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Arthritis and gene therapy

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https://www.readbyqxmd.com/read/29881347/a-novel-circulating-mirna-based-model-predicts-the-response-to-tripterysium-glycosides-tablets-moving-toward-model-based-precision-medicine-in-rheumatoid-arthritis
#1
Yanqiong Zhang, Hailong Wang, Xia Mao, Qiuyan Guo, Weijie Li, Xiaoyue Wang, Guangyao Li, Quan Jiang, Na Lin
Accumulating clinical evidence show that not all rheumatoid arthritis (RA) patients benefit to the same extent from a Tripterygium wilfordii Hook F (TwHF)-based therapy-Tripterysium glycosides tablets (TG tablets), which emphasizes the need of predictive biomarkers and tools for drug response. Herein, we integrated TG tablets' response-related miRNA and mRNA expression profiles obtained from the clinical cohort-based microarray, miRNA target prediction, miRNA-target gene coexpression, as well as gene-gene interactions, to identify four candidate circulating miRNA biomarkers that were predictive of response to TG tablets...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29880011/il-17a-induces-osteoblast-differentiation-by-activating-jak2-stat3-in-ankylosing-spondylitis
#2
Sungsin Jo, Sung Eun Wang, Young Lim Lee, Suman Kang, Bitnara Lee, Jinil Han, Il-Hoon Sung, Ye-Soo Park, Sang-Cheol Bae, Tae-Hwan Kim
BACKGROUND: IL-17A has recently emerged as a potential target that regulates the extensive inflammation and abnormal bone formation observed in ankylosing spondylitis (AS). Blocking IL-17A is expected to inhibit bony ankylosis. Here, we investigated the effects of anti IL-17A agents in AS. METHODS: TNFα, IL-17A, and IL-12/23 p40 levels in serum and synovial fluid from patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), osteoarthritis (OA), or healthy controls (HC) were measured by ELISA...
June 7, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29868252/treatment-of-collagenase-induced-osteoarthritis-with-a-viral-vector-encoding-tsg-6-results-in-ectopic-bone-formation
#3
Mathijs G A Broeren, Irene Di Ceglie, Miranda B Bennink, Peter L E M van Lent, Wim B van den Berg, Marije I Koenders, Esmeralda N Blaney Davidson, Peter M van der Kraan, Fons A J van de Loo
Objective: Tumor necrosis factor-inducible gene 6 (TSG-6) has anti-inflammatory and chondroprotective effects in mouse models of inflammatory arthritis. Because cartilage damage and inflammation are also observed in osteoarthritis (OA), we determined the effect of viral overexpression of TSG-6 in experimental osteoarthritis. Methods: Bone marrow-derived cells were differentiated to multinucleated osteoclasts in the presence of recombinant TSG-6 or after transduction with a lentiviral TSG-6 expression vector...
2018: PeerJ
https://www.readbyqxmd.com/read/29867920/phenotypic-and-transcriptomic-analysis-of-peripheral-blood-plasmacytoid-and-conventional-dendritic-cells-in-early-drug-na%C3%A3-ve-rheumatoid-arthritis
#4
Faye A H Cooles, Amy E Anderson, Andrew Skelton, Arthur G Pratt, Mariola S Kurowska-Stolarska, Iain McInnes, Catharien M U Hilkens, John D Isaacs
Objective: Dendritic cells (DCs) are key orchestrators of immune function. To date, rheumatoid arthritis (RA) researchers have predominantly focused on a potential pathogenic role for CD1c+ DCs. In contrast, CD141+ DCs and plasmacytoid DCs (pDCs) have not been systematically examined, at least in early RA. In established RA, the role of pDCs is ambiguous and, since disease duration and treatment both impact RA pathophysiology, we examined pDCs, and CD1c+ and CD141+ conventional DCs (cDCs), in early, drug-naïve RA (eRA) patients...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29808722/rna-sequencing-to-predict-response-to-tnf-%C3%AE-inhibitors-reveals-possible-mechanism-for-non-response-in-smokers
#5
Bart V J Cuppen, Marzia Rossato, Ruth D E Fritsch-Stork, Arno N Concepcion, Suzanne P Linn-Rasker, Johannes W J Bijlsma, Jacob M van Laar, Floris P J G Lafeber, Timothy R Radstake
BACKGROUND: Several studies have employed microarray-based profiling to predict response to tumor necrosis factor-alpha inhibitors (TNFi) in rheumatoid arthritis (RA); yet efforts to validate these targets have failed to show predictive abilities acceptable for clinical practice. METHODS: The eighty most extreme responders and non-responders to TNFi therapy were selected from the observational BiOCURA cohort. RNA-sequencing was performed on mRNA from peripheral blood mononuclear cells (PBMCs) collected before initiation of treatment...
