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Kinase and rheumatic disease

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https://www.readbyqxmd.com/read/29115440/aspirin-ameliorates-cerebral-infarction-through-regulation-of-tlr4-nf%C3%A2-%C3%AE%C2%BAb%C3%A2-mediated-endoplasmic-reticulum-stress-in-mouse-model
#1
Xin Wang, Bin Shen, Dezhou Sun, Xiangyu Cui
Cerebral infarction is a cerebrovascular disease caused by local brain ischemic necrosis or softening, which is associated with diabetes, obesity, hypertension and rheumatic heart arrhythmia. Previous studies have indicated that aspirin is a potential oral anticoagulant in the treatment of cerebral ischemic stroke. However, the potential mechanism mediated by aspirin in cerebral infarction therapy is not well understood. The present study analyzed the therapeutic effects of aspirin on cerebral infarction and investigated the underlying molecular mechanism of aspirin‑ameliorated benefits for thrombolysis...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29104639/snail1-is-positively-correlated-with-atrial-fibrosis-in-patients-with-atrial-fibrillation-and-rheumatic-heart-disease
#2
Furong Guo, Xin Yi, Mingjiang Li, Jinrong Fu, Sha Li
The present study investigated the association between Snail1 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD) and to determine the possible mechanism underlying this interrelation. A total of 19 patients were included in the current study and were divided into two groups: A sinus rhythm (SR) group (n=9) and an AF group (n=10). All patients underwent heart valve replacement surgery, during which ~200 mg right atrium tissue was obtained. Hematoxylin and eosin and Masson's trichrome-stained sections were used to evaluate the morphological changes of cardiomyocytes and the level of fibrosis...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29083085/cdk7-inhibition-suppresses-rheumatoid-arthritis-inflammation-via-blockage-of-nf-%C3%AE%C2%BAb-activation-and-il-1%C3%AE-il-6-secretion
#3
Honghai Hong, Yingmin Zeng, Wenxuan Jian, Lei Li, Liying Lin, Yousheng Mo, Meiling Liu, Shuhuan Fang, Yong Xia
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability. Anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARDs) may improve RA process. However, in most patients the treatment effect is still not satisfactory. Cyclin-dependent kinase 7 (CDK7) plays a well-established role in the regulation of the eukaryotic cell division cycle, and recent studies indicated that it exerted anti-inflammatory effect...
October 30, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29071117/variants-of-genes-implicated-in-type-1-interferon-pathway-and-b-cell-activation-modulate-the-eular-response-to-rituximab-at-24-weeks-in-rheumatoid-arthritis
#4
Pierre-Antoine Juge, Steven Gazal, Arnaud Constantin, Xavier Mariette, Bernard Combe, Jacques Tebib, Maxime Dougados, Jean Sibilia, Xavier Le Loet, Philippe Dieudé
BACKGROUND: The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 (IRF5 and IRF7), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24)...
2017: RMD Open
https://www.readbyqxmd.com/read/28854336/in-vitro-anti-inflammatory-activity-of-ilex-cornuta-extract-mediated-by-inhibition-of-extracellular-signal-regulated-kinase-phosphorylation
#5
Jisu Kim, Wonku Kang, Hyeyoung Min
Ilex cornuta, commonly known as Chinese holly, is an evergreen shrub from the family Aquifoliaceae, and it is widely distributed in Korea and China. In folk medicine, the leaves of I. cornuta are used for treatment of several disorders, including weakness of the waist and knees, arthrodynia, headache, acute conjunctivitis, toothache, urticaria, rheumatic arthralgia, and cardiovascular diseases. In this study, we investigated the anti-inflammatory effects of an I. cornuta leaf ethanol extract (ILE) and its underlying mechanisms of action...
October 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28831712/treatment-with-biologicals-in-rheumatoid-arthritis-an-overview
#6
REVIEW
Philipp Rein, Ruediger B Mueller
Management and therapy of rheumatoid arthritis (RA) has been revolutionized by the development and approval of the first biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumor necrosis factor (TNF) α at the end of the last century. Today, numerous efficacious agents with different modes of action are available and achievement of clinical remission or, at least, low disease activity is the target of therapy. Early therapeutic interventions aiming at a defined goal of therapy (treat to target) are supposed to halt inflammation, improving symptoms and signs, and preserving structural integrity of the joints in RA...
