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Arthritis and gene therapy

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https://www.readbyqxmd.com/read/28207896/rna-seq-analysis-of-chikungunya-virus-infection-and-identification-of-granzyme-a-as-a-major-promoter-of-arthritic-inflammation
#1
Jane A C Wilson, Natalie A Prow, Wayne A Schroder, Jonathan J Ellis, Helen E Cumming, Linden J Gearing, Yee Suan Poo, Adam Taylor, Paul J Hertzog, Francesca Di Giallonardo, Linda Hueston, Roger Le Grand, Bing Tang, Thuy T Le, Joy Gardner, Suresh Mahalingam, Pierre Roques, Phillip I Bird, Andreas Suhrbier
: Chikungunya virus (CHIKV) is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis of feet and lymph nodes at peak viraemia (day 2 post infection), acute arthritis (day 7) and chronic disease (day 30) in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated in CHIKV patients were also up-regulated in the mouse model. CHIKV sequence information was also obtained with up to ≈8% of the reads mapping to the viral genome; however, no adaptive viral genome changes were apparent...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28129106/a-synthetic-mammalian-therapeutic-gene-circuit-for-sensing-and-suppressing-inflammation
#2
Anže Smole, Duško Lainšček, Urban Bezeljak, Simon Horvat, Roman Jerala
Inflammation, which is a highly regulated host response against danger signals, may be harmful if it is excessive and deregulated. Ideally, anti-inflammatory therapy should autonomously commence as soon as possible after the onset of inflammation, should be controllable by a physician, and should not systemically block beneficial immune response in the long term. We describe a genetically encoded anti-inflammatory mammalian cell device based on a modular engineered genetic circuit comprising a sensor, an amplifier, a "thresholder" to restrict activation of a positive-feedback loop, a combination of advanced clinically used biopharmaceutical proteins, and orthogonal regulatory elements that linked modules into the functional device...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28121199/functional-analysis-of-choline-transporters-in-rheumatoid-arthritis-synovial-fibroblasts
#3
Masayuki Seki, Yuiko Kawai, Chikanao Ishii, Tsuyoshi Yamanaka, Masato Odawara, Masato Inazu
OBJECTIVES: In this study, we examined the functional characteristics of choline uptake and sought to identify the transporters in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: The expression of choline transporters was evaluated by quantitative real-time PCR, western blotting, and immunocytochemistry. Time course, Na(+)-dependency, and kinetics of [(3)H]choline uptake were investigated. Effects of cationic drugs on the uptake of [(3)H]choline, cell viability, and caspase-3/7 activity were also examined...
February 1, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28115015/early-changes-in-gene-expression-and-inflammatory-proteins-in-systemic-juvenile-idiopathic-arthritis-patients-on-canakinumab-therapy
#4
Arndt H Brachat, Alexei A Grom, Nico Wulffraat, Hermine I Brunner, Pierre Quartier, Riva Brik, Liza McCann, Huri Ozdogan, Lidia Rutkowska-Sak, Rayfel Schneider, Valeria Gerloni, Liora Harel, Maria Terreri, Kristin Houghton, Rik Joos, Daniel Kingsbury, Jorge M Lopez-Benitez, Stephan Bek, Martin Schumacher, Marie-Anne Valentin, Hermann Gram, Ken Abrams, Alberto Martini, Daniel J Lovell, Nanguneri R Nirmala, Nicolino Ruperto
BACKGROUND: Canakinumab is a human anti-interleukin-1β (IL-1β) monoclonal antibody neutralizing IL-1β-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA). METHODS: Gene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA)...
January 23, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28107378/polymorphisms-in-stat4-ptpn2-psors1c1-and-traf3ip2-genes-are-associated-with-the-response-to-tnf-inhibitors-in-patients-with-rheumatoid-arthritis
#5
Paola Conigliaro, Cinzia Ciccacci, Cristina Politi, Paola Triggianese, Sara Rufini, Barbara Kroegler, Carlo Perricone, Andrea Latini, Giuseppe Novelli, Paola Borgiani, Roberto Perricone
OBJECTIVE: Rheumatoid Arthritis (RA) is a progressive autoimmune disease characterized by chronic joint inflammation and structural damage. Remission or at least low disease activity (LDA) represent potentially desirable goals of RA treatment. Single nucleotide polymorphisms (SNPs) in several genes might be useful for prediction of response to therapy. We aimed at exploring 4 SNPs in candidate genes (STAT4, PTPN2, PSORS1C1 and TRAF3IP2) in order to investigate their potential role in the response to therapy with tumor necrosis factor inhibitors (TNF-i) in RA patients...