May 29, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29806111/what-s-new-in-psoriasis-treatment-an-analysis-of-systematic-reviews-published-in-2015
#6
REVIEW
A C Foulkes, F Ferguson, D J C Grindlay, H C Williams, C E M Griffiths, R B Warren
This review provides a summary of key findings from 27 systematic reviews of 51 articles first published or indexed during 2015, focusing on the treatment of psoriasis and on precision medicine in psoriasis. The evidence supports weight-loss interventions by dieting and exercise for improvement in disease severity in overweight and obese patients with psoriasis. No significant increased risk of serious infections was reported for the biologic therapies adalimumab, etanercept and ustekinumab compared with appropriate comparators...
May 27, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29773851/modeling-transcriptional-rewiring-in-neutrophils-through-the-course-of-treated-juvenile-idiopathic-arthritis
#7
Zihua Hu, Kaiyu Jiang, Mark Barton Frank, Yanmin Chen, James N Jarvis
Neutrophils in children with the polyarticular form of juvenile idiopathic arthritis (JIA) display abnormal transcriptional patterns linked to fundamental metabolic derangements. In this study, we sought to determine the effects of therapy on mRNA and miRNA expression networks in polyarticular JIA. Using exon and miRNA microarrays, we studied children with untreated active JIA (ADU, n = 35), children with active disease on therapy with methotrexate ± etanercept (ADT, n = 26), and children with inactive disease also on therapy (ID, n = 14)...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29743627/arthritis-gene-therapy-is-becoming-a-reality
#8
Christopher H Evans, Steven C Ghivizzani, Paul D Robbins
No abstract text is available yet for this article.
May 9, 2018: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/29667551/circulating-mir-10a-as-predictor-of-therapy-response-in-rheumatoid-arthritis-patients-treated-with-methotrexate
#9
Honghai Hong, Haihui Yang, Yong Xia
BACKGROUND: Anti-inflammatory drugs and DMARDs, especially methotrexate, have dramatically improved the outlook of RA patient. However, in some patients the treatment effect is still not satisfactory and needs to change therapeutic regimen in time. So, prediction of patient treatment effect timely is particularly important. METHODS: miRNAs are a large family of highly conserved noncoding genes and some of them become potential biomarker of disease diagnosis. In present study, we found circulating miR-10a was significantly decreased in RA patients compared to osteoarthritic patients and healthy people...
April 17, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29661045/recent-approaches-for-targeted-drug-delivery-in-rheumatoid-arthritis-diagnosis-and-treatment
#10
Sana Pirmardvand Chegini, Jaleh Varshosaz, Somayeh Taymouri
Rheumatoid arthritis (RA) is a chronic inflammatory disease with complex pathology characterized by inflammation of joints, devastation of the synovium, pannus formation, bones and cartilage destruction and often is associated with persistent arthritic pain, swelling, stiffness and work disability. In conventional RA therapy, because of short biological half-life, poor bioavailability, high and frequent dosing is required. Thereby, these anti-RA medications, which unable to selectively target affected zone, may cause severe side effects in extra-articular tissues...