August 22, 2017: Rheumatology and Therapy
https://www.readbyqxmd.com/read/28810598/differentially-methylated-regions-in-patients-with-rheumatic-heart-disease-and-secondary-pulmonary-arterial-hypertension
#7
Dawei Zheng, Xiaoying Chen, Ni Li, Lebo Sun, Qingyun Zhou, Huoshun Shi, Guodong Xu, Jing Liu, Limin Xu, Shiwei Duan, Guofeng Shao
The aim of the present study was to identify differentially methylated regions (DMRs) in patients with rheumatic heart disease and secondary pulmonary arterial hypertension (RHD-PAH). A genome-wide DNA methylation assay was performed between 6 patients with RHD-PAH and 6 healthy controls using an Illumina Infinium HumanMethylation450 BeadChip kit. The Limma software package was subsequently used to identify significant DMRs. A total of 40 hypome-thylated and 64 hypermethylated CpG sites were identified between the RHD-PAH group and the control group...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28741869/increased-baseline-runx2-caspase-3-and-p21-gene-expressions-in-the-peripheral-blood-of-disease-modifying-anti-rheumatic-drug-na%C3%A3-ve-rheumatoid-arthritis-patients-are-associated-with-improved-clinical-response-to-methotrexate-therapy
#8
Elena V Tchetina, Natalia V Demidova, Galina A Markova, Elena A Taskina, Svetlana I Glukhova, Dmitry E Karateev
OBJECTIVE: To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. METHODS: Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction...
July 25, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28676069/limited-cutaneous-systemic-sclerosis-skin-demonstrates-distinct-molecular-subsets-separated-by-a-cardiovascular-development-gene-expression-signature
#9
Emma C Derrett-Smith, Viktor Martyanov, Cecilia B Chighizola, Pia Moinzadeh, Corrado Campochiaro, Korsa Khan, Tammara A Wood, Pier Luigi Meroni, David J Abraham, Voon H Ong, Robert Lafyatis, Michael L Whitfield, Christopher P Denton
BACKGROUND: Systemic sclerosis (SSc; scleroderma) is an uncommon autoimmune rheumatic disease characterised by autoimmunity, vasculopathy and fibrosis. Gene expression profiling distinguishes scleroderma from normal skin, and can detect different subsets of disease, with potential to identify prognostic biomarkers of organ involvement or response to therapy. We have performed gene expression profiling in skin samples from patients with limited cutaneous SSc (lcSSc). METHODS: Total RNA was extracted from clinically uninvolved skin biopsies of 15 patients with lcSSc and 8 healthy controls (HC)...
July 4, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28664834/design-of-a-randomised-placebo-controlled-clinical-trial-of-nintedanib-in-patients-with-systemic-sclerosis-associated-interstitial-lung-disease-senscis%C3%A2
#10
Oliver Distler, Kevin K Brown, Jörg H W Distler, Shervin Assassi, Toby M Maher, Vincent Cottin, John Varga, Carl Coeck, Martina Gahlemann, Wiebke Sauter, Hendrik Schmidt, Kristin B Highland
OBJECTIVES: Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). The pathological pathways involved in fibrogenesis in IPF and interstitial lung disease associated with systemic sclerosis (SSc-ILD) show commonalities; both involve fibroblast activation, myofibroblast accumulation and deposition of extracellular matrix. The SENSCIS™ trial is a randomised, placebo-controlled Phase III trial that will evaluate the efficacy and safety of nintedanib in patients with SSc-ILD (NCT02597933)...
June 29, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28588731/anti-rheumatic-drug-iguratimod-protects-against-cancer-induced-bone-pain-and-bone-destruction-in-a-rat-model
#11
Yue Sun, Ying-Xing Wu, Peng Zhang, Guang Peng, Shi-Ying Yu
The bone is one of the most common sites of metastasis in patients with cancer. Current treatments for bone metastases include bisphosphonates, denosumab, non-steroidal anti-inflammatory drugs and analgesics, but each of them has certain limitations. Cytokines and mediators released from various cells in the bone microenvironment may drive a vicious cycle of osteolytic bone metastases. Iguratimod (T-614), a novel disease-modifying anti-rheumatic drug, has demonstrated therapeutic effects by suppressing the production of inflammatory cytokines in rats and patients with rheumatoid arthritis...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28397126/protein-tyrosine-phosphatases-in-systemic-sclerosis-potential-pathogenic-players-and-therapeutic-targets
#12
REVIEW
Cristiano Sacchetti, Nunzio Bottini
PURPOSE OF REVIEW: The pathogenesis of systemic sclerosis depends on a complex interplay between autoimmunity, vasculopathy, and fibrosis. Reversible phosphorylation on tyrosine residues, in response to growth factors and other stimuli, critically regulates each one of these three key pathogenic processes. Protein tyrosine kinases, the enzymes that catalyze addition of phosphate to tyrosine residues, are known players in systemic sclerosis, and tyrosine kinase inhibitors are undergoing clinical trials for treatment of this disease...
May 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28394822/janus-kinase-signal-transducer-and-activator-of-transcription-pathways-in-spondyloarthritis
#13
Smriti K Raychaudhuri, Siba P Raychaudhuri
PURPOSE OF REVIEW: Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway represents a group of several intracellular molecules with a key role in signal pathways activated by growth factors and cytokines. These kinase proteins are associated with the signaling process of multiple key cytokines, which regulates various T-cell subpopulations and their effector cytokines...
July 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28371574/tofacitinib-suppresses-disease-activity-and-febrile-attacks-in-a-patient-with-coexisting-rheumatoid-arthritis-and-familial-mediterranean-fever
#14
Kevser Gök, Gizem Cengiz, Kemal Erol, Salih Ozgocmen
Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK) inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA)...
