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Arthritis and gene therapy

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https://www.readbyqxmd.com/read/28511719/interleukin-10-producing-lag3-regulatory-t-cells-are-associated-with-disease-activity-and-abatacept-treatment-in-rheumatoid-arthritis
#1
Shinichiro Nakachi, Shuji Sumitomo, Yumi Tsuchida, Haruka Tsuchiya, Masanori Kono, Rika Kato, Keiichi Sakurai, Norio Hanata, Yasuo Nagafuchi, Shoko Tateishi, Hiroko Kanda, Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
BACKGROUND: Regulatory T cells (Tregs) play a role in the suppression of inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify the function of human IL-10-producing CD4(+)CD25(-)LAG3(+) T cells (LAG3(+) Tregs) and their association with rheumatoid arthritis (RA). METHODS: LAG3(+) Tregs of human peripheral blood mononuclear cells (PBMCs) were cultured with B cells and follicular helper T cells to examine antibody suppression effects...
May 16, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28505128/a-proposal-for-a-study-on-treatment-selection-and-lifestyle-recommendations-in-chronic-inflammatory-diseases-a-danish-multidisciplinary-collaboration-on-prognostic-factors-and-personalised-medicine
#2
Vibeke Andersen, Uffe Holmskov, Signe Bek Sørensen, Mohamad Jawhara, Karina W Andersen, Anette Bygum, Lone Hvid, Jakob Grauslund, Jimmi Wied, Henning Glerup, Ulrich Fredberg, Jan Alexander Villadsen, Søren Geill Kjær, Jan Fallingborg, Seyed A G R Moghadd, Torben Knudsen, Jacob Brodersen, Jesper Frøjk, Jens F Dahlerup, Ole Haagen Nielsen, Robin Christensen, Anders Bo Bojesen, Grith Lykke Sorensen, Steffen Thiel, Nils J Færgeman, Ivan Brandslund, Allan Stensballe, Erik Berg Schmidt, Andre Franke, David Ellinghaus, Philip Rosenstiel, Jeroen Raes, Berit Heitmann, Mette Boye, Charlotte Lindgaard Nielsen, Lars Werner, Jens Kjeldsen, Torkell Ellingsen
Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome...
May 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28493174/genomics-transcriptomics-and-proteomics-to-elucidate-the-pathogenesis-of-rheumatoid-arthritis
#3
REVIEW
Xinqiang Song, Qingsong Lin
Rheumatoid arthritis is an autoimmune disease that affects several organs and tissues, predominantly the synovial joints. The pathogenesis of this disease is not completely understood, which maybe involved in the genomic variations, gene expression, protein translation and post-translational modifications. These system variations in genomics, transcriptomics and proteomics are dynamic in nature and their crosstalk is overwhelmingly complex, thus analyzing them separately may not be very informative. However, various '-omics' techniques developed in recent years have opened up new possibilities for clarifying disease pathways and thereby facilitating early diagnosis and specific therapies...
May 10, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28482392/-three-cases-with-familial-mediterranean-fever-misdiagnosed-as-juvenile-idiopathic-arthritis
#4
J Li, Y Zhang, W Wang, L Q Zhong, H M Song
Objective: To explore the key points of diagnosis and treatment of familial Mediterranean fever(FMF). Method: The clinical data of 3 cases with FMF misdiagnosed as Juvenile idiopathic arthritis(JIA)seen from January 2014 to June 2016 in Peking Union Medical College Hospital were retrospectively collected. The clinical manifestations, gene mutation characteristics, treatment and prognosis were also evaluated. Result: Two cases were male and 1 was female. The mean age of onset was 17 months (3 months to 36 months), while the average age of diagnosis was 6 years and 8 months (24 months to 11 years)...
