vials dilutes the concentration of detrimental factors and significantly improves the isolation of the organism, novel PCR-based assays have enhanced sensitivity, shortened the time-to-detection of K...
October 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28887914/curcumin-attenuates-the-scurfy-induced-immune-disorder-a-model-of-ipex-syndrome-with-inhibiting-th1-th2-th17-responses-in-mice
#20
Gihyun Lee, Hwan-Suck Chung, Kyeseok Lee, Hyeonhoon Lee, Minhwan Kim, Hyunsu Bae
BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a lethal autoimmune disease caused by mutations in the Foxp3 gene scurfin (scurfy). Immunosuppressive therapy for IPEX patients has been generally ineffective and has caused severe side effects, however curcumin has shown immune regulation properties for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases without side effects. OBJECTIVE: The aim of this study was to investigate whether curcumin would attenuate symptoms of IPEX in mouse model and would prolong its survival period...
September 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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