January 2017: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28323847/role-of-the-mapks-tgf-%C3%AE-1-traf6-signaling-pathway-in-postoperative-atrial-fibrillation
#15
Daoliang Zhang, Xiaoqing Chen, Qian Wang, Shaohui Wu, Yue Zheng, Xu Liu
OBJECTIVES: To explore the relationship between the MAPKs/TGF-β1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD) and its role in atrial fibrillation (AF) after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis. METHODS: A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-β1, TRAF6, and connective tissue growth factor (CTGF), respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28290136/baricitinib-first-global-approval
#16
REVIEW
Anthony Markham
Baricitinib (Olumiant™) is an orally-administered, small-molecule, janus-associated kinase (JAK) inhibitor developed by Eli Lilly and Incyte Corporation for the treatment of rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus. JAKs transduce intracellular signals from cell surface receptors for various cytokines and growth factors involved in inflammation and immune function, suggesting JAK inhibitors may be of therapeutic benefit in inflammatory conditions. In February 2017, baricitinib was approved in the EU, as monotherapy or in combination with methotrexate, for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs)...
April 2017: Drugs
https://www.readbyqxmd.com/read/28264816/eular-recommendations-for-the-management-of-rheumatoid-arthritis-with-synthetic-and-biological-disease-modifying-antirheumatic-drugs-2016-update
#17
REVIEW
Josef S Smolen, Robert Landewé, Johannes Bijlsma, Gerd Burmester, Katerina Chatzidionysiou, Maxime Dougados, Jackie Nam, Sofia Ramiro, Marieke Voshaar, Ronald van Vollenhoven, Daniel Aletaha, Martin Aringer, Maarten Boers, Chris D Buckley, Frank Buttgereit, Vivian Bykerk, Mario Cardiel, Bernard Combe, Maurizio Cutolo, Yvonne van Eijk-Hustings, Paul Emery, Axel Finckh, Cem Gabay, Juan Gomez-Reino, Laure Gossec, Jacques-Eric Gottenberg, Johanna M W Hazes, Tom Huizinga, Meghna Jani, Dmitry Karateev, Marios Kouloumas, Tore Kvien, Zhanguo Li, Xavier Mariette, Iain McInnes, Eduardo Mysler, Peter Nash, Karel Pavelka, Gyula Poór, Christophe Richez, Piet van Riel, Andrea Rubbert-Roth, Kenneth Saag, Jose da Silva, Tanja Stamm, Tsutomu Takeuchi, René Westhovens, Maarten de Wit, Désirée van der Heijde
Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib)...
June 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28250461/the-emerging-safety-profile-of-jak-inhibitors-in-rheumatic-disease
#18
REVIEW
Kevin L Winthrop
Tofacitinib is the first Janus kinase (JAK) inhibitor commercially approved for the treatment of rheumatoid arthritis. This compound and a number of other JAK inhibitors are currently being tested in phase II and III trials for the treatment of a variety of autoimmune inflammatory diseases. Whereas a characteristic safety profile is emerging for some JAK inhibitors, differences between individual agents might emerge on the basis of distinct potency against their molecular targets. Similarly to biological therapy, JAK inhibition can lead to serious and opportunistic infections, and viral infections seem to be particularly frequent...
April 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28240592/analysis-of-non-melanoma-skin-cancer-across-the-tofacitinib-rheumatoid-arthritis-clinical-programme
#19
Jeffrey R Curtis, Eun Bong Lee, George Martin, Xavier Mariette, Ketti K Terry, Yan Chen, Jamie Geier, John Andrews, Mandeep Kaur, Haiyun Fan, Chudy I Nduaka
OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the incidence of non-melanoma skin cancer (NMSC) across the tofacitinib RA development programme. METHODS: NMSC events (through August 2013) were identified in patients receiving tofacitinib in two Phase (P)1, eight P2, six P3 and two long-term extension (LTE) studies. In P123 studies, tofacitinib was administered at various doses (1-30 mg twice daily [BID], 20 mg once daily), as monotherapy or with conventional synthetic disease-modifying anti-rheumatic drugs, mainly methotrexate...
July 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27912150/calea-uniflora-less-attenuates-the-inflammatory-response-to-carrageenan-induced-pleurisy-in-mice
#20
Julia Salvan da Rosa, Silvana Virginia Gagliotti Vigil de Mello, Geison Vicente, Yeo Jim K Moon, Felipe Perozzo Daltoé, Tamires Cardoso Lima, Rafaela de Jesus Souza, Maique Weber Biavatti, Tânia Silvia Fröde
Calea uniflora Less. (family Asteraceae), also named "arnica" and "erva-de-lagarto", is a native plant to the South and Southeast of Brazil. This species was used to treat rheumatism, respiratory diseases, and digestive problems in Brazilian folk medicine. In vitro studies have shown the important biological effects of C. uniflora. However no studies have focused on the mechanism of action of anti-inflammatory activity of C. uniflora. The aim of this study was to evaluate the anti-inflammatory effects of the crude extract, its fractions, and isolated compounds obtained from of C...
January 2017: International Immunopharmacology
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