May 4, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28413980/therapeutic-applications-of-liposomal-based-drug-delivery-and-drug-targeting-for-immune-linked-inflammatory-maladies-a-contemporary-view-point
#5
Mahfoozur Rahman, Sarwar Beg, Amita Verma, Imran Kazmi, Dines Kumar Patel, Firoz Anwar, Vikas Kumar
Immune-based inflammatory diseases are immune related dysregulation in different sites of body, which includes rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, atherosclerosis, etc. Advancements in molecular research have facilitated investigation of their pathogenesis which is involved with inflammatory cytokines cells and several genes. The available drug therapy provides suboptimal therapeutic effects and higher adverse effects. Emergence of liposomal systems of the drugs meant for the above mentioned disease have gained wider importance due to in their high treatment efficacy by means of optimal therapeutic drug delivery...
April 14, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28408801/effects-of-%C3%AE-d-mannuronic-acid-as-a-novel-non-steroidal-anti-inflammatory-medication-within-immunosuppressive-properties-on-il17-ror%C3%AE-t-il4-and-gata3-gene-expressions-in-rheumatoid-arthritis-patients
#6
Anis Barati, Ahmad Reza Jamshidi, Hossein Ahmadi, Zahra Aghazadeh, Abbas Mirshafiey
Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28382433/apoptosis-induced-by-low-level-laser-in-polymorphonuclear-cells-of-acute-joint-inflammation-comparative-analysis-of-two-energy-densities
#7
Lúcia Mara Januário Dos Anjos, Adenilson de Souza da Fonseca, Jacy Gameiro, Flávia de Paoli
Anti-inflammatory property of low-level laser therapy (LLLT) has been widely described in literature, although action mechanisms are not always clarified. Thus, this study aimed to evaluate apoptosis mechanisms in the LLLT anti-inflammatory effects on the arthritis experimental model in vivo at two different energy densities (3 and 30 Jcm(-2)). Arthritis was induced in mice by zymosan solution, animals were distributed into five groups, and morphological analysis, immunocytochemistry and gene expressions for apoptotic proteins were performed...
April 5, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28379201/sirna-delivery-strategies-a-comprehensive-review-of-recent-developments
#8
REVIEW
Katyayani Tatiparti, Samaresh Sau, Sushil Kumar Kashaw, Arun K Iyer
siRNA is a promising therapeutic solution to address gene overexpression or mutations as a post-transcriptional gene regulation process for several pathological conditions such as viral infections, cancer, genetic disorders, and autoimmune disorders like arthritis. This therapeutic method is currently being actively pursued in cancer therapy because siRNA has been found to suppress the oncogenes and address mutations in tumor suppressor genes and elucidate the key molecules in cellular pathways in cancer. It is also effective in personalized gene therapy for several diseases due to its specificity, adaptability, and broad targeting capability...
April 5, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28377787/tofacitinib-versus-biologic-treatments-in-moderate-to-severe-rheumatoid-arthritis-patients-who-have-had-an-inadequate-response-to-nonbiologic-dmards-systematic-literature-review-and-network-meta-analysis
#9
REVIEW
Evelien Bergrath, Robert A Gerber, David Gruben, Tatjana Lukic, Charles Makin, Gene Wallenstein
Objective. To compare the efficacy and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), as monotherapy and combined with disease-modifying antirheumatic drugs (DMARDs) versus biological DMARDs (bDMARDs) and other novel DMARDs for second-line moderate-to-severe rheumatoid arthritis (RA) patients by means of a systematic literature review (SLR) and network meta-analysis (NMA). Methods. MEDLINE®, EMBASE®, and Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials (RCTs) published between 1990 and March 2015...
2017: International Journal of Rheumatology
https://www.readbyqxmd.com/read/28374504/polymorphisms-in-the-promoter-region-of-inos-predispose-to-rheumatoid-arthritis-in-south-indian-tamils
#10
V S Negi, C M Mariaselvam, D P Misra, N Muralidharan, C Fortier, D Charron, R Krishnamoorthy, R Tamouza
Nitric oxide synthase (NOS) catalyses the production of nitric oxide (NO) from L-Arginine, which participates in diverse biological processes including inflammation and apoptosis. Macrophages, chondrocytes, osteoblasts and osteoclasts express inducible NOS (iNOS) at the site of synovial inflammation. NO produced at the inflamed joint may contribute to peri-articular bone loss, mediate apoptosis and regulate Th1/Th2 balance in rheumatoid arthritis (RA). Variations in the promoter region of NOS gene regulate the nitric oxide synthase expression and iNOS (NOS2) polymorphisms have been associated with susceptibility to autoimmune disorders...