2017: PloS One
https://www.readbyqxmd.com/read/28058501/-cytokine-neutralization-at-specific-cellular-source-a%C3%A2-new-therapeutic-paradigm-german-version
#6
A A Kruglov, S A Nedospasov
BACKGROUND: Currently, treatment of autoimmune diseases is based on manipulation of general control mechanisms, including those mediated by immunoregulatory cytokines. This approach is non-curative and may cause unwanted side effects due to numerous beneficial and non-redundant functions of a particular cytokine. METHODS: Techniques of reverse genetics, such as conditional gene targeting, were employed to uncover the contributions of two proinflammatory and immunomodulatory cytokines, tumour necrosis factor (TNF) and interleukin 6 (IL-6), in various disease states...
January 5, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28048692/mo-fg-207b-01-thorax-lung
#7
H Aerts
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048031/mo-fg-207b-02-breast
#8
H Li
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047352/mo-fg-207b-03-brain
#9
P Tiwari
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046682/mo-fg-207b-04-respond-to-therapy
#10
W Lu
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046637/mo-fg-207b-00-state-of-the-art-in-radiomics-in-radiology-and-radiation-oncology
#11
Maryellen Giger, Joseph Deasy
State-of-the-Art in Radiomics in Radiology and Radiation Oncology Radiomics is the science of converting medical images into mineable data, data that are descriptive of "phenotypes," which may provide diagnostic, prognostic, or therapeutic information. Genomics is the science of sequencing and analyzing the function and structure of genomes; the complete set of DNA in a single cell of an organism. In turn, imaging genomics (or radiogenomics) is concerned with the correlation between image-based features, as determined by radiomics, and gene expression, as determined by genomics...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28040706/familial-mediterranean-fever-associated-diseases-in-children
#12
Z Birsin Özçakar, Nilgün Çakar, Nermin Uncu, Banu Acar Çelikel, Fatoş Yalçınkaya
BACKGROUND: MEditerranean FeVer (MEFV) gene encodes for the pyrin protein and a mutated pyrin is associated with a prolonged or augmented inflammation. Hence, various diseases were reported to be associated with familial Mediterranean fever (FMF) or carriers of MEFV mutations. However, systematic evaluation of all associated diseases in children with FMF has not been done previously. AIM: The aim of this study was to investigate the frequency and type of FMF-associated diseases in children...
December 30, 2016: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28039611/alternative-new-mesenchymal-stem-cell-source-exerts-tumor-tropism-through-alcam-and-n-cadherin-via-regulation-of-microrna-192-and-218
#13
Ran Kim, Sang In Park, Chang Youn Lee, Jihyun Lee, Pilseog Kim, Sekyung Oh, Hojin Lee, Min Young Lee, Jongmin Kim, Yong-An Chung, Ki-Chul Hwang, Lee-So Maeng, Woochul Chang
Gliomas are the most common type of malignant primary brain tumors. Some treatments of gliomas exist, but they are rarely curative. Mesenchymal stem cells (MSCs) are emerging as potential modes of targeted cancer therapy owing to their capacity for homing toward tumor sites. It has been proposed that MSCs derived from various sources, such as bone marrow, adipose tissue and umbilical cord blood, can be used as cell-based therapy for brain tumors. Here, MSCs obtained from the synovial fluid of osteoarthritis or rheumatoid arthritis patients were investigated as therapeutic candidates...
March 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28028154/analysis-of-haematological-changes-in-tofacitinib-treated-patients-with-rheumatoid-arthritis-across-phase-3-and-long-term-extension-studies
#14
Hendrik Schulze-Koops, Vibeke Strand, Chudy Nduaka, Ryan DeMasi, Gene Wallenstein, Kenneth Kwok, Lisy Wang
OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The aim of this analysis was to characterize changes in haematological parameters following tofacitinib treatment, and to compare changes in haemoglobin with markers of disease activity, fatigue and vitality. METHODS: Changes in neutrophil counts, lymphocyte counts and haemoglobin levels were analysed in patients with RA from six phase 3 randomized controlled trials (n = 4271) of tofacitinib 5 or 10 mg bd, placebo or active comparators of up to 24 months' duration, and two long-term extension (LTE) studies (n = 4858) of tofacitinib of up to 84 months' duration...