April 16, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29643425/a-novel-two-score-system-for-interferon-status-segregates-autoimmune-diseases-and-correlates-with-clinical-features
#11
Y M El-Sherbiny, A Psarras, M Y Md Yusof, E M A Hensor, R Tooze, G Doody, A A A Mohamed, D McGonagle, M Wittmann, P Emery, E M Vital
Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity of the ISG transcriptome, cell-specific expression, response to IFN-subtypes and bimodality of expression. We developed and clinically validated a 2-score system (IFN-Score-A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN-annotated modules. We evaluated these scores using in-vitro IFN stimulation as well as in sorted cells then clinically validated in a cohort of 328 autoimmune disease patients and healthy controls...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29628928/impaired-cd27-igd-b-cells-with-altered-gene-signature-in-rheumatoid-arthritis
#12
Fanlei Hu, Wei Zhang, Lianjie Shi, Xu Liu, Yuan Jia, Liling Xu, Huaqun Zhu, Yingni Li, Dakang Xu, Liwei Lu, Xiaoyan Qiu, Wanli Liu, Junjie Qiao, Yongfu Wang, Zhanguo Li
Natural antibodies, particularly natural IgM, are proved to play indispensable roles in the immune defenses against common infections. More recently, the protective roles of these natural IgM were also recognized in autoimmune diseases. They are mainly produced by B-1 and innate-like B cells (ILBs). Human CD19+ CD27+ IgD+ B cells, also termed as un-switched memory B cells, were proposed to be a kind of ILBs. However, functional features and characteristics of these cells in rheumatoid arthritis (RA) remained poorly understood...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29625332/intra-articular-drug-delivery-systems-for-joint-diseases
#13
REVIEW
Muhammad Farooq Rai, Christine Tn Pham
Intra-articular (IA) injections directly deliver high concentrations of therapeutics to the joint space and are routinely used in various musculoskeletal conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, current IA-injected drugs are rapidly cleared and do not significantly affect the course of joint disease. In this review, we highlight recent developments in IA therapy, with a special emphasis on current and emerging therapeutic carriers and their potential to deliver disease-modifying treatment modalities for arthritis...
April 3, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29622035/ccl17-blockade-as-a-therapy-for-osteoarthritis-pain-and-disease
#14
Ming-Chin Lee, Reem Saleh, Adrian Achuthan, Andrew J Fleetwood, Irmgard Förster, John A Hamilton, Andrew D Cook
BACKGROUND: Granulocyte macrophage-colony stimulating factor (GM-CSF) has been implicated in the pathogenesis of a number of inflammatory diseases and in osteoarthritis (OA). We identified previously a new GM-CSF→Jmjd3→interferon regulatory factor 4 (IRF4)→chemokine (c-c motif) ligand 17 (CCL17) pathway, which is important for the development of inflammatory arthritis pain and disease. Tumour necrosis factor (TNF) can also be linked with this pathway. Here we investigated the involvement of the pathway in OA pain and disease development using the GM-CSF-dependent collagenase-induced OA (CiOA) model...
April 5, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29620718/kingella-kingae-as-the-main-cause-of-septic-arthritis-importance-of-molecular-diagnosis
#15
María Belén Hernández-Rupérez, María Del Carmen Suárez-Arrabal, Ángel Villa-García, Sara Zarzoso-Fernández, Marisa Navarro-Gómez, Mar Santos-Sebastián, Azucena García-Martín, Mercedes Marín, Felipe González-Martínez, Javier Narbona-Cárceles, Paloma Cervera-Bravo, José Luis González-López, Teresa Hernández-Sampelayo, Jesús Saavedra-Lozano
BACKGROUND: Kingella kingae is an emergent pathogen causing septic arthritis (SA) in children. OBJECTIVES: To analyze the etiology of SA in children before and after the implementation of universal 16S rRNA gene polymerase chain reaction and sequencing (16SPCR) in synovial fluid. METHODS: Children ≤ 14 years with acute SA from a Madrid cohort (2002-2013), were reviewed. Differences in etiology were analyzed before (Period 1) and after (Period 2) the implementation of bacterial 16SPCR in 2009...
March 31, 2018: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29616452/flavonoid-quercetin-methotrexate-combination-inhibits-inflammatory-mediators-and-matrix-metalloproteinase-expression-providing-protection-to-joints-in-collagen-induced-arthritis
#16
Nagaraja Haleagrahara, Kelly Hodgson, Socorro Miranda-Hernandez, Samuel Hughes, Anupama Bangra Kulur, Natkunam Ketheesan
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial tissues in joints, leading to progressive destruction of cartilage and joints. The disease-modifying anti-rheumatic drugs currently in use have side-effects. Thus, there is an urgent need for safe anti-inflammatory therapies for RA. This study aimed to evaluate the therapeutic effect of the flavonoid quercetin on arthritis in mice immunized with type II collagen (CII). An arthritis model was established in C57/BL6 mice by intradermal administration of chicken CII mixed with Freund's complete adjuvant...