April 4, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28370169/osteoclast-differentiation-gene-expression-profiling-reveals-chemokine-ccl4-mediates-rankl-induced-osteoclast-migration-and-invasion-via-pi3k-pathway
#11
Wenhua Xuan, Xiaoke Feng, Chen Qian, Liuying Peng, Yumeng Shi, Lingxiao Xu, Fang Wang, Wenfeng Tan
The migration of osteoclasts (OCs) from circulation and bone marrow into bone surface plays a critical role in the pathogenesis of some bone resorptive diseases, such as rheumatoid arthritis and osteoporosis. To date, how the migration of OCs remains unclear. We investigated gene expression profiling in osteoclastic differentiation of bone marrow-derived macrophages (BMMs) into OCs by microarray analysis. We identified 387 genes overexpressed in osteoclastic differentiation of BMMs. Among them, chemokine CCL4 showed a robust up-regulation signal...
April 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28367474/genetic-analysis-of-southwestern-iranian-patients-with-familial-mediterranean-fever
#12
Mahmoud Haghighat, Mozhgan Moghtaderi, Shirin Farjadian
BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive genetic disorder characterized by recurrent episodes of self-limited fever and serosal tissues inflammation. METHODS: To evaluate clinical symptoms and common genetic mutations in southwestern Iranian patients with FMF, 20 unrelated patients were enrolled in this study based on clinical criteria. A panel of 12 common MEFV gene mutations was tested. RESULTS: The most frequent clinical presentations of the patients were fever, colicky abdominal pain and arthritis...
April 2017: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28363827/a-multi-parameter-response-prediction-model-for-rituximab-in-rheumatoid-arthritis
#13
Tamarah D de Jong, Jérémie Sellam, Rabia Agca, Saskia Vosslamber, Birgit I Witte, Michel Tsang-A-Sjoe, Elise Mantel, Johannes W Bijlsma, Alexandre E Voskuyl, Mike T Nurmohamed, Cornelis L Verweij, Xavier Mariette
OBJECTIVES: To validate the IFN response gene (IRG) set for the prediction of non-response to rituximab in rheumatoid arthritis (RA) and assess the predictive performance upon combination of this gene set with clinical parameters. METHODS: In two independent cohorts of 93 (Cohort I) and 133 (Cohort II) rituximab-starting RA patients, baseline peripheral blood expression of eight IRGs was determined, and averaged into an IFN score. Predictive performance of IFN score and clinical parameters was assessed by logistic regression...
March 28, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28361333/in-the-pursuit-of-methotrexate-treatment-response-biomarker-in-juvenile-idiopathic-arthritis-are-we-getting-closer-to-personalised-medicine
#14
REVIEW
Justyna Roszkiewicz, Elzbieta Smolewska
PURPOSE OF REVIEW: Methotrexate (MTX) is the most widely used disease-modifying antirheumatic drug (DMARD) in paediatric rheumatology and the mainstay in the therapy of juvenile idiopathic arthritis (JIA). Despite its common use, about 30% of children fail to respond to this medicine that results in potentially irreversible joint damage. RECENT FINDINGS: No clinical biomarker that would predict the outcome of MTX therapy exists. Results of several studies focused on gene polymorphisms and outcome of this DMARD therapy have been published, but no reliable genetic marker useful to tailor the therapy has been discovered so far...