January 2017: Rheumatology
https://www.readbyqxmd.com/read/28027930/tocilizumab-improves-the-proatherothrombotic-profile-of-rheumatoid-arthritis-patients-modulating-endothelial-dysfunction-netosis-and-inflammation
#15
P Ruiz-Limón, R Ortega, I Arias de la Rosa, M C Abalos-Aguilera, C Perez Sanchez, Y Jimenez Gomez, E Peralbo-Santaella, P Font, D Ruiz-Vilches, G Ferrin, E Collantes-Estevez, A Escudero, C H López Pedrera, N Barbarroja
Tocilizumab (TCZ) is an effective treatment for rheumatoid arthritis (RA). However, the changes that occurred after TCZ therapy on endothelial dysfunction, monocyte activity, NETosis, and oxidative stress, the principal effectors of atherosclerosis and cardiovascular disease, have not been analyzed yet. A total of 20 RA patients received 162 mg per week subcutaneous TCZ for 6 months. Endothelial function was measured through postocclusive hyperemia using Laser Doppler. Oxidative stress markers in monocytes and neutrophils were analyzed by flow cytometry...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28002318/brahma-related-gene-1-induces-apoptosis-in-a-p53-dependent-manner-in-human-rheumatoid-fibroblast-like-synoviocyte-mh7a
#16
Hongli Hou, Weipeng Xing, Wuyin Li
Blocked apoptosis and aggressive inflammatory responses occur in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA) patients. Although Brahma-related gene 1 (BRG1) is considered as a tumor suppressor, few research covers its role in RA. This study aims to reveal effects and potential mechanisms of BRG1 in human FLS cell line MH7A.BRG1 expression in MH7A cells was altered by transfection of overexpression vectors or short hairpin RNAs (shRNAs). Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry after transfection...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27988396/total-sesquiterpene-lactones-prepared-from-inula-helenium-l-has-potentials-in-prevention-and-therapy-of-rheumatoid-arthritis
#17
Shuang Gao, Qun Wang, Xin-Hui Tian, Hui-Liang Li, Yun-Heng Shen, Xi-Ke Xu, Guo-Zhen Wu, Zhen-Lin Hu, Wei-Dong Zhang
BACKGROUNDS: Inula helenium L. is an herb with anti-inflammatory properties. Sesquiterpene lactones (SLs), mainly alantolactone (AL) and isoalantolactone (IAL), are considered as its active ingredients. However, the anti-inflammatory effects of SL-containing extracts of I. helenium have not been explored. Here we prepared total SLs from I. helenium (TSL-IHL), analyzed its chemical constituents, and performed cellular and animal studies to evaluate its anti-inflammatory activities. MATERIALS AND METHODS: The chemical profile of TSL-IHL was analyzed by HPLC-UV...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27960219/an-mri-evaluation-of-patients-who-underwent-treatment-with-a-cell-mediated-gene-therapy-for-degenerative-knee-arthritis-a-phase-iia-clinical-trial
#18
Jung Jong Cho, Saara Totterman, Randa K Elmallah, Tae Won Kim, Bumsup Lee, Michael A Mont
Multiple therapies have been developed to slow down the progression of knee osteoarthritis (OA), with the aim of avoiding or delaying TKA. One such potential method is cell-mediated gene therapy, which utilizes allogeneic human chondrocytes modified to express transforming growth factor-β1. Using magnetic resonance imaging (MRI), we evaluated patients who underwent treatment with this injection in a Phase II study and assessed structural changes in: (1) bone marrow edema lesions, (2) cartilage defect depth and surface area, (3) articular bone surface and osteophytes, and (4) meniscus structure and signal, as well as changes in (5) joint fluid, (6) periarticular inflammation, and (7) synovial inflammation...
December 13, 2016: Journal of Knee Surgery
https://www.readbyqxmd.com/read/27958380/influence-of-il6r-gene-polymorphisms-in-the-effectiveness-to-treatment-with-tocilizumab-in-rheumatoid-arthritis
#19
M Maldonado-Montoro, M Cañadas-Garre, A González-Utrilla, M Ángel Calleja-Hernández
In the present study, we aimed to investigate the influence of clinical parameters and single-nucleotide polymorphisms of interleukin-6 receptor (rs12083537, rs2228145, rs4329505 and rs11265618) on response to tocilizumab, TCZ (European League Against Rheumatism (EULAR) response, remission, low disease activity (LDA) and improvement of DAS28). We performed a retrospective cohort study in patients with Rheumatoid Arthritis (RA) treated with TCZ for 12 months. Multivariable analysis showed that the only variable independently associated to satisfactory EULAR response (odds ratio (OR): 0...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27912794/a-genetic-risk-score-composed-of-rheumatoid-arthritis-risk-alleles-hla-drb1-haplotypes-and-response-to-tnfi-therapy-results-from-a-swedish-cohort-study
#20
Xia Jiang, Johan Askling, Saedis Saevarsdottir, Leonid Padyukov, Lars Alfredsson, Sebastien Viatte, Thomas Frisell
BACKGROUND: To prevent debilitating and irreversible joint damage, rheumatoid arthritis (RA) is often treated with tumor necrosis factor inhibitor (TNFi), but many patients do not respond to this costly therapy. Few predictors for response are known, and it has been proposed that genetic factors which influence the development of RA may also influence disease severity and response to therapy. Several previous studies have attempted to confirm this but results remain inconclusive. We expand on previous studies by including more RA risk alleles, and maximize power by combining them into a genetic risk score...
December 3, 2016: Arthritis Research & Therapy
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