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Arthritis and gene therapy

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https://www.readbyqxmd.com/read/29667551/circulating-mir-10a-as-predictor-of-therapy-response-in-rheumatoid-arthritis-patients-treated-with-methotrexate
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
Nagaraja Haleagrahara, Kelly Hodgson, Socorro Miranda-Hernandez, Samuel Hughes, Anupama Bangra Kulur, Ketheesan Natkunum
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
#9
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
#10
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, inflammatory, 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...
March 28, 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
#11
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
#12
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
https://www.readbyqxmd.com/read/29561430/resistin-polymorphisms-are-associated-with-rheumatoid-arthritis-susceptibility-in-chinese-han-subjects
#13
Lihong Wang, Chih-Hsin Tang, Tingting Lu, Yi Sun, Guohong Xu, Chien-Chung Huang, Shun-Fa Yang, Chen-Ming Su
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease. To date, the specific mechanisms that drive RA disease remain unknown and provide the impetus for genetic investigations into the development of RA. Researchers hope to identify gene polymorphisms that could serve as treatment targets in patients with RA. We have previously suggested that the gene encoding the pro-inflammatory adipokine resistin (RETN) may correlate with RA development. In this report, we sought to determine whether selected RETN single nucleotide polymorphisms (SNPs) are associated with RA susceptibility and clinicopathological characteristics...
March 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29559718/type-i-interferon-in-rheumatic-diseases
#14
REVIEW
Theresa L Wampler Muskardin, Timothy B Niewold
The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including systemic lupus erythematosus, Sjögren syndrome, myositis, systemic sclerosis, and rheumatoid arthritis. In normal immune responses, type I interferons have a critical role in the defence against viruses, yet in many rheumatic diseases, large subgroups of patients demonstrate persistent activation of the type I interferon pathway. Genetic variations in type I interferon-related genes are risk factors for some rheumatic diseases, and can explain some of the heterogeneity in type I interferon responses seen between patients within a given disease...
March 21, 2018: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/29551126/role-of-mda-7-il-24-a-multifunction-protein-in-human-diseases
#15
Mitchell E Menezes, Praveen Bhoopathi, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B Fisher
Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24)...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/29545108/yinyang1-deficiency-ameliorates-joint-inflammation-in-a-murine-model-of-rheumatoid-arthritis-by-modulating-th17-cell-activation
#16
Jeong-Eun Kwon, Seon-Yeong Lee, Hyeon-Beom Seo, Young-Mee Moon, Jun-Geol Ryu, Kyung-Ah Jung, Joo-Yeon Jhun, Jin-Sil Park, Soo-Seok Hwang, Joo-Myeong Kim, Gap Ryol Lee, Sung-Hwan Park, Mi-La Cho
Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor that functions in cooperation with various cofactors to regulate gene expression. In the immune system, YY1 enhances cytokine production and T helper (Th) 2 effector cell differentiation, resulting in the activation of inflammation. However, no studies have reported the role of YY1 in Th17 cell regulation, which is implicated in rheumatoid arthritis (RA). We investigated the expression of YY1 in Th17 cells in vitro and revealed increased levels of YY1 mRNA and protein...
March 12, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29541795/the-role-of-lymphotoxin-%C3%AE-in-rheumatoid-arthritis
#17
REVIEW
Tomohiro Hirose, Yuri Fukuma, Ayumu Takeshita, Keiichiro Nishida
BACKGROUND: The role of tumor necrosis factor (TNF) in the inflammatory response in rheumatoid arthritis (RA) is well established, whereas less is known about the role of TNF's close homolog, lymphotoxin alpha (LTα). FINDINGS: Increased levels of LTα are found in the serum and synovial tissue of patients with RA, and in vitro studies found that LTα-induced proliferation of RA fibroblast-like synoviocytes was at a similar level to TNF. These findings support the idea that anti-LTα treatment could be beneficial in patients with RA, but pateclizumab, an anti-LTα antibody, was not as efficacious as the anti-TNF agent adalimumab in reducing symptoms of RA in a head-to-head study, suggesting that anti-LTα therapies might not represent a valid alternative treatment option in patients with RA...
March 14, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29520081/evaluation-of-a-clinical-pharmacogenetics-model-to-predict-methotrexate-response-in-patients-with-rheumatoid-arthritis
#18
Rosario López-Rodríguez, Aida Ferreiro-Iglesias, Aurea Lima, Miguel Bernardes, Andrzej Pawlik, Agnieszka Paradowska-Gorycka, Jerzy Świerkot, Ryszard Slezak, Isidoro Gonzalez-Alvaro, Javier Narvaez, Eva Pérez-Pampín, Antonio Mera-Varela, Laura Vidal-Bralo, José Gorgonio Acuña-Ochoa, Carmen Conde, Antonio Gonzalez
Variability of response to treatment hinders successful management of rheumatoid arthritis (RA). Consequently, a clinical pharmacogenetics model for predicting response to methotrexate (CP-MTX) has been previously proposed that includes four clinical variables (disease activity, sex, the presence of rheumatoid factor and smoking status) and four SNPs (rs2236225, rs17602729, rs1127354, and rs2372536) in genes of the folate pathway. It showed good performance, but failed to attract attention, likely, in relation with lack of clear clinical benefit...
March 8, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29519620/therapeutic-perspectives-for-interferons-and-plasmacytoid-dendritic-cells-in-rheumatoid-arthritis
#19
REVIEW
Ramzi Nehmar, Alexandre Mariotte, Aurore de Cauwer, Jean Sibilia, Seiamak Bahram, Philippe Georgel
Rheumatoid arthritis (RA) is a multifactorial immune disease exhibiting diverse clinical responses to specific therapeutic agents. Such heterogeneity reflects variable activation of signaling pathways. Consequently, RA physiopathology has been linked to many immune cells and factors, with controversial observations for interferons (IFNs). In this opinion article, we review the roles of these cytokines and the cells that produce them in light of recent data: clinical observations showing that expression of IFN-dependent genes does not reflect RA activity and RA mouse models in which the stimulation of IFN-dependent pathways provided disease protection...
March 5, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29486610/a-multicenter-double-blind-phase-iii-clinical-trial-to-evaluate-the-efficacy-and-safety-of-a-cell-and-gene-therapy-in-knee-osteoarthritis-patients
#20
Myung-Ku Kim, Chul-Won Ha, Yong In, Sung-Do Cho, Eui-Sung Choi, Jeong-Ku Ha, Ju-Hong Lee, Jae-Doo Yoo, Seong-Il Bin, Choong-Hyeok Choi, Hee-Soo Kyung, Myung-Chul Lee
OBJECTIVE: To test the clinical efficacy of TissueGene-C (TG-C), a cell and gene therapeutic for osteoarthritis consisting of non-transformed and transduced chondrocytes (3:1), retrovirally transduced to overexpress TGF-β1. DESIGN: We randomly assigned 163 with knee osteoarthritis to receive intra-articular TG-C or placebo in Kellgren-Lawrence grade 3 patients for clinical trial. Primary efficacy measures included criteria for subjective assessment by International Knee Documentation Committee (IKDC) and pain severity by Visual Analog Scale (VAS) for 52 weeks...
February 27, 2018: Human Gene Therapy. Clinical Development
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