April 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28343748/b-cells-expressing-the-iga-receptor-fcrl4-participate-in-the-autoimmune-response-in-patients-with-rheumatoid-arthritis
#15
Khaled Amara, Elizabeth Clay, Lorraine Yeo, Daniel Ramsköld, Julia Spengler, Natalie Sippl, James A Cameron, Lena Israelsson, Philip J Titcombe, Caroline Grönwall, Ilfita Sahbudin, Andrew Filer, Karim Raza, Vivianne Malmström, Dagmar Scheel-Toellner
The clinical efficacy of B cell targeting therapies highlights the pathogenic potential of B cells in inflammatory diseases. Expression of Fc Receptor like 4 (FcRL4) identifies a memory B cell subset, which is enriched in the joints of patients with rheumatoid arthritis (RA) and in mucosa-associated lymphoid tissue. The high level of RANKL production by this B cell subset indicates a unique pathogenic role. In addition, recent work has identified a role for FcRL4 as an IgA receptor, suggesting a potential function in mucosal immunity...
March 24, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28337018/rheumatoid-arthritis-fibroblast-like-synoviocyte-suppression-mediated-by-pten-involves-survivin-gene-silencing
#16
Danna Chen, Dongdong Liu, Dan Liu, Min He, Anping Peng, Jiarui Xu, Li Lin, Fudong Luo, Lin Chen, Xianzhang Huang, Junhua Zhuang, Jianhua Xu
Survivin is a proto-oncogene biomarker known for its anti-apoptotic and cell cycle regulating properties induced by the activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. In the context of non-cancer pathology, such as rheumatoid arthritis (RA), survivin has emerged as a feature associated with severe joint damage and poor treatment response. Phosphatase and tensin homolog (PTEN) is a phosphatase antagonizing all classes of PI3K. The interplay between survivin oncogenic mechanisms and proliferation suppression networks in RA has remained largely elusive...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331226/the-histone-deacetylase-inhibitor-givinostat-itf2357-exhibits-potent-anti-tumor-activity-against-crlf2-rearranged-bcp-all
#17
A M Savino, J Sarno, L Trentin, M Vieri, G Fazio, M Bardini, C Bugarin, G Fossati, K Davis, G Gaipa, S Izraeli, L H Meyer, G P Nolan, A Biondi, G Te Kronnie, C Palmi, G Cazzaniga
Leukemias bearing CRLF2 and JAK2 gene alterations are characterized by aberrant JAK/STAT signaling and poor prognosis. The HDAC inhibitor givinostat/ITF2357 has been shown to exert antineoplastic activity against both systemic juvenile idiopathic arthritis and myeloproliferative neoplasms through inhibition of the JAK/STAT pathway. These findings led us to hypothesize that givinostat might also act against CRLF2-rearranged BCP-ALL, which lack effective therapies. Here, we found that givinostat inhibited proliferation and induced apoptosis of BCP-ALL CRLF2-rearranged cell lines, positive for exon 16 JAK2 mutations...
March 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28296761/polymorphisms-and-pharmacogenomics-for-the-toxicity-of-methotrexate-monotherapy-in-patients-with-rheumatoid-arthritis-a-systematic-review-and-meta-analysis
#18
REVIEW
Qi Qiu, Jing Huang, Yang Lin, Xiaoming Shu, Huizheng Fan, Zhihua Tu, Youwen Zhou, Cheng Xiao
BACKGROUND: Methotrexate (MTX) is widely used and considered a first-line disease modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, 10% to 30% of patients discontinue therapy within a year of starting the treatment, usually because of undesirable side effects. Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX toxicity in RA patients, although inconsistent results have been reported...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28294321/artesunate-inhibits-rankl-induced-osteoclastogenesis-and-bone-resorption-in-vitro-and-prevents-lps-induced-bone-loss-in-vivo
#19
Cheng-Ming Wei, Qian Liu, Fang-Ming Song, Xi-Xi Lin, Yi-Ji Su, Jiake Xu, Lin Huang, Shao-Hui Zong, Jin-Min Zhao
Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs)...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28286757/effect-of-tumor-necrosis-factor-inhibitor-therapy-on-osteoclasts-precursors-in-rheumatoid-arthritis
#20
Inês P Perpétuo, Joana Caetano-Lopes, Ana Maria Rodrigues, Raquel Campanilho-Marques, Cristina Ponte, Helena Canhão, Mari Ainola, João E Fonseca
Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations...
2017: BioMed Research International
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