April 3, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29609200/il1rn-variation-influences-both-disease-susceptibility-and-response-to-human-recombinant-il-1ra-therapy-in-systemic-juvenile-idiopathic-arthritis
#17
Victoria L Arthur, Emily Shuldiner, Elaine F Remmers, Anne Hinks, Alexei A Grom, Dirk Foell, Alberto Martini, Marco Gattorno, Seza Özen, Sampath Prahalad, Andrew S Zeft, John F Bohnsack, Norman T Ilowite, Elizabeth D Mellins, Ricardo Russo, Claudio Len, Sheila Oliveira, Rae S M Yeung, Alan M Rosenberg, Lucy R Wedderburn, Jordi Anton, Johannes-Peter Haas, Angela Rösen-Wolff, Kirsten Minden, Ann Marie Szymanski, Wendy Thomson, Daniel L Kastner, Patricia Woo, Michael J Ombrello
OBJECTIVE: To determine whether systemic juvenile idiopathic arthritis (sJIA) susceptibility loci identified by candidate gene studies demonstrated association with sJIA in the largest study population assembled to date. METHODS: Single nucleotide polymorphisms (SNPs) from 11 previously reported sJIA risk loci were examined for association in 9 populations, including 770 sJIA cases and 6947 control subjects. The effect of sJIA-associated SNPs on gene expression was evaluated in silico in paired whole genome and RNA sequencing data from lymphoblastoid cell lines (LCL) of 373 European 1000 Genomes Project subjects...
April 2, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29589441/marbostat-100-defines-a-new-class-of-potent-and-selective-antiinflammatory-and-antirheumatic-histone-deacetylase-6-inhibitors
#18
Andreas Sellmer, Hubert Stangl, Mandy Beyer, Elisabeth Grünstein, Michel Leonhardt, Herwig Pongratz, Emerich Eichhorn, Sigurd Elz, Birgit Striegl, Zsuzsa Jenei-Lanzl, Stefan Dove, Rainer H Straub, Oliver H Krämer, Siavosh Mahboobi
Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+ -dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects...
April 26, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29579081/genetics-in-tnf-tnfr-pathway-a-complex-network-causing-spondyloarthritis-and-conditioning-response-to-anti-tnf%C3%AE-therapy
#19
Ada Aita, Daniela Basso, Roberta Ramonda, Stefania Moz, Mariagrazia Lorenzin, Filippo Navaglia, Carlo-Federico Zambon, Andrea Padoan, Mario Plebani, Leonardo Punzi
OBJECTIVES: We investigated whether polymorphisms (SNPs) in the promoter region of TNFA, or in the autoinflammatory TNFRSF1A and MEFV genes, concur with HLA-B27 in enhancing the risk of Spondyloarthritis (SpA) and/or in predicting the response to anti-TNFα treatment. METHODS: 373 controls and 137 SpA (82 with Psoriatic Arthritis-PsA and 55 with Ankylosing Spondylitis- AS; 98/137 under TNFα inhibitor therapy) from the Veneto Region (Italy) were studied. TNFA polymorphisms (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) and HLA-B27 were assayed by RT-PCR...
2018: PloS One
https://www.readbyqxmd.com/read/29571294/detection-of-neisseria-meningitidis-in-a-paediatric-patient-with-septic-arthritis-using-multiplexed-diagnostic-pcr-targeting-meningitis-encephalitis-me
#20
Donnchadh O'Sullivan, Barry Linnane, Amanda Mostyn, Nteimam Jonathan, Marie Lenihan, Nuala H O'Connell, Colum P Dunne
BACKGROUND: Neisseria meningitidis is associated with meningitis and septicemia. Septic meningococcal arthritis is relatively uncommon and its diagnosis associated with clinical and microbiological challenges. Early recognition and treatment is required to prevent joint destruction. PURPOSE: We describe a case of an eleven-year-old boy with septic arthritis and the first reported use of a multiplexed diagnostic PCR test, capable of simultaneous rapid detection of 14 pathogens directly from CSF samples, to determine presence of N...
March 23, 2018: Annals of Clinical Microbiology and Antimicrobials
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